Notes

Higher Intakes of Bioavailable Phosphate May Advertise Wide spread Oxidative Stress as well as General Calcification by Enhancing Mitochondrial Tissue layer Potential-Is Great Magnesium Standing a great Remedy?
Container geometries and heat transfer rates should be designed to match stresses related to protein integrity for equivalent mass fractions between both scales, which can be achieved with the assistance of CFD models. Innate regeneration following digit tip amputation is one of the few examples of epimorphic regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses, the digit tip blastema has been defined as a population of heterogeneous, lineage-restricted progenitor cells. These previous studies, however, do not comprehensively evaluate blastema heterogeneity or address lineage restriction of closely related cell types. In this report, we present single-cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and unamputated control digit tips and generate an atlas of the cell types participating in digit tip regeneration. We computationally define differentiation trajectories of vascular, monocytic, and fibroblastic lineages over regeneration, and while our data confirm broad lineage restriction of progenitors, our analysis reveals 67 genes enriched in blastema fibroblasts including a novel regeneration-specific gene, Mest. Most adult neurons and glia originate from radial glial progenitors (RGs), a type of stem cell typically extending from the apical to the basal side of the developing cortex. Precise regulation of the choice between RG self-renewal and differentiation is critical for normal development, but the mechanisms underlying this transition remain elusive. We show that the non-canonical tubulin Tuba8, transiently expressed in cortical progenitors, drives differentiation of RGs into apical intermediate progenitors, a more restricted progenitor type lacking attachment to the basal lamina. This effect depends on the unique C-terminal sequence of Tuba8 that antagonizes tubulin tyrosination and Δ2 cleavage, two post-translational modifications (PTMs) essential for RG fiber maintenance and the switch between direct and indirect neurogenesis and ultimately distinct neuronal lineage outcomes. Our work uncovers an instructive role of a developmentally regulated tubulin isotype in progenitor differentiation and provides new insights into biological functions of the cellular tubulin PTM "code." High levels of cancer aneuploidy are frequently associated with poor prognosis. To examine the relationship between aneuploidy and cancer progression, we analyzed a series of congenic cell lines that harbor single extra chromosomes. We found that across 13 different trisomic cell lines, 12 trisomies suppressed invasiveness or were largely neutral, while a single trisomy increased metastatic behavior by triggering a partial epithelial-mesenchymal transition. In contrast, we discovered that chromosomal instability activates cGAS/STING signaling but strongly suppresses invasiveness. By analyzing patient copy-number data, we demonstrate that specific aneuploidies are associated with distinct outcomes, and the acquisition of certain aneuploidies is in fact linked with a favorable prognosis. Thus, aneuploidy is not a uniform driver of malignancy, and different aneuploidies can uniquely influence tumor progression. At the same time, the gain of a single chromosome is capable of inducing a profound cell state transition, thereby linking genomic plasticity, phenotypic plasticity, and metastasis. Male fertility is driven by spermatogonial stem cells (SSCs) that self-renew while also giving rise to differentiating spermatogonia. Spermatogonial transitions are accompanied by a shift in gene expression, however, whether equivalent changes in metabolism occur remains unexplored. In this review, we mined recently published scRNA-seq databases from mouse and human testes to compare expression profiles of spermatogonial subsets, focusing on metabolism. Comparisons revealed a conserved upregulation of genes involved in mitochondrial function, biogenesis, and oxidative phosphorylation in differentiating spermatogonia, while gene expression in SSCs reflected a glycolytic cell. Here, we also discuss the relationship between metabolism and the external microenvironment within which spermatogonia reside. The capacity to undergo meiosis defines vertebrate germ cells, yet mechanisms driving initiation of this specialized process are largely undefined. In this issue of Developmental Cell,Ishiguro et al. (2020) identified the transcription factor MEIOSIN as a gatekeeper of meiotic initiation in both male and female germ cells. Phosphoinositides are signaling lipids that recruit effector proteins to membranes. Shin et al. show that a glucose-starvation-induced drop in cytosolic pH alters the protonation state of the phosphoinositide PI4P, resulting in dissociation of its effector Osh1 from the trans-Golgi network membrane and metabolic regulation of lipid and protein sorting. All plants must allocate limited resources to survival, growth, and reproduction. In natural species, allocation strategies reflect trade-offs between survivorship risk and subsequent fitness benefits and are therefore central to a species' ecology. Artificial selection on allocation has generated high-yielding crops that often invest the bare minimum in defense or longevity. Ecological, genetic, and evolutionary analyses of plant life history - particularly with respect to longevity and resource allocation along an axis from annual to perennial species - provides a framework to evaluate trade-offs in plant-environment interactions in natural and managed systems. Recent efforts to develop new model plant systems for research and to increase agricultural resilience and efficiency by developing herbaceous perennial crops motivates our critical assessment of traditional assumptions regarding differences between annual and perennial plant species. Here, we