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In this installment of the Longevity & Aging Series, Dr. Ming Yu and Namita Hattangady from the Fred Hutchinson Cancer Center in Seattle, join host Dr. Evgeniy Galimov to discuss a research paper they co-authored that was published as the cover for Volume 16, Issue 4 of Aging (Aging-US), entitled, “Mapping the core senescence phenotype of primary human colon fibroblasts.” DOI - https://doi.org/10.18632/aging.205577 Corresponding authors - William M. Grady - wgrady@fredhutch.org, and Ming Yu - myu@fredhutch.org Video interview - https://www.youtube.com/watch?v=eqSa7My_a7w Interview transcription - https://www.aging-us.com/interviews/longevity-aging-series-s2-e2-dr-ming-yu-and-namita-hattangady Abstract Advanced age is the largest risk factor for many diseases and several types of cancer, including colorectal cancer (CRC). Senescent cells are known to accumulate with age in various tissues, where they can modulate the surrounding tissue microenvironment through their senescence associated secretory phenotype (SASP). Recently, we showed that there is an increased number of senescent cells in the colons of CRC patients and demonstrated that senescent fibroblasts and their SASP create microniches in the colon that are conducive to CRC onset and progression. However, the composition of the SASP is heterogenous and cell-specific, and the precise senescence profile of colon fibroblasts has not been well-defined. To generate a SASP atlas of human colon fibroblasts, we induced senescence in primary human colon fibroblasts using various in vitro methods and assessed the resulting transcriptome. Using RNASequencing and further validation by quantitative RT-PCR and Luminex assays, we define and validate a ‘core senescent profile' that might play a significant role in shaping the colon microenvironment. We also performed KEGG analysis and GO analyses to identify key pathways and biological processes that are differentially regulated in colon fibroblast senescence. These studies provide insights into potential driver proteins involved in senescence-associated diseases, like CRC, which may lead to therapies to improve overall health in the elderly and to prevent CRC. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205577 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, senescence associated secretory phenotype, SASP, colorectal cancer, cancer About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Good evening and a huge welcome back to the show, I hope you've had a great day and you're ready to kick back and relax with another episode of Brett's old time radio show. Hello, I'm Brett your host for this evening and welcome to my home in beautiful Lyme Bay where it's lovely December night. I hope it's just as nice where you are. You'll find all of my links at www.linktr.ee/brettsoldtimeradioshow A huge thankyou for joining me once again for our regular late night visit to those dusty studio archives of Old Time radio shows right here at my home in the united kingdom. Don't forget I have an instagram page and youtube channel both called brett's old time radio show and I'd love it if you could follow me. Feel free to send me some feedback on this and the other shows if you get a moment, brett@tourdate.co.uk #sleep #insomnia #relax #chill #night #nighttime #bed #bedtime #oldtimeradio #drama #comedy #radio #talkradio #hancock #tonyhancock #hancockshalfhour #sherlock #sherlockholmes #radiodrama #popular #viral #viralpodcast #podcast #podcasting #podcasts #podtok #podcastclip #podcastclips #podcasttrailer #podcastteaser #newpodcastepisode #newpodcast #videopodcast #upcomingpodcast #audiogram #audiograms #truecrimepodcast #historypodcast #truecrime #podcaster #viral #popular #viralpodcast #number1 #instagram #youtube #facebook #johnnydollar #crime #fiction #unwind #devon #texas #texasranger #beer #seaton #seaside  #smuggler #colyton #devon #seaton #beer #branscombe #lymebay #lymeregis #brett #brettorchard #orchard #greatdetectives #greatdetectivesofoldtimeradio #detectives #johnnydollar #thesaint #steptoe #texasrangers   Yours Truly, Johnny Dollar is a radio drama that aired on CBS Radio from February 18, 1949 to September 30, 1962. The first several seasons imagined protagonist Johnny Dollar as a private investigator drama, with Charles Russell, Edmond O'Brien and John Lund portraying Dollar in succession over the years. In 1955 after a yearlong hiatus, the series came back in its best-known incarnation with Bob Bailey starring in "the transcribed adventures of the man with the action-packed expense account – America's fabulous freelance insurance investigator." There were 809 episodes (plus two not-for-broadcast auditions) in the 12-year run, and more than 710 still exist today. Jim Cox's book American Radio Networks: A History cites "886 total performances" which includes repeat performances. Format The format best remembered was instituted by writer-director Jack Johnstone. Each case usually started with a phone call from an insurance adjuster, calling on Johnny to investigate an unusual claim: a suspicious death, an attempted fraud, a missing person, or other mysterious circumstances. Each story required Johnny to travel to some distant locale, usually within the United States but sometimes abroad, where he was almost always threatened with personal danger in the course of his investigations. He would compare notes with the police officials who had first investigated each strange occurrence, and followed every clue until he figured out what actually happened. Johnny's file on each case was usually referenced as a "matter," as in "The Silver Blue Matter" or "The Forbes Matter". Later episodes were more fanciful, with titles like "The Wayward Trout Matter" and "The Price of Fame Matter" (the latter featuring a rare guest-star appearance by Vincent Price as himself; here Price and Dollar team up to retrieve a painting stolen by Price's insurance agent). Johnny usually stuck to business, but would sometimes engage in romantic dalliances with women he encountered in his travels; later episodes gave Johnny a steady girlfriend, Betty Lewis. Johnny's precious recreational time was usually spent fishing, and it was not uncommon for Johnny's clients to exploit this favorite pastime in convincing him to take on a job near good fishing locations. His past was rarely mentioned, but Dollar in “The Bennett Matter” described himself as a four-year US Marine veteran who then worked as a police officer for a decade before changing careers to insurance investigation.[5] In "The Blackburn Case" Dollar also refers to his time as a Pinkerton Detective. Each story was recounted in flashback, and every few minutes the action would be interrupted by Johnny listing a line item from his expense account, which served as an effective scene transition. Most of the expense account related to transportation, lodging, and meals, but no incidental expense was too small for Johnny to itemize, as in "Item nine, 10 cents. Aspirin. I needed them." The monetary amounts weren't always literal: the smallest line item Johnny ever recorded was "two cents: what I felt like" after a professional setback; the largest was "one million dollars" (the way he felt after finding a missing woman and her daughter in a snowbound cabin). The episodes generally finished with Johnny tallying up his expense account and traveling back to Hartford, Connecticut, where he was based. Sometimes Johnny would add a sardonic postscript under "Remarks," detailing the aftermath of the case. ("The Todd Matter," which especially disgusted Johnny, ended abruptly with "Remarks – nil!") In later seasons the program sometimes referred to itself, with other characters recognizing Dollar's voice from the radio; in the episode “The Salkoff Sequel Matter” Johnny's radio show becomes an important plot point. Original run As originally conceived, Johnny Dollar was a smart, tough, wisecracking detective who tossed silver-dollar tips to waiters and bellhops. Dick Powell starred in the audition show, recorded in 1948, but withdrew from the role in favour of other detective programs, Rogue's Gallery and Richard Diamond, Private Detective. The Johnny Dollar role went instead to Charles Russell. The show for which Powell auditioned was originally titled Yours Truly, Lloyd London, although the name of the show and its lead character were changed to avoid legal problems with the actual insurance company, Lloyd's of London, before the audition tape of December 7, 1948, was recorded. With the first three actors to play Johnny Dollar – radio actor Russell and movie tough-guy actors Edmond O'Brien and John Lund – there was little to distinguish Johnny Dollar from other detective series at the time (Richard Diamond, Philip Marlowe and Sam Spade). While always a friend of the police, Johnny wasn't necessarily a stickler for the strictest interpretation of the law. He was willing to let some things slide to satisfy his own sense of justice, as long as the interests of his employer were also protected. The series ended in September 1954. Revival CBS Radio revived Yours Truly, Johnny Dollar in October 1955 with a new leading man, a new director, and a new format. The program changed from a 30-minute, one-episode-per-week program to a 15-minute, five-nights-a-week serial (Monday through Friday, 8–8:15 pm EST) produced and directed by radio veteran Jack Johnstone. The new Johnny Dollar was Bob Bailey, who had just come off another network detective series, Let George Do It. With a new lead and 75 minutes of air time each week, it became possible to develop each storyline with more detail and with more characters. Almost all of the Johnny Dollar serials were presented by CBS Radio on a sustaining basis (unsponsored, with no commercials); only two of the 55 serials take time out for a sponsor's message. Bob Bailey was exceptionally good in this format, making Johnny more sensitive and thoughtful in addition to his other attributes. Vintage-radio enthusiasts often endorse Bailey as the best of the Johnny Dollars, and consider the 13-month run of five-part stories to be some of the greatest drama in radio history. The serial scripts were usually written by Johnstone, "John Dawson" (a pseudonym for E. Jack Neuman), Les Crutchfield, or Robert Ryf. Blake Edwards also contributed several scripts and the show was always produced and directed by Johnstone. The show featured a stock company of supporting actors, including Virginia Gregg, Harry Bartell, Vic Perrin, Lawrence Dobkin, Stacy Harris, Parley Baer, Howard McNear, John Dehner, Barney Phillips, Lillian Buyeff, Tony Barrett, Don Diamond, Alan Reed, and Forrest Lewis. Movie character actors appeared occasionally, including Jay Novello, Hans Conried, Frank Nelson, Leon Belasco, William Conrad, Edgar Barrier, Jeanne Bates, Gloria Blondell, and Billy Halop. In late 1956, CBS Radio retooled the show, which reverted to a weekly half-hour drama, airing on late Sunday afternoons. Bob Bailey continued in the leading role until 1960 and wrote one episode, "The Carmen Kringle Matter," under his first and middle names (Robert Bainter). Staff announcer Dan Cubberly introduced the program during the Edmond O'Brien run; Roy Rowan was the announcer for the first two years of Bob Bailey's run; he also was an announcer on CBS's I Love Lucy. In "The Laird Douglas Matter," the only Johnny Dollar serial played for laughs, Roy Rowan was written into the script as dog-show expert "Ray Roland." In 1957 Rowan was succeeded by Dan Cubberly, returning to the series. Changes at CBS CBS Radio tried to institute an economy measure in June 1959: its four remaining dramatic series (Yours Truly, Johnny Dollar; Suspense; Gunsmoke starring William Conrad; and Have Gun, Will Travel starring John Dehner) would be moved from Hollywood to New York. The plan met with some resistance, because the cast members and crews of Gunsmoke and Have Gun, Will Travel were willing to cancel the shows themselves rather than move to New York. The situation was stalemated for 17 months, as all four programs remained on the air. Finally, in November 1960, CBS Radio kept Gunsmoke in California, discontinued Have Gun, Will Travel, and moved Yours Truly, Johnny Dollar and Suspense to New York. Bob Bailey, unwilling to relocate, gave up the Johnny Dollar role. Bailey's last performance, aired November 27, 1960, was in a script titled "The Empty Threat Matter," perhaps writer Johnstone's editorial comment on CBS's intention to shut down production in California. In New York, CBS staff producer Bruno Zirato Jr. (who also directed TV game shows for CBS) took over Yours Truly, Johnny Dollar, although Johnstone continued to write the scripts. Former child actor Bob Readick took over the leading role in a manner reminiscent of the original Dollar, Charles Russell. After six months he was replaced by Mandel Kramer, who gave the role his own low-key interpretation. Many fans found Mandel Kramer second only to Bailey as the most effective Johnny Dollar. Both Readick and Kramer were members of CBS's stock company in New York, and both appeared in other CBS dramas. The end The final episodes of Yours Truly, Johnny Dollar and Suspense, airing on CBS, are often cited as the end of the golden age of radio. The last episode of Johnny Dollar, "The Tip-Off Matter", ended at 6:35 pm. Eastern Time on September 30, 1962, followed immediately by the final broadcast of Suspense. Although network radio drama returned to the airwaves – in ABC's Theater Five (1964–65), and CBS Radio Mystery Theater (1974–82) – these were more experimental "drama workshop" shows, and did not adhere to a continuing format or leading character, albeit the latter did spark a bit of a revival of drama on US commercial radio networks in the 1970s. The "Golden Age" of radio drama, as pioneered in the 1920s, died with Johnny Dollar in 1962. Three unsuccessful attempts were made to transfer the success of Yours Truly, Johnny Dollar to television. Charles Russell starred in a 1949 pilot directed by Ralph Levy, Bob Bailey starred in a 1958 pilot entitled The Adventures of Johnny Dollar (which failed because Bailey's 5-foot 9-inch, 150-pound physique didn't match the tough-guy characterization), and William Bryant starred in a 1962 pilot entitled Johnny Dollar. The latter was written, produced, and directed by Blake Edwards. Actors who portrayed Dollar Dick Powell (Audition show in 1948) Charles Russell (February 1949 – January 1950) Edmond O'Brien (February 1950 – September 1952) John Lund (November 1952 – September 1954) Gerald Mohr (Audition show in 1955) Bob Bailey (October 1955 – November 1960) Bob Readick (December 1960 – June 1961) Mandel Kramer (June 1961 – September 1962) Legacy Yours Truly, Johnny Dollar was so familiar to CBS Radio's listeners that the network's resident comedians, Bob and Ray, occasionally satirized it. Their version, "Ace Willoughby, International Detective," followed the Johnny Dollar format of exotic locales, continental officials, cool villains, and tense confrontations, with Ray Goulding doing a letter-perfect imitation of Bob Bailey's delivery. In the comedy version, however, the detective usually gave up on the case after being beaten up incessantly. Yours Truly, Johnny Dollar was a popular weekly radio mystery play in the 1960s and early 1970s on Radio Iran. The role of Johnny Dollar was played by Heidar Saremi, a popular radio performer. Contrary to the original, Johnny Dollar was more of a criminal investigator. At the end of each episode, the narrator asked the radio audience how Johnny found the perpetrators, making the show a mystery quiz as well as a drama; those who guessed correctly were entered into a raffle for a prize. In the 1970s and 1980s the comedy troupe The Firesign Theatre released a number of satirical record albums; several featured spoofs of old-time radio featuring the character Nick Danger, Third Eye, who was loosely based on Sam Spade and Johnny Dollar. The scripts included inside references to radio with lines such as, "It had been snowing in Santa Barbara ever since the top of the page," and riffs on radio sound effects. In 2003, Moonstone Books adapted the Yours Truly, Johnny Dollar radio program into a graphic novel illustrated by Éric Thériault and written by David Gallaher. The show has been the opening item on The Big Broadcast on WAMU in Washington, D.C. off and on since the early 1990s. As of August 2017, the show is being aired several times a day on KTQA FM 95.3 in Tacoma, WA and CHLU FM in Middle LaHave, Nova Scotia, Canada. In August 2021, the SiriusXM satellite radio network began airing many episodes of the show on its "Radio Classics" channel 148. As of February 2019, a documentary about the program, Last Man Standing – Johnny Dollar & the End of Old-Time Radio, has been produced.[12] In 2023, a new graphic novel series was launched with Johnny Dollar investigating cybercrimes of the modern age. "The man with the action packed expense account" is a cyberinsurance investigator, taking on ransomware actors in the modern age. sleep insomnia relax chill night nightime bed bedtime oldtimeradio drama comedy radio talkradio hancock tonyhancock hancockshalfhour sherlock sherlockholmes radiodrama popular viral viralpodcast podcast brett brettorchard orchard east devon seaton beer lyme regis village condado de alhama spain murcia   The Golden Age of Radio Also known as the old-time radio (OTR) era, was an era of radio in the United States where it was the dominant electronic home entertainment medium. It began with the birth of commercial radio broadcasting in the early 1920s and lasted through the 1950s, when television gradually superseded radio as the medium of choice for scripted programming, variety and dramatic shows. Radio was the first broadcast medium, and during this period people regularly tuned in to their favourite radio programs, and families gathered to listen to the home radio in the evening. According to a 1947 C. E. Hooper survey, 82 out of 100 Americans were found to be radio listeners. A variety of new entertainment formats and genres were created for the new medium, many of which later migrated to television: radio plays, mystery serials, soap operas, quiz shows, talent shows, daytime and evening variety hours, situation comedies, play-by-play sports, children's shows, cooking shows, and more. In the 1950s, television surpassed radio as the most popular broadcast medium, and commercial radio programming shifted to narrower formats of news, talk, sports and music. Religious broadcasters, listener-supported public radio and college stations provide their own distinctive formats. Origins A family listening to the first broadcasts around 1920 with a crystal radio. The crystal radio, a legacy from the pre-broadcast era, could not power a loudspeaker so the family must share earphones During the first three decades of radio, from 1887 to about 1920, the technology of transmitting sound was undeveloped; the information-carrying ability of radio waves was the same as a telegraph; the radio signal could be either on or off. Radio communication was by wireless telegraphy; at the sending end, an operator tapped on a switch which caused the radio transmitter to produce a series of pulses of radio waves which spelled out text messages in Morse code. At the receiver these sounded like beeps, requiring an operator who knew Morse code to translate them back to text. This type of radio was used exclusively for person-to-person text communication for commercial, diplomatic and military purposes and hobbyists; broadcasting did not exist. The broadcasts of live drama, comedy, music and news that characterize the Golden Age of Radio had a precedent in the Théâtrophone, commercially introduced in Paris in 1890 and available as late as 1932. It allowed subscribers to eavesdrop on live stage performances and hear news reports by means of a network of telephone lines. The development of radio eliminated the wires and subscription charges from this concept. Between 1900 and 1920 the first technology for transmitting sound by radio was developed, AM (amplitude modulation), and AM broadcasting sprang up around 1920. On Christmas Eve 1906, Reginald Fessenden is said to have broadcast the first radio program, consisting of some violin playing and passages from the Bible. While Fessenden's role as an inventor and early radio experimenter is not in dispute, several contemporary radio researchers have questioned whether the Christmas Eve broadcast took place, or whether the date was, in fact, several weeks earlier. The first apparent published reference to the event was made in 1928 by H. P. Davis, Vice President of Westinghouse, in a lecture given at Harvard University. In 1932 Fessenden cited the Christmas Eve 1906 broadcast event in a letter he wrote to Vice President S. M. Kinter of Westinghouse. Fessenden's wife Helen recounts the broadcast in her book Fessenden: Builder of Tomorrows (1940), eight years after Fessenden's death. The issue of whether the 1906 Fessenden broadcast actually happened is discussed in Donna Halper's article "In Search of the Truth About Fessenden"[2] and also in James O'Neal's essays.[3][4] An annotated argument supporting Fessenden as the world's first radio broadcaster was offered in 2006 by Dr. John S. Belrose, Radioscientist Emeritus at the Communications Research Centre Canada, in his essay "Fessenden's 1906 Christmas Eve broadcast." It was not until after the Titanic catastrophe in 1912 that radio for mass communication came into vogue, inspired first by the work of amateur ("ham") radio operators. Radio was especially important during World War I as it was vital for air and naval operations. World War I brought about major developments in radio, superseding the Morse code of the wireless telegraph with the vocal communication of the wireless telephone, through advancements in vacuum tube technology and the introduction of the transceiver. After the war, numerous radio stations were born in the United States and set the standard for later radio programs. The first radio news program was broadcast on August 31, 1920, on the station 8MK in Detroit; owned by The Detroit News, the station covered local election results. This was followed in 1920 with the first commercial radio station in the United States, KDKA, being established in Pittsburgh. The first regular entertainment programs were broadcast in 1922, and on March 10, Variety carried the front-page headline: "Radio Sweeping Country: 1,000,000 Sets in Use." A highlight of this time was the first Rose Bowl being broadcast on January 1, 1923, on the Los Angeles station KHJ. Growth of radio Broadcast radio in the United States underwent a period of rapid change through the decade of the 1920s. Technology advances, better regulation, rapid consumer adoption, and the creation of broadcast networks transformed radio from a consumer curiosity into the mass media powerhouse that defined the Golden Age of Radio. Consumer adoption Through the decade of the 1920s, the purchase of radios by United States homes continued, and accelerated. The Radio Corporation of America (RCA) released figures in 1925 stating that 19% of United States homes owned a radio. The triode and regenerative circuit made amplified, vacuum tube radios widely available to consumers by the second half of the 1920s. The advantage was obvious: several people at once in a home could now easily listen to their radio at the same time. In 1930, 40% of the nation's households owned a radio,[8] a figure that was much higher in suburban and large metropolitan areas. The superheterodyne receiver and other inventions refined radios even further in the next decade; even as the Great Depression ravaged the country in the 1930s, radio would stay at the centre of American life. 83% of American homes would own a radio by 1940. Government regulation Although radio was well established with United States consumers by the mid-1920s, regulation of the broadcast medium presented its own challenges. Until 1926, broadcast radio power and frequency use was regulated by the U.S. Department of Commerce, until a legal challenge rendered the agency powerless to do so. Congress responded by enacting the Radio Act of 1927, which included the formation of the Federal Radio Commission (FRC). One of the FRC's most important early actions was the adoption of General Order 40, which divided stations on the AM band into three power level categories, which became known as Local, Regional, and Clear Channel, and reorganized station assignments. Based on this plan, effective 3:00 a.m. Eastern time on November 11, 1928, most of the country's stations were assigned to new transmitting frequencies. Broadcast networks The final element needed to make the Golden Age of Radio possible focused on the question of distribution: the ability for multiple radio stations to simultaneously broadcast the same content, and this would be solved with the concept of a radio network. The earliest radio programs of the 1920s were largely unsponsored; radio stations were a service designed to sell radio receivers. In early 1922, American Telephone & Telegraph Company (AT&T) announced the beginning of advertisement-supported broadcasting on its owned stations, and plans for the development of the first radio network using its telephone lines to transmit the content. In July 1926, AT&T abruptly decided to exit the broadcasting field, and signed an agreement to sell its entire network operations to a group headed by RCA, which used the assets to form the National Broadcasting Company. Four radio networks had formed by 1934. These were: National Broadcasting Company Red Network (NBC Red), launched November 15, 1926. Originally founded as the National Broadcasting Company in late 1926, the company was almost immediately forced to split under antitrust laws to form NBC Red and NBC Blue. When, in 1942, NBC Blue was sold and renamed the Blue Network, this network would go back to calling itself simply the National Broadcasting Company Radio Network (NBC). National Broadcasting Company Blue Network (NBC Blue); launched January 10, 1927, split from NBC Red. NBC Blue was sold in 1942 and became the Blue Network, and it in turn transferred its assets to a new company, the American Broadcasting Company on June 15, 1945. That network identified itself as the American Broadcasting Company Radio Network (ABC). Columbia Broadcasting System (CBS), launched September 18, 1927. After an initially struggling attempt to compete with the NBC networks, CBS gained new momentum when William S. Paley was installed as company president. Mutual Broadcasting System (Mutual), launched September 29, 1934. Mutual was initially run as a cooperative in which the flagship stations owned the network, not the other way around as was the case with the other three radio networks. Programming In the period before and after the advent of the broadcast network, new forms of entertainment needed to be created to fill the time of a station's broadcast day. Many of the formats born in this era continued into the television and digital eras. In the beginning of the Golden Age, network programs were almost exclusively broadcast live, as the national networks prohibited the airing of recorded programs until the late 1940s because of the inferior sound quality of phonograph discs, the only practical recording medium at that time. As a result, network prime-time shows would be performed twice, once for each coast. Rehearsal for the World War II radio show You Can't Do Business with Hitler with John Flynn and Virginia Moore. This series of programs, broadcast at least once weekly by more than 790 radio stations in the United States, was written and produced by the radio section of the Office of War Information (OWI). Live events Coverage of live events included musical concerts and play-by-play sports broadcasts. News The capability of the new medium to get information to people created the format of modern radio news: headlines, remote reporting, sidewalk interviews (such as Vox Pop), panel discussions, weather reports, and farm reports. The entry of radio into the realm of news triggered a feud between the radio and newspaper industries in the mid-1930s, eventually culminating in newspapers trumping up exaggerated [citation needed] reports of a mass hysteria from the (entirely fictional) radio presentation of The War of the Worlds, which had been presented as a faux newscast. Musical features The sponsored musical feature soon became one of the most popular program formats. Most early radio sponsorship came in the form of selling the naming rights to the program, as evidenced by such programs as The A&P Gypsies, Champion Spark Plug Hour, The Clicquot Club Eskimos, and King Biscuit Time; commercials, as they are known in the modern era, were still relatively uncommon and considered intrusive. During the 1930s and 1940s, the leading orchestras were heard often through big band remotes, and NBC's Monitor continued such remotes well into the 1950s by broadcasting live music from New York City jazz clubs to rural America. Singers such as Harriet Lee and Wendell Hall became popular fixtures on network radio beginning in the late 1920s and early 1930s. Local stations often had staff organists such as Jesse Crawford playing popular tunes. Classical music programs on the air included The Voice of Firestone and The Bell Telephone Hour. Texaco sponsored the Metropolitan Opera radio broadcasts; the broadcasts, now sponsored by the Toll Brothers, continue to this day around the world, and are one of the few examples of live classical music still broadcast on radio. One of the most notable of all classical music radio programs of the Golden Age of Radio featured the celebrated Italian conductor Arturo Toscanini conducting the NBC Symphony Orchestra, which had been created especially for him. At that time, nearly all classical musicians and critics considered Toscanini the greatest living maestro. Popular songwriters such as George Gershwin were also featured on radio. (Gershwin, in addition to frequent appearances as a guest, had his own program in 1934.) The New York Philharmonic also had weekly concerts on radio. There was no dedicated classical music radio station like NPR at that time, so classical music programs had to share the network they were broadcast on with more popular ones, much as in the days of television before the creation of NET and PBS. Country music also enjoyed popularity. National Barn Dance, begun on Chicago's WLS in 1924, was picked up by NBC Radio in 1933. In 1925, WSM Barn Dance went on the air from Nashville. It was renamed the Grand Ole Opry in 1927 and NBC carried portions from 1944 to 1956. NBC also aired The Red Foley Show from 1951 to 1961, and ABC Radio carried Ozark Jubilee from 1953 to 1961. Comedy Radio attracted top comedy talents from vaudeville and Hollywood for many years: Bing Crosby, Abbott and Costello, Fred Allen, Jack Benny, Victor Borge, Fanny Brice, Billie Burke, Bob Burns, Judy Canova, Eddie Cantor, Jimmy Durante, Burns and Allen, Phil Harris, Edgar Bergen, Bob Hope, Groucho Marx, Jean Shepherd, Red Skelton and Ed Wynn. Situational comedies also gained popularity, such as Amos 'n' Andy, Easy Aces, Ethel and Albert, Fibber McGee and Molly, The Goldbergs, The Great Gildersleeve, The Halls of Ivy (which featured screen star Ronald Colman and his wife Benita Hume), Meet Corliss Archer, Meet Millie, and Our Miss Brooks. Radio comedy ran the gamut from the small town humor of Lum and Abner, Herb Shriner and Minnie Pearl to the dialect characterizations of Mel Blanc and the caustic sarcasm of Henry Morgan. Gags galore were delivered weekly on Stop Me If You've Heard This One and Can You Top This?,[18] panel programs devoted to the art of telling jokes. Quiz shows were lampooned on It Pays to Be Ignorant, and other memorable parodies were presented by such satirists as Spike Jones, Stoopnagle and Budd, Stan Freberg and Bob and Ray. British comedy reached American shores in a major assault when NBC carried The Goon Show in the mid-1950s. Some shows originated as stage productions: Clifford Goldsmith's play What a Life was reworked into NBC's popular, long-running The Aldrich Family (1939–1953) with the familiar catchphrases "Henry! Henry Aldrich!," followed by Henry's answer, "Coming, Mother!" Moss Hart and George S. Kaufman's Pulitzer Prize-winning Broadway hit, You Can't Take It with You (1936), became a weekly situation comedy heard on Mutual (1944) with Everett Sloane and later on NBC (1951) with Walter Brennan. Other shows were adapted from comic strips, such as Blondie, Dick Tracy, Gasoline Alley, The Gumps, Li'l Abner, Little Orphan Annie, Popeye the Sailor, Red Ryder, Reg'lar Fellers, Terry and the Pirates and Tillie the Toiler. Bob Montana's redheaded teen of comic strips and comic books was heard on radio's Archie Andrews from 1943 to 1953. The Timid Soul was a 1941–1942 comedy based on cartoonist H. T. Webster's famed Caspar Milquetoast character, and Robert L. Ripley's Believe It or Not! was adapted to several different radio formats during the 1930s and 1940s. Conversely, some radio shows gave rise to spinoff comic strips, such as My Friend Irma starring Marie Wilson. Soap operas The first program generally considered to be a daytime serial drama by scholars of the genre is Painted Dreams, which premiered on WGN on October 20, 1930. The first networked daytime serial is Clara, Lu, 'n Em, which started in a daytime time slot on February 15, 1932. As daytime serials became popular in the early 1930s, they became known as soap operas because many were sponsored by soap products and detergents. On November 25, 1960, the last four daytime radio dramas—Young Dr. Malone, Right to Happiness, The Second Mrs. Burton and Ma Perkins, all broadcast on the CBS Radio Network—were brought to an end. Children's programming The line-up of late afternoon adventure serials included Bobby Benson and the B-Bar-B Riders, The Cisco Kid, Jack Armstrong, the All-American Boy, Captain Midnight, and The Tom Mix Ralston Straight Shooters. Badges, rings, decoding devices and other radio premiums offered on these adventure shows were often allied with a sponsor's product, requiring the young listeners to mail in a boxtop from a breakfast cereal or other proof of purchase. Radio plays Radio plays were presented on such programs as 26 by Corwin, NBC Short Story, Arch Oboler's Plays, Quiet, Please, and CBS Radio Workshop. Orson Welles's The Mercury Theatre on the Air and The Campbell Playhouse were considered by many critics to be the finest radio drama anthologies ever presented. They usually starred Welles in the leading role, along with celebrity guest stars such as Margaret Sullavan or Helen Hayes, in adaptations from literature, Broadway, and/or films. They included such titles as Liliom, Oliver Twist (a title now feared lost), A Tale of Two Cities, Lost Horizon, and The Murder of Roger Ackroyd. It was on Mercury Theatre that Welles presented his celebrated-but-infamous 1938 adaptation of H. G. Wells's The War of the Worlds, formatted to sound like a breaking news program. Theatre Guild on the Air presented adaptations of classical and Broadway plays. Their Shakespeare adaptations included a one-hour Macbeth starring Maurice Evans and Judith Anderson, and a 90-minute Hamlet, starring John Gielgud.