Podcasts about Cell cycle

Let's learn about DNA Replication and the Cell Cycle. 

In our latest episode, Executive Editor Kara Hansell Keehan interviews lead author Dr. Michaela Patterson and first author Kaelin Akins (both at the Medical College of Wisconsin) along with expert Dr. Ana Vujic (University of Cambridge) about the new study by Akins et al. Given that the heart has limited regenerative potential, repairing damage to cardiomyocytes after a heart attack is particularly challenging. Cardioregeneration researchers worldwide are searching for potential targets that can stimulate cardiomyocyte proliferation and cardiac regeneration. However, because cardiomyocytes can undergo incomplete cell division, multinucleation, and polyploidization, it is difficult to study true cardiomyocyte proliferation. Akins et al. examined the effect of Runx1 on cardiomyocyte cell cycle during postnatal development and cardiac regeneration using cardiomyocyte-specific gain- and loss-of-function mouse models. Listen now to learn more about how the authors determined that Runx1 is sufficient but not required for cardiomyocyte cell cycle activation.   Kaelin A. Akins, Michael A. Flinn, Samantha K. Swift, Smrithi V. Chanjeevaram, Alexandra L. Purdy, Tyler Buddell, Mary E. Kolell, Kaitlyn G. Andresen, Samantha Paddock, Sydney L. Buday, Matthew B. Veldman, Caitlin C. O'Meara, Michaela Patterson Runx1 is sufficient but not required for cardiomyocyte cell-cycle activation Am J Physiol Heart Circ Physiol, published July 21, 2024. DOI: 10.1152/ajpheart.00782.2023

Here are the research papers to support what I talk about today: Cheng, CW, Adams, GB, Perin, L, Wei, M, Zhou, X, Lam, BS, De Sacoo, S, Mirisola, M, Quinn, DI, Dorff, TB, Kopchick, JJ, Longo, VD. Prolonged Fasting reduces IGF-1/PKA to promote hematopoietic stem cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014 Jun 5; 14(6): 810–823. PMID: 249051672. Wu, S. Fasting triggers stem cell regeneration of damaged old immune system. USC News. Link Here3. Marziali, C. Fasting weakens cancer in mice. USC News. Link Here Buono, R, Longo, VD. When fasting gets tought, the tough immune cells get going-or die. Cell. 2019 Aug 22;178(5):1038-1040. PMID: 31442398   Anft, M. Don't feed your head. John Hopkins Magazine. Link Here Traba, J, Geiger, SS, Kwarteng-Siaw, M, Han, K, Ra, OH, Siegel, RM, Gius, D, Sack, MN. Prolonged fasting suppresses mitochondrial NLRP3 inflammasome assembly and activation via SIRT3-mediated activation of superoxide dismutase 2. J Biol Chem. 2017 Jul 21;292(29):12153-12164. PMID: 28584055 Haas JT, Staels B. Fasting the Microbiota to Improve Metabolism? Cell Metab. 2017; 26(4): 584-585. PMID: 28978420 Pietrocola F, Pol J, Kroemer G. Fasting improves anticancer immunosurveillance via autophagy induction in malignant cells. Cell Cycle. 2016; 15 (24):3327-3328. PMCID: 5224452 Mihaylova MM, et al. Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Funciton during Homeostasis and Aging. 2018 May; 22(5): 769-778. PMID: 29727683See omnystudio.com/listener for privacy information.

No Time To Read podcast S3E3 SHR and SCR coordinate root patterning and growth early in the cell cycle Guest: Cara Winter, Associate Research Professor, Duke University Pablo Szekely, Postdoc, Benfey Lab, Duke University Host: Arif Ashraf, Assistant Professor, Department of Biology, Howard University Twitter/X: @aribidopsis --- Send in a voice message: https://podcasters.spotify.com/pod/show/no-time-to-read-podcast/message

Dr. Evan Noch interviews Dr. Chunzhang Yang about his and his team's recent manuscript entitled "Abrogation of the G2/M checkpoint as a chemo sensitization approach for alkylating agents" published online in Neuro-Oncology in December 2023 Read Paper

References J Immunol. 2018 Feb 1; 200(3): 915–927 Cells. 2020 Jan; 9(1): 198. Cells. 2022 Apr; 11(7): 1105 Nature Comm. 2020. volume 11, Article number: 35 Schubert F. 1829. Fantasie in F minor. D940 https://youtu.be/UyjzqPPXDcw?si=XW_SMP7j-Kza8pmq Winwood, Capaldi and Wood. 1967 (Traffic). "Dear Mr Fantasy" https://youtu.be/dyMiUmrouZU?si=1ZSdXupm3WFBAxTz --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

In this episode, we review the high-yield topic of ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Cell Cycle ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠from the Biochemistry section. Follow ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Medbullets⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://podcasters.spotify.com/pod/show/medbulletsstep1/message

Hi everyone! Today's episode goes over some of the principles of cell cycle regulation and introduces the concepts of checkpoints and CDKs. Hope you enjoy!

In a recent episode of the HBOT News Network, Dr. James "Jay" Stevens, M.D., the Medical Director of Extivita-RTP, a local HBOT clinic in Raleigh, NC, discusses the Longevity Challenge scheduled for January 8-20, 2023. Dr. Stevens provides valuable insights into the different types of fasting and the potential benefits of combining fasting with Hyperbaric Oxygen Therapy (HBOT).Types of Fasting:Water Fasting: Water fasting is the most extreme form of fasting and involves abstaining from all caloric intake. During a water fast, participants rely solely on water for sustenance. While it is a rigorous approach, combining water fasting with HBOT is the primary focus of the Longevity Challenge.Intermittent Fasting: Dr. Stevens highlights two types of intermittent fasting: time-restricted feeding and the fasting mimicking diet (FMD).Time-restricted feeding:** This approach involves limiting the hours during which you consume food, typically within a set window of the day (e.g., 12 pm to 7 pm). It aims to induce cellular changes associated with repair, inflammation reduction, and genetic stimulation.Fasting mimicking diet (FMD): FMD takes intermittent fasting further by allowing limited caloric intake (approximately 700 to 800 calories per day). This diet provides essential principles for feeding the body fewer calories while still promoting cellular repair, reducing inflammation, and improving cardiovascular health.Fasting + Hyperbaric Oxygen Therapy (HBOT):Dr. Stevens delves into the profound benefits of combining fasting with HBOT, emphasizing the following key points:Ketosis: Fasting induces ketosis, an anti-inflammatory state that promotes cellular repair and turns on certain genetic aspects. While some individuals may experience flu-like symptoms (keto flu) during the initial detox phase of ketosis, this phase is followed by remarkable improvements in mental clarity and reduced anxiety.Energy Production: Glucose is necessary for energy production in mitochondria, the cellular organelles responsible for generating energy. However, in ketosis, where glucose levels are low, HBOT supplies the required glucose under pressure, enabling efficient energy production. Ketones, derived from fat, provide six times more energy to the brain and neurons than glucose, resulting in improved mental clarity and reduced brain fog.Cell Cycle and Autophagy: Understanding the cell cycle is essential, as cells have the capability to recognize their position in this cycle. Fasting and lifestyle changes help move cells away from senescence, a state where cells secrete harmful inflammatory cytokines. Instead, they induce autophagy, a process akin to "spring cleaning" for cells, where old cellular components are recycled, leading to cellular rejuvenation.Immunosenescence: Prolonged water fasting, such as in the Longevity Challenge, assists in reversing misfolded proteins, contributing to improved immune system function. Immunosenescence, or aging of the immune system, is a critical factor in determining lifespan, making the optimization of immune function crucial as individuals age.Taking Minerals During Water Fasting:Dr. Stevens underscores the importance of mineral intake during water fasting, as deficiencies in magnesium and potassium are common. To maintain cellular integrity during an extreme calorie-restricted state, participants should include electrolytes or minerals in their fasting regimen. The Longevity Challenge package includes these essential minerals mixed with water for all participants.The Longevity Challenge offers participants a transformative experience, allowing them to realize that they don't need food in the same way they once thought. It's an opportunity to reset one's perspective on

