Vijayakumar Mavanji, Brianna Pomonis, Catherine M Kotz
{"title":"Orexin, serotonin, and energy balance.","authors":"Vijayakumar Mavanji, Brianna Pomonis, Catherine M Kotz","doi":"10.1002/wsbm.1536","DOIUrl":"https://doi.org/10.1002/wsbm.1536","url":null,"abstract":"<p><p>The lateral hypothalamus is critical for the control of ingestive behavior and spontaneous physical activity (SPA), as lesion or stimulation of this region alters these behaviors. Evidence points to lateral hypothalamic orexin neurons as modulators of feeding and SPA. These neurons affect a broad range of systems, and project to multiple brain regions such as the dorsal raphe nucleus, which contains serotoninergic neurons (DRN) important to energy homeostasis. Physical activity is comprised of intentional exercise and SPA. These are opposite ends of a continuum of physical activity intensity and structure. Non-goal-oriented behaviors, such as fidgeting, standing, and ambulating, constitute SPA in humans, and reflect a propensity for activity separate from intentional activity, such as high-intensity voluntary exercise. In animals, SPA is activity not influenced by rewards such as food or a running wheel. Spontaneous physical activity in humans and animals burns calories and could theoretically be manipulated pharmacologically to expend calories and protect against obesity. The DRN neurons receive orexin inputs, and project heavily onto cortical and subcortical areas involved in movement, feeding and energy expenditure (EE). This review discusses the function of hypothalamic orexin in energy-homeostasis, the interaction with DRN serotonin neurons, and the role of this orexin-serotonin axis in regulating food intake, SPA, and EE. In addition, we discuss possible brain areas involved in orexin-serotonin cross-talk; the role of serotonin receptors, transporters and uptake-inhibitors in the pathogenesis and treatment of obesity; animal models of obesity with impaired serotonin-function; single-nucleotide polymorphisms in the serotonin system and obesity; and future directions in the orexin-serotonin field. This article is categorized under: Metabolic Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 1","pages":"e1536"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Santiago Cerrizuela, Guillermo A Vega-Lopez, Karla Méndez-Maldonado, Iván Velasco, Manuel J Aybar
{"title":"The crucial role of model systems in understanding the complexity of cell signaling in human neurocristopathies.","authors":"Santiago Cerrizuela, Guillermo A Vega-Lopez, Karla Méndez-Maldonado, Iván Velasco, Manuel J Aybar","doi":"10.1002/wsbm.1537","DOIUrl":"https://doi.org/10.1002/wsbm.1537","url":null,"abstract":"<p><p>Animal models are useful to study the molecular, cellular, and morphogenetic mechanisms underlying normal and pathological development. Cell-based study models have emerged as an alternative approach to study many aspects of human embryonic development and disease. The neural crest (NC) is a transient, multipotent, and migratory embryonic cell population that generates a diverse group of cell types that arises during vertebrate development. The abnormal formation or development of the NC results in neurocristopathies (NCPs), which are characterized by a broad spectrum of functional and morphological alterations. The impaired molecular mechanisms that give rise to these multiphenotypic diseases are not entirely clear yet. This fact, added to the high incidence of these disorders in the newborn population, has led to the development of systematic approaches for their understanding. In this article, we have systematically reviewed the ways in which experimentation with different animal and cell model systems has improved our knowledge of NCPs, and how these advances might contribute to the development of better diagnostic and therapeutic tools for the treatment of these pathologies. This article is categorized under: Congenital Diseases > Genetics/Genomics/Epigenetics Congenital Diseases > Stem Cells and Development Congenital Diseases > Molecular and Cellular Physiology Neurological Diseases > Genetics/Genomics/Epigenetics.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 1","pages":"e1537"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nazanin Ebrahimi, Christopher Bradley, Peter Hunter