[22] Recordings of many of these programs survive. During the 1940s, Basil Rathbone and Nigel Bruce, famous for playing Sherlock Holmes and Dr. Watson in films, repeated their characterizations on radio on The New Adventures of Sherlock Holmes, which featured both original stories and episodes directly adapted from Arthur Conan Doyle's stories. None of the episodes in which Rathbone and Bruce starred on the radio program were filmed with the two actors as Holmes and Watson, so radio became the only medium in which audiences were able to experience Rathbone and Bruce appearing in some of the more famous Holmes stories, such as "The Speckled Band". There were also many dramatizations of Sherlock Holmes stories on radio without Rathbone and Bruce. During the latter part of his career, celebrated actor John Barrymore starred in a radio program, Streamlined Shakespeare, which featured him in a series of one-hour adaptations of Shakespeare plays, many of which Barrymore never appeared in either on stage or in films, such as Twelfth Night (in which he played both Malvolio and Sir Toby Belch), and Macbeth. Lux Radio Theatre and The Screen Guild Theater presented adaptations of Hollywood movies, performed before a live audience, usually with cast members from the original films. Suspense, Escape, The Mysterious Traveler and Inner Sanctum Mystery were popular thriller anthology series. Leading writers who created original material for radio included Norman Corwin, Carlton E. Morse, David Goodis, Archibald MacLeish, Arthur Miller, Arch Oboler, Wyllis Cooper, Rod Serling, Jay Bennett, and Irwin Shaw. Game shows Game shows saw their beginnings in radio. One of the first was Information Please in 1938, and one of the first major successes was Dr. I.Q. in 1939. Winner Take All, which premiered in 1946, was the first to use lockout devices and feature returning champions. A relative of the game show, which would be called the giveaway show in contemporary media, typically involved giving sponsored products to studio audience members, people randomly called by telephone, or both. An early example of this show was the 1939 show Pot o' Gold, but the breakout hit of this type was ABC's Stop the Music in 1948. Winning a prize generally required knowledge of what was being aired on the show at that moment, which led to criticism of the giveaway show as a form of "buying an audience". Giveaway shows were extremely popular through 1948 and 1949. They were often panned as low-brow, and an unsuccessful attempt was even made by the FCC to ban them (as an illegal lottery) in August 1949.[23] Broadcast production methods The RCA Type 44-BX microphone had two live faces and two dead ones. Thus actors could face each other and react. An actor could give the effect of leaving the room by simply moving their head toward the dead face of the microphone. The scripts were paper-clipped together. It has been disputed whether or not actors and actresses would drop finished pages to the carpeted floor after use. Radio stations Despite a general ban on use of recordings on broadcasts by radio networks through the late 1940s, "reference recordings" on phonograph disc were made of many programs as they were being broadcast, for review by the sponsor and for the network's own archival purposes. With the development of high-fidelity magnetic wire and tape recording in the years following World War II, the networks became more open to airing recorded programs and the prerecording of shows became more common. Local stations, however, had always been free to use recordings and sometimes made substantial use of pre-recorded syndicated programs distributed on pressed (as opposed to individually recorded) transcription discs. Recording was done using a cutting lathe and acetate discs. Programs were normally recorded at 331⁄3 rpm on 16 inch discs, the standard format used for such "electrical transcriptions" from the early 1930s through the 1950s. Sometimes, the groove was cut starting at the inside of the disc and running to the outside. This was useful when the program to be recorded was longer than 15 minutes so required more than one disc side. By recording the first side outside in, the second inside out, and so on, the sound quality at the disc change-over points would match and result in a more seamless playback. An inside start also had the advantage that the thread of material cut from the disc's surface, which had to be kept out of the path of the cutting stylus, was naturally thrown toward the centre of the disc so was automatically out of the way. When cutting an outside start disc, a brush could be used to keep it out of the way by sweeping it toward the middle of the disc. Well-equipped recording lathes used the vacuum from a water aspirator to pick it up as it was cut and deposit it in a water-filled bottle. In addition to convenience, this served a safety purpose, as the cellulose nitrate thread was highly flammable and a loose accumulation of it combusted violently if ignited. Most recordings of radio broadcasts were made at a radio network's studios, or at the facilities of a network-owned or affiliated station, which might have four or more lathes. A small local station often had none. Two lathes were required to capture a program longer than 15 minutes without losing parts of it while discs were flipped over or changed, along with a trained technician to operate them and monitor the recording while it was being made. However, some surviving recordings were produced by local stations. When a substantial number of copies of an electrical transcription were required, as for the distribution of a syndicated program, they were produced by the same process used to make ordinary records. A master recording was cut, then electroplated to produce a stamper from which pressings in vinyl (or, in the case of transcription discs pressed before about 1935, shellac) were moulded in a record press. Armed Forces Radio Service Frank Sinatra and Alida Valli converse over Armed Forces Radio Service during World War II The Armed Forces Radio Service (AFRS) had its origins in the U.S. War Department's quest to improve troop morale. This quest began with short-wave broadcasts of educational and information programs to troops in 1940. In 1941, the War Department began issuing "Buddy Kits" (B-Kits) to departing troops, which consisted of radios, 78 rpm records and electrical transcription discs of radio shows. However, with the entrance of the United States into World War II, the War Department decided that it needed to improve the quality and quantity of its offerings. This began with the broadcasting of its own original variety programs. Command Performance was the first of these, produced for the first time on March 1, 1942. On May 26, 1942, the Armed Forces Radio Service was formally established. Originally, its programming comprised network radio shows with the commercials removed. However, it soon began producing original programming, such as Mail Call, G.I. Journal, Jubilee and GI Jive. At its peak in 1945, the Service produced around 20 hours of original programming each week. From 1943 until 1949 the AFRS also broadcast programs developed through the collaborative efforts of the Office of the Coordinator of Inter-American Affairs and the Columbia Broadcasting System in support of America's cultural diplomacy initiatives and President Franklin Roosevelt's Good Neighbour policy. Included among the popular shows was Viva America which showcased leading musical artists from both North and South America for the entertainment of America's troops. Included among the regular performers were: Alfredo Antonini, Juan Arvizu, Nestor Mesta Chayres, Kate Smith,[26] and John Serry Sr. After the war, the AFRS continued providing programming to troops in Europe. During the 1950s and early 1960s it presented performances by the Army's only symphonic orchestra ensemble—the Seventh Army Symphony Orchestra. It also provided programming for future wars that the United States was involved in. It survives today as a component of the American Forces Network (AFN). All of the shows aired by the AFRS during the Golden Age were recorded as electrical transcription discs, vinyl copies of which were shipped to stations overseas to be broadcast to the troops. People in the United States rarely ever heard programming from the AFRS,[31] though AFRS recordings of Golden Age network shows were occasionally broadcast on some domestic stations beginning in the 1950s. In some cases, the AFRS disc is the only surviving recording of a program. Home radio recordings in the United States There was some home recording of radio broadcasts in the 1930s and 1940s. Examples from as early as 1930 have been documented. During these years, home recordings were made with disc recorders, most of which were only capable of storing about four minutes of a radio program on each side of a twelve-inch 78 rpm record. Most home recordings were made on even shorter-playing ten-inch or smaller discs. Some home disc recorders offered the option of the 331⁄3 rpm speed used for electrical transcriptions, allowing a recording more than twice as long to be made, although with reduced audio quality. Office dictation equipment was sometimes pressed into service for making recordings of radio broadcasts, but the audio quality of these devices was poor and the resulting recordings were in odd formats that had to be played back on similar equipment. Due to the expense of recorders and the limitations of the recording media, home recording of broadcasts was not common during this period and it was usually limited to brief excerpts. The lack of suitable home recording equipment was somewhat relieved in 1947 with the availability of magnetic wire recorders for domestic use. These were capable of recording an hour-long broadcast on a single small spool of wire, and if a high-quality radio's audio output was recorded directly, rather than by holding a microphone up to its speaker, the recorded sound quality was very good. However, because the wire cost money and, like magnetic tape, could be repeatedly re-used to make new recordings, only a few complete broadcasts appear to have survived on this medium. In fact, there was little home recording of complete radio programs until the early 1950s, when increasingly affordable reel-to-reel tape recorders for home use were introduced to the market. Recording media Electrical transcription discs   The War of the Worlds radio broadcast by Orson Welles on electrical transcription disc Before the early 1950s, when radio networks and local stations wanted to preserve a live broadcast, they did so by means of special phonograph records known as "electrical transcriptions" (ETs), made by cutting a sound-modulated groove into a blank disc. At first, in the early 1930s, the blanks varied in both size and composition, but most often they were simply bare aluminum and the groove was indented rather than cut. Typically, these very early recordings were not made by the network or radio station, but by a private recording service contracted by the broadcast sponsor or one of the performers. The bare aluminum discs were typically 10 or 12 inches in diameter and recorded at the then-standard speed of 78 rpm, which meant that several disc sides were required to accommodate even a 15-minute program. By about 1936, 16-inch aluminum-based discs coated with cellulose nitrate lacquer, commonly known as acetates and recorded at a speed of 331⁄3 rpm, had been adopted by the networks and individual radio stations as the standard medium for recording broadcasts. The making of such recordings, at least for some purposes, then became routine. Some discs were recorded using a "hill and dale" vertically modulated groove, rather than the "lateral" side-to-side modulation found on the records being made for home use at that time. The large slow-speed discs could easily contain fifteen minutes on each side, allowing an hour-long program to be recorded on only two discs. The lacquer was softer than shellac or vinyl and wore more rapidly, allowing only a few playbacks with the heavy pickups and steel needles then in use before deterioration became audible. During World War II, aluminum became a necessary material for the war effort and was in short supply. This caused an alternative to be sought for the base on which to coat the lacquer. Glass, despite its obvious disadvantage of fragility, had occasionally been used in earlier years because it could provide a perfectly smooth and even supporting surface for mastering and other critical applications. Glass base recording blanks came into general use for the duration of the war. Magnetic wire recording In the late 1940s, wire recorders became a readily obtainable means of recording radio programs. On a per-minute basis, it was less expensive to record a broadcast on wire than on discs. The one-hour program that required the four sides of two 16-inch discs could be recorded intact on a single spool of wire less than three inches in diameter and about half an inch thick. The audio fidelity of a good wire recording was comparable to acetate discs and by comparison the wire was practically indestructible, but it was soon rendered obsolete by the more manageable and easily edited medium of magnetic tape. Reel-to-reel tape recording Bing Crosby became the first major proponent of magnetic tape recording for radio, and he was the first to use it on network radio, after he did a demonstration program in 1947. Tape had several advantages over earlier recording methods. Running at a sufficiently high speed, it could achieve higher fidelity than both electrical transcription discs and magnetic wire. Discs could be edited only by copying parts of them to a new disc, and the copying entailed a loss of audio quality. Wire could be divided up and the ends spliced together by knotting, but wire was difficult to handle and the crude splices were too noticeable. Tape could be edited by cutting it with a blade and neatly joining ends together with adhesive tape. By early 1949, the transition from live performances preserved on discs to performances pre-recorded on magnetic tape for later broadcast was complete for network radio programs. However, for the physical distribution of pre-recorded programming to individual stations, 16-inch 331⁄3 rpm vinyl pressings, less expensive to produce in quantities of identical copies than tapes, continued to be standard throughout the 1950s. Availability of recordings The great majority of pre-World War II live radio broadcasts are lost. Many were never recorded; few recordings antedate the early 1930s. Beginning then several of the longer-running radio dramas have their archives complete or nearly complete. The earlier the date, the less likely it is that a recording survives. However, a good number of syndicated programs from this period have survived because copies were distributed far and wide. Recordings of live network broadcasts from the World War II years were preserved in the form of pressed vinyl copies issued by the Armed Forces Radio Service (AFRS) and survive in relative abundance. Syndicated programs from World War II and later years have nearly all survived. The survival of network programming from this time frame is more inconsistent; the networks started prerecording their formerly live shows on magnetic tape for subsequent network broadcast, but did not physically distribute copies, and the expensive tapes, unlike electrical transcription ("ET") discs, could be "wiped" and re-used (especially since, in the age of emerging trends such as television and music radio, such recordings were believed to have virtually no rerun or resale value). Thus, while some prime time network radio series from this era exist in full or almost in full, especially the most famous and longest-lived of them, less prominent or shorter-lived series (such as serials) may have only a handful of extant episodes. Airchecks, off-the-air recordings of complete shows made by, or at the behest of, individuals for their own private use, sometimes help to fill in such gaps. The contents of privately made recordings of live broadcasts from the first half of the 1930s can be of particular interest, as little live material from that period survives. Unfortunately, the sound quality of very early private recordings is often very poor, although in some cases this is largely due to the use of an incorrect playback stylus, which can also badly damage some unusual types of discs. Most of the Golden Age programs in circulation among collectors—whether on analogue tape, CD, or in the form of MP3s—originated from analogue 16-inch transcription disc, although some are off-the-air AM recordings. But in many cases, the circulating recordings are corrupted (decreased in quality), because lossless digital recording for the home market did not come until the very end of the twentieth century. Collectors made and shared recordings on analogue magnetic tapes, the only practical, relatively inexpensive medium, first on reels, then cassettes. "Sharing" usually meant making a duplicate tape. They connected two recorders, playing on one and recording on the other. Analog recordings are never perfect, and copying an analogue recording multiplies the imperfections. With the oldest recordings this can even mean it went out the speaker of one machine and in via the microphone of the other. The muffled sound, dropouts, sudden changes in sound quality, unsteady pitch, and other defects heard all too often are almost always accumulated tape copy defects. In addition, magnetic recordings, unless preserved archivally, are gradually damaged by the Earth's magnetic field. The audio quality of the source discs, when they have survived unscathed and are accessed and dubbed anew, is usually found to be reasonably clear and undistorted, sometimes startlingly good, although like all phonograph records they are vulnerable to wear and the effects of scuffs, scratches, and ground-in dust. Many shows from the 1940s have survived only in edited AFRS versions, although some exist in both the original and AFRS forms. As of 2020, the Old Time Radio collection at the Internet Archive contains 5,121 recordings. An active group of collectors makes digitally available, via CD or download, large collections of programs. RadioEchoes.com offers 98,949 episodes in their collection, but not all is old-time radio. Copyright status Unlike film, television, and print items from the era, the copyright status of most recordings from the Golden Age of Radio is unclear. This is because, prior to 1972, the United States delegated the copyrighting of sound recordings to the individual states, many of which offered more generous common law copyright protections than the federal government offered for other media (some offered perpetual copyright, which has since been abolished; under the Music Modernization Act of September 2018, any sound recording 95 years old or older will be thrust into the public domain regardless of state law). The only exceptions are AFRS original productions, which are considered work of the United States government and thus both ineligible for federal copyright and outside the jurisdiction of any state; these programs are firmly in the public domain (this does not apply to programs carried by AFRS but produced by commercial networks). In practice, most old-time radio recordings are treated as orphan works: although there may still be a valid copyright on the program, it is seldom enforced. The copyright on an individual sound recording is distinct from the federal copyright for the underlying material (such as a published script, music, or in the case of adaptations, the original film or television material), and in many cases it is impossible to determine where or when the original recording was made or if the recording was copyrighted in that state. The U.S. Copyright Office states "there are a variety of legal regimes governing protection of pre-1972 sound recordings in the various states, and the scope of protection and of exceptions and limitations to that protection is unclear."[39] For example, New York has issued contradicting rulings on whether or not common law exists in that state; the most recent ruling, 2016's Flo & Eddie, Inc. v. Sirius XM Radio, holds that there is no such copyright in New York in regard to public performance.[40] Further complicating matters is that certain examples in case law have implied that radio broadcasts (and faithful reproductions thereof), because they were distributed freely to the public over the air, may not be eligible for copyright in and of themselves. The Internet Archive and other organizations that distribute public domain and open-source audio recordings maintain extensive archives of old-time radio programs. Legacy United States Some old-time radio shows continued on the air, although in ever-dwindling numbers, throughout the 1950s, even after their television equivalents had conquered the general public. One factor which helped to kill off old-time radio entirely was the evolution of popular music (including the development of rock and roll), which led to the birth of the top 40 radio format. A top 40 show could be produced in a small studio in a local station with minimal staff. This displaced full-service network radio and hastened the end of the golden-age era of radio drama by 1962. (Radio as a broadcast medium would survive, thanks in part to the proliferation of the transistor radio, and permanent installation in vehicles, making the medium far more portable than television). Full-service stations that did not adopt either top 40 or the mellower beautiful music or MOR formats eventually developed all-news radio in the mid-1960s. Scripted radio comedy and drama in the vein of old-time radio has a limited presence on U.S. radio. Several radio theatre series are still in production in the United States, usually airing on Sunday nights. These include original series such as Imagination Theatre and a radio adaptation of The Twilight Zone TV series, as well as rerun compilations such as the popular daily series When Radio Was and USA Radio Network's Golden Age of Radio Theatre, and weekly programs such as The Big Broadcast on WAMU, hosted by Murray Horwitz. These shows usually air in late nights and/or on weekends on small AM stations. Carl Amari's nationally syndicated radio show Hollywood 360 features 5 old-time radio episodes each week during his 5-hour broadcast. Amari's show is heard on 100+ radio stations coast-to-coast and in 168 countries on American Forces Radio. Local rerun compilations are also heard, primarily on public radio stations. Sirius XM Radio maintains a full-time Radio Classics channel devoted to rebroadcasts of vintage radio shows. Starting in 1974, Garrison Keillor, through his syndicated two-hour-long program A Prairie Home Companion, has provided a living museum of the production, tone and listener's experience of this era of radio for several generations after its demise. Produced live in theaters throughout the country, using the same sound effects and techniques of the era, it ran through 2016 with Keillor as host. The program included segments that were close renditions (in the form of parody) of specific genres of this era, including Westerns ("Dusty and Lefty, The Lives of the Cowboys"), detective procedurals ("Guy Noir, Private Eye") and even advertising through fictional commercials. Keillor also wrote a novel, WLT: A Radio Romance based on a radio station of this era—including a personally narrated version for the ultimate in verisimilitude. Upon Keillor's retirement, replacement host Chris Thile chose to reboot the show (since renamed Live from Here after the syndicator cut ties with Keillor) and eliminate much of the old-time radio trappings of the format; the show was ultimately canceled in 2020 due to financial and logistics problems. Vintage shows and new audio productions in America are accessible more widely from recordings or by satellite and web broadcasters, rather than over conventional AM and FM radio. The National Audio Theatre Festival is a national organization and yearly conference keeping the audio arts—especially audio drama—alive, and continues to involve long-time voice actors and OTR veterans in its ranks. Its predecessor, the Midwest Radio Theatre Workshop, was first hosted by Jim Jordan, of Fibber McGee and Molly fame, and Norman Corwin advised the organization. One of the longest running radio programs celebrating this era is The Golden Days of Radio, which was hosted on the Armed Forces Radio Service for more than 20 years and overall for more than 50 years by Frank Bresee, who also played "Little Beaver" on the Red Ryder program as a child actor. One of the very few still-running shows from the earlier era of radio is a Christian program entitled Unshackled! The weekly half-hour show, produced in Chicago by Pacific Garden Mission, has been continuously broadcast since 1950. The shows are created using techniques from the 1950s (including home-made sound effects) and are broadcast across the U.S. and around the world by thousands of radio stations. Today, radio performers of the past appear at conventions that feature re-creations of classic shows, as well as music, memorabilia and historical panels. The largest of these events was the Friends of Old Time Radio Convention, held in Newark, New Jersey, which held its final convention in October 2011 after 36 years. Others include REPS in Seattle (June), SPERDVAC in California, the Cincinnati OTR & Nostalgia Convention (April), and the Mid-Atlantic Nostalgia Convention (September). Veterans of the Friends of Old Time Radio Convention, including Chairperson Steven M. Lewis of The Gotham Radio Players, Maggie Thompson, publisher of the Comic Book Buyer's Guide, Craig Wichman of audio drama troupe Quicksilver Audio Theater and long-time FOTR Publicist Sean Dougherty have launched a successor event, Celebrating Audio Theater – Old & New, scheduled for October 12–13, 2012. Radio dramas from the golden age are sometimes recreated as live stage performances at such events. One such group, led by director Daniel Smith, has been performing re-creations of old-time radio dramas at Fairfield University's Regina A. Quick Center for the Arts since the year 2000. The 40th anniversary of what is widely considered the end of the old time radio era (the final broadcasts of Yours Truly, Johnny Dollar and Suspense on September 30, 1962) was marked with a commentary on NPR's All Things Considered. A handful of radio programs from the old-time era remain in production, all from the genres of news, music, or religious broadcasting: the Grand Ole Opry (1925), Music and the Spoken Word (1929), The Lutheran Hour (1930), the CBS World News Roundup (1938), King Biscuit Time (1941) and the Renfro Valley Gatherin' (1943). Of those, all but the Opry maintain their original short-form length of 30 minutes or less. The Wheeling Jamboree counts an earlier program on a competing station as part of its history, tracing its lineage back to 1933. Western revival/comedy act Riders in the Sky produced a radio serial Riders Radio Theatre in the 1980s and 1990s and continues to provide sketch comedy on existing radio programs including the Grand Ole Opry, Midnite Jamboree and WoodSongs Old-Time Radio Hour. Elsewhere Regular broadcasts of radio plays are also heard in—among other countries—Australia, Croatia, Estonia,[46] France, Germany, Ireland, Japan, New Zealand, Norway, Romania, and Sweden. In the United Kingdom, such scripted radio drama continues on BBC Radio 3 and (principally) BBC Radio 4, the second-most popular radio station in the country, as well as on the rerun channel BBC Radio 4 Extra, which is the seventh-most popular station there.   Special thanks to Wikipedia. #starradio #totalstar #star1075 #heart #heartradio #lbc #bbc #bbcradio #bbcradio1 #bbcradio2 #bbcradio3 #bbcradio4 #radio4extra #absoluteradio #absolute #capital #capitalradio #greatesthitsradio #hitsradio #radio #adultcontemporary #spain #bristol #frenchay #colyton #lymeregis #seaton #beer #devon #eastdevon #brettorchard #brettsoldtimeradioshow fe2f4df62ffeeb8c30c04d3d3454779ca91a4871