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.24.550259v1?rss=1 Authors: Howell, J., Omwenga, S., Jimenez, M., Hammarton, T. C. Abstract: Promastigote Leishmania mexicana have a complex cell division cycle characterised by the ordered replication of several single-copy organelles, a prolonged S phase and very rapid G2 and cytokinesis phases, accompanied by cell cycle stage-associated morphological changes. Here we exploit these morphological changes to develop a high-throughput and semi-automated imaging flow cytometry (IFC) pipeline to analyse the cell cycle of L. mexicana in live cells. Firstly, we demonstrate that, unlike several other DNA stains, Vybrant DyeCycle Orange (DCO) is non-toxic and enables quantitative DNA imaging in live L. mexicana promastigotes. Secondly, by tagging the orphan spindle kinesin, KINF, with mNeonGreen, we describe KINFs cell cycle-dependent expression and localisation. Then, by combining manual gating of DCO DNA intensity profiles with automated masking and morphological measurements of parasite images, visual determination of the number of flagella per cell, and automated masking and analysis of mNG:KINF fluorescence, we provide a newly detailed description of L. mexicana promastigote cell cycle events that, for the first time, includes the durations of individual G2, mitosis and post-mitosis phases. By applying IFC in this way, we were able, in minutes, to capture tens of thousands of high quality brightfield and fluorescent images of live L. mexicana cells in solution, and to acquire quantitative data across multiple parameters for every image captured. Our custom-developed masking and gating scheme, allowed us to identify elusive G2 cells, show that cytokinesis commences during early mitosis and continues after mitosis is complete, and identify newly divided cells that were within the first 12 minutes of the new cell cycle. Our new pipeline offers many advantages over traditional methods of cell cycle analysis such as fluorescence microscopy and flow cytometry and paves the way for novel high-throughput analysis of Leishmania cell division. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this podcast episode, Cyclacel CEO and President, Spiro Rombotis, shares how the company, is exploiting deeper understanding of molecular oncology to develop novel precision medicines based on cell cycle, transcriptional regulation, and mitosis biology.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.30.533363v1?rss=1 Authors: Iuliani, I., Mbemba, G., Lagomarsino, M. C., Sclavi, B. Abstract: A long-standing hypothesis sees DNA replication control in E. coli as a central cell cycle oscillator at whose core is the DnaA protein. The consensus is that the activity of the DnaA protein, which is dependent on its nucleotide bound state, is an effector of initiation of DNA replication and a sensor of cell size. However, while several processes are known to regulate the change in DnaA activity, the oscillations in DnaA production and DnaA activity have never been observed at the single cell level, and their correlation with cell volume has yet to be established. Here, we measured the volume-specific production rate of a reporter protein under control of the dnaAP2 promoter in single cells. By a careful dissection of the effects of DnaA-ATP- and SeqA-dependent regulation of dnaAP2 promoter activity two distinct cell-cycle oscillators emerge. The first one, driven by both DnaA activity and SeqA repression, is strongly coupled to cell cycle and cell size, and its minima show the same "adder" behaviour as initiation events. The second, a reporter of DnaA activity in the absence of SeqA binding, is still coupled with cell size but not to the time of cell division, and its minima (corresponding to DnaA activity peaks) show a "sizer-like" behavior, hence deviating from actual initiations. These findings indicate that production of DnaA is tightly coupled to cell volume through the timing of gene duplication, positive and negative regulation by DnaA-ATP itself and SeqA repression, and that DnaA activity peaks are a necessary but not sufficient condition to trigger replication initiation, posing firmer quantitative bases for a mechanistic understanding of cell cycle progression in bacteria. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.27.534352v1?rss=1 Authors: Cai, P., Casas, C. J., Hua, L. L., Mikawa, T. Abstract: Individual homologous chromosomes are spatially segregated into haploid chromosome sets along the centrosome axis in an antipairing configuration. Disruption of the antipairing pattern occurs in cancer cells. However, little is known about how this spatial organization of chromosomes is established or maintained. Here, we report that there is a zone of diminished interchromosomal linkage and centromere components between haploid sets in primary and established human epithelial cell lines. Using 4-Dimensional live cell imaging analysis of centromere and centrosome tracking, we show ipsilateral restriction of chromosome oscillations along the diminished zone, coincident with the centrosome and apical-basal axis from mitosis onset to G1 interphase. We propose a biophysical model of axis-dependent ipsilateral restriction of chromosome oscillations for haploid set organization. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Cell 2012 148DOI: (10.1016/j.cell.2012.01.031) Biotechnology Journal 2016. Volume11, Issue1 Special Issue: Biotech Methods and Advances: 71-79. Molecular Cancer. 2020. volume 19, Article number: 39. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.24.534130v1?rss=1 Authors: Klemm, C., Olafsson, G., Thorpe, P. H. Abstract: Protein phosphorylation regulates multiple cellular processes including cell-cycle progression, which is driven by highly conserved cyclin-dependent kinases (CDKs). CDKs are controlled by the oscillating levels of activating cyclins and the activity peaks during mitosis to promote chromosome segregation. However, with some exceptions, we do not understand how the multitude of CDK-phosphorylated residues within the proteome drive cell-cycle progression nor which CDK phosphorylation events are necessary. To identify yeast proteins whose phospho-regulation is most critical for cell-cycle progression, we created a synthetic CDK complex and systematically recruited this to proteins involved in chromosome segregation using the Synthetic Physical Interactions (SPI) method. We found that targeted recruitment of synthetic CDK to the centromeric protein Mif2CENP-C leads to enrichment of Mif2CENP-C at centromeres and arrested cells in late mitosis. We then identified putative CDK consensus sites on Mif2CENP-C which aid Mif2CENP-C localisation at centromeres and showed that CDK-dependent Mif2CENP-C phosphorylation is important for its stable kinetochore localisation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.13.532331v1?rss=1 Authors: Cacioppo, R., Akman, H. B., Tuncer, T., Erson-Bensan, A. E., Lindon, C. Abstract: Aurora Kinase A (AURKA) is an oncogenic kinase with major roles in mitosis, but also exerts cell cycle- and kinase-independent functions linked to cancer. Therefore control of its expression, as well as its activity, is crucial. A short and a long 3'UTR isoform exist for AURKA mRNA, resulting from alternative polyadenylation (APA). We initially observed that in Triple Negative Breast Cancer, where AURKA is typically overexpressed, the short isoform is predominant and this correlates with faster relapse times of patients. The short isoform is characterized by higher translational efficiency since translation and decay rate of the long isoform are targeted by hsa-let-7a tumor-suppressor miRNA. Additionally, hsa-let-7a regulates the cell cycle periodicity of translation of the long isoform, whereas the short isoform is translated highly and constantly throughout interphase. Finally, disrupted production of the long isoform led to an increase in proliferation and migration rates of cells. In sum, we uncovered a new mechanism dependent on the cooperation between APA and miRNA targeting likely to be a route of oncogenic activation of AURKA. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.531344v1?rss=1 Authors: DeWitt, J. T., Chinwuba, J. C., Kellogg, D. R. Abstract: Severe defects in cell size are a nearly universal feature of cancer cells. However, the underlying causes are unknown. A previous study suggested that a hyperactive mutant of yeast Ras (ras2G19V) that is analogous to the human Ras oncogene causes cell size defects, which could provide clues to how oncogenes influence cell size. However, the mechanisms by which ras2G19V influences cell size are unknown. Here, we found that ras2G19V inhibits a critical step in cell cycle entry, in which an early G1 phase cyclin induces transcription of late G1 phase cyclins. Thus, ras2G19V drives overexpression of the early G1 phase cyclin Cln3, yet Cln3 fails to induce normal transcription of late G1 phase cyclins, leading to delayed cell cycle entry and increased cell size. ras2G19V influences transcription of late G1 cyclins via a poorly understood step in which Cln3 inactivates the Whi5 transcriptional repressor. Previous studies found that Ras relays signals via protein kinase A (PKA) in yeast; however, ras2G19V appears to influence G1 phase cyclin expression via novel PKA-independent signaling mechanisms. Together, the data define new mechanisms by which hyperactive Ras influences cell cycle entry and cell size in yeast. Expression of G1 phase cyclins is also strongly influenced by mammalian Ras via mechanisms that remain unclear. Therefore, further analysis of PKA-independent Ras signaling in yeast could lead to discovery of conserved mechanisms by which Ras family members control expression of G1 phase cyclins. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.01.530713v1?rss=1 Authors: Phongkitkarun, K., Chusorn, P., Kamkaew, M., Lam, E. W.- F., Promptmas, C., Sampattavanich, S. Abstract: Forkhead box protein M1 (FOXM1) is a proliferation-associated transcription factor contributing to the G2/M phase transition of the cell cycle. Although the upregulation of FOXM1 has been observed in different cancer types, how the regulation of FOXM1 dynamically alters during cell cycles and potentially contributes to tumorigenesis is not well understood. We showed here the development and application of a tunable FOXM1-DHFR (FOXM1-D) sensor that enables surveillance and manipulation of the FOXM1 abundance. Using trimethoprim (TMP) to stabilize the sensor, we measured the kinetics of FOXM1-D production, degradation, and cytosolic-to-nuclear translocation in the G1 and G2 cell-cycle phases. By controlling FOXM1-D stability in different synchronized cell cycle pools, we found that the G1- and S-synchronized cells finished their first cell division faster, although the G2-synchronized cells were unaffected. Our analysis of single-cell FOXM1-D dynamics revealed that the two-round dividing cells had a lower amplitude and later peak time than those arrested in the first cell division. Destabilizing FOXM1-D in the single-round dividing cells enabled these cells to re-enter the second cell division, proving that overproduction of FOXM1 causes cell cycle arrest and prevents unscheduled proliferation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) published a new review paper in Volume 15, Issue 4, entitled, “Cellular senescence: when growth stimulation meets cell cycle arrest.” In this review, researcher Mikhail V. Blagosklonny, M.D., Ph.D., from Roswell Park Comprehensive Cancer Center discusses cellular senescence—a natural process that occurs as cells age and eventually stop dividing. Recent research has revealed that cellular senescence can also be triggered by hypertrophy and hyperfunctions. “At the very moment of cell-cycle arrest, the cell is not senescent yet. For several days in cell culture, the arrested cell is acquiring a senescent phenotype. What is happening during this geroconversion? Cellular enlargement (hypertrophy) and hyperfunctions (lysosomal and hyper-secretory) are hallmarks of geroconversion.” In his comprehensive review paper, Dr. Blagosklonny explores the complex relationship between growth stimulation and cell cycle arrest in cellular senescence. He discusses the various mechanisms that can lead to senescence, markers of senescence and geroconversion, and the importance of understanding these mechanisms and markers in the development of anti-aging drugs. “The same pathways that drive geroconversion are involved in organismal aging and age-related diseases. The same drugs that slow down geroconversion also extend lifespan, as tested in animals so far. Targets of gerostatics (e.g., mTOR, PI3K) are involved in aging of animals from worms to mammals. Therefore, gerostatics are anti-aging drugs. The model of geroconversion is useful to discover anti-aging drugs.” Dr. Blagosklonny is a renowned expert in the field of aging research. He has focused on the molecular mechanisms of aging, the hyperfunction theory of aging and the development of new drugs to combat age-related diseases. Dr. Blagosklonny's research, perspectives and reviews have made significant contributions to our understanding of aging. Full Paper: DOI: https://doi.org/10.18632/aging.204543 Corresponding Author: Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com Keywords: rapamycin, mTOR, hyperfunction theory of aging, cell volume and enlargement, gerogenic conversion Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204543

