Academia biologyPub Date : 2026-01-01Epub Date: 2026-03-03DOI: 10.20935/acadbiol8131
Silvia Corvera, Michael P Czech
{"title":"Energy's long game: thermogenic adipocytes and the metabolic diseases of modern life.","authors":"Silvia Corvera, Michael P Czech","doi":"10.20935/acadbiol8131","DOIUrl":"10.20935/acadbiol8131","url":null,"abstract":"<p><p>The ability to generate, store, and mobilize energy is fundamental to life, and disruptions in these processes underlie metabolic disease. This review examines how these mechanisms evolved to rely profoundly on lipids, a large family of molecules that serve an unusually wide range of biological functions. From early evolutionary times, lipids have enabled chemiosmotic energy transduction, organized the endomembrane systems that synthesize and package neutral lipids, served as concentrated reservoirs of metabolic energy, and functioned as signaling molecules that coordinate cellular and systemic physiology. Adipocytes are specialized cells that can accumulate large amounts of lipid within specialized lipid droplet organelles. Over evolutionary time, mammals developed distinct adipocyte subtypes with tailored physiological roles. White adipocytes, characterized by a single large unilocular lipid droplet, coordinate energy storage and release in response to systemic cues. In contrast, the role of brown and beige adipocytes is to protect the organism from cold exposure by generating heat as a primary output of UCP1-mediated mitochondrial uncoupling. Crucially, this thermogenic process requires extensive systemic coordination: sympathetic neural input triggers lipolysis, vascular networks deliver fuel from multiple adipose depots, and hormonal signals integrate metabolic demand across organs. These requirements position thermogenic adipocytes as metabolic integration \"nodes\" that orchestrate whole-body fuel allocation and energy homeostasis. The presence of functional thermogenic adipocytes is strongly associated with improved cardiometabolic health, protecting against obesity, type 2 diabetes, and cardiovascular disease. Understanding how these specialized cells sense and respond to systemic signals offers a powerful entry point for developing strategies to counteract metabolic disease.</p>","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890168","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}
Subash Sapkota, Rami Shrestha, Sushma Katakam, Sagor C Roy, Karen P Briski
{"title":"VMN growth hormone-releasing hormone receptor regulation of counterregulatory transmission.","authors":"Subash Sapkota, Rami Shrestha, Sushma Katakam, Sagor C Roy, Karen P Briski","doi":"10.20935/acadbiol7623","DOIUrl":"10.20935/acadbiol7623","url":null,"abstract":"<p><p>Ventromedial hypothalamic nucleus (VMN) growth hormone-releasing hormone (Ghrh) neurotransmission governs counterregulatory hormone release. Recent studies document Ghrh control of hypoglycemia-sensitive counterregulatory neurotransmitter expression in dorsomedial VMN (VMNdm) Ghrh/steroidogenic factor-1 (SF-1) neurons. In this study, Ghrh receptor (Ghrh-R) gene silencing was implemented in vivo to determine if VMN Ghrh-R shapes counterregulation. Intra-VMN Ghrh-R siRNA augmented corticosterone secretion in vehicle or insulin-injected male rats, but this hormone was correspondingly refractory or inhibited in eu- versus hypoglycemic females. In each sex, gene knockdown up- or down-regulated baseline glucagon and growth hormone (GH) release, but hypoglycemia reversed the direction of Ghrh-R control of each hormone. Single-cell laser catapult-microdissected VMNdm Ghrh/SF-1 neuron multiplex qPCR analysis revealed contrary VMN Ghrh-R gene-silencing effects on eu- versus hypoglycemic SF-1 mRNA levels. In both sexes, Ghrh-R siRNA up-regulated mRNAs encoding counterregulation-repressive (γ-aminobutyric acid) or -enhancing (nitric oxide) transmitter protein markers, unrelated to plasma glycemic profiles. Ghrh-R regulation of Ghrh gene transcription was absent (euglycemic) or stimulatory (hypoglycemic) in females, and receptor control of glutaminase mRNA, a marker for the counterregulatory-augmenting neurochemical glutamate, was lost in hypoglycemic males. Ghrh-R gene silencing caused uniform up-regulation of 5'-AMP-activated protein kinase alpha-2 (AMPKα2) mRNA in each sex, independent of glucose status, but caused dissimilar changes in AMPKα1 transcription in eu- versus hypoglycemic females. The outcomes provide novel evidence that VMN Ghrh-R signaling imposes glucose-dependent control of counterregulatory hormone secretion and distinctive VMNdm neuron counterregulatory transmitter marker gene profiles. Data infer that this metabolic control may involve SF-1 (both sexes)- and AMPKα1 (female)-dependent mechanisms.</p>","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677118","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}
