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NOTE: audio quality is degraded; a full transcript is included, below. Using the story of Saul-turned-Paul, we start to unpack the beautiful concept of grace. Learn more about Blue Ocean Church at a2blue.org. You can find recordings of past services, learn where and when we meet in person, or get information about joining our live virtual service, by visiting a2blue.org/sunday-services/. Alright, we are starting a new sermon series this morning that we are calling Grace upon Grace. And so we're going to be using some of the stories and writings of the Apostle Paul to guide us as we explore this theme. And so to start us out, I just want to ask, like, what do we mean when we talk about grace? We were at dinner with some friends last night at Corner Brewery, one of my non-church going friends, like, what are you preaching about? But she never asks. And I was like, uh, Grace. She's like, what does that even mean? It's like, you need to kind of go through it a little bit. I thought, that's a good place to start because there's a lot of things we mean when we talk about that word. So I don't usually spend too much time on definitions or etymology unless it's useful. But I think in this case it would be helpful for us to define because we use the word so many different ways in English. And just to get a little bit crunchy for just a second. For those of you for whom it's helpful, maybe you're a more visual learner. You might want to look at the notes that I've given you there. So most of the New Testament was written in Greek. The word we translate is grace, in Greek is Keras, and it just means free gift. So grace is a free gift. And you might recognize that from that word, we get some other words like charism, charisma and charismatic and so on. And so with charism, it's just a specific free gift from God for the benefit of the community, right? So what we call the gifts of the Holy Spirit, we did a sermon series on some of those back in April and May, but things like prophecy and teaching and leadership and so on, those are called charisms. So charismatics then are people who exercise these free gifts of the spirit. That's that little root word that we translate as grace is just a free gift. And the concept of grace in the New Testament is actually pulling from a couple of different Hebrew words or ideas. And you'll have to forgive my pronunciation because I don't do gutturals very well. But those two are chen and chesed. Chen is something like unearned goodwill or favor, unearned approval. And chesed means something close to faithful, loving kindness. Only it's a little bit bigger than that. It's like faithful, loving kindness that's cultivated for the sake of repairing the world. And so the New Testament concept of grace is combining these two Hebrew ideas, right? Mixing this absolute unearned approval of chen, with the faithful, loving kindness and the healing of the world that chesed, it's a free gift of God's approval of us and God's love for us, for all of creation. And it's a love that causes God to be generous to us, for our healing and for our benefit, you might say, for our salvation to make us whole, right? So like grace is grace is where it's at, right? That's the foundation of Christianity. And the man who first spoke extensively about God's grace for humans was the apostle, Paul. And we know his name wasn't originally Paul, it was Saul. And some of you know about Saul, but some of us here may not. And so what I would like to do is tell you part of his story this morning. So a long time ago, in a land far, far away. About the time when Jesus was a teenager, there was another Jewish boy who was being born in a port city on the Mediterranean coast in the Roman Empire, and that city was called Tarsus. And it's in what today is the country of Turkey. Really gorgeous coastline down there. And this boy's parents called him Saul. And it's likely that he came from a family of tentmakers, since that was his trade as he became an adult. And Saul was a devout child, and as he matured, he found himself drawn into a more rigorous stream of his faith. And so he traveled to Jerusalem, and he studied with a really well-known teacher named Gamaliel the Elder, who was the grandson of the great sage Hillel. And so Saul came to acquire some top credentials in rabbinical education, although he's never referred to as a rabbi, and I don't think he was officially one that we know of. But he was very well educated, and he grew increasingly zealous as he grew into adulthood. And so at the same time that he was coming of age, there was a sect of Judaism that was just emerging called "The Way." And The Way was centered around the teachings of a rabbi called Jesus. And so many people were starting to follow this way, and they were finding life through it. And that includes some of the great rabbinic teachers and some of the top Jewish Pharisees and leaders. But the sect was viewed by skepticism by some others, including by Saul. And some of them, like Saul, became radicalized in their fear of The Way. And they grew violent toward people who were following it. And I want to be like super-duper cautious here and how I describe what was happening, because I don't want it to be heard here as like Saul, the Jewish man versus the early Christians or the early followers, because that's not really what was happening. It was another decade or so before someone was even called a Christian, and even then, it wasn't a separate religion, right? This is an internal tension that was happening, and it's not a great parallel, but you might think of it like today with Christianity in the United States, right? We might have a small percentage of people who are like super fundies or nationalists who might be enticed to do violence to other Christians. But the majority landscape of Christianity is not that, right? And the same with Judaism in Saul's time. It's not a great parallel because it's a little more complicated of a situation. But just know Saul is not representative of all Judaism here, it's just that his is the story of being one of the super radicalized people. Does that