Podcasts about homologous

Episode 264 – Evolution’s Deceptive Evidence – An Interview with Dr. Jonathan Sarfati Welcome to Anchored by Truth brought to you by Crystal Sea Books. In John 14:6, Jesus said, “I am the way, the truth, and the life.” The goal of Anchored by Truth is to encourage everyone to grow in the Christian faith by anchoring themselves to the secure truth found in the inspired, inerrant, and infallible word of God. Script Notes: With your wisdom and power you created the earth and spread out the heavens. The waters in the heavens roar at your command. You make clouds appear— you send the winds from your storehouse and make lightning flash in the rain. Jeremiah, Chapter 10, verses 12 and 13, Contemporary English Version God's eternal power and character cannot be seen. But from the beginning of creation, God has shown what these are like by all he has made. That's why those people don't have any excuse. Romans, chapter 1, verse 20, Contemporary English Version ******** VK: Hi! I’m Victoria K. Welcome to Anchored by Truth brought to you by Crystal Sea Books. Today we are beginning the wrap up of the series that we call The Truth in Genesis. This series has been an examination of whether the latest contemporary science supports or refutes the traditional view of the Genesis text regarding creation. We’ve been led on this journey by Dr. Jonathan Sarfati. Dr. Sarfati is an internationally known author and the lead scientist for Creation Ministries International. He has written a number of widely selling books that bring an understandable, yet comprehensive, scientific perspective on what empirical observations tell us about the age of the earth and the origin of life. Dr. Sarfati has sold hundreds of thousands of books such as Refuting Evolution volumes 1 and 2, By Design, The Greatest Hoax on Earth and The Genesis Account. During this series Dr. Sarfati has been answering questions about a wide variety of topics that pertain the evidence that supports the historicity of the literal Biblical account. These topics have included methods of assigning dates to long past events, what we really learn from studying dinosaurs, and how life cannot exist without the complex information system that is embedded in the DNA of all life. Our approach to our discussions has been to use reason, logic, and evidence to examine whether the Bible and science are indeed at odds with each other as is often asserted today. Thus far we have seen that nothing could be further from the truth than the assertion that we have to either accept either science or the content of the traditional Christian faith. So as we begin our wrap up of this series, today we’re going see that many of the arguments commonly used to support the truth of evolution actually turn out to be evidence against it. But before we get too far into our discussion, Dr. Sarfati would you like to say a word of greeting to the Anchored by Truth listeners and give us some general comments on the whole subject of science and the Bible? Dr. Sarfati: - Thanks for inviting me. It’s a pleasure to be on Anchored by Truth today. Introductory comments. VK: Dr. Sarfati, During our last several episodes we have seen that there is a substantial body of scientific evidence that demonstrates that the age of the universe cannot be as old as conventional science claims. The earth and universe are far more likely to be several thousand years old than several billion years old. As such, even assuming inanimate particles could somehow aggregate themselves to form self-replicating molecules there is insufficient time for those molecules to be transformed into the vast diversity of plant and animal species that currently exist on the earth, much less create a logical, purposive, ethically animated being such as man. Could you give us a brief summary of some of the evidence that points out how life is too complicated to arise from non-life by blind chance? Dr. Sarfati: Comments on how life cannot arise by blind chance VK: Thank you for those observations. So let’s get right to the main subject for today’s discussion - . Question List: a. Darwin made much of the homological nature of certain vertebrate structures as evidence of common descent. What is homology and what information do we now possess that Darwin did not? Why does homology fail as evidence for evolution? b. Darwin acknowledged that the absence of transitional fossil evidence present in his time did not support his theory, but he appealed to future discoveries that he believed would come to his rescue. Have subsequent discoveries vindicated Darwin’s confidence that the fossil record would one day demonstrate that evolution is true? c. The revolution is molecular biology did not take place until almost 100 years after Darwin’s publication of Origin of the Species. How have advances in our understanding of the atomic and molecular attributes of the cell affected the validity of the evolutionary hypothesis? d. From a probability standpoint, what does the complexity of life imply about the likelihood that life could have arisen by chance? e. The conventional explanation for the origin of life requires the existence of a widespread pre-biotic primordial soup. Is there any evidence that such a “soup” ever existed? f. Some proponents of evolution have argued that we have been able to see “evolution before our eyes.” For example some have pointed to Richard Lenski’s decades-long experiments on bacteria as having demonstrated the truth of evolution. Did Lenski’s experiments show that single-celled creatures could turn into critics or creationists? g. Are there any scientists who affirm the Genesis account and who do research into biological questions from a Creationist perspective? h. In your opinion what are the three or four of the most important facts that Christians should keep in mind when reading articles about the supposed latest discoveries that support evolution as a viable explanation? i. What resources would you recommend for Christians who want to study more about the scientific deficiencies in evolution as an explanation for life and biodiversity? VK: So the big takeaway from our discussion today is that many of the traditional “proofs” used to demonstrate the validity of evolution actually demonstrate its unreliability as a scientific hypothesis. Homologous structures more often than not do not share a common embryological origin. The absence of transitional fossils really is evidence that transitional species do not exist and Darwin’s original concern for their absence has never been alleviated. And molecular biology, far from supporting evolution, has just presented even more perplexing challenges for the evolutionary hypothesis. Dr. Sarfati, we’d really like to thank you for joining us on Anchored by Truth today and throughout this series. Your insights have been invaluable and I believe will continue to be a source of inspiration for everyone who is committed to the inspiration, inerrancy, and infallibility of scripture. Just as a reminder to our listeners, this show, as well as all Anchored by Truth episodes will be available by podcast shortly after the broadcast airing. So any listener today who has a friend or study group that could benefit from Dr. Sarfati’s depth of knowledge can go to their favorite podcast app and search on Anchored by Truth by Crystal Sea Books. Today for our closing prayer, let’s listen to a prayer for our nation, especially that the light of truth would once again shine in the hearts of all our friends and neighbors. ---- Prayer for the Nation. VK: We hope you’ll be with us next time and we hope you’ll take some time to encourage some friends to tune in too, or listen to the podcast version of this show. If you’d like to hear more, try out crystalseabooks.com where “We’re not famous but our Boss is!” (Bible Quotes from the American Standard Version) Jeremiah, Chapter 10, verses 12 and 13, Contemporary English Version Romans, chapter 1, verse 20, Contemporary English Version https://creation.com/the-evolution-trains-a-comin

In this episode, Colin C. Pritchard, MD, PhD, a pathologist, and Heather H. Cheng, MD, PhD, a medical oncologist, discuss optimal biomarker testing to guide treatment decisions in advanced prostate cancer, with topics including: Rationale for targeting PARP in prostate cancer with ARI combinationsStudy design nuances and findings from key randomized phase III clinical trials evaluating combination therapy with a PARP inhibitor and ARI, including PROpel, MAGNITUDE, and TALAPRO-2FDA approvals of combination therapy with a PARP inhibitor and ARI, including a comparison of populations based on mutations Optimal biomarker testing for gene mutations in homologous recombination and mismatch repair pathwaysTips for optimal coordination between pathology and medical oncologyPresenters: Heather H. Cheng, MD, PhDAssociate ProfessorDepartment of MedicineDivision of Hematology and OncologyAttending PhysicianDepartment of Genitourinary Medical OncologyFred Hutchinson Cancer CenterSeattle, WashingtonColin C. Pritchard, MD, PhDCo-DirectorGenetics and Solid Tumors LaboratoryUniversity of Washington Medical CenterProfessorDepartment of Laboratory Medicine and PathologyUniversity of WashingtonSeattle, WashingtonContent based on an online CME program supported by an independent educational grant from Pfizer, Inc.Link to full program: https://bit.ly/3PFagxb

Learn from experts in the field on optimizing PARP inhibitor outcomes in cancer therapy. The information presented during the podcast reflects solely the opinions of the presenter. The information and materials are not, and are not intended as, a comprehensive source of drug information on this topic. The contents of the podcast have not been reviewed by ASHP, and should neither be interpreted as the official policies of ASHP, nor an endorsement of any product(s), nor should they be considered as a substitute for the professional judgment of the pharmacist or physician.