review our present understanding of the genetic basis of physiological, developmental, and anatomical differences in wild and crop species and reach two broad conclusions. FSEN1 ic50 First, that perenniality and annuality should be considered syndromes comprised of many interacting traits, and that elucidating the genetic basis of these traits is required to assess models of evolution and to develop successful breeding strategies. Modern phenomic and biotechnology tools will facilitate these enquiries. Second, many classic assumptions about the difference between the two syndromes are supported by limited evidence. Throughout this Review, we highlight key knowledge gaps in the proximate and ultimate mechanisms driving life history variation, and suggest empirical approaches to parameterize trade-offs and to make progress in this critical area of direct relevance to ecology and plant performance in a changing world. That Bacteria, Archaea and Eukarya (eukaryotes) represent three separate domains of Life, no one having evolved from within any other, has been taken as fact for three decades. link2 Recent work shows this to be untrue. Eukarya arose from well within Archaea and are specifically related to newly discovered archaeal species with eukaryote-like features. Despite a conserved requirement in mediating chromosome segregation, kinetochores display remarkable plasticity in their structure and composition. New work in holocentric insect species highlights the molecular rewiring that occurs when key structural components of the kinetochore are lost and centromere structure is changed. Many animals use gravity as a spatial reference to help navigate their surroundings, but how they do so is not well understood. A new study reveals that a representative of our closest invertebrate relatives, the tunicate Ciona, processes light and gravity cues through a simple neural circuit to decide when and how to swim. Cell extrusion is a highly coordinated process allowing the removal of an epithelial cell from the tissue layer without disrupting its integrity. Two new studies shed new light on the complexity of cell-cell coordination at play during cell extrusion. A general problem of sensory systems is how to simultaneously encode prevailing input as well as deviations from this baseline. A new study shows how the fly visual system has solved this by using parallel processing. Allometric relationships between organism size and shape are often described in developmental or evolutionary terms. A new study characterizes a collapsing birch tree mutant and provides a genetic entry point into the biomechanical control of tree allometry. Chromatin profiling of a liverwort genome reveals an epigenomic landscape where the major mark of developmental silencing in later-branching land plants and in animals also targets subsets of transposons in this early-branching land plant lineage. A comparative approach to neuroscience can greatly increase our understanding of how mechanisms map onto behaviour. A new study comparing two predatory insects demonstrates how neurons that are homologous can nonetheless mediate different computations and behaviour. Tessler et al. demonstrate that a 'soft' robot causes less stress to a jellyfish while handling compared to a traditional 'hard' robot. Evidence from live gray whale strandings suggests that their navigation may be disrupted by increased radio frequency noise generated by solar storms, suggesting the potential for magnetoreception in this species. Friess et al. discuss the results of conservation efforts for mangrove forests in recent years. DeSantis et al. respond to the concerns raised by Van Valkenburgh et al. on their original study. Van Valkenburgh et al. challenge the conclusions of a recent study by DeSantis et al. that claimed that sabertooth cats and dire wolves did not compete for similar prey. In this Primer, Moreci and Lechler follow the lifetime of an epidermal cell from its birth to its ultimate death, and detail how this journey is necessary for epidermal function. Whitewoods introduces the plant genus Utricularia. Melanins are a unique class of pigments found throughout the biosphere with a wide variety of functions, structures, and presentations. Cordero and Casadevall highlight the wide range of places melanins are found and the diverse functions they play in nature. Lissencephaly (LIS), denoting a "smooth brain," is characterized by the absence of normal cerebral convolutions with abnormalities of cortical thickness. Pathogenic variants in over 20 genes are associated with LIS. The majority of posterior predominant LIS is caused by pathogenic variants in LIS1 (also known as PAFAH1B1), although a significant fraction remains without a known genetic etiology. We now implicate CEP85L as an important cause of posterior predominant LIS, identifying 13 individuals with rare, heterozygous CEP85L variants, including 2 families with autosomal dominant inheritance. We show that CEP85L is a centrosome protein localizing to the pericentriolar material, and knockdown of Cep85l causes a neuronal migration defect in mice. LIS1 also localizes to the centrosome, suggesting that this organelle is key to the mechanism of posterior predominant LIS. link3 Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific effects on neuronal migration in the posterior cortex, reflecting de novo variants in CEP85L. We show that CEP85L is required cell autonomously in vivo and in vitro for migration, that it localizes to the maternal centriole, and that it forms a complex with many other proteins required for migration, including CDK5, LIS1, NDE1, KIF2A, and DYNC1H1. Loss of CEP85L disrupts CDK5 localization and activation, leading to centrosome disorganization and disrupted microtubule cytoskeleton organization. Together, our findings suggest that CEP85L highlights a complex that controls CDK5 activity to promote neuronal migration.
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