make sense? Because that's the interesting, you know, his story is interesting. When we first meet him in the book of acts chapter seven, he's overseeing the stoning of a man who was really well respected in the community and was a follower of Jesus, whose name was Stephen. And his only crime was following The Way. And we're told that at this time Saul was a young man. And then we're told this in Acts 8. It says "That day a severe persecution began against the church in Jerusalem, and all except the apostles were scattered throughout the countryside of Judea and Samaria. Devout men buried Stephen, and they made loud lamentation over him. But Saul was ravaging the church by entering house after house, dragging off both men and women. He committed them to prison." So after terrorizing the believers and the followers of this way in the city, he decided he was going to go after the people who had fled to try and get away. Right? These are the people who had moved their families to cities like Antioch and Damascus to escape this persecution. And so Saul decided first to go to Damascus, and he obtained some letters that would let him go and extract any Jews who were worshiping in the synagogues, who were also part of The Way. And so he was out to round up any and all followers of Jesus up in Damascus. This is in Acts 9, it says, "Now as he was going along and he was approaching Damascus, suddenly a light from heaven flashed around him, and he fell to the ground. And he heard a voice saying to him, 'Saul, Saul, why do you persecute me?' And he asked, 'Who are you, Lord?' And the reply came, 'I am Jesus, whom you are persecuting. But get up. Enter the city and you will be told what you are to do.' And the men who were traveling with him, they stood speechless because they heard the voice, but they saw no one. And Saul got up from the ground, and though his eyes were open, he could see nothing. And so they led him by the hand and brought him into Damaskus. And for three days he was without sight, and neither ate nor drank." And so he had this powerful mystical encounter that left him blinded and wondering what to make of what had just happened to him. And then while he wasn't able to see, he's gone into the city. There's another man in that same city. And that man's name is Ananias. He's over here praying. And as Ananias prayed, God told him about Saul. He told him where Saul was staying. And God asked Ananias to go and to visit Saul. But he was scared because this guy had a reputation and he had heard about this guy, and he'd heard about the terror that he had brought on so many people, probably even people Ananias knew personally. He'd probably been helping welcome some of these people into the city as well. And God told Ananias, don't be afraid. And so he went, and he visited Saul, and he found him unable to see. And so he laid hands on him, and he prayed for him. And it says that the scales fell from Saul's eyes. And we're told that his sight was immediately restored, and he was filled with the Holy Spirit. And he emerged a changed man. And so really, Saul had two divine encounters, right? He had one on the road with the voice. And then he had the second one through his meeting with Ananias, who confirmed that God was indeed at work here, that this wasn't just like a little collective psychosis event that he'd experienced. The scales fell from his eyes, both literally and metaphorically. This experience just cracks Saul open like an egg. And you'd have this hard outer shell that was just, like, now totally shattered. It's just playing in an absolute mess all over the kitchen counter. Right. A lot of what he thought he had understood in his life, like what he thought was for sure understood, is now just in shambles. Okay, so this is a guy, he was like an Uber fundamentalist, right? He had a mystical experience with God. He came to realize that his quest for religious purity, right? His self-righteous actions of trying to persecute people who disagreed with him, that that quest had actually hurt the God that he'd been trying to serve. "Saul, Saul, why do you persecute me?" Now, I've worked with pastors over the years who have come to see their own life's work as profoundly damaging to people in certain areas of the ministry for different reasons, sometimes because they excluded women. Sometimes it was LGBTQ people. And by the time they come to me or to Ken, they are scared and they're sad and they're humbled and they've come to know, and I include myself in this because I know I have changed over the twenty-five years, right? We come to know God's grace for us and our human mistakes. And then I think that makes them better pastors, right? Because now there's humility in realizing that like false certainty and judgments can do a lot of damage to people. And this is how I see Saul. Right, he's one of these humbled leaders, only like he was actually killing people. Right? And dude, this is like a, this is up a level. I've lost some friends who have been killed for their faith and so Saul is more like the people who killed them. And he's more like the man who shot and killed my friend Bashir in Srinagar in 2006, or the man who shot and killed my friend Abdiwali near Garissa, Kenya in 2013. I spent Christmas Day, 2007 with Abdiwali all of his family and their kids in their homes. About three weeks ago, thirty-one Nigerian Christians were killed just because they're Christian. I was thinking about Saul and he's really more like the men who are overseeing things like that than the pastors reaching out to us, right? He was profoundly dangerous and violent on a level that's really hard for us to relate to, because we don't have that level of religious violence in our country. Thank God, and may it not be right. But his past deeply affected them and how he approached things pastorally. And you could just see his regret lingering through all of his writings. It really impacted his entire life. And so harming or harming others, we know it does violence to ourselves too. Right. And that needs tending and healing and that's what's going on with us. And because of this vision of Jesus that Saul had, of Jesus letting