Although molecular testing offers promising opportunities for diagnosis and targeted treatment of cancers, prostate cancer has lagged behind other types of cancer. Recently, homologous recombination repair testing in prostate cancer has provided a means to achieving targeted treatments for patients as well as opening new avenues of collaboration between pathologists and oncologists.On this episode of Inside the Lab, hosts Ms. Kelly Swails, MLS(ASCP), and Dr. Ali Brown, MD, FASCP are joined by Heather Cheng, a medical oncologist and associate professor of hematology and oncology at the University of Washington and Fred Hutchinson Cancer Center, and Colin Pritchard, molecular pathologist and professor of laboratory science and director of the Genetics and Solid Tumors Laboratory at the University of Washington Medical Center.Our panelists discuss the current treatment landscape for prostate cancer and how HRR testing can improve patient outcomes in this context.Topics Covered  An introduction to metastatic prostate cancer testing, and what types of tests are standard of care, and the rationale for targeting prostate cancer using PARPKey findings from recent phase III randomized clinical trialsStandards for optimal testing in prostate cancer, particularly concerning sample sources and the choice between next-generation sequencing (NGS) and polymerase chain reaction (PCR) methodscommon pitfalls or challenges in the arena of accurately reporting and interpreting findings from HRR testsPractical tips for optimal coordination among a multidisciplinary, cross-departmental team of healthcare providers and laboratory professionals when utilizing HRR testing in prostate cancer management.Connect with ASCPASCPASCP on FacebookASCP on InstagramASCP on Twitter Connect with Dr. ChengDr. Cheng on LinkedIn Connect with Dr. PritchardDr. Pritchard Connect with Ms. Swails & Dr. BrownMs. Swails on TwitterDr. Brown on Twitter ResourcesASCP Membership 2024Proposed FDA Regulation of Laboratory Developed TestsPublic Comment on the FDA's Proposed RuleInside the Lab in the ASCP Store 

In this paper, we uncover that Language Models (LMs), either encoder- or decoder-based, can obtain new capabilities by assimilating the parameters of homologous models without retraining or GPUs. Typically, new abilities of LMs can be imparted by Supervised Fine-Tuning (SFT), reflected in the disparity between fine-tuned and pre-trained parameters (i.e., delta parameters). We initially observe that by introducing a novel operation called DARE (Drop And REscale), most delta parameters can be directly set to zeros without affecting the capabilities of SFT LMs and larger models can tolerate a higher proportion of discarded parameters. Based on this observation, we further sparsify delta parameters of multiple SFT homologous models with DARE and subsequently merge them into a single model by parameter averaging. We conduct experiments on eight datasets from the GLUE benchmark with BERT and RoBERTa. We also merge WizardLM, WizardMath, and Code Alpaca based on Llama 2. Experimental results show that: (1) The delta parameter value ranges for SFT models are typically small, often within 0.005, and DARE can eliminate 99% of them effortlessly. However, once the models are continuously pre-trained, the value ranges can grow to around 0.03, making DARE impractical. We have also tried to remove fine-tuned instead of delta parameters and find that a 10% reduction can lead to drastically decreased performance (even to 0). This highlights that SFT merely stimulates the abilities via delta parameters rather than injecting new abilities into LMs; (2) DARE can merge multiple task-specific LMs into one LM with diverse abilities. For instance, the merger of WizardLM and WizardMath improves the GSM8K zero-shot accuracy of WizardLM from 2.2 to 66.3, retaining its instruction-following ability while surpassing WizardMath's original 64.2 performance. Codes are available at https://github.com/yule-BUAA/MergeLM. 2023: Le Yu, Bowen Yu, Haiyang Yu, Fei Huang, Yongbin Li https://arxiv.org/pdf/2311.03099v1.pdf