Academia biologyPub Date : 2025-01-01Epub Date: 2025-04-11DOI: 10.20935/acadbiol7628
Gary S Stein
{"title":"Reflections and perspectives on epigenetically mediated biological control: compromises in cancer and skeletal pathology.","authors":"Gary S Stein","doi":"10.20935/acadbiol7628","DOIUrl":"10.20935/acadbiol7628","url":null,"abstract":"<p><p>Establishing DNA as the genetic material, deciphering the genetic code and defining the double helical structure of the genome provided a foundation for pursuing a mechanistic understanding of gene expression that is operative for biological control and pathology. Equally important are a series of discoveries that have established epigenetic mechanisms, defined as the control of gene expression by non-DNA-encoded regulation, mediated by an evolving histone code that supports chromatin states, as complementary and obligatory determinants for biological activity. Evidence is accruing for pivotal contributions by epigenetic parameters of control to gene expression that is required for development and differentiation as well as for transient and sustained responsiveness to physiological regulatory cues that support cell structure, function, cell survival, tissue repair and remodeling. Epigenetic control is emerging as a decisive contributor to the regulatory compliance for the highly integrative processes that balance phenotypic function and tumor suppression with aberrant gene expression that accompanies the onset and progression of disease, strikingly illustrated with tumorigenesis and skeletal disorders.</p>","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985427","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}
Academia biologyPub Date : 2025-01-01Epub Date: 2025-06-26DOI: 10.20935/acadbiol7766
Elisa S Rezaie, Noortje J Visser, Alexander Y Shin, Chantal M A M van der Horst, Marco J P F Ritt, Allen T Bishop
{"title":"Biomechanical characteristics of frozen bone allografts after gene therapy-induced revascularization.","authors":"Elisa S Rezaie, Noortje J Visser, Alexander Y Shin, Chantal M A M van der Horst, Marco J P F Ritt, Allen T Bishop","doi":"10.20935/acadbiol7766","DOIUrl":"10.20935/acadbiol7766","url":null,"abstract":"<p><p>Segmental bone loss reconstruction using frozen bone allografts has a great advantage over amputation. Unfortunately, frozen allografts are avascular, and their use often results in infection, non-union, or fracture. We have attempted to overcome these complications by revascularizing the bone using gene therapy. Segmental tibial bone transplants were performed in 16 Yucatan minipigs. An arteriovenous (AV) bundle was placed intramedullary inside the allografts, which were transfected with growth factors vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in 8 out of the 16 pigs. Survival time was set at 20 weeks. Bone remodeling and biomechanical properties were tested using histology, compression testing, bone mineralization, and gait analysis. In the growth factor group, five out of eight pigs developed cutaneous vascular tumors, causing excessive bleeding, which led to the exclusion of one pig. Bone remodeling was significantly more present in the VEGF group compared to the control group. This correlated with the amount of pressure the pig allowed on the operated leg for 10 weeks, which was also significantly more (<i>p</i> = 0.029) than the control. Both bone mineralization (<i>p</i> = 0.156) of the area inside the cortex and the amount of stress the allograft could endure before breaking (<i>p</i> = 0.078) seemed to be no different for the VEGF group compared to its healthy contralateral side, which was the control group. We have shown that growth factor-induced frozen allograft bone revascularization using an intramedullary AV bundle results in significantly more bone remodeling and better biomechanical bone properties. However, we encountered benign vascular cutaneous tumors in five out of eight pigs, making the clinical application of this technique impossible at this time.</p>","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144985489","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}
Academia biologyPub Date : 2025-01-01Epub Date: 2025-02-26DOI: 10.20935/acadbiol7544
Dan Stoicov, Carolina A Bonin, Andre J van Wijnen, Eric A Lewallen