You've bought the ovulation test strips, maybe a fertility tracker like Inito, the basal body temp thermometer, and maybe even a Kegg. But girl- are you really ovulating? The truth is- it can be REALLY hard to tell, especially if your cycles are irregular or your hormones are off. Tune in to today's episode to grow in understanding this- and as always, share with a friend to empower them too in this amazing knowledge!  In His Grace, Bekah Learn more about the Fertility Framework Course: https://bekahyawn.com/course >>Save 20% when you use code SAVE20NOW Get a sneak peak inside the course: https://awesome-mover-7744.ck.page/a8fbf3e9e4 Join our free online community here: https://www.facebook.com/groups/802419477419221 Take The Hormone Imbalance Quiz: https://fertilitysetfree.outgrow.us/63dd4f901a925d39c424e3dc Schedule a FREE 10 minute consult: https://calendly.com/byawn/consult

We live in a  modern world, where tons of information about our fertility is at our fingertips (in more way than one)! But not all fertility monitors are the same -- and some are definitely not worth the big bucks. Today's episode discusses which fertility monitors are worth it, even to women fully knowledgeable about their cycle and fertility through fertility awareness based methods or natural family planning. You'll hear ClearBlue Fertility Monitor, Ava, TempDrop, Kegg, Ovusense, Mira, and Inito Fertility Monitors all mentioned -- but which ones will be "worth it?"SHOW NOTES: Inito Fertility Monitor Discount Code ($25 off): ref-4510deMira Fertility Monitor Discount Code (17% off): MBB17 Interested in learning about fertility awareness based methods, or specifically the Creighton Model System? You're in the right place! Register for Creighton Introductory Session: Register here for our next Introductory SessionLooking for ways to implement fertility awareness into your life and faith? Check out out most helpful resources: Substack Newsletter (free)Website Resources (free)Support the showThis podcast is provided for educational and informational purposes only and does not constitute providing medical advice or professional services. The information provided should not be used for diagnosing or treating a health problem or disease, and those seeking personal medical advice should consult with a licensed physician. Always seek the advice of your doctor or other qualified health provider regarding a medical condition. If you think you may have a medical emergency, call 911 or go to the nearest emergency room immediately. Neither Woven nor its staff, nor any contributor to this podcast, makes any representations, express or implied, with respect to the information provided herein or to its use.