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.22.546088v1?rss=1 Authors: Mikhova, M., Heyza, J. R., Meek, K., Schmidt, J. C. Abstract: Non-homologous end joining (NHEJ) is the predominant path-way that repairs DNA double-stranded breaks (DSBs) in vertebrates. The DNA termini of many DSBs must be processed to allow ligation while minimizing genetic changes that result from break repair. Emerging models propose that DNA termini are first synapsed approximately 115[A] apart in one of two long-range synaptic complexes. The first long-range complex can be formed with only the KU70/80 heterodimer and DNA-PKcs while the second long-range complex also includes XRCC4, XLF, and Ligase 4. Both long-range complexes inefficiently progress to short-range synaptic complexes that juxtapose DNA ends to facilitate ligation. Here we perform singlemolecule analyses of the recruitment of Halo-tagged NHEJ factors to DSBs. Our results provide direct evidence for stepwise maturation of NHEJ complex and precisely define kinetics of core NHEJ factor binding to DSBs in living cells. 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/2023.04.27.538600v1?rss=1 Authors: Cullati, S. N., Zhang, E., Shan, Y., Guillen, R. X., Chen, J.-S., Navarrete-Perea, J., Elmore, Z. C., Ren, L., Gygi, S. P., Gould, K. L. Abstract: The CK1 family are conserved serine/threonine kinases with numerous substrates and cellular functions. The fission yeast CK1 orthologues Hhp1 and Hhp2 were first characterized as regulators of DNA repair, but the mechanism(s) by which CK1 activity promotes DNA repair had not been investigated. Here, we found that deleting Hhp1 and Hhp2 or inhibiting CK1 catalytic activities in yeast or in human cells activated the DNA damage checkpoint due to persistent double-strand breaks (DSBs). The primary pathways to repair DSBs, homologous recombination and non-homologous end joining, were both less efficient in cells lacking Hhp1 and Hhp2 activity. In order to understand how Hhp1 and Hhp2 promote DSB repair, we identified new substrates using quantitative phosphoproteomics. We confirmed that Arp8, a component of the INO80 chromatin remodeling complex, is a bona fide substrate of Hhp1 and Hhp2 that is important for DSB repair. Our data suggest that Hhp1 and Hhp2 facilitate DSB repair by phosphorylating multiple substrates, including Arp8. 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/2023.04.19.537613v1?rss=1 Authors: Gupta, A., Ruturaj,, Mishra, M., Saha, S., Maji, S., Rodriguez-Boulan, E., Schreiner, R. Abstract: We suggest a model of apico-basolateral sorting in polarized epithelia using homologous Cu-ATPases as membrane cargoes. In polarized epithelia, upon copper treatment, homologous copper-ATPases ATP7A and ATP7B traffic from trans-Golgi network (TGN) to basolateral and apical membranes respectively. We characterized sorting pathways of Cu-ATPases between TGN and plasma-membrane and identified the machinery involved. ATP7A and ATP7B reside on distinct domains of TGN and in high copper, ATP7A traffics directly to basolateral membrane, whereas ATP7B traverses common-recycling, apical-sorting and apical-recycling endosomes en-route to apical membrane. Mass-spectrometry identified regulatory partners of ATP7A and ATP7B that include Adaptor Protein-1 complex. Upon knocking-out pan-AP-1, sorting of both copper-ATPases are disrupted. ATP7A loses polarity and localizes on both apical and basolateral surfaces in high copper. Contrastingly, ATP7B loses TGN-retention but retains apical polarity that becomes copper-independent. Using isoform-specific knockouts, we found that AP-1A provides directionality and TGN-retention for both Cu-ATPases, whereas, AP-1B governs polarized trafficking of ATP7B solely. Trafficking phenotypes of Wilson disease-causing ATP7B mutants that disrupts putative ATP7B-AP1 interaction further substantiates the role of AP-1 in apical sorting of ATP7B. 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/2023.02.06.527258v1?rss=1 Authors: He, J., Guo, Y., Deng, R., Li, L., Huang, C., Chen, R., Wang, Y., Huang, J., Cheng, J., Chen, G.-Q., Zheng, J., Zhao, X., Yu, J. Abstract: Homologous recombination (HR) repair for DNA double-strand breaks (DSBs) is critical for maintaining genome stability and cell survival. Nuclear PTEN plays a key role in HR repair, but the underlying mechanism remains largely elusive. We find that SUMOylated PTEN promotes HR repair but represses non-homologous end joining (NHEJ) repair by directly dephosphorylating 53BP1. During DNA damage responses (DDR), p14ARF was phosphorylated and then interacted efficiently with PTEN, thus promoting PTEN SUMOylation as an atypical SUMO E3 ligase. Interestingly, SUMOylated PTEN was subsequently recruited to the chromatin at DNA-break sites. This was because that SUMO1 conjugated to PTEN was recognized and bound by the SUMO-interacting motif (SIM) of BRCA1, which has been located to the core of 53BP1 foci on the chromatin during S/G2 stage. Further, these chromatin-loaded PTEN directly and specifically dephosphorylated pT543 of 53BP1, resulting in the dissociation of 53BP1-complex, which facilitated DNA end resection and ongoing HR repair. The SUMOylation-deficient PTENK254R mice also showed decreased DNA damage repair in vivo. Blocking PTEN SUMOylation pathway with either an SUMOylation inhibitor or a p14ARF(2-13) peptide sensitized tumor cells to chemotherapy. Our study therefore provides the new mechanistic understanding of PTEN in HR repair and clinical intervention of chemo-resistant tumors. 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/2023.01.22.524239v1?rss=1 Authors: Romero-Franco, A., Checa-Rodriguez, C., Castellano-Pozo, M., Miras, H., Wals, A., Huertas, P. Abstract: The maintenance of genomic stability is essential for cellular and organismal survival and fitness. Thus, when DNA gets damaged, is essential to repair it in the most accurate fashion. Among different DNA lesions, DNA double strand breaks are specially challenging. An exquisite regulatory network reacts to local and global cues to control the choice between different DNA double strand break repair mechanisms to maximize genomic integrity. Such regulation relies mostly at the level of DNA end resection, the initial steps of the homologous recombination repair pathway. On the other hand, most cellular and organismal activities follow a 24 h oscillation known as the circadian cycle. Such repetitive changes are controlled by an intrinsic, molecular clock built-in at the cellular level which core components are the heterodimers BMAL1-CLOCK and CRY-PER. These inherent rhythms control many different aspects of the cellular metabolism, including the fate of many different DNA transactions. Here we have explored the regulation of the choice between different DNA double strand break repair pathways along the circadian cycle. We observed that DNA end resection shows a circadian oscillation, with a peak at dawn followed by a progressive reduction until dusk. Such regulations depend on the cellular levels of the circadian clock core component CRY1. Consequently, repair by homologous recombination mirrors CRY1 expression levels. Such modulation is controlled through the circadian regulation of the anti-resection activity, but not the protein levels, of CCAR2, that limits CtIP-mediated resection preferentially at nightfall. Additionally, such regulation requires a crosstalk between the DNA damage-dependent phosphorylation of CRY1 by the kinase DNA-PK. Finally, such regulation has an impact in cancer progression and response to radiation therapy of specific tumors. One sentence summaryCCAR2-dependent inhibition of DNA end resection and homologous recombination is controlled by the intrinsic cellular circadian clock 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/2022.10.19.512819v1?rss=1 Authors: Rodriguez-Real, G., Prados-Carvajal, R., Bayona-Feliu, A., Balestra, F. R., Huertas, P. Abstract: The centrosome is a cytoplasmic organelle with roles in microtubule organization which has also been proposed to act as a hub for cellular signaling. For example, it has been suggested that some centrosomal component are required for full activation of the DNA Damage Response, the cellular signaling network that is activated upon the appearance of chromosome breaks. However, if the centrosome and/or some of its components regulate specific DNA repair pathways is not known. Double strand breaks are mostly repaired by two alternative mechanisms, the homology-independent non-homologous end-joining and the homology-driven homologous recombination. Here, we show that centrosomes presence is required to fully activate recombination, specifically to completely license its initial step, the so-called DNA end resection. Additionally, loss of centrosome upregulates the non-homologous end-joining repair pathway. Furthermore, we identify a centriolar structure, the subdistal appendages, and a specific factor, CEP170, as the critical centrosomal component involved in the regulation of recombination and resection, albeit it does not control end-joining repair. Cells lacking centrosomes or depleted for CEP170 are, consequently, hyper-sensitive to DNA damaging agents. Moreover, low levels of CEP170 in multiple cancer types correlate with an increase of the mutation burden associated with specific mutational signatures and a better prognosis, suggesting this protein can act as a driver mutation but also could be targeted to improve current oncological treatments. 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/2022.10.17.512236v1?rss=1 Authors: Galea, G., Kuodyte, K., Khan, M. M., Thul, P. J., Neumann, B., Lundberg, E., Pepperkok, R. Abstract: Cells are constantly exposed to a multitude of DNA-damaging agents that can lead to mutation, dysregulation, and possibly cell death. To ensure genomic integrity, DNA Damage Response (DDR) mechanisms are set in motion to repair and mitigate any damage to the DNA structure. Although these pathways are well-studied in the context of nuclear function, relatively little is known of the regulatory function of cytoplasmic organelles. Here we show the first example of DDR regulation at the Golgi complex, coordinating Homologous Recombination (HR)-mediated DNA repair. We found that RAD51C, a regulatory HR protein, localises to the Golgi and nuclear compartments and in response to double-strand DNA breaks, the Golgi protein population of RAD51C redistributes to form nuclear foci. Furthermore, we found that the Golgi localisation of RAD51C is dependent on the Golgin Giantin. Depletion of Giantin induces the redistribution of the RAD51C Golgi pool to form nuclear foci, independent of DNA damage induction, and concurrent with a significant increase in genomic instability and inhibition of HR signalling regulators. This study presents evidence for a novel pathway where the Golgi is a central regulatory hub for HR DDR and potentially other repair pathways, a finding with important therapeutic implications. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this episode: What are Functional groups Chemical families Homologous series Want to know more, or support the show? Become a Patreon supporter of the podcast and get more from each episode https://patreon.com/chemistrymadesimple?utm_medium=clipboard_copy&utm_source=copyLink&utm_campaign=creatorshare_creator (patreon.com/chemistrymadesimple) Check out the https://my.captivate.fm/chemistrymadesimple.net/program (Chemistry Made Simple academy)

Krigen i Ukraina fører til enorme flyktningstrømmer, særlig til Polen, som allerede har et overbelastet helsevesen grunnet pandemien. Mange flyktninger har kroniske sykdommer som ikke er direkte knyttet til krigen, og også disse har behov for helsehjelp. De mange sanksjonene mot Russland fører dessuten også til at den russiske befolkningen lider, særlig de som har behov for kreftbehandling. Hvorvidt det er riktig å boikotte russiske forskningsinstitusjoner diskuteres fortsatt – og hva betyr alt dette for den russiske koronavaksinen, Sputnik V? Det foreligger dessuten mer forskning på langtidseffekten av covid-19-sykdom, hvilke koronavaksiner som funker best som boosterdoser, bruk av litium mot demens og gjeld i forbindelse med bruk av helsetjenester i USA. Are Brean forteller om dette og mer i ukens episode.Tilbakemeldinger kan sendes til stetoskopet@tidsskriftet.no. Stetoskopet produseres av Caroline Ulvin Johansson, Are Brean og Julie Didriksen ved Tidsskrift for Den norske legeforening. Ansvarlig redaktør er Are Brean. Jingle og lydteknikk: Håkon Braaten / Moderne Media Coverillustrasjon: Stephen Lee Artikler nevnt:  Growing concern over Ukrainian refugee health Russia's war in Ukraine is killing cancer care in both countries Ukraine conflict: Global research community reviews links with Russia Covid-19: Ukraine conflict calls Russia's vaccine diplomacy into question Ukrainian researchers pressure journals to boycott Russian authors Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21 COVID's true death toll: much higher than official records Neuropsychiatric and Cognitive Outcomes in Patients 6 Months After COVID-19 Requiring Hospitalization Compared With Matched Control Patients Hospitalized for Non–COVID-19 Illness Association of Homologous and Heterologous Vaccine Boosters With COVID-19 Incidence and Severity in Singapore Association between lithium use and the incidence of dementia and its subtypes: A retrospective cohort study Association of Type of Oral Anticoagulant Dispensed With Adverse Clinical Outcomes in Patients Extending Anticoagulation Therapy Beyond 90 Days After Hospitalization for Venous Thromboembolism Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis Medical Debt Burdens Millions of US Adults

