Advances in biological regulation最新文献

{"title":"A consensus of evidence: The role of SPI-M-O in the UK COVID-19 response","authors":"Graham F. Medley","doi":"10.1016/j.jbior.2022.100918","DOIUrl":"10.1016/j.jbior.2022.100918","url":null,"abstract":"","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"86 ","pages":"Article 100918"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9136891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virus spread on a scale-free network reproduces the Gompertz growth observed in isolated COVID-19 outbreaks","authors":"Francesco Zonta ,&nbsp;Michael Levitt","doi":"10.1016/j.jbior.2022.100915","DOIUrl":"10.1016/j.jbior.2022.100915","url":null,"abstract":"<div><p>The counts of confirmed cases and deaths in isolated SARS-CoV-2 outbreaks follow the Gompertz growth function for locations of very different sizes. This lack of dependence on region size leads us to hypothesize that virus spread depends on the universal properties of the network of social interactions. We test this hypothesis by simulating the propagation of a virus on networks of different topologies or connectivities. Our main finding is that we can reproduce the Gompertz growth observed for many early outbreaks with a simple virus spread model on a scale-free network, in which nodes with many more neighbors than average are common. Nodes that have very many neighbors are infected early in the outbreak and then spread the infection very rapidly. When these nodes are no longer infectious, the remaining nodes that have most neighbors take over and continue to spread the infection. In this way, the rate of spread is fastest at the very start and slows down immediately. Geometrically we see that the \"surface\" of the epidemic, the number of susceptible nodes in contact with the infected nodes, starts to rapidly decrease very early in the epidemic and as soon as the larger nodes have been infected. In our simulation, the speed and impact of an outbreak depend on three parameters: the average number of contacts each node makes, the probability of being infected by a neighbor, and the probability of recovery. Intelligent interventions to reduce the impact of future outbreaks need to focus on these critical parameters in order to minimize economic and social collateral damage.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"86 ","pages":"Article 100915"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9575550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 models and expectations – Learning from the pandemic","authors":"John P.A. Ioannidis ,&nbsp;Stephen H. Powis","doi":"10.1016/j.jbior.2022.100922","DOIUrl":"10.1016/j.jbior.2022.100922","url":null,"abstract":"","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"86 ","pages":"Article 100922"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9136911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why COVID-19 modelling of progression and prevention fails to translate to the real-world","authors":"Carl J. Heneghan,&nbsp;Tom Jefferson","doi":"10.1016/j.jbior.2022.100914","DOIUrl":"10.1016/j.jbior.2022.100914","url":null,"abstract":"<div><p>Mathematical models were used widely to inform policy during the COVID pandemic. However, there is a poor understanding of their limitations and how they influence decision-making. We used systematic review search methods to find early modelling studies that determined the reproduction number and analysed its use and application to interventions and policy in the UK. Up to March 2020, we found 42 reproduction number estimates (39 based on Chinese data: R₀ range 2.1–6.47). Several biases affect the quality of modelling studies that are infrequently discussed, and many factors contribute to significant differences in the results of individual studies that go beyond chance. The sources of effect estimates incorporated into mathematical models are unclear. There is often a lack of a relationship between transmission estimates and the timing of imposed restrictions, which is further affected by the lag in reporting. Modelling studies lack basic evidence-based methods that aid their quality assessment, reporting and critical appraisal. If used judiciously, models may be helpful, especially if they openly present the uncertainties and use sensitivity analyses extensively, which need to consider and explicitly discuss the limitations of the evidence. However, until the methodological and ethical issues are resolved, predictive models should be used cautiously.