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.26.530133v1?rss=1 Authors: Memisoglu, G., Bohn, S., Krogan, N., Haber, J. E., Ruthenburg, A. J. Abstract: When faced with a DNA double strand break, cells activate an elaborate signaling cascade called the DNA damage response to protect genomic integrity. To identify novel factors that modulate the DNA damage response to DNA double strand breaks, we performed an epistatic miniarray profile analysis of Mec1 and Rad53, two essential kinases that coordinate the DNA damage response in budding yeast. Through this analysis, we discovered a genetic interaction between the kinase module (CKM) of the Mediator of transcription and Rad53. We find that all four subunits of the CKM, as well as CKM's kinase activity are critical for cell cycle re-entry following a DNA break, whereas the core Mediator subunits are dispensable. Notably, CKM mutants do not impair DNA repair by homologous recombination or confer sensitivity to DNA damaging reagents, suggesting that CKM specifically impinges on DNA damage signaling. In support of this, we find that Rad53 and CKM physically interact in response to DNA damage. Following the induction of a DNA break, CKM is a critical regulator of global transcription inhibition. In addition to this global effect, we illustrate that CKM functions locally at DNA breaks together with the core Mediator. In the absence of catalytically active CKM, the CKM-Mediator complexes at DNA breaks are replaced by RNAPII. Taken together, our results reveal a previously uncharacterized role for CKM in the DNA damage response. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

ゲストにまいんさんを迎え、共通テスト生物(2023)を解いてみての感想と解説、そしてどのような力が問われているのかについて議論しました。Shownotes 157. Litmus milk (Researchat.fm) … “ゲストにまいんさんを迎え、共通テストの特徴、共通テスト生物基礎(2023)を解いてみての感想と解説、そしてどのような力が問われているのかについて議論しました。” まいんさん 2023年度大学入学共通テスト 生物基礎 2023年度大学入学共通テスト 生物 2023年度大学入学共通テスト 追試 あいまいまいんの生物学 … まいん先生のブログ 2023年度大学入試共通テスト　生物基礎　所感 (あいまいまいんの生物学) … まいん先生による生物基礎解説 ぷらんちゅ … “植物を同定して進める恋愛ゲームです!” 是非プレイしてください。 ぷらんちゅの配信 by Researchat.fm … “分子生物学者がプレイする「植物同定恋愛ゲーム ぷらんちゅ」ぷらんちゅの作成者のまいんさんをお呼びし、ポッドキャスト番組Researchat.fmのメンバーで実況プレイしました。” YouTubeフォローしてください… 中間集計（最高得点に関する話) 得点調整について オペロン ジャコブとモノー … オペロン説の提唱により、1965年のノーベル生理学・医学賞を共同受賞 A Genetic Switch … 転写制御の第一人者であるMark Ptashneが書いた本。1st Editionが良いと聞く。結構薄くて大学で初めてちゃんと読み切った洋書。 ラクトースオペロン アラビノースオペロン RNA polymerase II …　「真核生物」で一般的な転写に用いられているRNA polymerase。他にもIとIIIがある。原核生物では一個しかないのでそもそも数に反応してしまった私が悪い…すぐ真核で考えちゃう… 細胞核 overexpression … 過剰に発現 シャジクモ 二次共生 マトリョーシカ …　関係ないけれどもマトリョーシカの起源が日本にある問題って本当なの？ “19世紀末、神奈川県箱根町にあったロシア正教会の避暑館にやってきたロシア人修道士が、本国への土産に持ち帰った箱根細工の七福神の入れ子人形がマトリョーシカの元になったという説。” 葉緑体から描ける系統樹と核ゲノムから描く系統樹の違い … Suisetzさんから拝借させていただきました。 盗タンパク質 Manabu Bessho-Uehara先生 … すいません！BeppuではなくBesshoさんです… さすがにミトコンドリアと真核生物の系統を見るに、シアノバクテリアが共生して葉緑体になる段階では真核細胞になっていたというべきか… ただそのプロセスは結構気になる。ミトコンドリアと葉緑体間におけるgene transferとかも起こっているのかな？（学生の時に調べた気はする….（要調査) とにかく、現存の真核細胞の祖先は一つであり、そこにはミトコンドリアがあったはずであることは、強調しておく必要がある（と主張してもいいよね？) LECA … LECA(The last eukaryotic common ancestor)の議論… ちょっと全然追えてないです… LECAとFECA … 元気な時にでも読みます… eukaryote = archea + bacteria説もまだ一説(だよね？)（要調査) Garg and Martin. GBE (2016) … “Mitochondria, the Cell Cycle, and the Origin of Sex via a Syncytial Eukaryote Common Ancestor” tadasuが最近面白いと思っているmitosis, meiosis, mitchondria, sexの進化についての考察。meiosisはmitosisよりも起源が古いのか。mitochondriaはmeiosis, sexの誕生に必要なのか、それともvice versa。 接合 … eukaryoteだとmating, bacteriaだとbacterrial conjugationかな。アーキアはわからん…（要調査) アーキアだとcell fusionしてrecombinationする例はあるらしいが、どのくらいまでやるの？？？もちろんRecAホモログはあるわけだが、染色体全体での相同組換えはしないよね？（要調査) sex … 基本的には配偶子がfusion(mating)して相同染色体間組換えを行うシステムを持つことをsexと言っていいようだが、もう少し調べていく必要がある。（要調査) a/alphaは酵母とかの真核生物で使われる。バクテリアだとF+, F-とかのイメージだが他にも色々あるのだろうか。 Meselsonの動画 … 最高の動画。Meselson and Stahlの実験から、mRNA、制限酵素の発見、そして政治の話まで幅広いインタビュー。インタビューをしているのは上で書いたGenetic Switchの著者であるMark Ptashne。現在は性やgene conversionについて興味あるっていってます。 Laine, Sackton, Meselson. Genetics (2022) … “Genomic signature of sexual reproduction in the bdelloid rotifer Macrotrachella quadricornifera” Meselsonの最新論文。Bdelloid rotifers（ヒルガタワムシの仲間)は長年無性であると考えられてきたがどのようにしてその種を保ち続けているのか。 赤の女王仮説 Muller's rachet … マラーだね。 ノドジロオマキザル … Cebus capucinus, 新世界ザル X inactivation 48. XXXXXYYYYY(Researchat.fm) … “レベルEのサキ王女編からスタートし、アメフラシ、ボネリムシ 、半倍数性、ヴォルバキアによる破壊、ゾウリムシ、カモノハシ、オスの三毛猫など、真核生物における多様な性決定システムと性染色体について話しました。” 遺伝子重複 … 遺伝子重複自体はかなり古くからアイデアがあったらしいがOhno (1970)で有名になった、とのことらしい。（要調査) 犬と色覚 … モノクロではなく二色？ 遺伝子座 対立遺伝子 gene drive 遺伝的浮動(genetic drift) 嗅球 ROS アクチン 母性・父性遺伝 … ミトコンドリアの母性遺伝を思い浮かべるんだけれども今回のような母性因子の遺伝に関してはちょっと枠組みが違うかも。 多湖輝 … リサチャリスナーなら必読の頭の体操の筆者。頭の体操の中で作者が試験官をしたテストを読みだけで解いていく話が掲載されている。受験テクニックではない笑 頭の体操 … え？読んだことない？今すぐ読みなさい。 プルテウス幼生 解いた時のテクスチャ … 何？？？？笑 大学入試数学　不朽の名問１００　大人のための“数学腕試し” (ブルーバックス) … 鈴木貫太郎先生のブルーバックスの本。円周率のあれとかああいうのが載ってる本。1/3ぐらいは解いた(T)。楽しい問題が多い。 ピーター・フランクルの中学生でも分かる大学生にも解けない数学問題集 … ピーターフランクル先生の本。一問目が中学生の時に解けず、いまだに一問目でスタックしております（15年以上経過)。昔の本は平太通信みたいなのが載っていて、そこに載っていた生物学者になったけれども早逝された研究者の方の話が記憶に残っている。なお問題はまだ解けないし、なんなら本はボストンに持ってきている。なお解けない(T)。 数学オリンピック問題にみる現代数学 … これの生物オリンピック版頼む！素数が無限にあることを証明せよ、みたいな問題だけ覚えている。 生物新・考える問題100選 (駿台受験シリーズ) … 新じゃないやつを解いていた記憶 まいん先生とたどる伝説の大学入試問題100選、まいん先生とたどる生物オリンピックにみる現代分子細胞生物学、出版希望 むしろ海外大学入試の伝説の一問とかみたい。北京大学2023とか。 Editorial Notes 2日連続で共通テストのアツい気持ちをtadasuさんとシェアできて楽しかったです！もし皆さんのイチオシシビれ問題があればぜひ教えてください。お待ちしております。(まいん) 頭パンパンでした。後半の疲れっぷりがひどい！体力つけなければ…まいん先生、ありがとうございました。あと、さっといろいろと疑問を振られた際あまりうまく答えられなかったので特に進化周りやsex周りは自分の中でちゃんともう一度組み立てておく必要があるなと感じました。アーキア周りも全然わからん。あやふやになっているままのところが非常によくわかったのでそう言う意味ではいい問題だなと思いました。シンプルゆえに強い。まいん先生の問題集きぼんぬ。ああ、そういえばあゆのモノマネするの忘れてた。(tadasu)