Our final session in our Creation series examines three more problems for Darwinian Evolution. Darwinian Evolution has used observed similarities in structures and species as evidence of evolution for decades. However more research and new technologies have allowed us to gain a better understanding of the human body and many other species. How do these traditionally held Darwinian beliefs hold up to the science? Help us keep this content free: https://evidence4faith.org/give/ (https://evidence4faith.org/give/) Music Credits: https://www.pond5.com/royalty-free-music/item/116117045-funky-sax-hipster-happy-upbeat-inspirational (Stock Music) provided by EnhancedVision, from https://www.pond5.com/ (Pond5)

My AP Biology Thoughts  Unit 7 Natural Selection EPISODE TITLE: Unit 7: Darwin's FinchesWelcome to My AP Biology Thoughts podcast, my name is Shrithik Sekar, Kyle Mason, Gabe Moriello, and I am your host for Unit 7: Examples of Evolution, Darwin's Finches. In episode 116, we will be discussing this topic and how it relates to the AP Biology Curriculum.  “We want to also thank our sources for the information presented in this podcast episode today which include (Britannica, Galapogosisland.org, and Crash course Biology on Youtube). You can find the citations and links to these sources in the show notes.” Segment 1: Overview of Darwin's finches  What are Darwin's finches?  Who is darwin? - Geologist and Biologist, who formed the theory of natural selection. Known for his contributions to Science of evolution. He studied many finches which were found in the galapagos islands located 1,000 km off the coast of Ecuador  What were the finches? - These finches were a Group of 18 different species found in the Galapagos island. Darwin found the finches were all closely related with small direct observations that he made during his time in the Galapagos islands  What did he study? -During his studies while in the Galapagos islands, he concluded the speciation of the finches which is known as the experiment of Darwin's finches   How does it relate to evolution? - It relates to evolution because it is an example of Direct observation  Segment 2: Evidence that supports Darwin's finches  Connection direct observation evolution  What is direct observation of evolution? - Through observation, in small population sizes, it can be found many changes of one species to then create many subspecies. Through direct observation of evidence in almost every species. THis idea had to do with the last universal ancestor, how all species are alike in many ways and all stemmed from the same ancestor. These finches dna is super similar, but these small differences of dna created a difference in appearance which was found ny darwin.  ( This begs the question of ) Why are the finches an example of evolution? All 18 species of Darwin's Finches were originally one finch species on the coast of south america. However, Darwin discovered that this species branched off into 18 different species on the Galapagos islands depending on the finches' environment  What Key pieces of evidence did darwin find? - Darwin found the difference, fruit eating finches had wide beaks, insect eating finches had narrow beaks, and based on different factors of each finches environment each species had a different characteristic change. - GO TO Image  Segment 3: Connection to the CourseThe 5 pieces of evidence - of evolution.  How do these ideas of evolution connect to our Biology class?   ( Relates to AP bio curriculum 7.2 - Natural Selection)  ( 7.4 - Population Genetics  (7.6 - Evidence of evolution  (7.7 - Common Ancestry  Direct observation is only one example of evolutionary evidence  5 other examples - Fossils, Geological evidence, Change in DNA, Homologous structures  All apart of either natural or physiological selection  Natural selection is a part of the 5 fingers of evolution ( Sexual Selection, Genetic Drift, Gene flow, Mutation)  Darwin's finches show that adaptive evolution among the finch populations - the finches evolved different beak types depending on which food they ate, showing how natural selection is a factor in pushing populations to evolve Thank you for listening to this episode of My AP Biology Thoughts. For more student-ran podcasts and digital content, make sure that you visit http://www.hvspn.com (www.hvspn.com). Ceeeyaaa!!!!!! Music Credits: "Ice Flow" Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 4.0 License...

Thank you so much for listening to today's PODCAST. Kindly leave your comment using the voice podscasv

Note: Sean B. Carroll the evolutionary biologist and Sean M. Carroll the quantum physicist are both equally awe-inspiring. They are not the same person. Sean’s new book A Series of Fortunate Events: Chance and the Making of the Planet, Life, and You (2020) can be found here: https://www.amazon.co.uk/Fortunate-Events-Chance-Making-Planet/dp/0691218900/ref=tmm_pap_swatch_0?_encoding=UTF8&qid=1611219491&sr=1-1 Sean’s classic book Endless Forms Most Beautiful: The New Science of Evo Devo and the Making of the Animal Kingdom (2005) can be found here: https://www.amazon.co.uk/Endless-Forms-Most-Beautiful-Science/dp/1849160481 His book and film The Serengeti Rules: The Quest to Discover How Life Works can be found here: https://www.seanbcarroll.com/the-serengeti-rules#:~:text=In%20The%20Serengeti%20Rules%2C%20award,the%20planet%20we%20depend%20upon. For more on Sean: https://www.seanbcarroll.com/ Follow Sean on Twitter @SeanBiolCarroll Further References Evo-Devo (Despacito Biology Parody) | A Capella Science - YouTube: https://www.youtube.com/watch?v=ydqReeTV_vk The Hox gene family synteny on chromosome 3 of Drosophila melanogaster... | Download Scientific Diagram (researchgate.net): https://www.researchgate.net/figure/The-Hox-gene-family-synteny-on-chromosome-3-of-Drosophila-melanogaster-and-the-segments_fig4_322698687 Introduction to Trilobites: https://www.trilobites.info/trilobite.htm Eye Development - an overview | ScienceDirect Topics: https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/eye-development Timestamps 03:00 Misunderstandings about chance and probability 04:42 The precise timing of the asteroid strike 66 million years 07:48 Quantum fibrillation in the structure of DNA 14:34 Redundancy in the genome 17:50 How small the differences are that matter 20:51 The central insight of evo devo 28:38 Genetic switches and the choreography of development 32:13 It’s ain’t what you have, it’s the way that you use it. How diversity is achieved. 38:52 Homologous modular structures 43:20 Hox genes and the GPS coordinate system for the body 45:00 Williston’s law and why we have leeway to experiment 49:47 Polarities, how changes in the embryo create changes in the animal 55:02 Chance and the individual

