Podcasts about tfam

BUFFALO, NY- April 9, 2024 – A new #researchpaper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 6, entitled, “CMS121: a novel approach to mitigate aging-related obesity and metabolic dysfunction.” Modulated by differences in genetic and environmental factors, laboratory mice often show progressive weight gain, eventually leading to obesity and metabolic dyshomeostasis. The geroneuroprotector CMS121 has a positive effect on energy metabolism in a mouse model of type 2 diabetes. In this new study, researchers Alcir L. Dafre, Saadia Zahid, Jessica Jorge Probst, Antonio Currais, Jingting Yu, David Schubert, and Pamela Maher from Salk Institute for Biological Studies, National University of Sciences and Technology (NUST) and Federal University of Santa Catarina investigated the potential of CMS121 to counteract the metabolic changes observed during the ageing process of wild type mice. “This comprehensive analysis aimed to further understand how CMS121 influences the metabolic landscape, paving the way for potential therapeutic applications beyond its established geroneuroprotective benefits.” Control or CMS121-containing diets were supplied ad libitum for 6 months, and mice were sacrificed at the age of 7 months. Blood, adipose tissue, and liver were analyzed for glucose, lipids, and protein markers of energy metabolism. The CMS121 diet induced a 40% decrease in body weight gain and improved both glucose and lipid indexes. Lower levels of hepatic caspase 1, caspase 3, and NOX4 were observed with CMS121 indicating a lower liver inflammatory status. Adipose tissue from CMS121-treated mice showed increased levels of the transcription factors Nrf1 and TFAM, as well as markers of mitochondrial electron transport complexes, levels of GLUT4 and a higher resting metabolic rate. Metabolomic analysis revealed elevated plasma concentrations of short chain acylcarnitines and butyrate metabolites in mice treated with CMS121. “The diminished de novo lipogenesis, which is associated with increased acetyl-CoA, acylcarnitine, and butyrate metabolite levels, could contribute to safeguarding not only the peripheral system but also the aging brain. By mimicking the effects of ketogenic diets, CMS121 holds promise for metabolic diseases such as obesity and diabetes, since these diets are hard to follow over the long term.” DOI - https://doi.org/10.18632/aging.205673 Corresponding authors - Pamela Maher - pmaher@salk.edu and Alcir L. Dafre - alcir.dafre@ufsc.br Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205673 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer's diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, 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

Innovation and the reimagining of Christianity is happening on the margins of our faith tradition. We chat a bit about TFAM and how our church found fellow travelers on our […]

Innovation and the reimagining of Christianity is happening on the margins of our faith tradition. We chat a bit about TFAM and how our church found fellow travelers on our […]

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.28.526030v1?rss=1 Authors: Schwartz, A. Z., Nance, J. Abstract: The mitochondrial genome (mtDNA) is packaged into discrete protein-DNA complexes called nucleoids. mtDNA packaging factor TFAM (mitochondrial transcription factor-A) promotes nucleoid compaction and is required for mtDNA replication. Here, we investigate how changing TFAM levels affects mtDNA in the Caenorhabditis elegans germ line. We show that increasing germline TFAM activity boosts mtDNA number and significantly increases the relative proportion of a selfish mtDNA mutant, uaDf5. We conclude that TFAM levels must be tightly controlled to ensure appropriate mtDNA composition in the germ line. 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/2022.10.12.511955v1?rss=1 Authors: Newman, L. E., Tadepalle, N., Novak, S. W., Schiavon, C. R., Rojas, G. R., Chevez, J. A., Lemersal, I., Medina, M., Rocha, S., Towers, C. G., Grotjahn, D. A., Manor, U., Shadel, G. S. Abstract: Maternally inherited mitochondrial DNA (mtDNA) encodes essential subunits of the mitochondrial oxidative phosphorylation system, but is also a major damage-associated molecular pattern (DAMP) that engages innate immune sensors when released into the cytoplasm, outside of cells or into circulation1. This function of mtDNA contributes to antiviral resistance, but unfortunately also causes pathogenic inflammation in many disease contexts2. Cells experiencing mtDNA stress due to depletion of the mtDNA-packaging protein, Transcription Factor A, Mitochondrial (TFAM), or HSV-1 infection exhibit elongated mitochondria, mtDNA depletion, enlargement of nucleoids (mtDNA-protein complexes), and activation of cGAS/STING innate immune signaling via mtDNA released into the cytoplasm3. However, the relationships between altered mitochondrial dynamics and mtDNA-mediated activation of the cGAS-STING pathway remain unclear. Here, we show that entire enlarged nucleoids are released from mitochondria that remain bound to TFAM and colocalize with cGAS. These nucleoids arise at sites of mtDNA replication due to a block in mitochondrial fission at a stage when endoplasmic reticulum (ER) actin polymerization would normally commence, which we propose is a fission checkpoint to ensure that mtDNA has completed replication and is competent for segregation into daughter mitochondria. Released nucleoids also colocalize with the early endosomal marker RAB5 as well as the late endosomal marker RAB7 in TFAM-deficient cells and in response to mtDNA stress caused by the HSV-1 UL12.5 protein. Loss of RAB7 increases interferon stimulated gene (ISG) expression. Thus, we propose that defects in mtDNA replication and/or segregation enact a late mitochondrial fission checkpoint that, if persistent, leads to selective removal of dysfunctional nucleoids by a mitochondrial-endosomal pathway. Early steps in this pathway are prone to mtDNA release and cGAS-STING activation, but the immunostimulatory mtDNA is ultimately disposed of through a mechanism involving RAB7-containing late endosomes to prevent excessive innate immune signaling. This mtDNA quality control pathway might represent a therapeutic target to prevent mtDNA-mediated inflammation and associated pathology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