BUFFALO, NY- February 29, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 4, entitled, “Mapping the core senescence phenotype of primary human colon fibroblasts.” Advanced age is the largest risk factor for many diseases and several types of cancer, including colorectal cancer (CRC). Senescent cells are known to accumulate with age in various tissues, where they can modulate the surrounding tissue microenvironment through their senescence associated secretory phenotype (SASP). Recently, researchers showed that there is an increased number of senescent cells in the colons of CRC patients and demonstrated that senescent fibroblasts and their SASP create microniches in the colon that are conducive to CRC onset and progression. However, the composition of the SASP is heterogenous and cell-specific, and the precise senescence profile of colon fibroblasts has not been well-defined. In this new study, to generate a SASP atlas of human colon fibroblasts, researchers Namita Ganesh Hattangady, Kelly Carter, Brett Maroni-Rana, Ting Wang, Jessica Lee Ayers, Ming Yu, and William M. Grady from Fred Hutchinson Cancer Center and the University of Washington School of Medicine induced senescence in primary human colon fibroblasts using various in vitro methods and assessed the resulting transcriptome. “[...] we utilized various relevant stressors to induce senescence in primary cultures of colon fibroblasts and perform RNA sequencing (RNASeq) to define an atlas of stressor-specific senescent profiles and a core senescent profile that is commonly regulated by all senescence inducers.” Using RNA Sequencing and further validation by quantitative RT-PCR and Luminex assays, the team define and validate a ‘core senescent profile' that might play a significant role in shaping the colon microenvironment. They also performed KEGG analysis and GO analyses to identify key pathways and biological processes that are differentially regulated in colon fibroblast senescence. These studies provide insights into potential driver proteins involved in senescence-associated diseases, like CRC, which may lead to therapies to improve overall health in the elderly and to prevent CRC. “Further studies will be needed to address the limitations of our study and to translate our understanding of the SASP and disease into clinical care.” DOI - https://doi.org/10.18632/aging.205577 Corresponding authors - William M. Grady - wgrady@fredhutch.org, and Ming Yu - myu@fredhutch.org Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205577 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, senescence associated secretory phenotype, SASP, colorectal cancer, cancer About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Each story started with a phone call from an insurance executive, calling on Johnny to investigate an unusual claim. Each story required Johnny to travel to some distant locale, usually within the United States but sometimes abroad, where he was almost always threatened with personal danger in the course of his investigations. Johnny's precious recreational time was usually spent fishing, and it was not uncommon for Johnny's clients to exploit this favorite pastime in convincing him to take on a job near good fishing locations. His past was rarely mentioned, but Dollar in one episode described himself as a four-year US Marine veteran who then worked as a police officer for a decade before changing careers to insurance investigation. Try the new "Tales of Escape & Suspense"- links below! ANDROID USERS- 1001 Tales of Escape & Suspense at Spotify - https://open.spotify.com/show/2HQYk53AJHTOgBTLBzyP3w 1001 Stories From The Old West at Spotify - https://open.spotify.com/show/0c2fc0cGwJBcPfyC8NWNTw 1001 Radio Crime Solvers at Spotify- https://open.spotify.com/show/0UAUS12lnS2063PWK9CZ37 1001's Best of Jack London at Spotify https://open.spotify.com/show/2HzkpdKeWJgUU9rbx3NqgF 1001 Radio Days at Spotify https://open.spotify.com/show/5jyc4nVoe00xoOxrhyAa8H 1001 Classic Short Stories & Tales at Spotify https://open.spotify.com/show/6rzDb5uFdOhfw5X6P5lkWn 1001 Heroes, Legends, Histories & Mysteries at Spotify https://open.spotify.com/show/6rO7HELtRcGfV48UeP8aFQ 1001 Sherlock Holmes Stories & The Best of Sir Arthur Conan Doyle at Spotify https://open.spotify.com/show/4dIgYvBwZVTN5ewF0JPaTK 1001 Ghost Stories & Tales of the Macabre on Spotify: https://open.spotify.com/show/5P4hV28LgpG89dRNMfSDKJ APPLE USERS New! 1001 Tales of Escape and Suspense at Apple Podcasts https://podcasts.apple.com/us/podcast/1001-tales-of-escape-and-suspense/id1689248043 Catch 1001 Stories From The Old West- https://podcasts.apple.com/us/podcast/1001-stories-from-the-old-west/id1613213865 Catch 1001's Best of Jack London- https://podcasts.apple.com/us/podcast/1001-best-of-jack-london/id1656939169 Catch 1001 Radio Crime Solvers- https://podcasts.apple.com/us/podcast/1001-radio-crime-solvers/id1657397371 Catch 1001 Heroes on Apple https://podcasts.apple.com/us/podcast/1001-heroes-legends-histories-mysteries-podcast/id956154836?mt=2  Catch 1001 Classic Short Stories at Apple Podcast https://podcasts.apple.com/us/podcast/1001-classic-short-stories-tales/id1078098622 Catch 1001 Stories for the Road at Apple Podcast now:  https://podcasts.apple.com/us/podcast/1001-stories-for-the-road/id1227478901 NEW Enjoy 1001 Greatest Love Stories on Apple Devices here: https://podcasts.apple.com/us/podcast/1001-greatest-love-stories/id1485751552 Catch 1001 RADIO DAYS now at Apple iTunes!  https://itunes.apple.com/us/podcast/1001-radio-days/id1405045413?mt=2 NEW 1001 Ghost Stories & Tales of the Macabre is now playing at Apple Podcasts! https://podcasts.apple.com/us/podcast/1001-ghost-stories-tales-of-the-macabre/id1516332327 NEW Enjoy 1001 History's Best Storytellers (Interviews) on Apple Devices here: https://podcasts.apple.com/us/podcast/1001-historys-best-storytellers/id1483649026 NEW Enjoy 1001 Sherlock Holmes Stories and The Best of Arthur Conan Doyle https://podcasts.apple.com/us/podcast/1001-sherlock-holmes-stories-best-sir-arthur-conan/id1534427618 Get all of our shows at one website: https://.1001storiespodcast.com My email works as well for comments: 1001storiespodcast@gmail.com SUPPORT OUR SHOW BY BECOMING A PATRON! https://.patreon.com/1001storiesnetwork. Its time I started asking for support! Thank you. Its a few dollars a month OR a one time. (Any amount is appreciated). YOUR REVIEWS ARE NEEDED AND APPRECIATED! Learn more about your ad choices. Visit podcastchoices.com/adchoices

PSA: Mere hours after I recorded this, I started experiencing symptoms of Covid and tested positive. Get your boosters!This week's episode is all about Meredith's trip to Washington to see Michael and get the turkey-bastering done. And IT HAPPENED. Thrice!! Meredith goes over using the Kegg fertility monitor and the Mosie Baby insemination kit.Hello Bello 20% off for new customers with code “MEREDITHB“Kegg Fertility Tracker Support The Backup Plan by purchasing Kegg Trackers at the above link. Kindred Bravely 15% off nursing and maternity wear with code “Meredith15“.Mosie Baby Support The Backup Plan by purchasing Mosie kits at the above link. Disclaimer: This post contains affiliate links. If you make a purchase, I may receive a commission at no extra cost to you.Support the showCreated, produced and hosted by Meredith Kate, co-produced by Julian Hagins. @backupplanpod on Instagram, TikTok, Pinterest, Facebook, and YouTube. backupplanpod.com for show notes, transcripts, partner links, and our newsletter.

A new research paper was published on the cover of Aging (Aging-US) Volume 15, Issue 15, entitled, “Natural aging and ovariectomy induces parallel phosphoproteomic alterations in skeletal muscle of female mice.” The loss of skeletal muscle strength mid-life in females is associated with the decline of estrogen. In this new study, researchers Mina P. Peyton, Tzu-Yi Yang, LeeAnn Higgins, Todd W. Markowski, Kevin Murray, Cha Vue, Laurie L. Parker, and Dawn A. Lowe from the University of Minnesota questioned how estrogen deficiency might impact the overall skeletal muscle phosphoproteome after contraction, as force production induces phosphorylation of several muscle proteins. “Importantly, identification of these altered phosphosites and candidate kinases and phosphatases sensitive to the presence of estrogen will help advance our understanding of the contributions of estrogen deficiency to muscle strength loss in aging females.” Phosphoproteomic analyses of the tibialis anterior muscle after contraction in two mouse models of estrogen deficiency, ovariectomy (Ovariectomized (Ovx) vs. Sham) and natural aging-induced ovarian senescence (Older Adult (OA) vs. Young Adult (YA)), identified a total of 2,593 and 3,507 phosphopeptides in Ovx/Sham and OA/YA datasets, respectively. Further analysis of estrogen deficiency-associated proteins and phosphosites identified 66 proteins and 21 phosphosites from both datasets. Of these, 4 estrogen deficiency-associated proteins and 4 estrogen deficiency-associated phosphosites were significant and differentially phosphorylated or regulated, respectively. Comparative analyses between Ovx/Sham and OA/YA using Ingenuity Pathway Analysis (IPA) found parallel patterns of inhibition and activation across IPA-defined canonical signaling pathways and physiological functional analysis, which were similarly observed in downstream GO, KEGG, and Reactome pathway overrepresentation analysis pertaining to muscle structural integrity and contraction, including AMPK and calcium signaling. IPA Upstream regulator analysis identified MAPK1 and PRKACA as candidate kinases and calcineurin as a candidate phosphatase sensitive to estrogen. “In summary, our results from contracted skeletal muscle highlight CAST Ser-82 as a candidate phosphosite, and MAPK1/ERK2, PRKACA, and calcineurin as candidate upstream regulators sensitive to estrogen deficiency that may contribute to changes in the force-generating capacity of skeletal muscle.” DOI - https://doi.org/10.18632/aging.204959 Corresponding author - Dawn A. Lowe - lowex017@umn.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204959 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, estrogen deficiency, CAST, MAPK, PKA, calcineurin About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

In this episode, we talk to Kristina Cahojova, Founder and CEO of Kegg, the world's first 2-in-1 fertility tracking kegel ball. We discuss the biology of cervical mucus and why it's important for fertility and can be used as a measure of a woman's health. This episode was first released in 2020, so there may be one or two references that are slightly out of date. There's some golden content here though, so let's get into it.Remember to like, rate and subscribe and enjoy the episode!Guest bioKristina Cahojova had always struggled with tracking her fertility. Stress and traveling meant that ovulation tests and temperature methods provided limited information and none about her fertile window. After refusing to “fix the problem” with hormonal contraceptives, Kristina was told by a fertility specialist to track her cycles. But as is so often the case in women's health, there was no technology to help. So, after more than 7 years working at Amazon and eBay, Kristina decided to launch Kegg - the worlds first 2-in-1 fertility tracking kegel ball. For decades, women have not been taught that fertility is about more than just making babies. In fact, our fertility is our fifth vital sign.Organization bioKegg is an intuitive fertility tracker that measures changes in electrolyte levels of the cervical mucus —the golden metric to pinpointing your fertile window within each menstrual cycle. By using advanced sensing technology known as impedance, kegg can reveal your fertile window using your unique cycle data.Following the 2 minute daily reading, kegg will send your reading data to the cloud for analysis. In real-time, the kegg app displays your daily kegg readings, cyclical trends, and fertility predictions. With consistent, once a day use, you can gain deeper insight into your own unique fertility pattern.FemTech Focus Podcast bioThe FemTech Focus Podcast is brought to you by FemHealth Insights, the leader in Women's Health market research and consulting. In this show, Dr. Brittany Barreto hosts meaningfully provocative conversations that bring FemTech experts - including doctors, scientists, inventors, and founders - on air to talk about the innovative technology, services, and products (collectively known as FemTech) that are improving women's health and wellness. Though many leaders in FemTech are women, this podcast is not specifically about female founders, nor is it geared toward a specifically female audience. The podcast gives our host, Dr. Brittany Barreto, and guests an engaging, friendly environment to learn about the past, present, and future of women's health and wellness.FemHealth Insights bioLed by a team of analysts and advisors who specialize in female health, FemHealth Insights is a female health-specific market research and analysis firm, offering businesses in diverse industries unparalleled access to the comprehensive data and insights needed to illuminate areas of untapped potential in the nuanced women's health market.Call to Action!Don't forget to subscribe to the FemTech Focus podcast, and leave us a review!Episode ContributorsKristina CahojovaLinkedIn: @Kristina CahojovaTwitter: @KristinCahojovaKeggWebsite: https://kegg.tech/LinkedIn: @keggTwitter: @kegg_techInstagram: @kegg_techDr. Brittany BarretoLinkedIn:  @Brittany Barreto, Ph.D.Twitter: @DrBrittBInstagram: @drbrittanybarretoFemTech Focus PodcastWebsite: https://femtechfocus.org/LinkedIn: https://www.linkedin.com/company/femtechfocusTwitter: @FemTech_FocusInstagram: @femtechfocusFemHealth InsightsWebsite: https://www.femhealthinsights.com/LinkedIn: @FemHealth InsightsResourceshttps://kegg.tech/