My AP Biology ThoughtsEpisode #15Welcome to My AP Biology Thoughts podcast, my name is Alex Jing and I am your host for episode 15 called Homologous Vestigial and Analogous Structures.  Today we will be discussing what these different structures are and how they relate to evolutionary biology. Segment 1: Introduction to Homologous Vestigial and Analogous StructuresSo, what are homologous, vestigial, and analogous structures? Each of these terms refers to the structure of something about an organism in a different way.  Homologous structures are organs or skeletal elements that, due to similarity, suggest that they come from a common ancestor. These structures do not necessarily look the same, but are instead just structurally similar. Analogous structures are similar structures that evolved to serve the same purpose. These structures were not from some common ancestor, but instead were developed in multiple species independently to adapt to a similar environment.  Vestigial structures are remnants of some past feature of the organism that is no longer useful. It usually occurs when a species inhabits a new environment, or is in a new niche, that does not require an old structure. Segment 2: Example of Homologous Vestigial and Analogous StructuresAn example of a Homologous structure are the wings of birds. The wings of birds come from some evolutionary ancestor, but have become diverse due to different birds needing different wings for their environment. Many predatory birds have wings that are specifically good at catching air so they can accelerate fast enough to catch prey. On the other hand, smaller birds that get sustenance off of fruit have wings that work better when flapping, and are used to maintain stability while eating in the air. An example of an analogous structure are the wings of a penguin and the flippers of a seal. Antarctica is a cold, barren environment, filled with sheets of ice and freezing water. Both the wings of a penguin, and the flippers of a seal were adapted to inhabit this environment. Despite the structure not coming from a recent ancestor, both animals use these limbs to be able to both traverse slippery ice, and swim in freezing water.  An example of a vestigial structure is the leg bone of a whale, where despite being a waterbound creature, it has remnants of a limb that was used for movement on land. This is because whales came from an ancestor that is shared with pigs. This ancestor was a land animal, but since whales only swim, they did not need this leg anymore. Due to lack of use, this limb became a smaller and smaller part of the whale, and eventually came to be this small separated bone in the whale's skeleton. Segment 3: Digging Deeper Homologous Vestigial and Analogous StructuresNow why are these things important? Well, these structures are extremely useful for understanding the evolutionary history of animals. Homologous structures are useful for studying divergent evolution. Some traits that come from an evolutionary ancestor appear on multiple different organisms, but are changed through adaptations for each individual species. Analogous structures are useful for studying convergent evolution. Species that migrate to a new area need certain adaptations to survive, no matter what species they are. Vestigial structures, similar to homologous structures, are also useful for studying divergent evolution. Vestigial structures can show how a species no longer requires some trait passed down from their ancestors, usually due to a new environment that has no need for this trait. Thank you for listening to this episode of My AP Biology Thoughts. For more student-ran podcasts, make sure that you visithttp://www.hvspn.com/ ( www.hvspn.com). Thanks for listening!  Music Credits:"Ice Flow" Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 4.0 License http://creativecommons.org/licenses/by/4.0/ Subscribe to our...

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.19.389494v1?rss=1 Authors: Shan, Y., Zhang, X., Song, C., Liu, Y., Ke, P., Kuo, Y.-C., Wang, Y. Abstract: Plexins are semaphorin receptors that play essential roles in neuronal axon guidance and in many other important biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism, and is modulated by small signaling GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations we showed that RND1 reinforces plexin dimerization interface whereas RhoD destabilizes it due to their differential interaction with cell membrane. Upon binding plexin dimers at the Rho-GTPase binding (RBD) domains, RND1 and RhoD interact differently with the inner leaflet of cell membrane, and exert opposite effects on the dimerization interface via an allosteric network involving the RBD domain, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively-charged membrane interface. Copy rights belong to original authors. Visit the link for more info

Dr. Haber begins his talk by explaining that broken chromosomes frequently arise during the process of DNA replication. In healthy cells, these double strand breaks (DSBs) are repaired by homologous recombination, an orderly process that preserves the genome.  If the homologous recombination machinery is impaired, DNA truncations, translocations, and deletions often occur, resulting in genome instability and cancer. All mechanisms of homologous recombination have one common principal; the broken ends of the DNA are repaired by base pairing with a sequence that is identical or nearly identical and acts as a template for repair enzymes.  Haber explains the general principles of homologous recombination and its critical role in maintaining genome stability.

Dr. Haber begins his talk by explaining that broken chromosomes frequently arise during the process of DNA replication. In healthy cells, these double strand breaks (DSBs) are repaired by homologous recombination, an orderly process that preserves the genome.  If the homologous recombination machinery is impaired, DNA truncations, translocations, and deletions often occur, resulting in genome instability and cancer. All mechanisms of homologous recombination have one common principal; the broken ends of the DNA are repaired by base pairing with a sequence that is identical or nearly identical and acts as a template for repair enzymes.  Haber explains the general principles of homologous recombination and its critical role in maintaining genome stability.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.08.370601v1?rss=1 Authors: Gilchrist, C. L. M., Booth, T. J., Chooi, Y.-H. H. Abstract: Genes involved in coordinated biological pathways, including metabolism, drug resistance and virulence, are often collocalised as gene clusters. Identifying homologous gene clusters aids in the study of their function and evolution, however existing tools are limited to searching local sequence databases. Tools for remotely searching public databases are necessary to keep pace with the rapid growth of online genomic data. Here, we present cblaster, a Python based tool to rapidly detect collocated genes in local and remote databases. cblaster is easy to use, offering both a command line and a user-friendly graphical user interface (GUI). It generates outputs that enable intuitive visualisations of large datasets, and can be readily incorporated into larger bioinformatic pipelines. cblaster is a significant update to the comparative genomics toolbox. cblaster source code and documentation is freely available from GitHub under the MIT license (https://www.github.com/gamcil/cblaster). Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.04.367136v1?rss=1 Authors: Roy, U., Kwon, Y., Marie, L., Symington, L., Sung, P., Lisby, M., Greene, E. C. Abstract: Homologous recombination (HR) is essential for the maintenance of genome integrity. Rad51 paralogs fulfill a conserved, but undefined role in HR, and their mutations are associated with increased cancer risk in humans. Here, we use single-molecule imaging to reveal that the Saccharomyces cerevisiae Rad51 paralog complex Rad55-Rad57 promotes the assembly of Rad51 recombinase filaments through transient interactions, providing evidence that it acts as a classical molecular chaperone. Srs2 is an ATP-dependent anti-recombinase that downregulates HR by actively dismantling Rad51 filaments. Contrary to the current model, we find that Rad55-Rad57 does not physically block the movement of Srs2. Instead, Rad55-Rad57 promotes rapid re-assembly of Rad51 filaments after their disruption by Srs2. Our findings support a model in which Rad51 is in flux between free and ssDNA-bound states, the rate of which is dynamically controlled though the opposing actions of Rad55-Rad57 and Srs2. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.31.363416v1?rss=1 Authors: Martinez-Espinosa, P. L., Yang, C., Xia, X., Lingle, C. J. Abstract: Adrenal chromaffin cells (CCs) in rodents express a rapidly inactivating, TTX-sensitive sodium current. The current has generally been attributed to Nav1.7, although a possible role for Nav1.3 has also been suggested. Nav channels in rat CCs rapidly inactivate into two separable pathways, which differ in their time course of recovery from inactivation. One population recovers with time constants similar to traditional fast inactivation and the other about 10-fold slower. Inactivation properties suggest that the two pathways result from a single homogeneous population of channels. Here we probe the properties and molecular components of the Nav current present in mouse CCs. We first confirm that functional properties of Nav current in rat and mouse cells are generally similar in terms of activation range, steady-state inactivation, and dual pathway fast inactivation. The results then show that all inward Nav current is absent in CCs from Nav1.3 KO mice. Subsequently, in a mouse with KO of fibroblast growth factor homology factor 14 (FGF14), we find that the slow component of recovery from fast inactivation is completely absent in most CCs, with no change in the time constant of fast recovery. Experiments probing the use-dependence of Nav current diminution between WT and FGF14 KO mice directly demonstrate a role of slow recovery from inactivation in determination of Nav current availability. Overall, the results indicate that the FGF14-mediated inactivation is the major determinant in defining use-dependent changes in Nav availability in CCs. We also consider the potential impact that inactivating FGFs with different recovery kinetics can exert on differential use-dependent changes in Nav availability. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.14.338756v1?rss=1 Authors: Heyne, M., Shirian, J., Cohen, I., Peleg, Y., Radisky, E. S., Papo, N., Shifman, J. M. Abstract: Each protein-protein interaction (PPI) has evolved to possess binding affinity that is compatible with its cellular function. As such, cognate enzyme/inhibitor interactions frequently exhibit very high binding affinities, while structurally similar non-cognate PPIs possess substantially weaker binding affinities. To understand how slight differences in sequence and structure could lead to drastic changes in PPI binding free energy ({Delta}{Delta}Gbind), we study three homologous PPIs that span nine orders of magnitude in binding affinity and involve a serine protease interacting with an inhibitor BPTI. Using state-of-the-art methodology that combines protein randomization and affinity sorting coupled to next-generation sequencing and data normalization, we report quantitative binding landscapes consisting of {Delta}{Delta}Gbind values for the three PPIs, gleaned from tens of thousands of single and double mutations in the BPTI binding interface. We demonstrate that the three homologous PPIs possess drastically different binding landscapes and lie at different points in respect to the landscape maximum. Furthermore, the three PPIs demonstrate distinct patterns of coupling energies between two simultaneous mutations that depend not only on positions involved but also on the nature of the mutation. Interestingly, we find that in all three PPIs positive epistasis is frequently observed at hot-spot positions where mutations lead to loss of high affinity, while conversely negative epistasis is observed at cold-spot positions, where mutations lead to affinity enhancement. The new insights on PPI evolution revealed in this study will be invaluable in understanding evolution of other biological complexes and can greatly facilitate design of novel high-affinity protein inhibitors. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.19.304949v1?rss=1 Authors: Huang, Y.-T., Liu, P.-Y., Shih, P.-W. Abstract: Nanopore sequencing has been widely used for reconstruction of a variety of microbial genomes. Owing to the higher error rate, the assembled genome requires further error correction. Existing methods erase many of these errors via deep neural network trained from Nanopore reads. However, quite a few systematic errors are still left on the genome. This paper proposed a new model trained from homologous sequences extracted from closely-related genomes, which provides valuable features missed in Nanopore reads. The developed program (called Homopolish) outperforms the state-of-the-art Racon/Medaka and MarginPolish/HELEN pipelines in metagenomic and isolates of bacteria, viruses and fungi. When Homopolish is combined with Medaka or with HELEN, the genomes quality can exceed Q50 on R9.4 flowcells. The genome quality can be also improved on R10.3 flowcells (Q50-Q90). We proved that Nanopore-only sequencing can now produce high-quality genomes without the need of Illumina hybrid sequencing. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.227033v1?rss=1 Authors: Carney, S. M., Moreno, A. T., Piatt, S. C., Cisneros-Aguirre, M., Lopezcolorado, F. W., Stark, J. M., Loparo, J. J. Abstract: Non-homologous end joining (NHEJ) is the predominant pathway that repairs DNA double strand breaks in vertebrates. During NHEJ DNA ends are held together by a multi-protein synaptic complex until they are ligated. Here we investigate the role of the intrinsically disordered C-terminal tail of XLF, a critical factor in end synapsis. We demonstrate that the XLF tail along with the Ku binding motif (KBM) at the extreme C-terminus are required for end joining. While the underlying sequence of the tail can be varied, a minimal tail length is required for NHEJ. Single-molecule FRET experiments that observe end synapsis in real-time show that this defect is due to a failure to closely align DNA ends. Our data supports a model in which a single C-terminal tail tethers XLF to Ku while allowing XLF to form interactions with XRCC4 that enable synaptic complex formation. Copy rights belong to original authors. Visit the link for more info