Saul know that his actions were actually hurting the heart of God. He completely changed his ways. And eventually he changed his name to Paul to reflect that transition, that transformation. So then as soon as he was able to, he made his way back to Jerusalem because he wanted to go and he wanted to meet with the leaders of the Jesus movement to apologize to them and to try to make things right and to join them. But understandably, they didn't want to have anything to do with him. They thought it was a trap. He had been so dangerous and so conniving that they were like, it would be just like this guy to try and work his way into the inner circle so that he could do damage. And so they said no. But there was a man called Barnabas. Barnabas is probably my favorite character in the Bible, aside from Jesus for many reasons. But Barnabas went to Saul and he made space for him to tell his story. And it just took time to listen to what was going on with him. And he believed him. And he was really open hearted, and he withheld judgment. And so he took him to the other leaders, and he advocated for Saul. And so Barnabas was the reason that Saul was eventually accepted by the leadership as being sincere. And then after that meeting that he had with the leaders, Saul went away for a few years to go to pray and to study over in Arabia and Syria. I kind of call this as deconstruction era, right? He had to kind of figure out like how to, how to like, sort of rethink about his faith in a way that was healthier. There's no indication that he planned to become a leader in the early Jesus movement. It seems like he just went off to live a quieter life out of the limelight. He's like, you know, a dog with a tail between his legs. And it's only after many years that his old friend and advocate, Barnabas, came to fetch him. And Barnabas had kept Paul in the back of his mind. He remembered him, and he went. And he brought him to Antioch to disciple him. He was like, come see what God's doing. We'll talk more about that in about three weeks. But I want us to understand about grace today, is that the man who first started putting this concept together theologically, deeply understood what it meant to receive the free, unearned favor and love of God. Alright, that he was a man who had been violent and self-righteous and overly zealous, who introduced so much terror into a community, and yet he was still considered a beloved son by God. Maybe a wayward son, but always worthy of love and belonging. And if you treat your kids and your grandkids and your nieces and nephews right, like no matter what kind of foolishness they get up to in this life, you're always going to love them, right? And that's a Dolly Parton song, "I will always love you." You will always long for a good relationship with those that you love. The theologian C Baxter Kruger, who says Grace invites us into the assurance that we are always God's beloved children. We're always welcome at the table. With God's people as well. We are always welcome in their homes or welcome in God's fellowship. We're welcome in the relationship of the Trinity. We are always welcomed to the spiritual inheritance that they promised to all humankind. He says that shame is the lie that replaces this true identity. Shame is the lie that replaces this true identity, and shame tells us we're not worthy of God's love and acceptance because of our own pain, or because of our own limitations. There's something about us, or something we've done or not done. But our deepest truth is that grace is always available to us. The free gift of God's love and presence and power in our lives. No matter how many times we mess up, no matter how many times we let ourselves or let other people down. I know Doctor Brené Brown has been everywhere in the last decade, right? You've probably heard at least some of what she said about things like shame and resilience, but I think it's worth repeating because it's so core to our well-being, right, her research. Research shows that the biggest thing that keeps people from moving forward in life and having meaningful connections with other people is shame. And shame is that feeling that we don't belong or we're not lovable because there's something inherently wrong with who we are, or because that we've acted in ways that make us feel shame, not guilt. Right? She always draws a little distinction there. Like guilt is actually usually a healthy response to doing something that hurts someone else, but shame is different. Guilt says, I did something bad. Shame says I am bad, right? And saying I am a bad person, we know was different than saying I am behaving badly. I know you parents teach your kids this all the time. You're not a bad kid who's making bad choices, right? But even when we know the difference between these things, it is hard to be free from shame stories because they come at us from all sides of our culture just seeping in, right? All of those not enough stories. You're not successful enough, you're not buff enough, you're not thin enough, you're not friendly enough. You don't have enough willpower to get clean. You don't have enough money or social skills or whatever it is, those shame voices in our heads. The Apostle Paul reminds us that there's a story with a deeper truth than these not enough stories that we tell ourselves. And the deeper truth is that God's grace covers this multitude of seeming limitations. It meets us in our darkest moments and our feelings of weakness and our feelings of inadequacy. And it reminds us of who we are and of whose we are, and that we are loved by God, our creator, and we are accepted. And this creator wants to meet us in our hardest moments with kindness, with generosity. And Paul's life changed completely when he received God's grace, because God's generosity doesn't leave us immobilized, right? God's grace creates movement and it creates freedom in our lives. It gives us the freedom to become different and to choose differently, and to repair what's been damaged, even when that takes a really long time. It gives us the freedom to participate in God's healing of the world. And as the late, great Dolly