2023 Student Scholar Reflections

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.18.549581v1?rss=1 Authors: Nguyen, V., Kravitz, J., Gao, C., Hochman, M. L., Meng, D., Chen, D., Wang, Y., Jegga, A. G., Nelson, S., Tan, W. Abstract: Port Wine Birthmark (PWB) is a congenital vascular malformation in the skin, occurring in 1-3 per 1,000 live births. We recently generated PWB-derived induced pluripotent stem cells (iPSCs) as clinically relevant disease models. The metabolites associated with the pathological phenotypes of PWB-derived iPSCs are unknown, which we aimed to explore in this study. Metabolites were separated by ultra-performance liquid chromatography and were screened with electrospray ionization mass spectrometry. Orthogonal partial least-squares discriminant analysis, multivariate and univariate analysis were used to identify differential metabolites (DMs). KEGG analysis was used for the enrichment of metabolic pathways. A total of 339 metabolites were identified. There were 22 DMs confirmed with 9 downregulated DMs including sphingosine and 13 upregulated DMs including glutathione in PWB iPSCs as compared to controls. Pathway enrichment analysis confirmed the upregulation of glutathione and downregulation of sphingolipid metabolism in PWB-derived iPSCs as compared to normal ones. We next examined the expression patterns of the key factors associated with glutathione metabolism in PWB lesions. We found that hypoxia-inducible factor 1 (HIF1), glutathione S-transferase Pi 1 (GSTP1), {gamma}-glutamyl transferase 7 (GGT7), and glutamate cysteine ligase modulatory subunit (GCLM) were upregulated in PWB vasculatures as compared to blood vessels in normal skins. Our data demonstrate that there are perturbations in sphingolipid and cellular redox homeostasis in the PWB vasculature, which may facilitate cell survival and pathological progression. Our data imply that upregulation of glutathione may contribute to laser-resistant phenotypes in the PWB vasculature. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.12.548684v1?rss=1 Authors: Pranty, A. I., Wruck, W., Adjaye, J. Abstract: Bilirubin induced neurological damage (BIND), which is also known as Kernicterus, occurs as a consequence of defects in the bilirubin conjugation machinery, thus resulting in unconjugated bilirubin (UCB) to cross the blood brain barrier (BBB) and accumulation. Severe hyperbilirubinemia can be caused by a mutation within the UGT1A1 encoding gene. This mutation has a direct contribution towards bilirubin conjugation leading to Kernicterus as a symptom of Crigler Najjar Syndromes (CNS1, CNS2) and Gilbert syndrome, which results in permanent neurological sequelae. In this comparative study, we used human induced pluripotent stem cells (hiPSCs) derived 3D-brain organoids to model BIND in vitro and unveil the molecular basis of the detrimental effects of UCB in the developing human brain. hiPSC derived from healthy and CNS patients were differentiated into day 20 brain organoids, these were then stimulated with 200nM UCB. Analyses at 24 and 72 hrs post-treatment point at UCB induced neuro-inflammation in both cell lines. Transcriptome and associated KEGG and Gene Ontology analyses unveiled activation of distinct inflammatory pathways such as cytokine cytokine receptor interaction, MAPK signaling, calcium signaling, NFkB activation. Furthermore, both mRNA expression and secretome analysis confirmed an upregulation of proinflammatory cytokines such as IL6 and IL8 upon UCB stimulation. In summary, this novel study has provided insights into how a human iPSC derived 3D-brain organoid model can serve as a prospective platform for studying the etiology of BIND Kernicterus. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.23.546309v1?rss=1 Authors: Xuan, W., Cheng, F., Han, X., Tipparaju, S., Ashraf, M. Abstract: Background: Extensive studies have been conducted in skeletal muscle and myocardium affected by Duchenne Muscular Dystrophy (DMD) disease but there is a significant gap of research in the role of vascular smooth muscle cells (VSMCs) in DMD. Here, we investigated the role of dystrophin deficiency in the maintenance of VSMCs contractile phenotype. Methods: 12-14 months old mdx mice and DMD induced pluripotent stem cells (iPSC) derived VSMCs were used as disease models. Morphological and immunohistochemistry analyses were performed to determine histological changes and the expression of contractile markers. Transmission Electron Microscopy (TEM) was used to assess ultrastructural changes in the VSMCs. Mito-tracker staining and TUNEL staining were performed to determine mitochondria fission-fusion and apoptosis respectively. mRNA Sequencing for normal iPSC derived VSMCs (WT-VSMCs) and DMD iPSC derived VSMCs (DMD-VSMCs) with or without oxidative stress was performed. KEGG signaling pathway enrichment, Go function enrichment and Gene set enrichment analysis (GESA) were conducted to explore the potential mechanism responsible for these changes. In addition, transcription factor enrichment analysis was performed to unravel mechanistic pathways of regulatory networks. Results: Spontaneous abnormal VSMCs proliferation, loss of vascular structure and degenerative changes occurred in VSMCs in aorta from 12-14 months old mdx mice. The DMD-VSMCs showed maturation defect, loss of mitochondrial hemostasis, and increased vulnerability to oxidative stress compared with WT-VSMCs. Transcriptome analysis revealed dysregulation of smooth muscle proliferation, differentiation, and vascular development in DMD-VSMCs. Transcriptional factor, target, and motif discovery analysis of the dysregulated gene set suggested potential contributions of transcriptional factors GADD45A, SOX9, TIA1, RBBP9 and FOXM to the phenotypes of DMD-VSMCs. Under oxidative stress, initiation of apoptotic process was significantly enhanced in DMD-VSMCs while their response to hypoxia and oxidative stress was downregulated. Conclusions: Dystrophin deficiency induced VSMCs phenotype switching and disrupted mitochondrial metabolism. The findings in this study underscore the importance of vascular dysfunction in DMD disease and therapeutic interventions to restore VSMC phenotype may ameliorate the propensity of disease progression. It is suggested that the transcriptome analysis may allow the discovery of potential signaling pathways involved in the dysregulation of transcription factors. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.02.530846v1?rss=1 Authors: Li, Y., Liu, C., Bai, X., Li, M., Duan, C. Abstract: The cell proliferation-quiescence decision plays fundamental roles in tissue formation and regeneration, and its dysregulation can lead to human diseases. In this study, we performed transcriptomics and genetic analyses using a zebrafish model to identify pathways and genes involved in epithelial cell quiescence-proliferation regulation. In this in vivo model, a population of GFP-labeled epithelial cells known as ionocytes were induced to reenter the cell cycle by a physiological stress. Transcriptomics analysis identified 1168 genes up-regulated and 996 genes down-regulated in the reactivated cells. GO and KEGG pathway analyses revealed that genes involved in transcription regulation, cell cycle, Foxo signaling, and Wnt signaling pathway are enriched among the up-regulated genes, while those involved in ion transport, cell adhesion, and oxidation-reduction are enriched among the down-regulated genes. Among the top up-regulated genes is FK506 binding protein 5 (Fkbp5), a member of the conserved immunophilin family. CRISPR/Cas9-mediated Fkbp5 deletion abolished ionocyte reactivation and proliferation. Pharmacological inhibition of Fkbp5 had similar effects. Further analyses showed that genetic deletion and inhibition of Fkbp5 impaired Akt signaling. Forced expression of a constitutively active form of Akt rescued the defects caused by Fkbp5 inhibition. These results uncover a previously unrecognized role of Fbkp5 in regulating the quiescence-proliferation decision via Akt signaling. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In episode #215 of The Hormone P.U.Z.Z.L.E Podcast, our guest Kristina Cahojova talks about Cervical Mucus and Your Fertility. More about Kristina: Kristina is an experienced marketer. She managed Growth and GTM at early-stage startups, Amazon and eBay. Inspired by her personal difficulties with cycle and fertility tracking, Kristina began prototyping kegg in 2017; she launched the brand under the Lady Technologies umbrella in 2020. Over time, Kristina's vision is to expand kegg's reach beyond fertility to help improve overall women's health. Thank you for listening! This episode is made possible by @kegg_tech Follow Kristina on Instagram: @kegg_tech Subscribe to Kegg's newsletter HERE. Follow Dr. Kela on Instagram: @kela_healthcoach Get your FREE Fertility Meal Plan: https://coachkela.com/ FTC Affiliate Disclaimer: The disclosure that follows is intended to fully comply with the Federal Trade Commission's policy of the United States that requires to be transparent about any and all affiliate relations the Company may have on this show. You should assume that some of the product mentions and discount codes given are "affiliate links", a link with a special tracking code This means that if you use one of these codes and purchase the item, the Company may receive an affiliate commission. This is a legitimate way to monetize and pay for the operation of the Website, podcast, and operations and the Company gladly reveals its affiliate relationships to you. The price of the item is the same whether it is an affiliate link or not. Regardless, the Company only recommends products or services the Company believes will add value to its users. The Hormone Puzzle Society and Coach Kela will receive up to 30% affiliate commission depending on the product that is sponsored on the show. For sponsorship opportunities, email HPS Media at podcast@coachkela.com.

Yours Truly, Johnny Dollar was a radio drama that aired on CBS Radio from February 18, 1949, to September 30, 1962. The first several seasons imagined protagonist Johnny Dollar as a standard private investigator drama. Listen to our radio station Old Time Radio https://link.radioking.com/otradio Listen to other Shows at My Classic Radio https://www.myclassicradio.net/ Remember that times have changed, and some shows might not reflect the standards of today's politically correct society. The shows do not necessarily reflect the views, standards, or beliefs of Entertainment Radio

In this episode of the Curious Women podcast, we provide a summary of the prior few episodes as we found them to be so engaging and in-depth. We want to ensure that you not only have adequate time to go over all of them but that we also draw your attention to anything you may have overlooked. [03:33] Pregnancy – We explore the significance and applicability of the two pregnancy-related episodes, in which we address what you need to know before purchasing prenatal vitamins and what to eat during pregnancy, postpartum, and breastfeeding. [09:15] How To Track Cervical Mucus: Your Vagina Know Best! - In this episode, Kristina explains the KEGG device and how it helps women monitor their fertility and other cervical mucus-related issues. [11:29] Birth Control 101 with Dr. Basma Faris - Learn about BC, its effects on your body, and the questions you've always wanted to ask. [15:51] Check out - Listen to episodes 26,28 and 36, respectively, if you're interested in hearing Dr. E's functional medicine perspective on Hashimoto's and Hypothyroidism, Bea Boas's insights into breathwork, and Heather Lastma's explanation of what it means to live an Embodied Life. [20:00] Suggestions - Get in touch with us and share your opinions and feedback. Resources: Mentioned in the episode: 031 Prenatal Vitamins with Ayla Barmmer: What You NEED Know Before Buying: 031-prenatal-vitamins-with-ayla-barmmer-what-you-need/ 034 What to Eat For Pregnancy, Postpartum and Breastfeeding with Lily Nichols: 034-what-to-eat-for-pregnancy-postpartum-and/ 030 How To Track Cervical Mucus: Your Vagina Know Best! with Founder of Kegg, Kristina Cahojova: 030-how-to-track-cervical-mucus-your-vagina-know-best/ 025 Birth Control 101 with Dr. Basma Faris: 025-birth-control-101-with-dr-basma-faris-what-bc-is/ 028 ThetaBreathwork with Bea Boas:028-thetabreathwork-with-bea-boas/ 036 to know what it means to live an Emobied Life with Heather Last: 036-embodiment-what-it-means-to-live-an-emobied-life 026 An Functional Medicine Approach to Hashimoto's and Hypothyroidism with Dr. E: 026-an-functional-medicine-approach-to-hashimotos/ --- Support this podcast: https://anchor.fm/curious-women/support

Release Date: January 07, 2011Johnny Dollar is called in to find an insured stolen necklace.Originial Air Date: November 11, 1950Support the show monthly at patreon.greatdetectives.netSupport the show on a one-time basis at http://support.greatdetectives.net.Mail a donation to: Adam Graham, PO Box 15913, Boise, Idaho 83715Take the listener survey at http://survey.greatdetectives.netGive us a call at 208-991-4783Follow us on Instagram at http://instagram.com/greatdetectivesFollow us on Twitter @radiodetectives

Voices in the episode in order of appearance:Josh Paskewicz, Talent Acquisition Manager at HylantAllison Garcia, Talent Acquisition Leader at HylantKevin Ray, Vice President of Learning & Development at Erie Insurance GroupMeaghen Paterson, District Sales Manager at Erie Insurance GroupWill Kegg, Insurance & Risk Management Student at University of Cincinnati, GIS Chapter PresidentBenjamin J. Kegg, Information Technology Student at University of Cincinnati, Executive GIS MemberMary Jo Zimmer, User Experience Manager at Erie Insurance GroupLee'a Thigpen, Information Technology Supervisor & IT Intern Program Lead at Erie Insurance GroupLearn More!https://www.gammaiotasigma.org/https://www.gammaiotasigma.org/sustaining-partners

Artist: Kounty Road Kegg Ig @kountyroadkegg Song Name: Can't Be Killaz(unreleased) New Age Blues(unreleased) website: https://linktr.ee/KountyRoadK booking: 1275kartel.llc@gmail.com Manager: @tatyana.the.goddess Website: https://linktr.ee/CoCoGoddessExperience --- Send in a voice message: https://anchor.fm/clifton-mcdaniel/message Support this podcast: https://anchor.fm/clifton-mcdaniel/support

The cervical mucus test is keeping track of how your cervical mucus varies throughout your menstrual cycle. This week on the Curious women podcast, we are having an amazing guest who is the CEO of KEGG; a medical-grade fertility device that gives you personalized fertility tracking through the cervical fluid. Kristina joins us today to dive into the KEGG device and how it helps women to have a close eye on being fertile and other concerns regarding cervical mucus. Kristina was a person who travels a lot. Due to the stress and traveling, her cycle was not regular, and found out tracking vaginal fluid might help but there was no device to do that. She completed her training on the Creighton Model and the Sympto-Thermal Method of fertility awareness and after some time identified that those methods are not easy to learn. She spent 7+ years working on eBay and Amazon and decided to create KEGG. Kristina currently lives in San Francisco, California, the United States with her husband. In this episode we cover, [08.49] Background - Starting the conversation, Kristina dives into her story, how she got into the field and how KEGG started. [19.39] The device – Kristina shares KEGG helps you to get the data of your vagina without going to a doctor. [21.17] Being empowered – Kristina dives into what the device can currently offer for any woman who uses it like, the possibility of having infections, PCOS, conceiving, and more before going to the doctor. [23.36] Tracking – Kristina dives into the methods by which women can track cervical fluid and how difficult it is to track it for women who have irregular periods. [32.21] Birth control – We dive into how women are used to getting birth control which doesn't fix problems because it only conceals the problem. [35.26] What is KEGG – Kristina dives into what KEGG is, how it works, what benefits women can get from it, and how it served women including herself. [41.27] Pelvic floor – Pelvic floor holds the weight of everything when you are pregnant. Kristina shares how women get problems in the pelvic floor after childbirth and how to avoid that. [46.09] Manual cervix fluid tracking – Kristina shares how to both track manual cervix fluid and KEGG tracking and how it helps fertilization. [56.09] Processing with knowledge - Kristina dives into how women should know about things like egg quality, and timing to conceive because most women get frustrated after the first four months due to the lack of knowledge. Resources Connect with Kristina https://kegg.tech/ https://www.linkedin.com/in/kristinacahojova/ https://twitter.com/kristincahojova?lang=en https://www.ease.com/ Chart your fertility https://www.instagram.com/fertilitycharting/?hl=en Period Guru https://mobile.twitter.com/jennalongoria https://www.instagram.com/jennalongoriahealth/?hl=en Fix Your Period By Nicole Jardim https://books.google.lk/books/about/Fix_Your_Period.html?id=xs-lDwAAQBAJ&redir_esc=y --- Support this podcast: https://anchor.fm/curious-women/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.27.509283v1?rss=1 Authors: Fongang, B., Satizabal, C. L., Kautz, T. F., Ngouongo, Y. W., SherraeMuhammad, J. A., Vasquez, E., Mathews, J., Goss, M., Saklad, A. R., Himali, J., Beiser, A., Cavazos, J. E., Mahaney, M. C., Maestre, G., DeCarli, C., Shipp, E. L., Vasan, R. S., Seshadri, S. Abstract: A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p-values less than 0.001), as well as better executive function (p-values less than 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and {beta}-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