Beyond the Guidelines: Perspectives on the Role of PARP Inhibition in the Management of Ovarian Cancer — Interview with Dr Coleman on the following topics: Clinical implications of the Phase III VELIA study assessing veliparib in combination with carboplatin/paclitaxel and as continuation maintenance therapy for newly diagnosed advanced OC (00:00) Homologous recombination deficiency testing and implications for treatment decision-making in newly diagnosed advanced OC (4:11) Risks with combining PARP inhibitor therapy and chemotherapy for advanced OC; optimizing the use of chemotherapy, bevacizumab and a PARP inhibitor in the front-line setting (7:19) CME information and select publications

HOPA Now is the official podcast of the Hematology/Oncology/Pharmacy Association, an organization dedicated to supporting pharmacy practitioners and promoting the advancement of Hematology/Oncology/Pharmacy to optimize the care of individuals impacted by cancer.   These educational podcasts are part of our BCOP Preparatory and Recertification Course, which is designed to prepare oncology pharmacists preparing to sit for the BCOP Certification Exam, as well as meet the BPS requirement to complete a BCOP Preparatory/Recertification Review Course.   In this episode of HOPA Now, Dr. Jennifer Godden addresses the top ten clinical pearls of molecular pathways and pharmacogenomics with the goal of ensuring that oncology pharmacists have a strong understanding of the key concepts related to oncology precision medicine, including tumor genomic test processes and test results, and to make accurate resulting treatment recommendations. Topics covered include classifications of cancers and characteristics of genetic mutations, treatment implications and gene alteration implications, signal transduction pathways, and the impact of semantic and germline alterations on treatment selections.   In this episode you will learn:   Molecular Pathways and Pharmacogenomics Classification of cancers and characteristics of genetic mutations as the cause of cancer Prognostic and predictive tumor molecular profiling processes and standards Functional and clinical impacts of alterations Treatment implications and decisions based on various gene alteration implications and their functions The two major signal transduction pathways that facilitate signaling from the extracellular domain to the nucleus Homologous recombination deficiencies and mismatch repairs How semantic and germline alterations in cancer genes can impact treatment selection and medication response   Mentioned in This Episode: HOPA   Quotes: “The application of molecular pathways and the treatment of oncology patients is expanding at a rapid pace.” — Dr. Jennifer Godden   “Cancer is a process that develops as a result of dysregulated pathways.” — Dr. Jennifer Godden   “It is important to recognize that a VUS should not routinely be used as part of treatment decision making.” — Dr. Jennifer Godden   “It is becoming increasingly important for oncology pharmacists to understand molecular pathways and pharmacogenomics.” — Dr. Jennifer Godden  

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.19.162065v1?rss=1 Authors: O'Reilly, C., Elsabbagh, M. Abstract: Whether neuronal populations exhibit zero-lag (in-phase or in-antiphase) functional connectivity is a fundamental question when conceptualizing communication between cell assemblies. It also has profound implications on how we assess such interactions. Given that the brain is a delayed network due to the finite conduction velocity of the electrical impulses traveling across its fibers, the existence of zero-lag functional connectivity may be considered improbable. However, in this study, using intracranial recordings we demonstrate that most inter-hemispheric connectivity between homologous cerebral regions is zero-lagged and that this type of connectivity is ubiquitous. Volume conduction can be safely discarded as a confounding factor since it is known to drop almost completely within short inter-electrode distances (< 20 mm) in intracranial recordings. This finding should guide future electrophysiological connectivity studies and highlight the importance of considering the role of zero-lag connectivity in our understanding of communication between cell assemblies. Copy rights belong to original authors. Visit the link for more info

