Advances in biological regulation最新文献_第10页

Flimsy Overlay 脆弱的叠加

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100951

引用次数: 0

Silencing effects of mutant RAS signalling on transcriptomes 突变体RAS信号对转录组的沉默作用

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100936

Christine Sers , Reinhold Schäfer

{"title":"Silencing effects of mutant RAS signalling on transcriptomes","authors":"Christine Sers , Reinhold Schäfer","doi":"10.1016/j.jbior.2022.100936","DOIUrl":"10.1016/j.jbior.2022.100936","url":null,"abstract":"<div><p>Mutated genes of the RAS family encoding small GTP-binding proteins drive numerous cancers, including pancreatic, colon and lung tumors. Besides the numerous effects of mutant RAS gene expression on aberrant proliferation, transformed phenotypes, metabolism, and therapy resistance, the most striking consequences of chronic RAS activation are changes of the genetic program. By performing systematic gene expression studies in cellular models that allow comparisons of pre-neoplastic with RAS-transformed cells, we and others have estimated that 7 percent or more of all transcripts are altered in conjunction with the expression of the oncogene. In this context, the number of up-regulated transcripts approximates that of down-regulated transcripts. While up-regulated transcription factors such as MYC, FOSL1, and HMGA2 have been identified and characterized as RAS-responsive drivers of the altered transcriptome, the suppressed factors have been less well studied as potential regulators of the genetic program and transformed phenotype in the breadth of their occurrence. We therefore have collected information on downregulated RAS-responsive factors and discuss their potential role as tumor suppressors that are likely to antagonize active cancer drivers. To better understand the active mechanisms that entail anti-RAS function and those that lead to loss of tumor suppressor activity, we focus on the tumor suppressor HREV107 (alias PLAAT3 [Phospholipase A and acyltransferase 3], PLA2G16 [Phospholipase A2, group XVI] and HRASLS3 [HRAS-like suppressor 3]). Inactivating HREV107 mutations in tumors are extremely rare, hence epigenetic causes modulated by the RAS pathway are likely to lead to down-regulation and loss of function.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"87 ","pages":"Article 100936"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9173956","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}

引用次数: 0

Novel aspects of intra-islet communication: Primary cilia and filopodia 胰岛内通讯的新方面:初级纤毛和丝状足

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100919

Noah Moruzzi, Barbara Leibiger, Christopher J. Barker, Ingo B. Leibiger, Per-Olof Berggren

{"title":"Novel aspects of intra-islet communication: Primary cilia and filopodia","authors":"Noah Moruzzi, Barbara Leibiger, Christopher J. Barker, Ingo B. Leibiger, Per-Olof Berggren","doi":"10.1016/j.jbior.2022.100919","DOIUrl":"10.1016/j.jbior.2022.100919","url":null,"abstract":"<div><p>Pancreatic islets are micro-organs composed of a mixture of endocrine and non-endocrine cells, where the former secrete hormones and peptides necessary for metabolic homeostasis. Through vasculature and innervation the cells within the islets are in communication with the rest of the body, while they interact with each other through juxtacrine, paracrine and autocrine signals, resulting in fine-tuned sensing and response to stimuli. In this context, cellular protrusion in islet cells, such as primary cilia and filopodia, have gained attention as potential signaling hubs. During the last decade, several pieces of evidence have shown how the primary cilium is required for islet vascularization, function and homeostasis. These findings have been possible thanks to the development of ciliary/basal body specific knockout models and technological advances in microscopy, which allow longitudinal monitoring of engrafted islets transplanted in the anterior chamber of the eye in living animals. Using this technique in combination with optogenetics, new potential paracrine interactions have been suggested. For example, reshaping and active movement of filopodia-like protrusions of δ-cells were visualized <em>in vivo</em>, suggesting a continuous cell remodeling to increase intercellular contacts. In this review, we discuss these recent discoveries regarding primary cilia and filopodia and their role in islet homeostasis and intercellular islet communication.</p></div>","PeriodicalId":7214,"journal":{"name":"Advances in biological regulation","volume":"87 ","pages":"Article 100919"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180901","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}

引用次数: 2

Sixty-third international symposium on biological regulation and enzyme activity in normal and neoplastic tissues 第六十三届正常和肿瘤组织的生物调控和酶活性国际研讨会

Advances in biological regulation Pub Date : 2023-01-01 DOI: 10.1016/j.jbior.2022.100949

引用次数: 0

Understanding the exceptional pre-vaccination Era East Asian COVID-19 outcomes 了解疫苗接种前东亚地区特殊的COVID-19结果

Advances in biological regulation Pub Date : 2022-12-01 DOI: 10.1016/j.jbior.2022.100916

Jay Bhattacharya , Phillip Magness , Martin Kulldorff

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引用次数: 1

A consensus of evidence: The role of SPI-M-O in the UK COVID-19 response 证据共识:SPI-M-O在英国COVID-19应对中的作用

Advances in biological regulation Pub Date : 2022-12-01 DOI: 10.1016/j.jbior.2022.100918

Graham F. Medley

引用次数: 8

Virus spread on a scale-free network reproduces the Gompertz growth observed in isolated COVID-19 outbreaks 病毒在无标度网络上的传播再现了在孤立的COVID-19爆发中观察到的冈珀茨生长

Advances in biological regulation Pub Date : 2022-12-01 DOI: 10.1016/j.jbior.2022.100915

Francesco Zonta , Michael Levitt

{"title":"Virus spread on a scale-free network reproduces the Gompertz growth observed in isolated COVID-19 outbreaks","authors":"Francesco Zonta , 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}

引用次数: 3

COVID-19 models and expectations – Learning from the pandemic COVID-19模型和期望-从大流行中吸取教训

Advances in biological regulation Pub Date : 2022-12-01 DOI: 10.1016/j.jbior.2022.100922

John P.A. Ioannidis , Stephen H. Powis

引用次数: 0

Why COVID-19 modelling of progression and prevention fails to translate to the real-world 为什么COVID-19的进展和预防模型无法应用于现实世界

Advances in biological regulation Pub Date : 2022-12-01 DOI: 10.1016/j.jbior.2022.100914

Carl J. Heneghan, Tom Jefferson

{"title":"Why COVID-19 modelling of progression and prevention fails to translate to the real-world","authors":"Carl J. Heneghan, 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: R<sub>0</sub> 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}

引用次数: 2

Establishing COVID-19 trials at scale and pace: Experience from the RECOVERY trial 以规模和速度建立COVID-19试验:来自康复试验的经验

Advances in biological regulation Pub Date : 2022-12-01 DOI: 10.1016/j.jbior.2022.100901

Leon Peto , Peter Horby , Martin Landray

{"title":"Establishing COVID-19 trials at scale and pace: Experience from the RECOVERY trial","authors":"Leon Peto , Peter Horby , 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}

引用次数: 9