We're back! We'll be releasing short-form podcasts on topics like Cover bands: How they affect the music scene, lead singer syndrome, how to market yourself, and so much more! Join the conversation leave a comment or shoot us a message through TunesForAMinute.com Featured artists: Stop. Drop. Rewing. - I was Portrait Joe Marcinek Band - Dance factory   

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.02.365874v1?rss=1 Authors: Langley, M. R., Ghaisas, S., Palanisamy, B., Ay, M., Jin, H., Anantharam, V., Kanthasamy, A., Kanthasamy, A. Abstract: Mitochondrial dysfunction has been implicated as a key player in the pathogenesis of Parkinson's disease (PD). The MitoPark mouse, a transgenic mitochondrial impairment model developed by specific inactivation of TFAM in dopaminergic neurons, spontaneously exhibits progressive motor deficits and neurodegeneration, recapitulating several features of PD. Since non-motor symptoms are now recognized as important features of the prodromal stage of PD, we monitored the clinically relevant motor and nonmotor symptoms from ages 8-24 wks in MitoPark mice and their littermate controls. As expected, motor deficits in MitoPark mice began around 12-14 wks and became severe by 16-24 wks. Interestingly, male MitoPark mice showed spatial memory deficits before female mice, beginning at 8 wks and becoming most severe at 16 wks, as determined by Morris water maze. When compared to age-matched control mice, MitoPark mice exhibited olfactory deficits in novel and social scent tests as early as 10-12 wks. MitoPark mice between 16-24 wks spent more time immobile in forced swim and tail suspension tests, and made fewer entries into open arms of the elevated plus maze, indicating a depressive and anxiety-like phenotype, respectively. Importantly, depressive behavior as determined by immobility in forced swim test was reversible by antidepressant treatment with desipramine. Collectively, our results indicate that MitoPark mice progressively exhibit deficits in cognitive learning and memory, olfactory discrimination, and anxiety- and depression-like behaviors. Thus, MitoPark mice can serve as an invaluable model for studying motor and non-motor symptoms in addition to studying pathology in PD. Copy rights belong to original authors. Visit the link for more info

In this episode we're chatting about our last Tunes for a Night event back in October and our upcoming Tunes for a Night event on Saturday 2/29/2020. 