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"86 ","pages":"Article 100914"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9136864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing COVID-19 trials at scale and pace: Experience from the RECOVERY trial","authors":"Leon Peto ,&nbsp;Peter Horby ,&nbsp;Martin Landray","doi":"10.1016/j.jbior.2022.100901","DOIUrl":"10.1016/j.jbior.2022.100901","url":null,"abstract":"<div><p>The Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial was set up in March 2020 to evaluate treatments for people hospitalised with COVID-19. To maximise recruitment it was designed to fit into routine clinical care throughout the UK, and as a result it has enrolled more patients than any other COVID-19 treatment trial. RECOVERY has shown four drugs to be life-saving – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab – and a further six have been shown to be of little or no benefit. In each case, results from RECOVERY were clear enough to rapidly influence global practice. Some of the reasons for this success relate to its particular setting in the UK during the SARS-CoV-2 pandemic, but many are generalisable to other contexts. In particular, its focus on recruiting large numbers of patients to identify or rule out moderate but worthwhile benefits of treatment, and the design decisions that followed from this. Similar large streamlined trials could produce similarly clear answers about the treatment of many other common diseases.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"86 ","pages":"Article 100901"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gaining insight into the role of FoxO1 in the progression of disuse-induced skeletal muscle atrophy","authors":"Natalia Vilchinskaya ,&nbsp;Erzhena Altaeva ,&nbsp;Yulia Lomonosova","doi":"10.1016/j.jbior.2022.100903","DOIUrl":"10.1016/j.jbior.2022.100903","url":null,"abstract":"<div><p>Expression of FoxO transcription factors increases during certain forms of atrophy. In a dephosphorylated state, FoxOs participate in ubiquitin-mediated proteasomal degradation through the transcriptional activation of E3-ubiquitin ligases such as MAFbx/atrogin-1 and MuRF1. There is exhaustive research demonstrating that FoxO3a is sufficient to induce MAFbx/atrogin-1 and MuRF-1 expressions. In contrast, the data are conflicting on the requirement of FoxO1 signaling in the activation of the E3-ubiquitin ligases. Moreover, no reports currently exist on the particular role of FoxO1 in the molecular mechanisms involved in the progression of physiological muscle wasting. Here, we have applied the most extensively used rodent model of microgravity/functional unloading to stimulate disuse-induced skeletal muscle atrophy such as rat hindlimb suspension (HS). We showed that inhibition of FoxO1 activity by a selective inhibitor AS1842856 completely reversed an increase in expression of MuRF-1, but not MAFbx/atrogin-1, observed upon HS. Furthermore, we demonstrated that FoxO1 induced upregulation of another E3-ubiquitin-ligase of a MuRF protein family MuRF-2 in skeletal muscle subjected to disuse. Prevention of the MuRF increase upon HS impeded upregulation of transcript expression of a negative regulator of NFATc1 pathway calsarcin-2, which was associated with a partial reversion of MyHC-IId/x and MyHC-IIb mRNA expressions. Importantly, FoxO1 inhibition induced a marked increase in p70S6k phosphorylation, an important stage in the initiation of protein translation, concomitant with the restoration of global protein synthesis in the skeletal muscle of the HS rats. Examination of eIF3f expression and the eEF2k/eEF2 pathway, other factors controlling translation initiation and elongation respectively, did not reveal any impact of FoxO1 on their activity. Lastly, we observed a decrease in transcript levels of Sesn3, but not Sesn1 and Sesn2, upon disuse, which was completely reversed by FoxO1 inhibition. These data demonstrate that FoxO1 signaling contributes to the development of disuse-induced skeletal muscle atrophy, including slow to fast MyHC isoform shift, mostly through upregulation of MuRF-1 and MuRF-2 expression. Furthermore, FoxO1 inhibition is required to recover Sesn3 mRNA expression in atrophic conditions, which likely contributes to the enhanced p70S6k activity and restoration of the protein synthesis rate.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"85 ","pages":"Article 100903"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212492622000434/pdfft?md5=032267105d296d0306025777dea3e5e1&pid=1-s2.0-S2212492622000434-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10376354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sphingolipids and their role in health and disease in the central nervous system","authors":"Andrés Felipe Leal ,&nbsp;Diego A. Suarez ,&nbsp;Olga Yaneth Echeverri-Peña ,&nbsp;Sonia Luz Albarracín ,&nbsp;Carlos Javier Alméciga-Díaz ,&nbsp;Ángela Johana Espejo-Mojica","doi":"10.1016/j.jbior.2022.100900","DOIUrl":"10.1016/j.jbior.2022.100900","url":null,"abstract":"<div><p><span>Sphingolipids<span> (SLs) are lipids<span> derived from sphingosine, and their metabolism involves a broad and complex network of reactions. Although SLs are widely distributed in the body, it is well known that they are present in high concentrations within the central nervous system (CNS). Under physiological conditions, their abundance and distribution in the CNS depend on brain development and cell type. Consequently, </span></span></span>SLs metabolism<span><span> impairment may have a significant impact on the normal CNS function, and has been associated with several disorders, including </span>sphingolipidoses, Parkinson's, and Alzheimer's. This review summarizes the main SLs characteristics and current knowledge about synthesis, catabolism, regulatory pathways, and their role in physiological and pathological scenarios in the CNS.