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.02.526815v1?rss=1 Authors: Hosseini, K., Frenzel, A., Fischer-Friedrich, E. Abstract: Epithelial-mesenchymal transition (EMT) is a key cellular transformation for many physiological and pathological processes ranging from cancer over wound healing to embryogenesis. Changes in cell migration, cell morphology and cellular contractility were identified as hallmarks of EMT. These cellular properties are known to be tightly regulated by the actin cytoskeleton. EMT-induced changes of actin-cytoskeletal regulation were demonstrated by previous reports of cell-cycle-dependent changes of actin cortex mechanics in conjunction with characteristic modifications of cortex-associated f-actin and myosin. However, at the current state, the changes of upstream actomyosin signalling that lead to corresponding mechanical and structural changes of the cortex are not well understood. In this work, we show in breast epithelial cancer cells MCF-7 that EMT results in characteristic changes of the cortical signalling of Rho-GTPases Rac1, RhoA and RhoC and downstream actin regulators cofilin, mDia1 and Arp2/3. In the light of our findings, we propose that cell-cycle-dependent EMT-induced changes in cortical mechanics rely on two hitherto unknown signalling paths - i) a cell-cycle-dependent feedback between Rac1 and RhoC and ii) a negative feedback between Arp2/3 activity and cortical association of myosin II. 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/2023.01.31.526419v1?rss=1 Authors: Bragulat-Teixidor, H., Ishihara, K., Szucs, G. M., Otsuka, S. Abstract: The endoplasmic reticulum (ER) is physically connected to the cell nucleus via junctions with the nuclear envelope (NE). These ER-NE junctions are essential for supplying the NE with lipids and transmembrane proteins that are synthesized in the ER. Despite the important role of ER-NE junctions, their biogenesis, architecture and maintenance across the cell cycle has remained elusive. In this study, by combining live cell imaging with quantitative three-dimensional electron microscopy, we systematically elucidated the ultrastructure of ER-NE junctions in mammalian cells. We discovered that ER-NE junctions exhibit a constricted hourglass shape that is different from the junctions within the ER. When ER-NE junctions are newly built during NE assembly at mitotic exit, their morphology resembles ER-ER junctions, but they become constricted starting in telophase. Altogether, our findings imply novel mechanisms that remodel ER-NE junctions and have functional implications for the lipid and protein traffic that are crucial for nuclear function. 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/2023.01.23.525185v1?rss=1 Authors: Calderon, A., Mestvirishvili, T., Boccalatte, F., Ruggles, K., David, G. Abstract: To maintain blood homeostasis, millions of terminally differentiated effector cells are produced every day. At the apex of this massive and constant blood production lie hematopoietic stem cells (HSCs), a rare cell type harboring unique self-renewal and multipotent properties. A key feature of HSCs is their ability to temporarily exit the cell cycle in a state termed quiescence. Defective control of cell cycle progression can eventually lead to bone marrow failure or malignant transformation. Recent work in embryonic stem cells has suggested that cells can more robustly respond to differentiation cues in the early phases of the cell cycle, owing to a discrete chromatin state permissive to cell fate commitment. However, the molecular mechanisms tying cell cycle re-entry to cell fate commitment in adult stem cells such as HSCs remain elusive. Here, we report that the chromatin-associated Sin3B protein is necessary for HSCs' commitment to differentiation, but dispensable for their self-renewal or survival. Transcriptional profiling of hematopoietic stem and progenitor cells (HSPCs) genetically inactivated for Sin3B at the single cell level reveals aberrant cell cycle gene expression, correlating with the defective engagement of discrete signaling programs. In particular, the loss of Sin3B in the hematopoietic compartment results in aberrant expression of cell adhesion molecules and essential components of the interferon signaling cascade in LT-HSCs. Finally, chromatin accessibility profiling in LT-HSCs suggests a link between Sin3B-dependent cell cycle progression and priming of hematopoietic stem cells for differentiation. Together, these results point to controlled progression through the G1 phase of the cell cycle as a likely regulator of HSC lineage commitment through the modulation of chromatin features. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