An update in the world of TFAM.  Featured artists:  Highest Low Moore    

This episode is an audio experience of Summer Stomp Music Festival in McHenry, IL. So many links and so little time, therefore, we'll leave the description at that.  Bands The Big Wu Terrapin Flyer Miles Over Mountains Teed Urban Pioneers Vendors #PhillipStrods Handpainted Vinyls #FunstyleBoutique Intrinsic Arts Joyful Bubbles #CosmicDesigns

Colin had the chance to take the stage with Victor Wooten for his clinic/show at Elgin Community College but before that he interviews some of the talented artists Victor took on tour with him.  Other updates include: Recording with Myna McArthur. Working on something special with Matt Holmes from The Echo Mill studio. Joining Sneaker Heartz! And shows ... of course we didn't forget upcoming shows!    Love,  TFAM 

The family continues to grow, and in the newest TFAM episode featuring Drew Doepke (Rebel Soul Revival), it's more evident than ever. We continue to meet professionals in the music industry that genuinely want to see other projects succeed as much as their own. Drew is no exception. He has a big heart, and you can tell by the way he talks about other bands that for him it's not a competition, he just loves music. Brock Galauner (White Buffalo Music Fest, Dreamers & Doers) also joins us in this episode as we talk about projects we're involved in, how Rebel Soul Revival put together their 6-week tour, recording at IV Lab in Chicago, and much MUCH so MUCH oh so mucho more! Wait, I didn't even mention how ROCK that one-minute tune is. Well ... it's ROCK. Make sure to use headphones!

Podcast episode #2 and video session #16 are here. This time it's Gary, aka Sleepless out of Elgin IL. We had a great time with Sleepless; this guy is genuine, passionate, and believes in what he's doing. We cover the beginning, i.e. why he started playing, to present day happenings all in under 21 minutes. Let us know what you guys think and be honest! Much love. TFAM

Join us for our first Trinity Family Conversations Podcast. In this podcast you will hear from 2 Trinity Family staff members, Danny White and Anna Callison. Danny introduces the Deep Rootz Summer Program and Anna shares her experience working with the girls in Trinity Gardens.

Join us for our first Trinity Family Conversations Podcast. In this podcast you will hear from 2 Trinity Family staff members, Danny White and Anna Callison. Danny introduces the Deep Rootz Summer Program and Anna shares her experience working with the girls in Trinity Gardens.

In this episode, that was recorded at The Fellowship of Affirming Ministries Convocation in July, I talk with Davie Floyd about her multi-faith practice that includes Christianity, Judaism, Buddhism, and Sufism (amongst other work). How do we become a personal sanctuary of inclusion for people to help them discover their own paths? How do we support the seeker, and how can we help people find what they need? What does it mean for someone to be spiritual? How are we evolving as a society and as human beings? This episode was recorded on location at City of Refuge UCC during The Fellowship of Affirming Ministries Convocation on July 17, 2015. Davie Floyd is a life-long member of the Pilgrim Rest Missionary Baptist Church in Dallas, TX where Rev. Curtis W. Wallace is the pastor. She is currently pursuing her PhD in Cognitive Studies and Education at Columbia University in New York. While in New York, she has joined Romemu, a Jewish renewal synagogue where David Ingber is Rabbi. She also regularly attends services at Rivers of Living Waters where Rev. Vanessa Brown is the senior pastor and often practices mindfulness with the Riverside Sangha which follows the Buddhist teachings of Thich Nhat Hanh. She is involved with several interfaith organizations in New York City. Though she is deeply spiritual and religious, her beliefs are largely agnostic. She lives a life oriented around realizing her full potential and coaching others to do the same. Links Email: davie.floyd@gmail.com Romemu Synagogue: http://romemu.org/ Rivers of Living Water Church: http://www.riversoflivingwaternj.com/

This week we talk with Schmian Evans about education, marginalization, and what we can do about it. What is considered normal? How do we educate and empower people, especially children, when they have be constantly told by the system they are stupid, can’t learn, or not worth people’s time? How do we navigate the grey areas? We also talk about spoken word. how their spoken word ministry can connect to others on a deep level, and how art is treated in our (U.S.) culture.   This episode was recorded on location at City of Refuge UCC during The Fellowship of Affirming Ministries Convocation on July 17, 2015.    Schmian Evans is a Master of Divinity and Certificate of Sexuality and Religion student at Pacific School of Religion. She also serves as the student representative on the Inter-Cultural Justice Committee and student trustee on the Board of Trustees. She holds a Certificate of Ministries Studies from PSR and a B.A. in Gender Studies from California State University Stanislaus. Schmian has served as an advocate for those considered at-risk and marginalized, for several years, as an educator, mentor and organizational leader. A poet, performer, and City of Refuge Minister, Schmian remains dedicated to the work and service of creating a more just world.   Links Lost Voices by Darius Simpson and Scout Bostly (Spoken word piece on YouTube) Email: schmian@att.net