The first several seasons imagined protagonist Johnny Dollar as a private investigator drama, with Charles Russell, Edmond O'Brien and John Lund portraying Dollar in succession over the years. In 1955 after a yearlong hiatus, the series came back in its best-known incarnation with Bob Bailey starring in "the transcribed adventures of the man with the action-packed expense account – America's fabulous freelance insurance investigator." There were 809 episodes (plus two not-for-broadcast auditions) in the 12-year run, and more than 710 still exist today. Jim Cox's book American Radio Networks: A History cites "886 total performances" which includes repeat performances. Format. The format best remembered was instituted by writer-director Jack Johnstone. Each case usually started with a phone call from an insurance adjuster, calling on Johnny to investigate an unusual claim: a suspicious death, an attempted fraud, a missing person, or other mysterious circumstances. Each story required Johnny to travel to some distant locale, usually within the United States but sometimes abroad, where he was almost always threatened with personal danger in the course of his investigations. He would compare notes with the police officials who had first investigated each strange occurrence, and followed every clue until he figured out what actually happened. Johnny's file on each case was usually referenced as a "matter," as in "The Silver Blue Matter" or "The Forbes Matter". Later episodes were more fanciful, with titles like "The Wayward Trout Matter" and "The Price of Fame Matter" (the latter featuring a rare guest-star appearance by Vincent Price as himself; here Price and Dollar team up to retrieve a painting stolen by Price's insurance agent). Johnny usually stuck to business, but would sometimes engage in romantic dalliances with women he encountered in his travels; later episodes gave Johnny a steady girlfriend, Betty Lewis. Johnny's precious recreational time was usually spent fishing, and it was not uncommon for Johnny's clients to exploit this favorite pastime in convincing him to take on a job near good fishing locations. His past was rarely mentioned, but Dollar in “The Bennett Matter” described himself as a four-year US Marine veteran who then worked as a police officer for a decade before changing careers to insurance investigation. In "The Blackburn Case" Dollar also refers to his time as a Pinkerton Detective. Each story was recounted in flashback, and every few minutes the action would be interrupted by Johnny listing a line item from his expense account, which served as an effective scene transition. Most of the expense account related to transportation, lodging, and meals, but no incidental expense was too small for Johnny to itemize, as in "Item nine, 10 cents. Aspirin. I needed them." The monetary amounts weren't always literal: the smallest line item Johnny ever recorded was "two cents: what I felt like" after a professional setback; the largest was "one million dollars" (the way he felt after finding a missing woman and her daughter in a snowbound cabin). The episodes generally finished with Johnny tallying up his expense account and traveling back to Hartford, Connecticut, where he was based. Sometimes Johnny would add a sardonic postscript under "Remarks," detailing the aftermath of the case. ("The Todd Matter," which especially disgusted Johnny, ended abruptly with "Remarks – nil!") In later seasons the program sometimes referred to itself, with other characters recognizing Dollar's voice from the radio; in the episode “The Salkoff Sequel Matter” Johnny's radio show becomes an important plot point.

Pelvic Floor Health - Pre-Postnatal with Dr. Marcy Crouch In episode #189 of The Hormone P.U.Z.Z.L.E Podcast, our guest Dr. Marcy Crouch talks about Pelvic Floor Health - Pre-Postnatal. More about Dr. Marcy Crouch: Dr. Marcy Crouch is a passionate and down-to-earth Physical Therapist focusing on all aspects of birth prep, pelvic floor dysfunction, pregnancy, and postpartum musculoskeletal issues. Guides women through pregnancy and sexual health courses and teaches continuing education courses for physical therapists both nationally and internationally. Has candid and empowering conversations about women's health and how we can do better to care for women everywhere. She is the mother to 2 amazing boys and has first-hand experience of pregnancy, birth, and the postpartum period. She loves a good glass of wine, horses, belly laughs, and drives a minivan shamelessly.  Thank you for listening! This episode is made possible by @kegg_tech  Kegg is a fertility monitor that tracks your most important fertility indicator - cervical mucus - to discover your full fertile window -the 5-6 days when you have the highest chances of conceiving. Start tracking your fertility with kegg to never ever miss those most important days of your peak fertility. Visit kegg.tech to get your kegg with a 12-month pregnancy guarantee meaning you will get 100% of your money back if you don't become pregnant.  Use the code PODCAST10 at checkout to get $10 off. Follow Dr. Marcy on Instagram: @thedowntheredoc Follow Coach Kela on Instagram: @kela_healthcoach Get your FREE Fertility Meal Plan: https://coachkela.com/ For sponsorship opportunities, email HPS Media at podcast@coachkela.com.

Welcome to our NFP through the seasons series! We'll go from Adolescence to Perimenopause and everything in between.This week's topic is NFP when TTC (trying to conceive) when it's "difficult". Courtney Warday is joining us this week. What we mean by difficult is when you've been in this season for a while, maybe you're working with fertility specialists or a NaPro doctor, maybe you go in and out of hope, disappointment, resentment, longing, and so many more emotions. This episode is for you!I offer NFP/FA Mindset coaching and NFP Method Match coaching! Wondering what that is? Check out episode 62 or book a free 10 minute discovery call.If you are interested in booking a coaching session with me, click here for NFP/FA mindset coaching and click here for method match coaching.Reach out at instagram.com/chartingtowardintimacy/ or chartingtowardintimacy@gmail.comThank you to Kegg for sponsoring today's episode. Use code charting10 for $10 off at kegg.tech

On this episode of the Yak Legion podcast our host Zach Coriell chats with Melissa Keg from the Strictly Sail kayak team here in Cincinnati Ohio. She also has a very interesting and informative YouTube channel called GirlGoneFishing. We chat about her kayak fishing adventures where she travels all over Ohio fishing local tournament trails like the Buckeye Kayak Fishing Trail and Cincinnati Kayak Fishing. Along with being a kayak angler Melissa was also a professional Foosball player and still teaches Ski lessons up at Perfect North Slopes. Grab ya a cold beer and come sit around the camp fire as we chat with this interesting and cheerful lady. Thanks for listening! Check out Melissa on YouTube at https://www.youtube.com/c/GirlGoneFishing You can listen to the Yak Legion podcast on most major podcast apps like Apple Podcasts and Spotify. You can also listen in at https://anchor.fm/TheYakLegionPodcast/ You can follow Yak Legion on Facebook at https://www.facebook.com/TheYakLegionPodcast You can follow on Instagram at https://www.instagram.com/theyaklegionpodcast/#theyaklegionpodcast #zachcoriellfishing #yaklegion Follow along on TikTok for informative and comedic fishing videos @yaklegion You can email me at theyaklegionpodcast@gmail.com --- Send in a voice message: https://anchor.fm/TheYakLegionPodcast/message Support this podcast: https://anchor.fm/TheYakLegionPodcast/support

In episode #182 of The Hormone P.U.Z.Z.L.E Podcast, our guest Charlotte Grand talks about How to Have a Fertility Kitchen. More about Charlotte Grand: Charlotte Grand is a registered Nutritional Therapist, fertility nutrition expert and creator of the popular Instagram channel @thefertilitykitchen where she shares her wholesome balanced approach alongside deliciously simple, everyday recipes. Charlotte has spent almost ten years specialising in preconception and fertility, and in her private practice supports her clients to transform their health in preparation for conception and pregnancy. Thank you for listening! This episode is made possible by @kegg_tech  Did you know that focusing on the day of ovulation is already too late when you are trying to get pregnant? LH strips and basal body temping misses the mark. You are most likely to conceive 2 to 3 days before the day of ovulation. But how do you know when are in those days? That brings us to today's sponsor: Kegg.  Kegg is a fertility monitor that tracks your most important fertility indicator - cervical mucus - to discover your full fertile window -the 5-6 days when you have the highest chances of conceiving. Start tracking your fertility with kegg to never ever miss those most important days of your peak fertility. Visit kegg.tech to get your kegg with a 12-month pregnancy guarantee meaning you will get 100% of your money back if you don't become pregnant.  Use the code PODCAST10 at checkout to get $10 off. Follow Charlotte Grand on Instagram: @thefertilitykitchen Follow Coach Kela on Instagram: @kela_healthcoach Get your FREE Fertility Meal Plan: https://coachkela.com/ For sponsorship opportunities, email HPS Media at podcast@coachkela.com.

In episode #179 of The Hormone P.U.Z.Z.L.E Podcast, our guest Dr. Angeline Beltsos talks about Kindbody and Your Fertility. More about Dr. Angeline Beltsos: Dr. Angeline N. Beltsos is the CEO, Clinical at Kindbody. Kindbody is a leading fertility and family-building care company offering state-of-the-art technology, comprehensive virtual and in-person care, and an employer benefits solution. Dr. Beltsos is double board certified in Obstetrics and Gynecology and Reproductive Endocrinology and Infertility (REI). Dr. Beltsos has served as REI Division Education Director for the Obstetrics and Gynecology residency programs of Illinois Masonic Medical Center, Lutheran General Hospital, St. Joseph's Hospital Chicago, and Mercy Chicago. She is also a Clinical Assistant Professor for the Department of Obstetrics and Gynecology at University of Illinois at Chicago.  Thank you for listening! This episode is made possible by @kegg_tech  Did you know you can quadruple your chances of conception by accurately timing your efforts during your fertile window? Yes, you heardthat right. How can you do it? That brings us to today's sponsor Kegg. Kegg is a fertility monitor that tracks your most important fertility indicator - cervical mucus - to discover your full fertile window. - the 5-6 days when you have the highest chances of conceiving. Do you want to know when you have the highest chance of getting pregnant? Start tracking your fertility with Kegg. Visit kegg.tech to get your Kegg with a 12-month pregnancy guarantee meaning you will get 100% of your money back if you don't become pregnant. Use the code PODCAST10 at checkout to get $10 off. Follow Dr. Beltsos on Instagram: @angiebeltsosmd_fertility Follow Coach Kela on Instagram: @kela_healthcoach Get your FREE Fertility Meal Plan: https://coachkela.com/ For sponsorship opportunities, email HPS Media at podcast@coachkela.com.

Billy talks with Strictly Sail and Kayak pro staff member Melissa Kegg. If you want to check out more content from Melissa head over to YouTube and check out her channel https://youtube.com/c/GirlGoneFishing --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

Josh and Brad host Melissa Kegg, Strictly Sail & Kayak's newest fishing team member to talk about her experiences fishing off the new Hobie Lynx. Waypoint TV- https://waypointtv.com Patreon-https://www.patreon.com/paddlenfin Podcast & Website- www.paddlenfin.com YouTube- https://www.youtube.com/paddlenfin Email- paddlenfin@gmail.com Social Media- @paddlenfin Yak Gadget- www.yakgadget.com 153 Baits- www.the153anglers.com Pelican Professional- www.pelican.com Rocktown paddlesports - rocktownadventures.com JigMasters Jigs- https://jigmasters.com Learn more about your ad choices. Visit megaphone.fm/adchoices

Prečo by meranie meštruačného cyklu nemohlo byť tak jednoduché ako keď nám hodinky merajú všetky pohybové činnosti, či kvalitu spánku? Aj to je jedna z otázok, ktorú si zakladateľka Keggᵀᴹ položila pri založení jej projektu. Nepravidelné cykly, neznalosť o sebe a priebehu svojho cyklu, netušíme prečo nemôžeme otehotnieť alebo hľadáme ochranu, ktorá nám neničí zdravie. Keggᵀᴹ je zariadenie určené na sledovanie menštruačného cyklu najmä pre ženy s nepravidelným cyklom alebo ženy, ktoré hľadajú jednoduchého a praktického pomocníka na sledovanie svojho cyklu. Viac o Keggᵀᴹ nájdeš na www.kegg.tech alebo na IG: @kegg_tech

Prečo by meranie meštruačného cyklu nemohlo byť tak jednoduché ako keď nám hodinky merajú všetky pohybové činnosti či kvalitu spánku? Aj to je jedna z otázok, ktorú si zakladateľka Keggᵀᴹ položila pri založení jej projektu. Nepravidelné cykly, neznalosť o sebe a priebehu svojho cyklu, netušíme prečo nemôžeme otehotnieť či hľadáme ochrnau, ktorá nám neničí zdravie. Keggᵀᴹ je zariadené určené na sledovanie menštruačného cyklu najmä pre ženy s nepravidelným cyklom či ženy, ktoré hľadajú jednoduchého a praktického pomocníka k sledovaniu svojho cyklu.Viac o Keggᵀᴹ nájdeš na www.kegg.tech alebo na IG: @kegg_tech

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.20.391912v1?rss=1 Authors: Choudhary, K. S., Fahy, E., Coakley, K., Sud, M., Maurya, M. R., Subramaniam, S. Abstract: With the advent of high throughput mass spectrometric methods, metabolomics has emerged as an essential area of research in biomedicine with the potential to provide deep biological insights into normal and diseased functions in physiology. However, to achieve the potential offered by metabolomics measures, there is a need for biologist-friendly integrative analysis tools that can transform data into mechanisms that relate to phenotypes. Here, we describe MetENP, an R package, and a user-friendly web application deployed at the Metabolomics Workbench site extending the metabolomics enrichment analysis to include species-specific pathway analysis, pathway enrichment scores, gene-enzyme information, and enzymatic activities of the significantly altered metabolites. MetENP provides a highly customizable workflow through various user-specified options and includes support for all metabolite species with available KEGG pathways. MetENPweb is a web application for calculating metabolite and pathway enrichment analysis. Copy rights belong to original authors. Visit the link for more info

Peter Kegg, former Chief Executive Of Bournemouth Churches Housing Association (BCHA), joins Blair on Hope FM's Community Now! FIRST BROADCAT: 28/10/20

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.378752v1?rss=1 Authors: Killinger, B. A., Marshall, L., Chatterjee, D., Chu, Y., Kordower, J. Abstract: The intracellular misfolding and accumulation of alpha-synuclein into structures collectively called Lewy pathology is a central phenomenon for the pathogenesis of Parkinsons disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy. Understanding the molecular architecture of Lewy pathology is crucial for understanding disease origins and progression. Here we developed a method to label, extract, and purify molecules from Lewy pathology of formalin fixed PD and DLB brain for blotting and mass spectrometry analysis. Using the biotinylation antibody recognition (BAR) technique, we labeled phosphoserine 129 alpha-synuclein positive pathology and associated molecules with biotin. Formalin crosslinks were then reversed, protein extracted, and pathology associated molecules isolated with streptavidin beads. Results showed superior immunohistochemical staining of Lewy pathology following the BAR protocol when compared to standard avidin biotin complex (ABC) based detection. The enhanced staining was particularly apparent for fibers of the medial forebrain bundle and punctate pathology within the striatum and cortex, which otherwise were weakly labeled or not detected. Subsequent immunoblotting BAR-labeled Lewy pathology extracts revealed the presence of high molecular weight alpha-synuclein, ubiquitin protein conjugates, and phosphoserine 129 alpha-synuclein. Mass spectrometry analysis of BAR-labeled Lewy pathology extracts from PD and DLB patients identified 815 proteins with significant enrichment for many pathways. Notably the most significant KEGG pathway was Parkinsons disease (FDR = 2.48 X 10-26) and GO Cellular compartment was extracellular exosomes (GO Cellular Compartment; FDR = 2.66x 10-34). We used enrichment data to create a functional map of Lewy Pathology from primary disease tissues, which implicated Vesicle Trafficking as the primary disease associated pathway in DLB and PD. In summary, this protocol can be used to enrich for Lewy pathology from formalin fixed human primary tissues, which allows the determination of molecular signatures of Lewy pathology. This technique has broad potential to help understand the phenomenon of Lewy pathology in primary human tissue and animal models. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.05.370528v1?rss=1 Authors: Lin, j., Liu, G., Han, Z., Gao, Q., Wang, Z., Chang, Z., Gao, Y., Ma, D. Abstract: Backgroundl Xingnaojing injection (XNJ) is extracted from the Chinese ancient prescription "An-Gong-Niu-Huang Pill", is widely used for stroke in China. We mainly observe the effect of XNJ (Xingnaojing) injection on the gut microbiota in stroke model mice. Methods: Forty-two 7- to 8-week-old male C57 mice weighing 22-24 g were chosen for the experiment. There were 6 mice in each group; the 7 groups were the normal group (NG), the MCAO group (CG), the MCAO+XNJ group (EG), the sham surgery group (SG), the sham germ-free normal group (SGFNG), the sham germ-free+MCAO group (SGFCG), and the sham germ-free+MCAO+XNJ group (SGFEG). Two days before modeling, we abdominally administered Xingnaojing (6 mg/kg) the SGFEG and EG groups. The processing time of sustained XNJ was 5 days. Three days after modeling, 1 ~ 2 mouse feces were collected, and after a MiSeq PE library was constructed, an Illumina MiSeq PE 300 platform was used for high-throughput sequencing. After cleaning the sequencing data, the microbiome and microbiomeseq packages were used for analysis using R software (version 3.6.2). Results: Alpha diversity analysis revealed that the diversity was not different between the CG and EG. The Simpson index was different between the SGFCG and SGFEG. XNJ increased the levels of Sutterellaceae and decreased the level of Deferribacteres and Morganella. LEfSe analysis showed that SGFCG mice were also enriched with Morganella. XNJ increased the concentrations of the SCFAs PA (propionate), VA (valerate), IBA (isobutyrate), and IVA (isovalerate) in the feces of the SGFEG group. BA (butyrate) had greater positive correlation with gut bacteria than other acids in the SGFCG, and XNJ changed this trend. KEGG analysis showed that peptidoglycan biosynthesis was most different between the CG and EG. Conclusion: Ischemic stroke (IS) causes dysbiosis of some specific bacteria in the gut microbiota in MCAO mice. Xingnaojing ameliorated this condition by increasing the levels of Sutterellaceae and decreasing the level of Deferribacteres and Morganella. These results are in accordance with other research on Chinese medicines for IS that affect the gut microbiota. Enrichment analysis of SCFAs revealed that XNJ improved the levels of SCFAs through an energy metabolism-related pathway. Copy rights belong to original authors. Visit the link for more info

In the last part of my conversation with Kristina, Co-Founder and CEO of Kegg, we talk about the cold, hard challenges for startups in the femtech space, and the discrimination female founders constantly face in trying to raise money from investors in Silicon Valley. Kristina has built Kegg, a medical device that helps women track their fertility and strengthen their pelvic floor muscles. Her customers (which includes me, by the way) love her product. But it is incredibly challenging for Kristina to raise money from mostly male investors, who are uncomfortable with the idea of a product that goes inside the vagina, and that solves a problem that they don't understand the need for. Kristina has learnt some important lessons from her mum and her female investors on how to succeed. She shares all her wisdom with us here! In this conversation, neither of us is holding back, so you'll get a real look at what we think of the state of fundraising for women in startups. Enjoy!