ゲストにまいんさんを迎え、共通テストの特徴、共通テスト生物基礎(2023)を解いてみての感想と解説、そしてどのような力が問われているのかについて議論しました。Shownotes まいんさん 2023年度大学入学共通テスト 生物基礎 2023年度大学入学共通テスト 生物 共通テストの目的（声明？) あいまいまいんの生物学 … まいん先生のブログ 2023年度大学入試共通テスト　生物基礎　所感 (あいまいまいんの生物学) … まいん先生による生物基礎解説 ぷらんちゅ … “植物を同定して進める恋愛ゲームです!” 是非プレイしてください。 ぷらんちゅの配信 by Researchat.fm … “分子生物学者がプレイする「植物同定恋愛ゲーム ぷらんちゅ」ぷらんちゅの作成者のまいんさんをお呼びし、ポッドキャスト番組Researchat.fmのメンバーで実況プレイしました。” YouTubeフォローしてください… 共通一次、 センター試験 … 昭和・平成を感じる (T) 令和５年度大学入学者選抜に係る大学入学共通テスト出題教科・科目の出題方法等及び問題作成方針 共通テストの役割 大学入学共通テスト実施方針策定に当たっての考え方 大学入学共通テスト：実施の趣旨 - 文部科学省 Molecular Biology of the Cell … 通称Cell。買っても持て余すか、ディスプレーの高さ調整台になるか、ダンベルになるか、鈍器になるか、君の血肉になるかは君次第(T) Essential Cell Biology … 上記の本を薄くしたやつ。それでもきっつい… (T) 以下ネタバレ注意 真核生物 原核生物 マーギュリスの細胞内共生説 … 最初に勉強した時、ちびるぐらい感動したよね… (T) ミトコンドリア … もう名前がかっこええんよ(T) 葉緑体 代謝経路 … 高校生の時に解糖系とTCA回路は覚えた記憶 卵 坐骨神経 呼吸 … やっぱりあの漫画が流行ったし、みんな呼吸について深く考えたよな？っていう出題なのかな…(T) シアノバクテリア パラサイトイブ … これ読んだらミトコンドリアにワクワクすること必至(T) ミトコンドリアや葉緑体の一部の遺伝子が核内ゲノムに移行している（移行中）なのを知った時はちびったよね。マジで感動した (T)。 遺伝子 … DNAとゲノム、遺伝子、染色体の違いを説明せよ(R5 researchat.fm)みたいなのはまとめておくと便利。 G1, S, G2, M … 覚えていくしかない… 間期 (interphase), 分裂期 (mitosis) meiosis … 減数分裂　真核生物のロマン(T) 生物I・II … 平成 生物基礎・生物に変わったのは平成24年～26年くらい？らしいです（指導要領上では24） コオロギとキリギリスの見極め方　… 働き者じゃないのがキリギリス (T) ヌクレオソーム 30nmクロマチン線維は存在しない！ クロマチン 酢酸カーミン 減数分裂 … ワクワクするな！(T) 二倍体 … 倍数性の変化をしっかり理解していこう。(T) 半保存的複製 Meselson・Stahlの実験 MeselsonとStahlのインタビュー動画 … もう好きすぎて何十回かはみた。本当に良い(T)。 3G bp x 2 = 6G bp フローサイトメトリー … あの細胞のラベルわけの図はよくみる。 EdUでラベルしよう ユークロマチンとヘテロクロマチン … 転写が活性化している部位とそうではない部位。ユークロマチンから複製が始まるといわれているため、DNA標識する物質を入れるタイミングをかえることで染め分けられる。言い忘れましたが、短時間で標識するっていう文言も大事でしたね。(T) single replication origin … 何て言ったか忘れたのですがシングルなのはバクテリアで、アーキアは複数のはず… 細胞を同調させてイメージングする実験でひたすら起きていた日のことや午前二時に自転車で爆走してラボに来た日のことを思い出しまして涙出ました(e.g., Nozaki et al., 2017 Figure 5AB) リトマスミルク リトマスゴケ … え、リトマスってここから来てるの？(T) NK細胞 弱酸性ビオレ 免疫系 T細胞 B細胞 はたらく細胞 … 見たことないのであまり知らない(T) 窒素循環 … これからは窒素循環を感じていく。 草じゃなくて葉っぱ(T) 以下、なんとなくtadasuが大学生(高校生)で読んだ本シリーズ 生物進化を考える … 高校生の時に生物IIで読んだ木村資生先生の名前と中立説というのが気になって借りて読んだ本。進化のロマンを感じた。 大いなる仮説 … 大野乾先生のこと知って大学で借りて読んだ本。 進化する階層―生命の発生から言語の誕生まで … 大学生の時に読んだジョンメイナードスミスの本。他の本は数式だらけでわけわかめだったがこの本は読みやすくて色々考えた気がする（違ってたらすいません) 進化の特異事象 … 大学生の時に読んだChristian deDuveの名著。進化について考える時にはこの本を読むとかなりガイドになると思う。高校生でも読める、とおもう。 ワンダフルライフ … グールドの本。古生物学にかなり興味が湧いた。 A Genetic Switch … 転写制御の第一人者であるMark Ptashneが書いた本。1st Editionが良いと聞く。結構薄くて大学で初めてちゃんと読み切った洋書。 利己的な遺伝子 … ドーキンスの本。周りのみんなは結構読んでいたが実は大学院生ぐらいまで読んでいなかったのだった… Garg and Martin. GBE (2016) … “Mitochondria, the Cell Cycle, and the Origin of Sex via a Syncytial Eukaryote Common Ancestor” tadasuが最近面白いと思っているmitosis, meiosis, mitchondria, sexの進化についての考察。meiosisはmitosisよりも起源が古いのか。mitochondriaはmeiosis, sexの誕生に必要なのか、それともvice versa。 Editorial Notes Researchatに出してもらうなんて光栄すぎて改めて感謝です。ただの趣味で問題解いてる人間なので間違った説明などしてたらごめんなさい。共通テストは楽しいぞ！！！(まいん) 高校生マジですごい。自分が高校生だった時だったら絶対に解けないです。受験生のみなさん勉強がんばって！問題見ながら話すの以上につかれました…後半ガス欠。まいん先生ありがとう！(tadasu)