</span></p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"85 ","pages":"Article 100900"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10739546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoregulation of the ATP synthase beta subunit stimulates mitochondrial activity for G2/M progression","authors":"Ana Cláudia Leite ,&nbsp;Telma Silva Martins ,&nbsp;Ana Campos ,&nbsp;Vítor Costa ,&nbsp;Clara Pereira","doi":"10.1016/j.jbior.2022.100905","DOIUrl":"10.1016/j.jbior.2022.100905","url":null,"abstract":"<div><p><span><span><span>Mitochondrial ATP synthase is a multifunctional </span>enzyme complex involved in ATP production. We previously reported that the ATP synthase catalytic </span>beta subunit (Atp2p in yeast) is regulated by the 2A-like </span>protein phosphatase<span> Sit4p, which targets Atp2p at T124/T317 impacting on ATP synthase levels and mitochondrial respiration.</span></p><p><span>Here we report that Atp2-T124/T317 is also potentially regulated by Cdc5p, a polo-like mitotic kinase. Since both Cdc5p and Sit4p have established roles in cell cycle regulation<span><span>, we investigated whether Atp2-T124/T317 phosphorylation was cell cycle-related. We present evidence that Atp2p levels and phosphorylation vary during cell cycle progression, with an increase at G2/M phase. Atp2-T124/T317 phosphorylation stimulates </span>mitochondrial membrane potential<span>, respiration and ATP levels at G2/M phase, indicating that dynamic Atp2p phosphorylation contributes to mitochondrial activity at this specific cell cycle phase. Preventing Atp2p phosphorylation delays G2/M to G1 transition, suggesting that enhanced </span></span></span>bioenergetics<span> at G2/M may help meet the energetic demands of cell cycle progression. However, mimicking constitutive T124/T317 phosphorylation or overexpressing Atp2p leads to mitochondrial DNA instability, indicating that reversible Atp2p phosphorylation is critical for homeostasis.</span></p><p>These results indicate that transient phosphorylation of Atp2p, a protein at the core of the ATP production machinery, impacts on mitochondrial bioenergetics and supports cell cycle progression at G2/M.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"85 ","pages":"Article 100905"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10739574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation-mediated regulation of the Nem1-Spo7/Pah1 phosphatase cascade in yeast lipid synthesis","authors":"Shoily Khondker,&nbsp;Gil-Soo Han,&nbsp;George M. Carman","doi":"10.1016/j.jbior.2022.100889","DOIUrl":"10.1016/j.jbior.2022.100889","url":null,"abstract":"<div><p>The <em>PAH1</em>-encoded phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to produce diacylglycerol, controls the divergence of phosphatidate into triacylglycerol synthesis and phospholipid synthesis. Pah1 is inactive in the cytosol as a phosphorylated form and becomes active on the nuclear/endoplasmic reticulum membrane as a dephosphorylated form by the Nem1-Spo7 protein phosphatase complex. The phosphorylation of Pah1 by protein kinases, which include casein kinases I and II, Pho85-Pho80, Cdc28-cyclin B, and protein kinases A and C, controls its cellular location, catalytic activity, and susceptibility to proteasomal degradation. Nem1 (catalytic subunit) and Spo7 (regulatory subunit), which form a protein phosphatase complex catalyzing the dephosphorylation of Pah1 for its activation, are phosphorylated by protein kinases A and C. In this review, we discuss the functions and interrelationships of the protein kinases in the control of the Nem1-Spo7/Pah1 phosphatase cascade and lipid synthesis.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"84 ","pages":"Article 100889"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9378635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CARD11 signaling in regulatory T cell development and function","authors":"Nicole M. Carter,&nbsp;Joel L. Pomerantz","doi":"10.1016/j.jbior.2022.100890","DOIUrl":"10.1016/j.jbior.2022.100890","url":null,"abstract":"<div><p>Regulatory T cells (Tregs) are a critical subset of CD4 T cells that modulate the immune response to prevent autoimmunity and chronic inflammation. CARD11, a signaling hub and scaffold protein that links antigen receptor engagement to activation of NF-κB and other downstream signaling pathways, is essential for the development and function of thymic Tregs. Mouse models with deficiencies in CARD11 and CARD11-associated signaling components generally have Treg defects, but some mouse models develop overt autoimmunity and inflammatory disease whereas others do not. Inhibition of CARD11 signaling in Tregs within the tumor microenvironment can potentially promote anti-tumor immunity. In this review, we summarize evidence for the involvement of CARD11 signaling in Treg development and function and discuss key unanswered questions and future research opportunities.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"84 ","pages":"Article 100890"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9732571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}