Join us for the second part of the story of how Kristina built Kegg: a medical device that both helps us understand our fertility and strengthen our pelvic floor muscles (which is great for intimacy

Kristina is the Co-Founder and CEO of Kegg, a 2-1 fertility tracker that also helps you strengthen your pelvic floor muscles. Like many founders in the Femtech space, her story of how she got started is an unusual one. Here, I asked her about what it was like to grow up in Slovakia, her experiences working in big tech companies and startups, and how she made her way to San Francisco and Silicon Valley. She offers some great words of wisdom to young, ambitious girls on how to graduate without student debt, and pursue causes that you are really passionate about. Talking to Kristina was very inspiring for me, so I hope you enjoy! You can find out more about Kegg and Kristina at www.kegg.tech.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.19.344887v1?rss=1 Authors: Tang, M., Zeng, L., Zeng, Z., Liu, J., Yuan, J., Wu, D., Lu, Y., Zi, J., Ye, M. Abstract: Colorectal cancer (CRC) is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions will promote early medical intervention and treatment, thus reducing morbidity and mortality. Proteins are generally considered key biomarkers of cancer. Herein, we performed a quantitative, tissue-original proteomics study in a cohort of ninety patients from pre-cancerous to cancerous conditions by liquid chromatography-tandem mass spectrometry. A total of 134,812 peptides, 8,697 proteins, 2,355 (27.08%) union differentially expressed proteins (DEPs), and 409 shared DEPs (compared with adjacent tissues) were identified. The number of DEPs showed a positive correlation with increasing severity of illness. The union and shared DEPs were both enriched in the KEGG pathway of focal adhesion, metabolism of xenobiotics by cytochrome P450, and drug metabolism - cytochrome P450. Among the 2,355 union DEPs, 32 were selected for identification and validation by multiple reaction monitoring from twenty plasma specimens. Of these, three proteins, transferrin receptor protein 1 (TFR1), adenosylhomocysteinase (SAHH), and immunoglobulin heavy variable 3-7 (HV307), were significantly differentially expressed and displayed the same expression pattern in plasma as observed in the tissue data. In conclusion, TFR1, SAHH, and HV307 may be considered as potential biomarkers for screening of CRC. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.15.341115v1?rss=1 Authors: Tan, Y., Zhao, X., Zhao, J., Ji, Q., Xiao, L., Hao, D. Abstract: The polyphagous pest Apolygus lucorumhas become the dominant insect in Bacillus thuringiensis (Bt) cotton fields. The hormone 20-hydroxyecdysone (20E) regulates multiple events in insect development and physiology. 20E responses are controlled by pathways triggered by phospholipase C (PLC)-associated proteins. However, 20E-modulated genes whose expression is affected by PLC remain unknown. Here, isobaric tag for relative and absolute quantitation (iTRAQ) and immunoblot were carried out for comparing differentially expressed proteins (DEPs) in A. lucorumin response to 20E and the PLC inhibitor U73122, respectively. Totally 1624 DEPs were, respectively, found in the 20E/control, U73122/control, and 20E+U73122/control groups. Venn diagram analysis further revealed 8 DEPs that were shared among the three groups. Immunoblot validated these findings, which corroborated and highlighted the reliability of proteomics. KEGG enrichment analysis showed that the DEPs were included in diverse signaling pathways. The largest portion of DEPs among the three groups were categorized in metabolic pathways. In addition, DEPs among the three groups were also found to regulate the Ras-MAPK and PI3K-AKT pathways. This is the first time that iTRAQ was carried out to assess proteome alteration in A. lucorum nymphs in response to 20E and a PLC inhibitor. These findings provide novel insights into protein expression in A. lucorumin response to 20E, and a more comprehensive understanding of the function of PLC in 20E signal transduction. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.07.329516v1?rss=1 Authors: Schulz, C., Almaas, E. Abstract: Approaches for systematizing information of relatedness between organisms is important in biology. Phylogenetic analyses based on sets of highly conserved genes are currently the basis for the Tree of Life. Genome-scale metabolic reconstructions contain high-quality information regarding the metabolic capability of an organism and are typically restricted to metabolically active enzyme-encoding genes. While there are many tools available to generate draft reconstructions, expert-level knowledge is still required to generate and manually curate high-quality genome-scale metabolic models and to fill gaps in their reaction networks. Here, we use the tool AutoKEGGRec to construct $975$ genome-scale metabolic draft reconstructions encoded in the KEGG database without further curation. The organisms are selected across all three domains, and their metabolic networks serve as basis for generating phylogenetic trees. We find that using all reactions encoded, these metabolism-based comparisons give rise to a phylogenetic tree with close similarity to the Tree of Life. While this tree is quite robust to reasonable levels of noise in the metabolic reaction content of an organism, we find a significant heterogeneity in how much noise an organism may tolerate before it is incorrectly placed in the tree. Furthermore, by using the protein sequences for particular metabolic functions and pathway sets, such as central carbon-, nitrogen-, and sulfur-metabolism, as basis for the organism comparisons, we generate highly specific phylogenetic trees. We believe the generation of phylogenetic trees based on metabolic reaction content, in particular when focused on specific functions and pathways, could aid the identification of functionally important metabolic enzymes and be of value for genome-scale metabolic modellers and enzyme-engineers. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.21.305847v1?rss=1 Authors: Hasegawa, K., Yamaguchi, Y., Pengjam, Y. Abstract: Pyruvic acid therapy is used for various diseases, but the therapeutic effect decreases at high doses. The molecular mechanism of high-dose pyruvate is not well understood. The purpose of this study was to identify the effects of high dose pyruvate addition on skeletal muscle using C2C12. The gene expression profile for the GSE5497 dataset was taken from the Gene Expression Omnibus database. GEO2R was used to identify specifically expressed genes (DEGs). Functional analysis and pathway enrichment analysis of DEG were performed using the DAVID database. The protein-protein interaction (PPI) network was built in the STRING database and visualized using Cytoscape. GO analysis showed that up-regulated DEG was primarily involved in angiogenesis, cell adhesion, and inflammatory response. We also showed that down-regulated DEG is involved in the regulation of muscle contraction, skeletal muscle fiber development. In addition, the upregulated KEGG pathway of DEG included Rheumatoid arthritis, Chemokine signaling pathway, and Cytokine-cytokine receptor interaction. Downregulated DEG included Calcium signaling pathway, hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy, Neuroactive ligand-receptor interaction, and Cardiac muscle contraction. Further, analysis of two modules selected from the PPI network showed that high-dose pyruvate exposure to C2C12 was primarily associated with muscle contraction, muscle organ morphogenesis, leukocyte chemotaxis, and chemokine activity. In conclusion, High-dose pyruvate treatment of C2C12 was found to be associated with an increased inflammatory response and decreased skeletal muscle formation. However, further studies are still needed to verify the function of these molecules at high doses of pyruvate. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.15.285551v1?rss=1 Authors: Ali, A., Shehwana, H., Hanif, A., Fatima, A., Shabbir, M., Rafiq, M. Abstract: Sepsis is a serious health situation caused by uncontrolled infection and septic shock is a severe condition of sepsis. RHBDD2 is a member of the rhomboid superfamily which is overexpressed in different types of cancer and associated with ER stress and estrogen receptor. Using microarray gene expression data and using different computational techniques this study investigated the role of RHBDD2 in sepsis and septic shock. Finds functional annotation of RHBDD2 using co-expression analysis and identified the deregulation of RHBDD2 in sepsis using differential expression analysis. Results show that RHBDD2 is overexpressed in sepsis and septic shock. The GO enrichment analysis, KEGG pathways, and biological functions of the RHBDD2 co-expressed genes module show that it is involved in most of the sepsis-related biological functions and also plays a role in most of the infection-related pathways which lead to sepsis and septic shock. RHBDD2 is regulated by STAT5 and SP1 transcriptional factors in sepsis and septic shock. The identification of the RHBDD2 as a biomarker may facilitate in septic shock diagnosis, treatment, and prognosis. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.18.256735v1?rss=1 Authors: Gu, H., Yuan, G. Abstract: There is an urgent need to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) that leads to COVID-19 and respiratory failure. Our study is to discover differentially expressed genes (DEGs) and biological signaling pathways by using a bioinformatics approach to elucidate their potential pathogenesis. The gene expression profiles of the GSE150819 datasets were originally produced using an Illumina NextSeq 500 (Homo sapiens). KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) were utilized to identify functional categories and significant pathways. KEGG and GO results suggested that the Cytokine-cytokine receptor interaction, P53 signaling pathway, and Apoptosis are the main signaling pathways in SARS-CoV-2 infected human bronchial organoids (hBOs). Furthermore, NFKBIA, C3, and CCL20 may be key genes in SARS-CoV-2 infected hBOs. Therefore, our study provides further insights into the therapy of COVID-19. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.09.243444v1?rss=1 Authors: Gu, H., Yuan, G. Abstract: The COVID-19 pandemic has infected millions of people and overwhelmed many health systems globally. Our study is to identify differentially expressed genes (DEGs) and associated biological processes of COVID-19 using a bioinformatics approach to elucidate their potential pathogenesis. The gene expression profiles of the GSE152075 datasets were originally produced by using the high-throughput Illumina NextSeq 500. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed to identify functional categories and biochemical pathways. GO and KEGG results suggested that several biological pathways such as Fatty acid metabolism and Cilium morphogenesis are mostly involved in the development of COVID-19. Moreover, several genes are critical for virus invasion and adhesion including FLOC, DYNLL1, FBXL3, and FBXW11 and show significant differences in COVID-19 patients. Thus, our study provides further insights into the underlying pathogenesis of COVID-19. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.31.230599v1?rss=1 Authors: Miller, R., Willighagen, E., Evelo, C., Kutmon, M., Waagmeester, A., Bohler, A. Abstract: Background To grasp the complexity of biological processes, the biological knowledge is often translated into schematic diagrams of biological pathways, such as signalling and metabolic pathways. These pathway diagrams describe relevant connections between biological entities and incorporate domain knowledge in a visual format that is easier for humans to interpret. It has already been established that these diagrams can be represented in machine readable formats, as done in KEGG, Reactome, and WikiPathways. However, while humans are good at interpreting the message of the creator of such a diagram, algorithms struggle when the diversity in drawing approaches increases. WikiPathways supports multiple drawing styles, and therefore needs to harmonize this to offer semantically enriched access via the Resource Description Framework format. Particularly challenging in the normalization of diagrams are the interactions between the biological entities, so that we can glean information about the connectivity of the entities represented. These interactions include information about the type of interaction (metabolic conversion, inhibition, etc.), the direction, and the participants. Availability of the interactions in a semantic and harmonized format enables searching the full network of biological interactions and integration with the linked data cloud. Results We here study how the graphically modelled biological knowledge in diagrams can be semantified and harmonized efficiently, and exemplify how the resulting data can be used to programmatically answer biological questions. We find that we can translate graphically modelled biological knowledge to a sufficient degree into a semantic model of biological knowledge and discuss some of the current limitations. Furthermore, we show how this interaction knowledge base can be used to answer specific biological questions. Conclusion This paper demonstrates that most of the graphical biological knowledge from WikiPathways is modelled in the semantic layer of WikiPathways with the semantic information intact and connectivity information preserved. The usability of the WikiPathways pathway and connectivity information has shown to be useful and has been integrated into other platforms. Being able to evaluate how biological elements affect each other is useful and allows, for example, the identification of up or downstream targets that will have a similar effect when modified. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.30.229690v1?rss=1 Authors: Levitt, P., Eagleson, K. L., Villanueva, M., Southern, R. M. Abstract: Exposure to early-life stress (ELS) increases risk for poor mental and physical health outcomes that emerge at different stages across the lifespan. Yet, how age interacts with ELS to impact the expression of specific phenotypes remains largely unknown. An established limited-bedding paradigm was used to induce ELS in mouse pups over the early postnatal period. Initial analyses focused on the hippocampus, based on documented sensitivity to ELS in humans and various animal models, and the large body of data reporting anatomical and physiological outcomes in this structure using this ELS paradigm. An unbiased discovery proteomics approach revealed distinct adaptations in the non-nuclear hippocampal proteome in male versus female offspring at two distinct developmental stages: juvenile and adult. Gene ontology and KEGG pathway analyses revealed significant enrichment in proteins associated with mitochondria and the oxidative phosphorylation (OXPHOS) pathway in response to ELS in female hippocampus only. To determine whether the protein adaptations to ELS reflected altered function, mitochondrial respiration (driven through complexes II-IV) and complex I activity were measured in isolated hippocampal mitochondria using a Seahorse X96 Flux analyzer and immunocapture ELISA, respectively. ELS had no effect on basal respiration in either sex at either age. In contrast, ELS increased OXPHOS capacity in juvenile males and females, and reduced OXPHOS capacity in adult females but not adult males. A similar pattern of ELS-induced changes was observed for complex I activity. These data suggest that initial adaptations in juvenile hippocampus due to ELS were not sustained in adults. Mitochondrial adaptations to ELS were also exhibited peripherally by liver. Overall, the temporal distinctions in mitochondrial responses to ELS show that ELS-generated adaptations and outcomes are complex over the lifespan. This may contribute to differences in the timing of appearance of mental and physical disturbances, as well as potential sex differences that influence only select outcomes. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.23.156653v1?rss=1 Authors: Tiihonen, J., Koskuvi, M., Lähteenvuo, M., Trontti, K., Ojansuu, I., Vaurio, O., Cannon, T. D., Lönnqvist, J., Therman, S., Suvisaari, J., Cheng, L., Tanskanen, A., Taipale, H., Lehtonen, S., Koistinaho, J. Abstract: The molecular pathophysiological mechanisms underlying schizophrenia have remained unknown, and no treatment exists for primary prevention. Studies using stem cell-derived neurons have investigated differentially expressed genes (DEGs) and GO and KEGG pathways between patients and controls, but not analyzed data-driven causal molecular pathways involved. We used Ingenuity Pathway Analysis (IPA) to analyze canonical and causal pathways in two different datasets, including patients from Finland and USA. The most significant findings in canonical pathway analysis were observed for glutamate receptor signaling, hepatic fibrosis, and glycoprotein 6 (GP6) pathways in the Finnish dataset, and GP6 and hepatic fibrosis pathways in the US dataset. In data-driven causal pathways, ADCYAP1, ADAMTS, and CACNA genes were involved in the majority of the top 10 pathways differentiating patients and controls in both Finnish and US datasets. In contrast, no dopamine-specific genes were consistently involved. Results from a Finnish nation-wide database showed that the risk of schizophrenia relapse was 41% lower among first-episode patients during the use of losartan, the master regulator of an ADCYAP1, ADAMTS, and CACNA-related pathway, compared to those time periods when the same individual did not use the drug. This association was not attributable to general adherence to drug treatments. The results from the two independent datasets suggest that the GP6 signaling pathway, and the ADCYAP1, ADAMTS, and CACNA-related purine, oxidative stress, and glutamatergic signaling pathways are primary pathophysiological alterations in schizophrenia among patients with European ancestry. While no reproducible dopaminergic alterations were observed, the results imply that agents such as losartan, and ADCYAP1/PACAP-deficit alleviators, such as metabotropic glutamate 2/3 agonist MGS0028 and 5-HT7 antagonists, which have shown beneficial effects in an experimental Adcyap1 -/- mouse model for schizophrenia, could be potential treatments before the full manifestation of illness involving dopaminergic abnormalities. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.11.147314v1?rss=1 Authors: Ying, M., Rehani, P., Roussos, P., Wang, D. Abstract: Strong phenotype-genotype associations have been reported across brain diseases. However, understanding underlying gene regulatory mechanisms remains challenging, especially at the cellular level. To address this, we integrated the multi-omics data at the cellular resolution of the human brain: cell-type chromatin interactions, epigenomics and single cell transcriptomics, and predicted cell-type gene regulatory networks linking transcription factors, distal regulatory elements and target genes (e.g., excitatory and inhibitory neurons, microglia, oligodendrocyte). Using these cell-type networks and disease risk variants, we further identified the cell-type disease genes and regulatory networks for schizophrenia and Alzheimer's disease. The cell-type regulatory elements (e.g., enhancers) in the networks were also found to be potential pleiotropic regulatory loci for a variety of diseases. Further enrichment analyses including gene ontology and KEGG pathways revealed potential novel cross-disease and disease-specific molecular functions, advancing knowledge on the interplays among genetic, transcriptional and epigenetic risks at the cellular resolution between neurodegenerative and neuropsychiatric diseases. Finally, we summarized our computational analyses as a general-purpose pipeline for predicting gene regulatory networks via multi-omics data. Copy rights belong to original authors. Visit the link for more info