Cyclacel Pharmaceuticals is a clinical-stage, biopharmaceutical company, developing innovative cancer medicines based on cell cycle, transcriptional regulation, and mitosis biology with a focus on oncology and hematology indications. Their lead drug candidate, fadraciclib is a dual CDK2/9 inhibitor currently undergoing investigation of dose escalation in a Phase 1/2 trial.Spiro Rombotis is the founding CEO of Cyclacel. Prior to joining Cyclacel, Spiro served in a number of management positions at public and private biotechs including Centocor, Bristol Myers Squibb, and the Liposome Company. He earned his MBA at Northwestern University's Kellogg School of Business.In this episode, we discuss cell cycle dysregulation in cancer, precision targeting of proteins in the drug design process, and unique clinical trial design.Hosted by Joe Varriale.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.22.521599v1?rss=1 Authors: Keller, D., Stinus, S., Umlauf, D., Gourbeyre, E., Biot, E., Olivier, N., Mahou, P., Beaurepaire, E., Andrey, P., Crabbe, L. Abstract: Genome organization within the 3D nuclear volume influences major biological processes but is completely lost during mitosis, which represents a major challenge to maintain cellular identity and cell fate. To restore a functional G1 nucleus for the next cell cycle, it is imperative to reestablish genome organization during post-mitotic nuclear assembly. Importantly, the configuration of linear chromosomes has been shown to directly impact spatial genome architecture. Both centromeres and telomeres are known to associate with nuclear structures, such as the nuclear envelope, and support chromatin distribution. Here, using high-resolution 3D imaging combined with 3D spatial statistics and modeling, we showed that telomeres generally followed a regular distribution compared to what is expected under a random organization. While the preferential localization of telomeres at nuclear periphery was restricted to early G1, we found a strong clustering of centromeres in addition to their predominant peripheral localization at all cell cycle stages. We then conducted a targeted screen using MadID to identify the molecular pathways driving or maintaining telomere anchoring to the nuclear envelope. Among these factors, we could show that LAP2 transiently localizes to telomeres in anaphase, at a stage where LAP2 initiates the reformation of the nuclear envelope. Moreover, co-depletion of LAP proteins and their partner BAF impacted telomere redistribution in the next interphase. There results suggest that in addition to their crucial role in genome protection, telomeres also participate in reshaping functional G1 nuclei after mitosis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The "cell cycle" describes discrete steps in the process of cell division.  The progression is mediated by a series of gatekeeping biochemical activities that ensure complete replication of DNA, and surveil it for fidelity. Precise execution of cell cycle is necessary for normal growth and development.  At the same time, loss of cell cycle coordination can lead to aberrant cell proliferation that can become genetically unstable, a condition recognized as cancer. Many drugs target the enzymes that control cell cycle progression, and several appear to be attractive candidates for future therapeutics. Spiro Rombotis of Cyclacel Pharmaceuticals describes targeting the cell cycle, along with new drugs that show promise in slowing, arresting, or possibly reversing some challenging subtypes of cancers. 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.30.518453v1?rss=1 Authors: Ji, X., Lin, J. Abstract: Accurate timing of division and size homeostasis is crucial for cells. A potential mechanism for cells to decide the timing of division is the differential scaling of regulatory protein copy numbers with cell size. However, it remains unclear whether such a mechanism can lead to robust growth and division, and how the scaling behaviors of regulatory proteins affect the cell size distribution. In this study, we formulate a mathematical model combining gene expression and cell growth, in which the cell-cycle inhibitors scale sublinearly with cell size while the activators scale superlinearly. The cell divides once the ratio of their concentrations reaches a threshold value. We find that the cell can robustly grow and divide within a finite range of the threshold value. Intriguingly, the cell size at birth is proportional to the ploidy, in agreement with experiments. In a stochastic version of the model, the cell size at division is uncorrelated with that at birth. Also, the more differential the cell-size scaling of the cell-cycle regulators is, the narrower the cell-size distribution is. Finally, after the deletion of a regulator, the average cell size can change significantly while the coefficient of variation of cell size remains roughly the same, consistent with experimental observations. 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/2022.11.17.516906v1?rss=1 Authors: Johnson, C. S., Sham, K., Belluschi, S., Wang, X., Lau, W., Kaufmann, K. B., Krivdova, G., Calderbank, E. F., Mende, N., McLeod, J., Mantica, G., Williams, M. J., Grey-Wilson, C., Drakopoulos, M., Sinha, S., Diamanti, E., Basford, C., Green, A. R., Wilson, N. K., Howe, S. J., Dick, J. E., Gottgens, B., Francis, N., Laurenti, E. Abstract: Loss of long-term haematopoietic stem cell function (LT-HSC) hampers the success of ex vivo HSC gene therapy and expansion procedures, but the kinetics and the mechanisms by which this occurs remain incompletely characterized. Here through time-resolved scRNA-Seq, matched in vivo functional analysis and the use of a reversible in vitro system of early G1 arrest, we define the sequence of transcriptional and functional events occurring during the first ex vivo division of human LT-HSCs. We demonstrate that contrary to current assumptions, loss of long-term repopulation capacity during culture is independent of cell cycle progression. Instead it is a rapid event that follows an early period of adaptation to culture, characterised by transient gene expression dynamics and constrained global variability in gene expression. Cell cycle progression however contributes to the establishment of differentiation programmes in culture. Our data have important implications for improving HSC gene therapy and expansion protocols. 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/2022.11.09.515885v1?rss=1 Authors: Biber, J. C., Sullivan, A., Brazzo, J. A., Krajnik, A., Heo, Y., Poppenberg, K. E., Tutino, V. M., Heo, S.-J., Kolega, J., Lee, K., Bae, Y. Abstract: Stiffened arteries are a pathology of atherosclerosis, hypertension, and coronary artery disease and a key risk factor for cardiovascular disease events. The increased stiffness of arteries triggers the hypermigration and hyperproliferation of vascular smooth muscle cells (VSMCs), leading to neointimal hyperplasia and accelerated neointima formation, but the mechanism of this trigger is not known. Our analyses of whole-transcriptome microarray data sets from mouse VSMCs cultured on stiff hydrogels simulating arterial pathology and from injured mouse femoral arteries revealed 80 genes that were differentially regulated (74 upregulated and 6 downregulated) relative to expression in control VSMCs cultured on soft hydrogels and in uninjured femoral arteries. A functional enrichment analysis revealed that these stiffness-sensitive genes are linked to cell cycle progression and proliferation. Furthermore, we found that survivin, a member of the inhibitor of apoptosis protein family, mediates stiffness-sensitive cell cycling and proliferation in vivo and in vitro as determined by gene network and pathway analyses, RT-qPCR, and immunoblotting. The stiffness signal is mechanotransduced via FAK and Rac signaling to regulate survivin expression, establishing a regulatory pathway for how the stiffness of the cellular microenvironment affects VSMC behaviors. Our findings indicate that survivin is necessary for VSMC cycling and proliferation and regulates stiffness-responsive phenotypes. 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/2022.11.08.515652v1?rss=1 Authors: Alao, J.-P., Rallis, C. Abstract: Caffeine is among the most widely consumed neuroactive compounds in the world. It induces DNA damage checkpoint signalling override and enhances sensitivity to DNA damaging agents. However, the precise underlying mechanisms have remained elusive. The Ataxia Telangiectasia Mutated (ATM) orthologue Rad3 has been proposed as the cellular target of caffeine. Nevertheless, recent studies suggest that the Target of Rapamycin Complex 1 (TORC1) might be the main target. In the fission yeast Schizosaccharomyces pombe (S. pombe), caffeine mimics the effects of activating the Sty1-regulated stress response and the AMP-Activated Protein Kinase (AMPK) homologue Ssp1-Ssp2 pathways on cell cycle progression. Direct inhibition of TORC1 with the ATP-competitive inhibitor torin1, is sufficient to override DNA damage checkpoint signalling. It is, therefore, plausible, that caffeine modulates cell cycle kinetics by indirectly suppressing TORC1 through activation of Ssp2. Deletion of ssp1 and ssp2 suppresses the effects of caffeine on cell cycle progression. In contrast, direct inhibition of TORC1 enhances DNA damage sensitivity in these mutants. These observations suggest that caffeine overrides DNA damage signalling, in part, via the indirect inhibition of TORC1 through Ssp2 activation. The AMPK-mTORC1 signalling axis plays an important role in aging and disease and presents a potential target for chemo- and radio-sensitization. Our results provide a clear understanding of the mechanism of how caffeine modulates cell cycle progression in the context of Ssp1-AMPKalphaSsp2-TORC1 signalling activities and can potentially aid in the development of novel dietary regimens, therapeutics, and chemo-sensitizing agents. 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/2022.11.03.514885v1?rss=1 Authors: Burclaff, J., Bliton, R. J., Breau, K. A., Cotton, M. J., Hinesley, C. M., Ok, M. T., Sweet, C. W., Zheng, A., Bankaitis, E. D., Ariel, P., Magness, S. T. Abstract: Background and Aims: The transcription factor SOX9 is expressed in many stem/progenitor cell populations and has biphasic correlations with proliferation rates across different biological systems. In murine intestinal crypts, distinct Sox9 levels mark three phenotypically different cell types, with lowest levels marking rapidly-dividing transit-amplifying (TA) cells, intermediate levels marking intestinal stem cells (ISCs), and highest levels marking slowly dividing label retaining secretory precursors. SOX9 expression levels and the impact of these levels on cell cycle and stem cell activity have not been characterized for humans. Methods: Monolayers of primary human ISCs isolated from healthy organ donors were engineered with stable SOX9-knockout (KO) and/or SOX9-overexpression (OE) genomic modifications to assess the impact of SOX9 levels on proliferative capacity by DNA content analysis, cell cycle phase length by live imaging for a PIPFUCCI reporter, stem cell activity via organoid formation assays, and cell fate after ISC differentiation by qPCR. Results: SOX9 was expressed at diverse levels in human intestinal crypt lineages in vivo, repressed proliferation in human ISC monolayers, and predominantly lengthened G1 by greater than 40% with lesser lengthening of S and G2/M phases. Over-expression of SOX9 caused slower proliferation yet increased organoid forming efficiency. Higher SOX9 levels biased ISC differentiation towards tuft cell and follicle-associate epithelium fates while loss of SOX9 biased cells toward absorptive enterocyte, goblet cell, BEST4 cell, and enteroendocrine cell fates. Conclusions: SOX9 is a master regulator of stem cell activity in human ISCs, lengthening cell cycle, promoting stemness, and altering differentiation fate. Interestingly, differences are noted between species, highlighting the importance of analyzing regulatory mechanisms in primary healthy human 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/2022.10.17.512486v1?rss=1 Authors: Basier, C., Nurse, P. Abstract: Proliferating eukaryotic cells grow and undergo cycles of cell division. Growth is continuous whilst the cell cycle consists of discrete events. How the production of biomass is controlled as cells increase in size and proceed through the cell cycle is important for understanding the regulation of global cellular growth. This has been studied for decades but has not yielded consistent results. Previous studies investigating how cell size, the amount of DNA, and cell cycle events affect the global cellular production of proteins and RNA molecules have led to highly conflicting results, probably due to perturbations induced by the synchronisation methods used. To avoid these perturbations, we have developed a system to assay unperturbed exponentially growing populations of fission yeast cells. We generated thousands of single-cell measurements of cell size, of cell cycle stage, and of the levels of global cellular translation and transcription. This has allowed us to determine how cellular changes arising from progression through the cell cycle and cells growing in size affect global cellular translation and transcription. We show that translation scales with size, and additionally increases at late S-phase/early G2, then increases early in mitosis and decreases later in mitosis, suggesting that cell cycle controls are operative over global cellular translation. Transcription increases with both size and the amount of DNA, suggesting that the level of transcription of a cell may be the result of a dynamic equilibrium between the number of RNA polymerases associating and disassociating from DNA. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Cell cycle regulation helps our cells control when they want to divide and when they do not. In this episode, we dive into cyclins, cyclin-dependant kinases, mautration-promoting factors, platelet-derived growth factors, and p53.