Parton, Our Lady of the holler, once said, if you don't like the road you're walking, start paving another one. Grace frees us from shame, and it helps us to stand back up and to walk a different path. Speaking of Dolly Parton, I was like, I got a stick her in this. I've already written the sermon. I was like, I gotta put her in a sermon on grace, right? If you want an example of a person who personifies grace, there we have it. That's why everybody loved her. I look at her and I think of that. That is a Christian woman right there. Right. She personified and reflected the grace of God that everybody she met, they knew that she didn't judge them because of anything about their background. She had this quiet confidence in her own identity and her belovedness by God. She was like, I know who I am, and she knew she had made mistakes, but she still knew very deep down who she was made to be. Right behind the scenes, she just meted out gifts to help repair the world and to empower other people to do that. So I didn't even know this because I barely on social media, but Rachel saw on Facebook that our Archbishop, Bishop Yvette Flunder, had posted right after Dolly died, that she actually gave TFAM a really significant donation some years back, which I didn't know. Right. Who would know? She's just like quietly doing this stuff, doling out her money. And I thought that was really cool. I also think it's interesting that after Dolly died, like her music awards were more like a footnote, even though like, wow, what an accomplished artist. Eleven Grammys, ten CMAs, a National Medal of Arts and so on. But what people talked about was her kindness and her character and her joy and her generosity and her forgiveness and her deep care for the working-class people and for people who live in poverty, and her ability to let people just be themselves around her. So find out who you are and do it on purpose, right? That is grace personified. Who am I made to be? And she's like, I just knew what I was supposed to do. I knew that God loved me, and I knew that I was supposed to go and be a singer and do this. So I know our belovedness in God and like, know who you are and go out and do it on purpose. Grace is the mercy of discovering that our life is way bigger than the worst thing we've done, and it's way larger than the worst thing that's happened to us. Amen. Right. Our failures and our traumas are real, and they can feel terrible, but they are not the final word in our life. They do not get to write the ending to our stories. There is always more story left to tell, because the grace of God is boundless and unceasing. And Saul turned Paul, he knows what it's like to look backwards at a complicated life. Right. He was puritanical and he was wrong. And he caused a lot of harm to a lot of people. And he was absolutely certain about things that he came to see differently. And yet when he looked back at his life, he wrote almost with astonishment in first Corinthians, "For I am the least of the apostles, unfit to be called an apostle, because I persecuted the church of God. But by the grace of God, I am what I am, and his grace toward me has not been in vain." For Paul, as for all of us, grace meant that there could be a tomorrow that his younger self couldn't have imagined. And God pours grace into us imperfect vessels. And he somehow says, here, take this, carry this to the world instead. Amen. All right. We need to take a minute here just for some silence or guided meditation. But let's just take about a minute of silence. People make noise. Let's just make space for God to, um, just remind us of our belovedness. And if there's something that you're carrying that you're wanting to just take time to present before God, this is a great time to do that as well. So come Holy Spirit in this space. Lord, we thank you that there's absolutely nothing that can separate us from your love. In that silence I was reminded of that passage that Paul wrote in Romans about how nothing, absolutely nothing can keep us from God; neither height or death or anything else in all of creation. Nothing we've done, nothing about who we are. We don't have to get to a certain place in our life for you to be ready to use us. Lord, we just thank you that you meet us in the immediacy of our everyday lives right where we're at. And God, I ask that you would just help us to experience that grace and that free love and that presence that you feel your love toward us, just as we go through our week this week. And I ask that you would open our hearts as you're teaching us about grace over these next few weeks. In Your name we pray, Amen.

I receive a lot of health questions about how to remedy various debilitating conditions. One of the more concerning questions I receive frequently is regarding kidney failure. Why is there an epidemic of people with failing kidney function? It comes down to mitochondria dysfunction. Instead of focusing in one one study like most health educators do, my goal with these short shows is to paint broad strokes and cover the entire subject from a birds eye view all the way down to the mitochondrial level. Most importantly, as I cover various health conditions in future episodes, I will focus very heavily on the solutions, citing research and mechanisms to back up each of the proposed supplements or protocols. In the case of the kidneys, it comes down to one protein: mitochondrial transcription factor A, or TFAM. When that critical protein inside mitochondria in your kidneys becomes deficient, energy production falls and tissue function decreases, hence, kidney failure. It always comes back to mitochondria. My website: www.matt-blackburn.com Mitolife products: www.mitolife.co Music by George Henner: https://georgehenner.bandcamp.com Two studies I referenced: Mitochondrial Energetics in the Kidneys https://pmc.ncbi.nlm.nih.gov/articles/PMC5965678/#:~:text=The%20kidney%20is%20one%20of,pressure%20in%20the%20glomeruli5. Loss of Mitochondrial Transcription Factor A (TFAM) in Tubule Cells Causes Renal Failure https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3346980  

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.