Susan Bratton is an ardent sexual biohacker, and trusted intimacy wellness expert to millions. A champion and advocate for all who desire passionate relationships, she is considered the “Dear Abby of Sex". Susan’s fresh approach and original ideas have helped millions of people of all ages and across the gender spectrum transform sex into passion. In today's episode, we present a thorough anatomy lesson on the female and male sex organs, as well as potent techniques to enhance your sexual vitality, build better relationships, and slow down the aging process. SHOW NOTES: 1:21 Welcome to the show!1:30 Our special guest, Susan Bratton4:37 Sex drive & libido in relation to vitality5:36 “It all starts with poo”6:14 Why detoxification matters6:23 Different microbiomes throughout the body6:58 Being susceptible to vaginal infections7:51 Candida & yeast in women9:01 Addressing nutrition for gut health9:58 The Hormonal decline10:29 Nitric oxide13:27 Susan’s “Flow” supplement14:16 Arginine/Herpes/EBV connection16:25 KETO + NO Supplementation16:54 Folate & fortified foods17:52 MTFHR gene18:28 High-quality multivitamins21:28 Susan’s libido vitamin23:44 Maca & Cacao24:14 All about the vagina26:08 How vaginal tone decreases over time27:28 How male body parts diminish28:33 A quick anatomy lesson31:03 The real G-Spot 32:02 Why hormones aren’t always to blame33:47 How to achieve natural lubrication35:15 Homologous parts (vagina to penis)36:50 Self pleasuring 37:10 30-Day Masturbation Challenge37:59 Incorporating sex toys 39:10 3-point “sexual stool”39:47 Health benefits of sex!41:41 Regenerative medicine for biohacking43:42 PRP (Platelet Rich Plasma) – P-Shot & O-Shot44:25 Shock wave therapy (GAINSwave, FemiWave)45:12 Red Light Therapy & the V-Fit 46:43 Capillus Red Light cap for hair growth49:56 How PRP works53:35 “Orgasmanaut”55:55 Lasers for internal tissues: RF & CO258:33 The Wing Lift59:22 Avoiding “saggy” tissue1:00:58 Vagazzle!1:01:57 The Whopper1:03:06 Self-care at home during Quarantine1:03:40 13-Week Protocol1:04:40 Hormone Replacement1:07:14 Nutrition for good hormones1:08:42 Thanks for tuning in!RESOURCES: Susan's Bio & LinksInstagramYouTube ChannelFLOW Nitric Oxide Booster SupplementLibido Vitamin SupplementvFit Device for Women O-Shot and P-ShotGAINSWaveFemiWave www.capillus.com/SUSANWing LiftDr. Robyn Benson (Regenerative Medicine Specialist)PumpingGuide.com

Genomic Assays in the “Real” Oncology World — Part 2: Genomic Assays in Prostate and Breast Cancer — Featuring a roundtable discussion with Drs Emmanuel S Antonarakis, Johanna Bendell, Ian E Krop and Andrew McKenzie. NGS for Metastatic Prostate Cancer (mPC) and the Potential Clinical Significance of Genomic Alterations Genetic alterations assessed in routine practice, including MSI status, BRCA mutations and AR-V7 variants; role of multiplex testing Presentation (Dr Antonarakis): Biomarker assessment in mPC; detection of DNA damage repair abnormalities and prediction of benefit with PARP and PD-1 inhibitors Landscape of DNA damage repair mutations in newly diagnosed and metastatic prostate cancer Rationale for the use of PARP inhibitors for prostate cancer with BRCA or ATM mutations Genetic testing of primary and metastatic tumors for alterations in the DNA repair and androgen receptor (AR) signaling pathways Clinical significance and genetic detection of AR splice variants Results of the CARD trial: Cabazitaxel versus enzalutamide or abiraterone for patients with mCRPC previously treated with docetaxel who experience rapid disease progression on an AR-targeted agent Efficacy of olaparib for mCRPC Available data with rucaparib, niraparib and talazoparib for mCRPC Role of radium-223 dichloride for patients with mPC; novel combination approaches with radium-223 under investigation Sensitivity of BRCA1, BRCA2 and ATM mutations to PARP inhibitors Activity of PARP inhibitors in patients with breast, ovarian, prostate and pancreatic cancers with BRCA mutations Homologous recombination deficiency and response to PARP inhibitors Case (Dr Antonarakis): A man in his mid-40s with mCRPC and a BRCA2 mutation attains a complete response to olaparib Case (Dr Antonarakis): A man in his mid-60s diagnosed with de novo mPC and MSI-high status, high tumor mutation burden and an MSH2 mutation experiences an excellent response to pembrolizumab after multiple lines of therapy Association of ductal and intraductal prostate cancer with a high prevalence of DNA damage repair gene mutations Predictors of benefit with immune checkpoint inhibitors Multigene Testing and Detection of Genomic Alterations in Metastatic Breast Cancer (mBC) Role of MSI testing and multiplex genomic assays in mBC Assessment of PIK3CA and BRCA mutations and assays for ESR1 Presentation (Dr Krop): Biomarker assessment in mBC — ER-positive and triple-negative disease PTEN loss and implications for therapeutic decision-making for mBC ESR1 mutations and resistance to hormone therapy Efficacy of PARP inhibitors in patients with BRCA mutations HER2 expression in HER2 nonamplified cancers; activity of trastuzumab deruxtecan in HER2-low breast cancer PD-L1 and other biomarkers predictive of benefit from immunotherapy in triple-negative breast cancer (TNBC) Case (Dr Krop): A woman in her late 50s with de novo TNBC receives atezolizumab/nab paclitaxel as first-line therapy Case (Dr Krop): A woman in her early 60s with ER-positive, HER2-negative mBC and a germline BRCA2 mutation whose disease progresses through multiple therapies attains a partial response to olaparib The Sarah Cannon Experience with Molecular Tumor Boards The use of molecular tumor boards to review molecular profiling data and facilitate therapeutic decision-making CME information and select publications

The gang gets together to record their first episode back from the holidays. And what better topic to discuss than hyoliths, those strange shelly Cambrian fossils. Specifically, the gang discusses two papers that look at new discoveries of the soft tissue and the hard shells of these hylothis to try and determine the evolutionary placement of hyoliths. Are hyoliths molluscs? Are hyoliths brachiopods? Are they somewhere in between? Meanwhile, Amanda hears some good news, Curt does his best hyolith impression, and James hits some unexpected snags when he discusses the ramifications of his ideal super powers.   Up-Goer Five (Amanda Edition):  Today our friends talk about animals that are big at one end and small at another end. They might be close to things with two parts that are good to eat, or they might be close to things with two parts that are not good to eat. Some people have said not long ago that they are more close to the things with two parts that are not good to eat. Our friends look at two papers that talk about these strange animals that are big at one end and small at the other. One paper says that yes, these animals are more close to the things with two parts that are not good to eat, and says that this is shown by the fact that they have a long thing that makes them stick to the ground. Animals with two parts that are good to eat don't have this long thing that makes them stick to the ground, but animals that have two parts that don't aren't good to eat do. Our friends don't really know if this thing is actually a part that makes the strange animals that are big at one end and small at the other stick to the ground, and would like to see some cool pictures taken to help show more things. The second paper tells us that actually these strange things that are bigger at one end and smaller at another are sort of between the things with two parts that are good to eat and the things with two parts that are not good to eat. They do this by looking at the hard parts that make up the strange things that are big at one end and small at the other, and then looking at the hard parts of the animals with two parts (both good and not good to eat). They look at these hard parts very, very close up. It is very cool.     References:  Sun, Haijing, et al. "Hyoliths with pedicles illuminate the origin of the brachiopod body plan." Proceedings of the Royal Society B: Biological Sciences 285.1887 (2018): 20181780.   Li, Luoyang, et al. "Homologous shell microstructures in Cambrian hyoliths and molluscs." Palaeontology (2018).

Dr Heeke speaks with ecancer at ASCO 2017 about the prevalence of haematology recombination deficiency among 53,000 tumour types.