In this episode, recorded after the multi-faith traditions panel at The Fellowship of Affirming Ministries Convocation, we talk to Queen Mother about syncretism and the way that spirit works in the world. She describes the traditions that she belongs to and how they work together for her. We discuss the responsibilities of priests, aspects of initiation, and how magick, and the gospel, is a tool of spirit that can be used for both good and ill.  We also discuss her role at City of Refuge and how she relates to Jesus. What can both traditions learn from each other and how do we navigate the misinformation and misconceptions of each?   This episode was recorded on location at City of Refuge UCC during The Fellowship of Affirming Ministries Convocation on July 17, 2015.    Oloya Adedapoidle Tyehimba-Ford carries the title of MaShiAat (Queen Mother), and is co-founder and presiding Queen Mother and Spiritual Leader of the Temples and Kemetic Spiritual organization: The Kindred of ShiEndra and its conglomeration of affiliated Temples. MaShiAat Oloya is an ordained Kemetic Priest, an Iyanifa in the Ifa tradition and an Ordained High Priestess within the original Dianic lineage of the Wiccan Goddess/Great Mother tradition. She is also a Holistic and Spiritual Practitioner and Midwife, holding numerous degrees and certifications in nursing, Iridology, Esthetics, indigenous and complementary healing. She is co-founder of the Kephra Holistic Institute and co-creator of the Kephric Transformational Platform both dedicated to the concepts of complete wellness through holistic, indigenous, and naturopathic modalities. MaShiAat Oloya lectures and facilitates workshops with many local and national community activists and spiritual leaders. She is often considered a bridge between mainstream religious churches and indigenous spirituality, making it a personal crusade to dispel myths, expose the truth and similarities between the philosophies of these religious groups with the intent to build understanding, respect and unity among the people as a whole.   Links Facebook: https://www.facebook.com/mashiaat Website: http://www.ancestoralley.com/

Mitochondria are often described as molecular power stations of the cell as they generate most of the energy that drives cellular processes. Mitochondria are eukaryotic organelles with bacterial origin that contain an extra-nuclear source of genetic information. Although most mitochondrial proteins are encoded in the nucleus, the mitochondrial genome still encodes key components of the oxidative phosphorylation machinery that is the major source for cellular adenosine 5’-triphosphate (ATP). The mitochondrial genome is transcribed by a singlesubunit DNA-dependent RNA polymerase (RNAP) that is distantly related to the RNAP of bacteriophage T7. Unlike its T7 homolog, mitochondrial RNA polymerase (mtRNAP) relies on two transcription factors, TFAM and TFB2M, to initiate transcription. The previously solved structure of free mtRNAP has revealed a unique pentatricopeptide repeat (PPR) domain, a N-terminal domain (NTD) that resembles the promoter-binding domain of T7 RNAP and a C-terminal catalytic domain (CTD) that is highly conserved in T7 RNAP. The CTD adopts the canonical right-hand fold of polymerases of the pol A family, in which its ‘thumb’, ‘palm’ and ‘fingers’ subdomains flank the active center. Since the structure represents an inactive “clenched” conformation with a partially closed active center, only limited functional insights into the mitochondrial transcription cycle have been possible so far. This work reports the first crystal structure of the functional human mtRNAP elongation complex, determined at 2.65 Å resolution. The structure reveals a 9-base pair DNA-RNA hybrid formed between the DNA template and the RNA transcript and one turn of DNA both upstream and downstream of the hybrid. Comparisons with the distantly related T7 RNAP indicate conserved mechanisms for substrate binding and nucleotide incorporation, but also strong mechanistic differences. Whereas T7 RNAP refolds during the transition from initiation to elongation, mtRNAP adopts an intermediary conformation that is capable of elongation without NTD refolding. The intercalating hairpin that melts DNA during mtRNAP and T7 RNAP initiation additionally promotes separation of RNA from DNA during mtRNAP elongation. The structure of the mtRNAP elongation complex (this work) and free mtRNAP (previously published) demonstrate that mtRNAP represents an evolutionary intermediate between singlesubunit and multisubunit polymerases. Furthermore, it illustrates the adaption of a phage-like RNAP to a new role in mitochondrial gene expression.