{"title":"Seasonal patterns of mercury bioaccumulation in lobsters (<i>Homarus americanus</i>) from Maine.","authors":"Dan Stoicov, Carolina A Bonin, Andre J van Wijnen, Eric A Lewallen","doi":"10.20935/acadbiol7544","DOIUrl":"https://doi.org/10.20935/acadbiol7544","url":null,"abstract":"<p><p>Mercury (Hg) pollutes marine ecosystems and accumulates in benthic species. This ecological case study investigated the temporal accumulation of Hg in American lobster (<i>Homarus americanus; H. Milne Edwards, 1837</i>) from coastal Maine (Casco Bay, ME, USA). We analyzed total Hg levels in legal-sized lobsters (carapace length: 8.255-12.5 cm; n = 34) collected during the early (May-July 1) or late (July 15-October) recreational harvest seasons. Morphometric data show that body size correlates with body weight (R<sup>2</sup> = 0.76; p < 0.001), and average body sizes were similar in early and late seasons. The average chelipod size was ~7% larger in male lobsters (p < 0.02), reflecting sexual dimorphism. Hg levels in select tissues from boiled lobsters were analyzed using atomic absorption spectroscopy. Hg in ambient water was undetectable, indicating that Hg in tissues reflects bioaccumulation. Hg content correlated with the lengths (cm) and weights (g) of cephalothorax, carapace, chelipod, and hepatopancreas in both male and female lobsters. Total Hg levels in most tissues were within safe and acceptable limits for human consumption (<0.2 ppm). Compared to late-season lobsters, early-season lobsters had significantly higher Hg levels in tail (~55% increase; 0.130 ppm vs. 0.084 ppm; p < 0.05) and hepatopancreas tissues (~29% increase; 0.099 ppm vs. 0.077 ppm; p < 0.05), suggesting that seasonal factors influence Hg content (e.g., spring river runoff, lobster migration, inert biological cycles). Observed seasonal fluctuations in lobster Hg levels may inform future strategies for mitigating pollution in coastal marine ecosystems.</p>","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001741","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}
Academia biologyPub Date : 2025-01-01Epub Date: 2025-06-18DOI: 10.20935/acadbiol7750
Paul M Wassarman, Eveline S Litscher
{"title":"Acrosomal Matrix Proteins sp56 and AM67 and Gamete Adhesion in Mammals.","authors":"Paul M Wassarman, Eveline S Litscher","doi":"10.20935/acadbiol7750","DOIUrl":"10.20935/acadbiol7750","url":null,"abstract":"<p><p>Binding of free-swimming sperm to unfertilized eggs is an early step in the complex process of fertilization in mammals. Sperm bind by their head to the relatively thick, fibrillar extracellular matrix (ECM) or <i>zona pellucida</i> (ZP) that completely surrounds the plasma membrane of unfertilized eggs. Bound sperm penetrate the ZP, reach the space between the ZP and plasma membrane (perivitelline space), and a single sperm fuses with the egg's plasma membrane to produce a fertilized egg or zygote. In mice (<i>Mus musculus</i>), capacitated, acrosome-intact sperm recognize and bind to ZP3, one of three glycosylated proteins (ZP1-3) that constitute the unfertilized egg's ZP. Sperm protein-56 (sp56) or ZP3-receptor (ZP3R) was identified as a binding partner for ZP3 by photoaffinity crosslinking with <sup>125</sup>I-Denny-Jaffe reagent covalently linked to purified ZP3. sp56 is transiently associated with the surface of sperm heads following capacitation of sperm. AM67 is a guinea pig protein found in sperm that is orthologous with sp56 from mouse and both proteins are components of the sperm's acrosomal matrix. sp56 and AM67 are members of the C3/C4 superfamily of protein receptors (complement 4B-binding protein <i>α</i>) and each consists of several Sushi domains or short consensus repeats (SCR). sp56 is present during spermiogenesis in meiotic, late pachytene spermatocytes, haploid spermatids, and mature sperm, but not in other cell types. Purified native sp56 and recombinant sp56 bind to the ZP of unfertilized eggs and inhibit fertilization <i>in vitro</i>. On the other hand, targeted deletion of the gene encoding sp56 in males apparently has no effect on sperm binding to unfertilized eggs or on male fertility. The latter findings suggest that mouse sp56 may not be <i>essential</i> for fertilization <i>in vivo</i> or <i>in vitro</i>, perhaps as a consequence of functional redundancy. These and other aspects of sp56 and AM67 are reviewed here.</p>","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623540","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}
Surekha, Asha Rani Sheoran, Nita Lakra, Prof. (Dr.) Baljeet Singh Saharan, Annu Luhach, Neelam Kumari Mandal, Chandra Shekhar Seth, Deepansh Sharma, A. Santal, P. K. Sadh, Vishnu D. Rajput, J. S. Duhan