References Dr Guerra's membrane lecture notes Biochimica et BiophysicaActa (BBA) - Molecular and Cell Biology of Lipids.2014. Volume 1841, Issue 9, September Pages 1241-1246 BioEssays, Volume: 40, Issue: 5, First published: 30 March 2018, DOI: (10.1002/bies.201800007) International Journal of Molecular Sciences. 2015. 16(1):1928-48 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

In this episode of the Jack Westin MCAT Podcast, Phil Hawkins, Lead Instructor and Director of MCAT Prep and Harvard Medical Student Azaii Calderón Muñiz discuss cell replication. More specifically, Azaii and Phil discuss cancer. In this episode you will learn how cells replicate, how cancer bypasses normal genetic barriers, and what you need to know for the MCAT. 0:00 Intro 5:43 Cell Cycle 13:51 The MCAT and Cancer 16:00 Replicating DNA 20:45 Genes in Cancer 38:15 What Cancer Cells Actually Do 1:00:48 Outro About Jack Westin - The team at Jack Westin is dedicated to a single goal: giving students the highest quality learning resources. Jack Westin understands that students can't crush the MCAT without the perfect blend of critical thinking and fundamental science knowledge. To this end, Jack Westin is dedicated to providing students with cutting edge comprehensive tools, courses, and practice materials. The Jack Westin MCAT science and CARS courses, taught by the world's best and most engaging MCAT instructors, are designed to do more than just teach students the MCAT—it supercharges studying and encourages lifelong learning. Want to learn more? Shoot us a text at 415-805-6292 Free Resources: https://jackwestin.com Live Education Sessions: https://jackwestin.com/sessions Courses: https://jackwestin.com/courses Tutoring: https://jackwestin.com/tutoring Follow Us On Instagram: https://www.instagram.com/jackwestinmcat

Cell cycle biology is key to understanding cancer. You have to hit the cancer cells early before they become smart and adapt. There is a stage in the cell cycle called mitosis. This is where, if done right, can cause cancer cells to suicide. This is where the biotech company, Cyclacel comes in with all their research into the cell cycle of cancer. Join Ammon Rivera as he talks to Spiro Rombotis about some of Cyclacel's cell cycle therapies. Spiro is the CEO of Cyclacel. His mission is to use cell cycle biology to treat cancer and other serious diseases. Ammon and Spiro go over the use of Cyclin-dependent Kinase and its role in the cell cycle. Spiro also talks about Cyclacel's pipeline and drug candidates. They also go through discussion strategy, the drug approval process, and what it means to fail fast.

References Dr Guerra's synthesis of lecture material Histochemistry and Cell Biology volume 145, pages275–286 (2016) Biol Rev Camb PhilosSoc.. 2018 May;93(2):827-844. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Cell Cycle Cell Division

Mitosis is important for development, growth and cell replacement. Today we learn about cell replication.Find us on the internet!Our website - Teachmescience.co.ukEmail - teachmegcsescience@gmail.comTwitter - twitter.com/teachmegcsesciInstagram - @teachmegcsescience

In this season we will chat about Anti-cancer drugs. To better understand them we need to look at where it all goes down, the site of action. This episode gives an overview of what happens in the cell so as to make drug application easier.

Eukaryotic cells reproduce themselves by going through the cell cycle, which divides one cell into two. The cell cycle comprises two main phases, interphase and mitosis, both of which are further broken down into steps, as well as a separate resting phase. When a cell divides appropriately, this allows our bodies to fix damaged tissue and replace old layers of cells. However, when the cell cycle happens either at an inappropriate time or without stopping, cancers can develop. This is why the cell cycle is highly regulated with multiple checkpoints and myriad regulatory proteins. Next, we'll go over the steps of the cell cycle and dive into the complex regulatory mechanisms that prevent cancers from forming. After listening to this Audio Brick, you should be able to: Outline the four main stages of the cell cycle. Describe the role of cyclins and cyclin-dependent kinases in promoting cell cycle progression. Describe the cell cycle checkpoints. Outline the process of mitosis. You can also check out the original brick from our Cellular and Molecular Biology collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/ from our Musculoskeletal, Skin, and Connective Tissue collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.

My AP Biology Thoughts  Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Alex Jing and I am your host for episode #96 called Unit 4 Cell Communication and Cell Cycle: Regulation of Cell Cycle. Today we will be discussing How cells regulate their division Segment 1: Introduction to Cell Cycle Regulation The cell cycle includes 4 main stages: G1, S, G2, and mitosis. These phases are responsible for the division of cells. However, how do the cells determine when they can proceed to the next stage of the cell cycle? Cells regulate their advancement in the cell cycle through the use of Cyclin-dependent kinases, or CDKs, and CDK inhibitors. When CDKs are active, they phosphorylate other enzymes in the cell responsible for activating the next stage of the cell cycle. CDK inhibitors are receptors that when activated, will inhibit the CDKs, preventing the cell from going to the next stage.  Segment 2: More About the Regulation of the Cell Cycle A prominent example of why CDKs and their inhibitors are so important is the development of cancer. Cancers form when cells are growing at an rapid, unrestricted rate, and are usually caused by some mutations in the cell which results in either overactive CDKs or inactive CDK inhibitors. P53 is a CDK inhibitor which is responsible for ensuring that DNA is not damaged during the replication process. If it detects damaged DNA it will send out signals to inhibit the CDKs. If a mutation caused the P53 to not be responsive, than cells could be able to divide with damaged DNA, leading to a new cancer to form. Segment 3: Connection to the Course Regulation of the cell cycle is an essential part of all living organisms. Being able to conduct mitosis is what allows organisms to grow and replace damaged cells, and being able to regulate this process is extremely important to ensuring that division is done correctly.  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).   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 Podcast https://podcasts.apple.com/us/podcast/my-ap-biology-thoughts/id1549942575 (Apple Podcasts) https://open.spotify.com/show/1nH8Ft9c9f6dmo75V9imCk (Spotify) https://podcasts.google.com/search/my%20ap%20biology%20thoughts (Google Podcasts )   https://www.youtube.com/channel/UC07e_nBHLyc_nyvjF6z-DVg (YouTube)  Connect with us on Social Media Twitterhttps://twitter.com/thehvspn ( @thehvspn)

My AP Biology Thoughts  Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Chloe McGregor and I am your host for episode #93 called Unit 4 Cell Communication and Cell Cycle: The Cell Cycle. Today we will be discussing the basics of the cell cycle including how it works and what products are made.  Segment 1: Introduction to the Cell CycleThe cell cycle is split up into 2 different parts, each with their own purpose. The first part of the cell cycle is called interphase. The cell spends a majority of its time in this phase. Interphase itself is made up of 3 different stages. These stages are the G1, S, and G2 phase. The first step in interphase is G1. During this step, the cell spends its time growing in size and gaining a sufficient amount of resources. With this abundance of resources, the cell is able to replicate its DNA and intracellular components during the S phase. The third step is G2 where the cell continues its growth and will stop its progression to the mitotic phase if there are any issues or damaged DNA. The second part of the cell cycle is the mitotic phase which has 2 parts. The first part is mitosis. Mitosis consists of four steps: Prophase, metaphase, anaphase, and telophase. More details about these steps will be discussed later in the episode, but generally they work together in order to separate the replicated DNA. The second part of the mitotic phase is cytokinesis where the cell actually splits into 2 new identical daughter cells. Overall, each step in the cell cycle is important to grow the cell and its resources in order to produce 2 identical daughter cells, each with the same copies of DNA. Another important part of the cell cycle is the G0 phase. Although this isn't the generic path of cell replication , a cell may enter the G0 phase if there is a non sufficient amount of resources and nutrients available to proceed to healthy replication. Cells may also enter G0 if they are adult cells that are not necessarily looking to replicate. For example, a lot of cells in your brain and nervous system stop replicating once you reach adulthood, so an injury in these areas could be extremely difficult, or impossible, to heal. Segment 2: More About the Cell CycleTo go more in depth, let's talk about the different steps in mitosis. Once again, these steps are prophase, metaphase, anaphase, and telophase. The goal of mitosis is to separate the replicated DNA on opposite sides of the cell, with both sides having identical copies of the DNA. Prophase begins once G2 is finished and the cell has grown enough. In prophase, the DNA condenses, and the replicated chromosomes have a more visible shape to them. The replicated chromosomes are called sister chromatids and are linked together at a point called the centromere. The next step, metaphase, is when the replicated chromosomes line up in the center of the cell in a line. Anaphase is next, and this is where the spindle fibers on each side of the cell attach to the centromere region on each sister chromatid. Then, the fibers pull the sister chromatids apart, leaving opposite sides of the cell with identical genetic material. Telophase is the last stage of mitosis where each side of the cell begins to form a nuclear envelope around the new genetic material. The chromosomes also unravel back into chromatin. Once mitosis is complete, the cell membrane scrunches in the middle of the cell causing it to physically separate into two identical daughter cells. This step is called cytokinesis. Another important point to touch on is the checkpoints that occur during the cell cycle. Although there is a separate episode on cell cycle regulation, it is important to understand that the cell reaches checkpoints throughout the entire cell cycle which ensure that it is healthy, and that the DNA is replicating correctly. There are 3 checkpoints. These are near the end of G1, between G2 and the M phase, and one...