{"title":"An integrative multiscale view of early cardiac looping.","authors":"Nazanin Ebrahimi, Christopher Bradley, Peter Hunter","doi":"10.1002/wsbm.1535","DOIUrl":"https://doi.org/10.1002/wsbm.1535","url":null,"abstract":"<p><p>The heart is the first organ to form and function during the development of an embryo. Heart development consists of a series of events believed to be highly conserved in vertebrates. Development of heart begins with the formation of the cardiac fields followed by a linear heart tube formation. The straight heart tube then undergoes a ventral bending prior to further bending and helical torsion to form a looped heart. The looping phase is then followed by ballooning, septation, and valve formation giving rise to a four-chambered heart in avians and mammals. The looping phase plays a central role in heart development. Successful looping is essential for proper alignment of the future cardiac chambers and tracts. As aberrant looping results in various congenital heart diseases, the mechanisms of cardiac looping have been studied for several decades by various disciplines. Many groups have studied anatomy, biology, genetics, and mechanical processes during heart looping, and have proposed multiple mechanisms. Computational modeling approaches have been utilized to examine the proposed mechanisms of the looping process. Still, the exact underlying mechanism(s) controlling the looping phase remain poorly understood. Although further experimental measurements are obviously still required, the need for more integrative computational modeling approaches is also apparent in order to make sense of the vast amount of experimental data and the complexity of multiscale developmental systems. Indeed, there needs to be an iterative interaction between experimentation and modeling in order to properly find the gap in the existing data and to validate proposed hypotheses. This article is categorized under: Cardiovascular Diseases > Genetics/Genomics/Epigenetics Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 1","pages":"e1535"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Seven challenges in the multiscale modeling of multicellular tissues.","authors":"Alexander G Fletcher, James M Osborne","doi":"10.1002/wsbm.1527","DOIUrl":"10.1002/wsbm.1527","url":null,"abstract":"<p><p>The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviors, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short- and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regenerative medicine is to understand how relationships between scales produce emergent tissue-scale behaviors. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionized our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modeling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics, and signaling. Yet such models remain challenging: modeling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarize recent progress in multiscale modeling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation, and validation of such models. This article is categorized under: Reproductive System Diseases > Computational Models Metabolic Diseases > Computational Models Cancer > Computational Models.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 1","pages":"e1527"},"PeriodicalIF":4.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11478939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transferability of tigecycline resistance: Characterization of the expanding Tet(X) family.","authors":"Chao-Yue Cui, Qiwei Chen, Qian He, Chong Chen, Rong-Min Zhang, Youjun Feng, Jian Sun","doi":"10.1002/wsbm.1538","DOIUrl":"https://doi.org/10.1002/wsbm.1538","url":null,"abstract":"<p><p>Tetracycline and its derivative tigecycline are clinical options against Gram-negative bacterial infections. The emergence of mobile Tet(X) enzymes that destruct tetracycline-type antibiotics is posing a big challenge to antibacterial therapy and food/environmental securities. Here, we present an update on a growing number of Tet(X) variants. We describe structure and action of Tet(X) enzyme, and discuss the evolutional origin. In addition, potential Tet(X) inhibitors are given. This mini-review might benefit better understanding of Tet(X)-mediated tigecycline resistance. This article is categorized under: Infectious Diseases > Genetics/Genomics/Epigenetics Infectious Diseases > Environmental Factors Infectious Diseases > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 1","pages":"e1538"},"PeriodicalIF":3.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunohistochemical evidence for adult human neurogenesis in health and disease.","authors":"Natalie Gault, Francis G Szele","doi":"10.1002/wsbm.1526","DOIUrl":"https://doi.org/10.1002/wsbm.1526","url":null,"abstract":"<p><p>Postnatal and adult neurogenesis in the subventricular zone and subgranular zone of animals such as rodents and non-human primates has been observed with many different technical approaches. Since most techniques used in animals cannot be used in humans, the majority of human neurogenesis studies rely on postmortem immunohistochemistry. This technique is difficult in human tissue, due to poor and variable preservation of antigens and samples. Nevertheless, a survey of the literature reveals that most published studies provide evidence for childhood and adult neurogenesis in the human brain stem cell niches. There are some conflicting results even when assessing the same markers and when using the same antibodies. Focusing on immunohistochemical studies on post-mortem human sections, we discuss the relative robustness of the literature on adult neurogenesis. We also discuss the response of the subventricular and subgranular zones to human disease, showing that the two niches can respond differently and that the stage of disease impacts neurogenesis levels. Thus, we highlight strong evidence for adult human neurogenesis, discuss other work that did not find it, describe obstacles in analysis, and offer other approaches to evaluate the neurogenic potential of the subventricular and subgranular zones of Homo sapiens. This article is categorized under: Neurological Diseases > Stem Cells and Development Reproductive System Diseases > Stem Cells and Development.