This episode discusses Chapter XIV where Darwin applies his ideas of evolution and descent with modification to explain the developing "natural system" of classification, the unity of embryos and why organisms have rudimentary or vestigial organs.  Classification From the most remote period in the history of the world organic beings have been found to resemble each other in descending degrees, so that they can be classed in groups under groups. This classification is not arbitrary like the grouping of the stars in constellations. The existence of groups would have been of simple significance, if one group had been exclusively fitted to inhabit the land, and another the water; one to feed on flesh, another on vegetable matter, and so on; but the case is widely different, for it is notorious how commonly members of even the same sub-group have different habits.Cuvier in 1817 proposed a system of classification that recognized animals as belonging to one of four forms  - Vertebrata, Mollusca, Articulata (arthropods) and radially shaped animals (Radiata). image from http://www.buffalolib.org/content/milestones-science/georges-cuvierDarwin argues that the hierarchical system of classification mirrors his idea that new species formation mirrors the pattern of inheritance and genealogy we see in family tree.   A nice example is the phylogeny of placental mammals, those are mammals different from marsupial mammals (kangaroos, opossums, etc.) and monotremes (egg laying mammals like platypus)  in that they retain the embryo internally in a placental sac where they feed and protect the developing embryo. Placental mammals represent the majority of extant species of mammals today and seem to have evolved from three major geographical locations - Africa, Laurasia and South America. This is a a beautiful artistic representation of the placental mammal phylogenetic tree.http://eurwentala.deviantart.com/art/Eutheria-345487389A comparison of early development of placental mammals from the Afrotheria clade (left most branch) shows similarities and divergences in the different types of mammals. [A.. Tenrec [tenrecoidea], B. Golden mole [Chrysochloridae] C. Elephant shrew [Macroscelididae] D. aardvark [Tubulidentata] E. Bush elephant [Proboscidae] F. dugong [Sirenia] G. hyrax [Hyracoidea] Image from Hautier, Lionel, et al. "Patterns of ossification in southern versus northern placental mammals." Evolution 67.7 (2013): 1994-2010.Modern phylogeny and classification is based on Darwin's ideas of descent with modification and we now use DNA, RNA, and protein sequences to expand and improve our understanding of the relatedness of organismsEmbryology We have seen that the members of the same class, independently of their habits of life, resemble each other in the general plan of their organisation. This resemblance is often expressed by the term "unity of type;" or by saying that the several parts and organs in the different species of the class are homologous. The whole subject is included under the general term of Morphology. This is one of the most interesting departments of natural history, and may almost be said to be its very soul. What can be more curious than that the hand of a man, formed for grasping, that of a mole for digging, the leg of the horse, the paddle of the porpoise, and the wing of the bat, should all be constructed on the same pattern, and should include similar bones, in the same relative positions? Homologous bone structure of tetrapod limbsJames attempted to differentiate homologous structures from analogous structures but showed how complicated it can be when discussing flying adaptations in mammals. As you can see in the figure above, the limbs of birds, bats, humans, seals and turtles contain the same bones in the same configuration making them homologous in morphology. What changes in the relative size to each other not their relative position. In vertebrates, the evolution of powered flight occurred independently three times - in Pterosaurs (reptiles), bats (mammals), and birds (again reptiles) so their wings are functionally analogoussince they are wings constructed of different specific materials. James erroneously said that the pterodactyl wing was from a super elongated index finger but in fact it is the 4th digit what we associate with the pinky finger.  We colored the figure below of a pterodactyl wing to conform to the color legend in the figure above. Embryology Earnst Haeckel was a famous scientist in Darwin's time who applied Darwin's idea of the evolution of organisms in his studies of the embryonic stages of chordatesAs Sarah mentioned this set of illustrations were updated but the overall conclusion does not differ. Follow this link to read a wonderful summary of the Haeckel embryo controversy with modern drawings and interpretation. Overall embryo development does show that chordates exhibit very similar and distinct stages of development whereas the adult forms can be quite different in form.Rudimentary Organs Humans exhibit a number of traits, that we see in other mammals, but are degraded or rudimentary in their form. Some classic examples we discussed were the coccyx (tail bone), wisdom teeth and appendix but failed to mention the degrading nictating membrane in the corner of our eyes. In other chordates it is semitransparent film that can over the eye to clean and protect it. Ours is reduced to a little nubbin in the corner of our eye.http://www.bio.miami.edu/dana/pix/nictitans.jpgThe opening and closing theme to Discovering Darwin is "May" by Jared C. Balogh. http://freemusicarchive.org/music/Balogh/Revitalized_Eyes/MAY interlude music is Otrov by Black Bear Combo http://freemusicarchive.org/music/Black_Bear_Combo/

Dr Kaklamani talks to ecancertv at SABCS 2015 about a pooled analysis of five phase II studies showing that homologous recombination deficiency predicts response to neo-adjuvant platinum-based therapy in patients with triple-negative breast cancer. Indeed, significantly higher pathologic complete response (pCR) rates were observed when women had TNBC tumours that were homologous recombination deficient than when tumours were not (44% vs. 8% (p < 0.01), even after adjusting for potential confounding factors. Prospective studies are needed before a test for homologous recombination deficiency is commercially available, Dr Kaklamani observes.

TLP40 is the first complex immunophilin which was described from plant chloroplasts (Fulgosi et al., 1998). For this protein a role in regulation of PSII protein phosphorylation has been suggested (Fulgosi et al., 1998; Vener et al., 1999; Rokka et al., 2000). Homologous proteins were found in Arabidopsis thaliana and in Synechocystis. In Synechocystis, different from higher plants, the relevant PSII proteins are not phosphorylated. The main topic of this work was therefore to characterise the homologous protein of TLP40 in Synechocystis (named cTLP40, cyanobacterial TLP40). The investigation shows: • cTLP40 contains the major structural domains of TLP40 both at the N- and at the C-termini. A higher homology is found in the immunophilin domain located at the C-terminal end. • As in chloroplasts, cTLP40 is also located in the thylakoid lumen where it is present in free form or associated to the membrane. • A Synechocystis strain lacking cTLP40 ( ∆sll0408) could grow photoautotrophycally under normal grown conditions in a way comparable to wild-type. However, after adaptation to strong light the mutant strain showed higher photosensibility. Under these conditions, there was a decrease in oxygen evolution. • The total amount of PSII dimer was reduced in the mutant under high light. The lower amount of PSII can be attributed to a slower assembly rate of the complex and/or to higher degradation rate. Protein synthesis was not impaired under any of the tested conditions. • The PPIAse activity of cTLP40 was tested in vitro on synthetic prolinecontaining peptides of PSII proteins which are exposed to the lumenal face in thylakoids. The in vitro assays showed that cTLP40 possesses PPIAse activity on control peptides but can not efficiently isomerise the specific synthetic peptides.

Zoo-FISH with human whole-chromosome paint probes delineated syntenic association of human homologous chromosome segments 3-21, 14-15, 16-19, 4-8, 7-16 and 12-22 (twice) in the European mole (Talpa europaea, Talpidae, Eulipotyphla, Mammalia). These segment associations represent shared ancestral Boreo-Eutherian traits, half of which were previously not described for Eulipotyphla. The karyotype of the European mole acquired a minimum of 19 translocations and six inversions compared to the presumed Boreo-Eutherian ancestor. Copyright (c) 2006 S. Karger AG, Basel.

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species.

Agrin is thought to mediate the motor neuron-induced aggregation of AChRs and AChE on the surface of muscle fibers at neuromuscular junctions. We have isolated a cDNA from a chick brain library that, based on sequence homology and expression experiments, codes for active agrin. Examination of the sequence reveals considerable similarity to homologous cDNAs previously isolated from ray and rat libraries. A conspicuous difference is an insertion of 33 by in chick agrin cDNA, which endows the encoded protein with AChR/AChE aggregating activity. Homologous transcripts having the 33 by insertion were detected in the ray CNS, which indicates that an insertion of similar size is conserved in agrin in many, if not all, vertebrate species. Results of in situ hybridization studies and PCR experiments on mRNA isolated from motor neuron-enriched fractions of the spinal cord indicate that, consistent with the agrin hypothesis, motor neurons contain transcripts that code for active agrin.

Thu, 1 Jan 1981 12:00:00 +0100 https://epub.ub.uni-muenchen.de/8335/1/8335.pdf Scriba, Peter Christian; Wood, W. G.; Müller, O. A.; Giesemann, G.; Stalla, G. ddc:610, M