A new episodeSupport this podcast at — https://redcircle.com/yours-truly-johnny-dollar/donationsAdvertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy

Kristina Cahojova is the Founder and CEO of Kegg, the world's first 2-in-1 fertility tracking kegel ball. While strengthening the pelvic floor, Kegg also uses sensors to monitor cervical mucus and notifies the wearer when they are fertile. We speak about the biology of cervical mucus and why it's important for fertility and can be used as a measure of a woman's health. Pre-order kegg now at kegg.tech ! Rate, review, and subscribe to the podcast!

Here is episode number 8 of Keiks Presents All About House! Kegg is on the Guest Mix.

501111 071 www.apparacity.com

Yours Truly, Johnny Dollar was a radio drama about a "fabulous" freelance insurance investigator "with the action-packed expense account." The show aired on CBS Radio from January 14, 1949 to September 30, 1962. There were 811 episodes in the 12-year run, and more than 720 still exist today. Each story started with a phone call from an insurance executive, calling on Johnny to investigate an unusual claim. Each story required Johnny to travel to some distant locale, usually within the United States but sometimes abroad, where he was almost always threatened with personal danger in the course of his investigations. Johnny's file on each case was usually referenced as a "matter," as in "The Silver Blue Matter" or "The Forbes Matter." Later episodes were more fanciful, with titles like "The Wayward Trout Matter" and "The Price of Fame Matter" (the latter featuring a rare guest-star appearance: Vincent Price). Each story was recounted in flashback, as Johnny listed each line item from his expense account. Most of the items related to transportation and lodging, but no incidental expense was too small for Johnny to itemize, as in "Item nine, 10 cents. Aspirin. I needed them." Johnny usually stuck to business, but would engage in romantic dalliances with women he encountered in his travels; later episodes gave Johnny a steady girlfriend, Betty Lewis. Johnny's precious recreational time was usually spent fishing, and it was not uncommon for Johnny's clients to exploit this favorite pastime in convincing him to take on a job. The episodes generally finished with Johnny tallying up his account, making final remarks on the report, and traveling back to Hartford, Connecticut, where he was based. --- Send in a voice message: https://anchor.fm/daniel-lantz/message

On today’s episode, I travelled to Champion, PA to sit down the folks from Kegg Brewing.  Kegg Brewing is the retirement project of Frank and Tracy Kegg.  After retiring from school teaching in 2015, Frank decided to start a brewery literally in their garage.  Four years later, they’re pumping out some awesome beers from their tiny brewery and even doing some light distribution. What’s most impressive about their operation isn’t the size of it, it’s the passion that Frank and Tracy have for the craft.  Frank has admitted to me that there are times when he wakes up in the middle of the night to come down and check on his beers- one of the perks of having a brewery in your home. Listen to today’s episode to learn more about the tiniest, and most unique, breweries this podcast has been recorded at.

Happy Holidays Bleeders! On this episode, Mary brings on Kristina Cahojova from Kegg Tech to talk about Kegg! Tune in!  Follow their insta and twitter @kegg_tech and ours @tampontalkwmary 

If you like this episode, check out https://otrpodcasts.com for even more classic radio shows! Learn more about your ad choices. Visit megaphone.fm/adchoices

Ex Mormon Files - 208 - Roger Kegg by The Ex-Mormon Files

Ex Mormon Files - 209 - Linda Kegg by The Ex-Mormon Files

This audio tour will guide you through the buildings and shops of Old Bedford Village, located just off the PA Turnpike and I-99 in Bedford, PA. Learn more at oldbedfordvillage.com, or follow us on Facebook at facebook.com/oldbedfordvillage, or Twitter and Instagram @BedfordVillage.

Erle Stanley Gardner, the creator of Perry Mason, brings you A Life in Your Hands – a courtroom mystery drama that puts you in the middle of a murder trial. Follow Jonathan Kegg – neither prosecutor nor defense lawyer, but amicus curiae – an impartial observer dedicated to finding the truth. Kegg questions witnesses on both sides to ensure that the truth comes out and to see that justice is done. Carlton KaDell plays Kegg in “Judge Cook Shot,” originally aired on NBC on August 29, 1950.

Susumu Goto (http://www.bit.ly/olXYKt) gives a clear outline of the computer-assisted - but substantially manual - methods his group use to construct the metabolic network visualizations behind the widely-used KEGG resource. He demonstrates how these visualizations help in functional interpretation of omics data, allow network comparison across multiple species, and can predict new pathways, including non-metabolic networks. This talk was presented at VIZBI 2011, an international conference series on visualizing biological data (http://www.vizbi.org) funded by NIH & EMBO.

Background: Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies. Methods: Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors. Results: We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were `ECM-receptor interaction', `Complement and Coagulation cascades', and `PPAR signaling pathway'. Conclusion: The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.

Background: miRNAs are small, non-coding RNA molecules that mainly act as negative regulators of target gene messages. Due to their regulatory functions, they have lately been implicated in several diseases, including malignancies. Roughly half of known miRNA genes are located within previously annotated protein-coding regions ("intragenic miRNAs"). Although a role of intragenic miRNAs as negative feedback regulators has been speculated, to the best of our knowledge there have been no conclusive large-scale studies investigating the relationship between intragenic miRNAs and host genes and their pathways. Results: miRNA-containing host genes were three times longer, contained more introns and had longer 5' introns compared to a randomly sampled gene cohort. These results are consistent with the observation that more than 60% of intronic miRNAs are found within the first five 5' introns. Host gene 3'-untranslated regions (3'-UTRs) were 40% longer and contained significantly more adenylate/uridylate-rich elements (AREs) compared to a randomly sampled gene cohort. Coincidentally, recent literature suggests that several components of the miRNA biogenesis pathway are required for the rapid decay of mRNAs containing AREs. A high-confidence set of predicted mRNA targets of intragenic miRNAs also shared many of these features with the host genes. Approximately 20% of intragenic miRNAs were predicted to target their host mRNA transcript. Further, KEGG pathway analysis demonstrated that 22 of the 74 pathways in which host genes were associated showed significant overrepresentation of proteins encoded by the mRNA targets of associated intragenic miRNAs. Conclusions: Our findings suggest that both host genes and intragenic miRNA targets may potentially be subject to multiple layers of regulation. Tight regulatory control of these genes is likely critical for cellular homeostasis and absence of disease. To this end, we examined the potential for negative feedback loops between intragenic miRNAs, host genes, and miRNA target genes. We describe, how higher-order miRNA feedback on hosts' interactomes may at least in part explain correlation patterns observed between expression of host genes and intragenic miRNA targets in healthy and tumor tissue.

This thesis applies quantitative mass spectrometry to research topics in relation to cancer. Proteome-wide quantification at the protein expression level and phosphorylation level were achieved. The technologies developed and used here cover the latest improvements in instrumentation in mass spectrometry, strategies in phosphopeptide enrichment in large scale, algorithms in data analysis and their streamlined implementation, and data mining in downstream bioinformatics. For each of the projects described in this thesis, proteome mapping routinely resulted in identification and quantitation of around 4,000 proteins and phosphoproteome mapping often lead to quantitation of more than 5,000 phosphorylation sites. This ‘systems-wide’ quantitation of the proteome and phosphoproteome is a completely novel development, which has not been used in cancer related topics before. Three major biology topics are studied in this thesis. In the first project, the phosphoproteome of a mouse liver cancer cell line Hepa1-6 was analyzed in-depth, by using phosphatase inhibitors (calyculin A, deltamethrin, and Na-pervanadate) to boost phosphorylation. The characterization of the phosphoproteome revealed a broad spectrum of cellular compartmentalization and biological functions. Quantitation of phosphatase inhibitor treatment using the Stable Isotope Labeling by Amino Acids in Cell culture (SILAC) method revealed the quantitative effects of these inhibitor compounds on the whole phosphoproteome. To our surprise, these three broadband phosphatase inhibitors displayed very different efficiency, with tyrosine phosphorylation significantly boosted but serine/threonine phosphorylation much less affected. Additionally, a method to estimate an upper bound of the stoichiometry of phosphorylation was introduced by comparing phosphorylation in three SILAC conditions: non-treated cells, stimulated cells (e.g. with insulin), and only phosphatase inhibitor treated cells. The methods developed here can be used directly in development of drugs directed against kinases and phosphatases, key regulators in cancer and other diseases. The second project continues with the application of phosphoproteomics techniques. Kinase inhibitors influence cellular signal transduction processes and therefore are of great potential in rescuing aberrant cellular signaling in tumors. In fact they constitute a significant portion of drug developing programs in pharmaceutical industry. With the aim of quantifying the effect of kinase inhibitors over the entire signaling network, the second project first set out to study two very commonly used kinase inhibitor compounds for MAPKs: U0126 and SB202190. Their effect on epidermal growth factor (EGF) signal transduction was quantified and compared using the HeLa cell system. The study confirmed that the MAPK cascades are the predominant signaling branches for propagating the EGF signaling at early time points of stimulation. These large scale examinations also suggest that U0126 and SB202190 are quite specific inhibitors for MAPKs as the majority of regulated phosphopeptides appears to belong to the MAPK pathways. In the second part of the project, the effect on phosphoproteome changes of the chemical compound dasatinib, which was demonstrated to effectively inhibit the constitutively activated fusion protein BCR-ABL and was recently approved for chronic myelogenous leukemia (CML) therapy, was quantified in the human CML cell line K562. Bioinformatic analysis revealed that the most influenced signal transduction branch was the Erk1/2 cascade. Overall more than 500 phosphorylation sites were found to be regulated by dasatinib, the vast majority not described in the literature yet. The third project compared the proteomes of mouse hepatoma cell line Hepa1-6 with the non-transformed mouse primary hepatocytes. This was performed by combining the SILAC heavy labeled form of Hepa1-6 with the primary hepatocytes. To characterize the features of these two proteomes, quantitation information (i.e. protein ratios between the two cell types) was used to divide all proteins into five quantiles. Each quantile was clustered according to the Gene Ontology and KEGG pathway databases to assess their enriched functional groups and signaling pathways. To integrate this information at a higher level, hierarchical clustering based on the p-value from the first Gene Ontology and KEGG clustering was performed. Using this improved bioinformatic algorithm for data mining, the proteomic phenotypes of the primary cells and transformed cells are immediately apparent. Primary hepatocytes are enriched in mitochondrial functions such as metabolic regulation and detoxification, as well as liver functions with tissue context such as secretion of plasma and low-density lipoprotein (LDL). In contrast, the transformed cancer cell line Hepa1-6 is enriched in cell cycle and growth functions. Interestingly, several aspects of the molecular basis of the “Warburg effect” described in many cancer cells became apparent in Hepa1-6, such as increased expression of glycolysis markers and decreased expression of markers for tricarboxylic acid (TCA) cycle. Studies in this thesis only provide examples of the application of mass spectrometry-based quantitative proteomics and phosphoproteomics in cancer research. The connection to clinical research, especially the assessment of drug effects on a proteome wide scale, is a specific feature of this thesis. Although this development is only in its infancy, it reflects a trend in the quantitative mass spectrometry field. We believe that more and more clinical related topics can and will be studied by these powerful methods.

Halophilic archaea inhabit hypersaline environments and share common physiological features such as acidic protein machineries in order to adapt to high internal salt concentrations as well as electron transport chains for oxidative respiration. Surprisingly, nutritional demands were found to differ considerably amongst haloarchaeal species, though, and in this project several complete genomes of halophilic archaea were analysed to predict their metabolic capabilities. Comparative analysis of gene equipments showed that haloarchaea adopted several strategies to utilize abundant cell material available in brines such as the acquisition of catabolic enzymes, secretion of hydrolytic enzymes, and elimination of biosynthesis gene clusters. For example, metabolic genes of the well-studied Halobacterium salinarum were found to be consistent with the known degradation of glycerol and amino acids. Further, the complex requirement of H. salinarum for various amino acids and vitamins in comparison with other halophiles was explained by the lack of several genes and gene clusters, e.g. for the biosynthesis of methionine, lysine, and thiamine. Nitrogen metabolism varied also among halophilic archaea, and the haloalkaliphile Natronomonas pharaonis was predicted to apply several modes of N-assimilation to cope with severe ammonium deficiencies in its highly alkaline habitat. This species was experimentally shown to possess a functional respiratory chain, but comparative analysis with several archaea suggests a yet unknown complex III analogue in N. pharaonis. Respiratory chains of halophilic and other respiratory archaea were found to share similar genes for pre-quinone electron transfer steps but show great diversity in post-quinone electron transfer steps indicating adaptation to changing environmental conditions in extreme habitats. Finally, secretomes of halophilic and non-halophilic archaea were predicted proposing that haloarchaea secretion proteins are predominantly exported via the twin-arginine pathway and commonly exhibit a lipobox motif for N-terminal lipid anchoring. In N. pharaonis, lipoboxcontaining proteins were most frequent suggesting that lipid anchoring might prevent protein extraction under alkaline conditions. By contrast, non-halophilic archaea seem to prefer the general secretion pathway for protein translocation and to retain only few secretion proteins by N-terminal lipid anchors. Membrane attachment was preferentially observed for interacting components of ABC transporters and respiratory chains and might further occur via postulated C-terminal anchors in archaea. Within this project, the complete genome of the newly sequenced N. pharaonis was analysed with focus on curation of automatically generated data in order to retrieve reliable gene prediction and protein function assignment results as a basis for additional studies. Through the development of a post-processing routine and expert validation as well as by integration of proteomics data, a highly reliable gene set was created for N. pharaonis which was subsequently used to assess various microbial gene finders. This showed that all automatic gene tools predicted a rather correct gene set for the GC-rich N. pharaonis genome but produced insufficient results in respect to their start codon assignments. Available proteomics results for N. pharaonis and H. salinarum were further analysed for posttranslational modifications, and N-terminal peptides of haloarchaeal proteins were found to be commonly processed by N-terminal methionine cleavage and to some extent further modified by N-acetylation. For general function assignment of predicted N. pharaonis proteins and for enzyme assignment in H. salinarum, similarity-based searches, genecontext methods such as neighbourhood analysis but also manual curation were applied in order to reduce the number of hypothetical proteins and to avoid cross-species transfer of misassigned functions. This permitted to reliably reconstruct the metabolism of H. salinarum and N. pharaonis. Generated metabolic data were stored in a newly developed metabolic database that also integrates experimental data retrieved from the literature. The pathway data can be assessed as coloured KEGG maps and were combined with data resulting from transcriptomics and proteomics techniques. In future, expert-curated reaction entries of the created metabolic database will be a valuable source for the design of metabolic experiments and will deliver a reliable input for metabolic models of halophilic archaea.