My AP Biology Thoughts  Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Morgan and I am your host for episode #89 called Unit 4 Cell Communication and Cell Cycle: transduction; secondary receptors. Today we will be discussing secondary receptors and their role in the signal transduction Segment 1: Introduction to transduction pathwaysIn signal transduction, there are three things that are necessary for the cell to do.  First, the signal, or ligand, must bind to the receptor, either on the cell's surface or inside the membrane. This is the first component, which is known as reception.  From there, the transduction occurs, where proteins are activated, and it is the component that includes secondary messengers.  Lastly, the transduction pathway eventually elicits a response from the cell, which is the overall goal of cell signaling. This response can be anything from activating an enzyme to initiating apoptosis, which is programmed cell death.  After the ligand binds to its receptor and changes the shape, the cell sets off with a series of signaling events, all designed to amplify the signal and eventually reach a response. This chain of events is what we call the transduction pathway. The first way transduction occurs is through protein phosphorylation, where a series of proteins are activated by phosphorylases. The other way transduction can occur is by secondary messengers, so let's learn more about those! Segment 2: More About secondary messengersSecondary messengers are small molecules that are specifically not proteins, although proteins play a huge role in the cell cycle. These secondary messengers are the ones that receive the signal from the first ligand when it binds to its receptor. The signal, or ligand, is thought of as the first messenger, so these little molecules that pick up and carry along the signal are therefore secondary messengers. Two examples of secondary messengers are calcium ions and cyclic AMP. First, calcium in the form of Ca2+ ions are a very common secondary messenger in cells. They are stored in the endoplasmic reticulum, which is purposeful so they are isolated from the rest of the cell until they are needed and released. The pathway starts with a signal that binds to and opens one of the ligand-gated calcium ion channels in the cell. With an open ion channel, calcium ions from the extracellular space are able to flow freely into the cell and greatly increase the concentration of Ca2+ ions in the cytoplasm. From there, the abundance of calcium ions bind with various proteins in the cell, changing their shape and function to initiate a response. Secondary messengers are nonspecific, so the signals can lead to many types of responses based on the proteins present and type of cell. The next example of a secondary messenger is cyclic AMP. Cyclic AMP is made when an enzyme gets a specific signal and converts ATP into the new molecule of cyclic AMP, also referred to as cAMP. Once it is made from the ATP, cAMP activates protein kinase A, a molecule that phosphorylates other proteins and passes along the signal to produce different responses. Segment 3: Connection to the CourseSecondary messengers have many connections to this unit of cell communication and the cell cycle, as well as the overall biology course. To start, it is important to understand signal transduction pathways and the three components before diving deeper into secondary messengers. We must know the purpose of these signaling pathways, as well as how they are started and what happens, which would be our three components of reception, transduction, and response. Additionally, we know that the purpose of secondary messengers is to amplify a signal and achieve a response, which we can see physically by responses in our body. For example, one of the secondary messengers we talked about earlier was calcium, which has a specific signaling pathway in...

My AP Biology Thoughts  Unit 4 Cell Communication and Cell CycleWelcome to My AP Biology Thoughts podcast, my name is Corrinna and I am your host for episode #88. This is Unit 4 Cell Communication and Cell Cycle and today, we will be talking about transduction phosphorylation cascades Segment 1: Introduction to transduction: phosphorylation cascadesTransduction is the second step in cell signaling pathways. It comes after reception, where the signal (which is called the ligand) is received by the receptor.  In order for the signal to start a response in the protein, the receptor needs to be activated. For the cell to produce a response, the next proteins in the chain also need to be activated. These proteins can be activated and deactivated like an on/off switch.  One of the ways that the signaling molecules are activated is phosphorylation. For a molecule to be phosphorylated, phosphate is added to the molecule. Phosphate groups are typically linked to either tyrosine, threonine, or serine, since these amino acids have hydroxyl groups in their side chains.  Phosphorylation is what can activate or deactivate the signaling molecules. It can also make the proteins more active (like an enzyme) or cause it to be broken down. Additionally, phosphorylation generally isn't permanent. To de-phosphorylate a protein, cells have enzymes called phosphatases that remove the phosphate groups from the phosphorylated protein.  A phosphorylation cascade is when multiple signaling molecules in the cell signaling chain are phosphorylated, which transports the signal to another molecule to produce the end result.  Segment 2: examples of transduction: phosphorylation cascadesIn order to better understand phosphorylation cascades, let's look at an example.  One example of a phosphorylation cascade is the epidermal growth factor (EGF) pathway.  When growth factor ligands bind to the receptors, the receptors act as kinases and attach phosphate groups to each other's intracellular tails. These receptors are now activated, triggering a series of events. Since these events don't include phosphorylation, we won't cover them in detail and will instead talk about the parts after that series that do involve phosphorylation.  Those events activate kinase Raf. This activated Raf phosphorylates and activates MEK, which in turn phosphorylates and activates ERKs. The ERKs then phosphorylate and activate other target molecules that then promote cell growth and division.  This specific pathway is called a mitogen-activated protein kinase cascade.  Because this specific pathway used multiple phosphorylation events that triggered other phosphorylations, it can be classified as a phosphorylation cascade.  Segment 3: Connection to the Course Phosphorylation cascades are extremely important in cell signaling pathways because they allow the cell to respond to more than one cell signal. Phosphorylation cascades trigger multiple cellular responses, because the phosphorylation of one protein leads to the phosphorylation of another.  Additionally, if phosphorylation cascades become out of control, especially cascades that signal for growth factor, cancer can occur. This shows that being able to stop cell signaling is extremely important, since if cell growth and division goes unregulated, it becomes dangerous.  To stop cell growth and division, the cell may receive a signal to undergo apoptosis, or cell death. This usually happens if a cell doesn't pass a checkpoint in the cell cycle, which is explained in further detail in another episode.  Thank you for listening to this episode of My AP Biology Thoughts. For more student-run podcasts and digital content, make sure that you visit http://www.hvspn.com (www.hvspn.com). See you next time on My AP Biology thoughts Podcast! Music Credits: "Ice Flow" Kevin MacLeod (incompetech.com) Licensed under...

In this top-performing research perspective published by Aging on February 12, 2021, entitled, “DNA- and telomere-damage does not limit lifespan: evidence from rapamycin,” Dr. Mikhail Blagosklonny — an adjunct faculty member at Roswell Park Comprehensive Cancer Center and the Editor-in-Chief of Aging, Oncotarget, Oncoscience, and Cell Cycle — gleaned an important new perspective from recent aging studies, which some may have overlooked. Rapamycin is a macrolide antibiotic that has immunosuppressive properties, regulates a key cellular growth pathway (mTOR), and has been at the center of numerous studies of aging since it's discovery in 1964. Dr. Blagosklonny explains that, based on findings from recent mouse-model studies of rapamycin's effects on short-lived mice, normal aging is not caused by the accumulation of molecular damage or telomere shortening. “Here I discussed new evidence that normal aging is not caused by accumulation of molecular damage or telomere shortening: while extending normal lifespan in mice, rapamycin failed to do so in mice dying from molecular damage (Figure 1).” To date, this research paper has generated an Altmetric Attention score of 43. Altmetric Attention scores, located at the top-left of trending Aging papers, provide an at-a-glance indication of the volume and type of online attention the research has received. Top Aging publications rated by Altmetric score: https://www.aging-us.com/news_room/altmetric DOI - https://doi.org/10.18632/aging.202674 Full text - https://www.aging-us.com/article/202674/text Correspondence to: Mikhail V. Blagosklonny email: Blagosklonny@oncotarget.com Keywords: quasi-programmed aging, hyperfunction theory, antagonistic pleiotropy, natural selection, mTOR, rapamycin About Aging Launched in 2009, Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl​ Facebook - https://www.facebook.com/AgingUS/​ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

This episode covers cancer drugs and the cell cycle!

Covering the following points: Model the processes involved in cell replication, including but not limited to: mitosis and meiosis DNA replication using the Watson and Crick DNA model, including nucleotide composition, pairing and bonding  Thanks to STEM Reactor for sponsoring this podcast. They provide everything you need to do biotechnology at school, check them out at www.stemreactor.com.au