In which I discuss the anxieties of attempting to finance the indie film To Find A Monster with producers Joshua Porter, Matthew Donaldson, and Amelia Belle, and actress Alanna Ubach. We discuss also their reasons behind wanting to create this 80's love letter of a film about two boys wanting to become the youngest horror filmmakers ever.

Topic I Molecular basis of RNA polymerase III transcription repression by Maf1 RNA polymerase III (RNAP III) is a conserved 17-subunit enzyme that transcribes genes encoding short untranslated RNAs such as transfer RNAs (tRNAs) and 5S ribosomal RNA (rRNA). These genes are essential and involved in fundamental processes like protein biogenesis; hence RNAP III activity needs to be tightly regulated. RNAP III is repressed upon stress and this is regulated by Maf1, a protein conserved from yeast to humans. Many stress pathways were shown to converge on Maf1 and result in its phosphorylation, followed by its nuclear import and eventual repression of RNAP III activity. However, the molecular mechanisms of this repression activity were not known at the beginning of these studies. This work establishes the mechanism of RNAP III specific transcription repression by Maf1. The crystal structure of Maf1 was solved. It has a globular fold with surface accessible NLS sequences, which sheds new light on already published results and explains how stress-induced phopshorylation leads to import of Maf1 into the nucleus. Additionally, cryo EM studies and competition assays show that Maf1 binds RNAP III at its clamp domain and thereby induces structural rearrangements of RNAP III, which inhibits the interaction with Brf1, a subunit of the transcription initiation factor TFIIIB. This specifically impairs recruitment of RNAP III to its promoters and implies that Maf1 is a repressor of transcription initiation. Competition and transcription assays show that Maf1 also binds RNAP III that is engaged in transcription, leaving RNAP III activity intact but preventing re-initiation. Topic II Structure of human mitochondrial RNA polymerase The nuclear-encoded human mitochondrial RNAP (mitoRNAP) transcribes the mitochondrial genome, which encodes rRNA, tRNAs and mRNAs. MitoRNAP is a single subunit (ss) polymerase, related to T7 bacteriophage and chloroplast polymerases. All share a conserved C-terminal core, whereas the N-terminal parts of mitoRNAP do not show any homology to other ss RNAPs. Unlike phage RNAPs, which are self-sufficient, human mitoRNAP needs two essential transcription factors for initiation, TFAM and TFB2M. Both of these factors are likely to control the major steps of transcription initiation, promoter binding and melting. Thus human mitoRNAP has evolved a different mechanism for transcription initiation and exhibits a unique transcription system. Structural studies thus far concentrated on the nuclear enzymes or phage RNAPs, whereas the structure of mitochondrial RNA polymerase remained unknown. The structural organization of human mitoRNAP and the molecular mechanisms of promoter recognition, binding and melting were subject of interest in these studies. In this work the crystal structure of human mitoRNAP was solved at 2.4 Å resolution and reveals a T7-like C-terminal catalytic domain, a N-terminal domain that remotely resembles the T7 promoter-binding domain (PBD), a novel pentatricopeptide repeat (PPR) domain, and a flexible N-terminal extension. MitoRNAP specific adaptions in the N-terminus include the sequestering of one of the key promoter binding elements in T7 RNAP, the AT-rich recognition loop, by the PPR domain. This sequestration and repositioning of the N-terminal domain explain the need for the additional initiation factor TFAM. The highly conserved active site within the C-terminal core was observed to bind a sulphate ion, a well known phosphate mimic, and thereby suggests conserved substrate binding and selection mechanisms between ss RNAPs. However, conformational changes of the active site were observed due to a movement of the adjacent fingers subdomain. The structure reveals a clenching of the active site by a repositioned fingers subdomain and an alternative position of the intercalating -hairpin. This explains why the conserved transcription factor TFB2M is required for promoter melting and initiation. A model of the mitochondrial initiation complex was build to further explore the initiation mechanism, and to rationalize the available biochemical and genetic data. The structure of mitoRNAP shows how this enzyme uses mechanisms for transcription initiation that differ from those used by phage and cellular RNAPs, and which may have enabled regulation of mitochondrial gene transcription and adaptation of mitochondrial function to changes in the environment.