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"13 6","pages":"e1526"},"PeriodicalIF":3.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39586035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Computational anatomy and diffeomorphometry: A dynamical systems model of neuroanatomy in the soft condensed matter continuum.","authors":"","doi":"10.1002/wsbm.1524","DOIUrl":"https://doi.org/10.1002/wsbm.1524","url":null,"abstract":"","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"13 6","pages":"e1524"},"PeriodicalIF":3.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wsbm.1524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39586036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Morawska, Jhonatan A. Hernandez-Valdes, O. Kuipers
{"title":"Diversity of bet‐hedging strategies in microbial communities—Recent cases and insights","authors":"L. Morawska, Jhonatan A. Hernandez-Valdes, O. Kuipers","doi":"10.1002/wsbm.1544","DOIUrl":"https://doi.org/10.1002/wsbm.1544","url":null,"abstract":"Abstract Microbial communities are continuously exposed to unpredictable changes in their environment. To thrive in such dynamic habitats, microorganisms have developed the ability to readily switch phenotypes, resulting in a number of differently adapted subpopulations expressing various traits. In evolutionary biology, a particular case of phenotypic heterogeneity that evolved in an unpredictably changing environment has been defined as bet‐hedging. Bet‐hedging is a risk‐spreading strategy where isogenic populations stochastically (randomly) diversify their phenotypes, often resulting in maladapted individuals that suffer lower reproductive success. This fitness trade‐off in a specific environment may have a selective advantage upon the sudden environmental shift. Thus, a bet‐hedging strategy allows populations to persist in very dynamic habitats, but with a particular fitness cost. In recent years, numerous examples of phenotypic heterogeneity in different microorganisms have been observed, some suggesting bet‐hedging. Here, we highlight the latest reports concerning bet‐hedging phenomena in various microorganisms to show how versatile this strategy is within the microbial realms. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"14 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41891937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shangyu Gong, Yichi Zhang, Aiguo Tian, Wu-Min Deng
{"title":"Tumor models in various Drosophila tissues.","authors":"Shangyu Gong, Yichi Zhang, Aiguo Tian, Wu-Min Deng","doi":"10.1002/wsbm.1525","DOIUrl":"10.1002/wsbm.1525","url":null,"abstract":"<p><p>The development of cancer is a complex multistage process. Over the past few decades, the model organism Drosophila melanogaster has been crucial in identifying cancer-related genes and pathways and elucidating mechanisms underlying growth regulation in development. Investigations using Drosophila has yielded new insights into the molecular mechanisms involved in tumor initiation and progression. In this review, we describe various tumor models that have been developed in recent years using different Drosophila tissues, such as the imaginal tissue, the neural tissue, the gut, the ovary, and hematopoietic cells. We discuss underlying genetic alterations, cancer-like characteristics, as well as similarities and key differences among these models. We also discuss how disruptions in stem cell division and differentiation result in tumor formation in diverse tissues, and highlight new concepts developed using the fly model to understand context-dependent tumorigenesis. We further discuss the progress made in Drosophila to explore tumor-host interactions that involve the innate immune response to tumor growth and the cachexia wasting phenotype. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics Cancer > Stem Cells and Development Cancer > Molecular and Cellular Physiology.</p>","PeriodicalId":29896,"journal":{"name":"WIREs Mechanisms of Disease","volume":"13 6","pages":"e1525"},"PeriodicalIF":3.1,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/35/b1/WSBM-13-e1525.PMC8566734.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39586034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}