{"title":"Enduring drought: effects and strategies for Brassica crop resilience","authors":"Surekha, Asha Rani Sheoran, Nita Lakra, Prof. (Dr.) Baljeet Singh Saharan, Annu Luhach, Neelam Kumari Mandal, Chandra Shekhar Seth, Deepansh Sharma, A. Santal, P. K. Sadh, Vishnu D. Rajput, J. S. Duhan","doi":"10.20935/acadbiol6265","DOIUrl":"https://doi.org/10.20935/acadbiol6265","url":null,"abstract":"","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"103 30","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141821695","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":"The crucial role of 5hmC in neuroprotection and repair after cerebrovascular injury","authors":"Y. Tsenkina","doi":"10.20935/acadbiol7285","DOIUrl":"https://doi.org/10.20935/acadbiol7285","url":null,"abstract":"","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":" 1278","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141822959","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}
Academia biologyPub Date : 2024-01-01Epub Date: 2024-05-27DOI: 10.20935/AcadBiol6245
Andre J van Wijnen, Eric A Lewallen
{"title":"Natural selection and evolution: evolving concepts.","authors":"Andre J van Wijnen, Eric A Lewallen","doi":"10.20935/AcadBiol6245","DOIUrl":"10.20935/AcadBiol6245","url":null,"abstract":"<p><p>Many recent studies in evolutionary biology have expanded and refined definitions of biological evolution and natural selection. Current evolutionary models incorporate different adaptive and non-adaptive processes based on molecular genetic changes and how DNA is modified over time in unicellular species, or in germline versus somatic cells in metazoan species. Cogent arguments can be raised for the view that natural selection should be considered a biological law, consistent with quantitative mathematical equations that describe the fitness of individuals, as well as variations within and among populations. Evolution is an overarching framework that incorporates the laws of natural selection and clarifies why phenotypic variation can increase in prevalence and result in species adaptations. The conceptual framework for biological evolution incorporates many cohesive principles that collectively have a predictive value. This framework will continue to evolve with improvements in high-resolution technologies that enable us to examine both adaptive and non-adaptive changes that drive biological phenotypes.</p>","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11175172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319491","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}
Academia biologyPub Date : 2024-01-01Epub Date: 2024-11-27DOI: 10.20935/acadbiol7428
Ravindra Kumar, Rajrani Ruhel, Andre J van Wijnen
{"title":"Unlocking biological complexity: the role of machine learning in integrative multi-omics.","authors":"Ravindra Kumar, Rajrani Ruhel, Andre J van Wijnen","doi":"10.20935/acadbiol7428","DOIUrl":"https://doi.org/10.20935/acadbiol7428","url":null,"abstract":"<p><p>The increasing complexity of biological systems demands advanced analytical approaches to decode the underlying mechanisms of health and disease. Integrative multi-omics approaches use multi-layered datasets such as genomic, transcriptomic, proteomic, and metabolomic data to understand biological processes much more comprehensively compared to the single-omics analysis and to provide a comprehensive view of cellular and molecular processes. However, these integrative approaches have their own computational and analytical challenges due to the large volume and nature of multi-omics data. Machine learning has emerged as a powerful tool to help and resolve these challenges. It offers sophisticated algorithms that can identify and discover hidden patterns and provide insights into complex biological networks. By integrating machine learning in multi-omics, we can enhance our understanding of drug discovery, disease, pathway, and network analysis. Machine learning and ensemble methods allow researchers to model nonlinear relationships and manage high-dimensional data, improving the precision of predictions. This approach paves the way for personalized medicine by identifying unique molecular signatures for individual patients, which can provide valuable insights into treatment planning and support more effective treatment. As machine learning continues to evolve, its role in multi-omics analysis will be pivotal in advancing our ability to interpret biological complexity and translate findings into clinical applications.</p>","PeriodicalId":519944,"journal":{"name":"Academia biology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019619","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}