Physiology最新文献

There is a fundamental need to consider plant physiology in relation to human health as it encompasses a number of often overlooked issues, from plant based medicines, to nutrition. The goal here is to provide a historical narrative of plant physiological and biological responses to rising CO₂ and climate variability while addressing current controversies. Finally a "next steps" overview of current links between plants and human health, and crucial, unmet research needs.

Endocytosis in non-neuronal cells requires gradual recruitment of proteins to endocytic sites for inducing membrane curvature and forming contractile scaffolds around the neck of endocytic pits. This recruitment process is thought to be rate-limiting, requiring tens of seconds. In contrast, a form of endocytosis in neurons called ultrafast endocytosis is much faster, requiring only 100 milliseconds for endocytosis of synaptic vesicle proteins. In this review, we compare the mechanisms of protein recruitment during clathrin-mediated endocytosis in non-neuronal cells and ultrafast endocytosis in neurons and discuss how endocytosis can complete within 100 milliseconds. We then discuss the potential clinical relevance of this endocytic pathway.

In recent years, the introduction of mRNA vaccines for SARS-CoV2 and RSV has highlighted the success of the mRNA technology platform. Designing mRNA sequences involves multiple components and requires balancing several parameters, including enhancing transcriptional efficiency, boosting antigenicity, and minimizing immunogenicity. Moreover, changes in the composition and properties of delivery vehicles can also affect vaccine performance. Traditional methods of experimentally testing these conditions are time-consuming, labor-intensive and costly, necessitating advanced optimization strategies. Recently, the rapid development of computational tools has significantly accelerated the optimization process for mRNA vaccines. In this review, we systematically examine computation-aided approaches for optimizing mRNA components, including coding and non-coding regions, and for improving the efficiency of lipid nanoparticle (LNP) delivery systems by focusing on their composition, ratios, and characterization. The use of computational tools can significantly accelerate mRNA vaccine development, enabling rapid responses to emerging infectious diseases and supporting the development of precise, personalized therapies. These approaches may guide the future direction of mRNA vaccine development. Our review aims to provide integrated constructive support for computer-aided mRNA vaccine design.

Early-life undernutrition is known to be a potentially important risk factor for the development of diabetes mellitus in adult life. Additionally, some literature suggests that undernutrition during later life or adulthood may lead to metabolic consequences, including diabetes, despite an individual's normal nutritional status earlier in life. Notably, individuals with diabetes and undernutrition show some unique features that do not fit the usual phenotype of type 2 diabetes mellitus - such as a low body mass index of <18.5 kg/m², resistance to ketosis, and low serum C-peptide levels. Many global descriptions of this unique phenotype have led to a controversy that 'Undernutrition-associated diabetes mellitus' is a distinct form of diabetes, deserving a separate diabetes category in the WHO classification of diabetes. However, a few investigators argue that undernutrition-associated diabetes mellitus is one of the variants of the classical forms of diabetes. The second controversy is whether adult undernutrition is independently associated with metabolic abnormalities. Its pathophysiology has been difficult to determine, given confounding factors such as infections that can complicate the direct effects of malnutrition. Studies have shown that insulin deficiency due to pancreatic β cell impairment is likely to contribute to the development of undernutrition-associated diabetes. To examine these controversies, further research is warranted to understand the role of undernutrition in the pathogenesis of undernutrition-associated diabetes. This review aims to shed more light on these controversies, focusing on whether diabetes in malnourished individuals represents a distinct diabetes category and the association between malnutrition and diabetes in adults.

Brown adipose tissue (BAT) thermogenesis results from the uncoupling of mitochondrial inner membrane proton gradient mediated by uncoupling protein 1 (UCP-1), which is activated by lipolysis-derived fatty acids. Norepinephrine (NE) secreted by sympathetic innervation not only activates BAT lipolysis and UCP-1 but, uniquely in brown adipocytes, promotes "futile" metabolic cycles and enhances BAT thermogenic capacity by increasing UCP-1 content, mitochondrial biogenesis, and brown adipocyte hyperplasia. NE exerts these actions by triggering signaling in the canonical G protein-coupled β-adrenergic receptors, cAMP, and protein kinase A (PKA) pathway, which in brown adipocytes is under a complex and intricate cross talk with important growth-promoting signaling pathways such as those of mechanistic target of rapamycin (mTOR) complexes 1 (mTORC1) and 2 (mTORC2). This article reviews evidence suggesting that mTOR complexes are modulated by and participate in the thermogenic, metabolic, and growth-promoting effects elicited by NE in BAT and discusses current gaps and future directions in this field of research.

Quiescence is operationally defined as a reversible proliferation arrest. This cellular state is central to both organism development and homeostasis, and its dysregulation causes many pathologies. The quiescent state encompasses very diverse cellular situations depending on the cell type and its environment. Further, quiescent cell properties evolve with time, a process that is thought to be the origin of aging in multicellular organisms. Microtubules are found in all eukaryotes and are essential for cell proliferation as they support chromosome segregation and intracellular trafficking. Upon proliferation cessation and quiescence establishment, the microtubule cytoskeleton was shown to undergo significant remodeling. The purpose of this review is to examine the literature in search of evidence to determine whether the observed microtubule reorganizations are merely a consequence of quiescence establishment or if they somehow participate in this cell fate decision.

The small ubiquitin-like modifier (SUMO) protein pathway governs a panoply of vital biological processes including cell death, proliferation, differentiation, metabolism, and signal transduction by diversifying the functions, half-lives, and partnerships of target proteins in situ. More recently, SUMOylation has emerged as a key regulator of ion homeostasis and excitability across multiple tissues due to the regulation of a plethora of ion channels expressed in a range of tissue subtypes. Altogether, the balance of SUMOylation states among relevant ion channels can result in graded biophysical effects that tune excitability and contribute to a range of disease states including cardiac arrhythmia, epilepsy, pain transmission, and inflammation. Here, we consolidate these concepts by focusing on the role of ion channel SUMOylation in the central nervous system, peripheral nervous system, and cardiovascular system. In addition, we review what is known about the enigmatic factors that regulate the SUMO pathway and consider the emerging role of small molecule SUMO modulators as potential therapeutics in a range of diseases.

Olfactory deficits are increasingly recognized in a variety of neurological, neurodevelopmental, psychiatric, and viral diseases. While the pathology underlying olfactory loss is likely to differ across diseases, one shared feature may be an immune response mediated by microglia. Microglia orchestrate the brain's response to environmental insults and maintain neurodevelopmental homeostasis. Here, we explore the potential involvement of microglia in olfactory development and loss in disease. The effects of microglia-mediated immune response during development may be of special relevance to the olfactory system, which is unique in both its vulnerability to environmental insults as well as its extended period of neurogenesis and neuronal migration.

Multiple insect lineages have successfully reinvaded the aquatic environment, evolving to complete either part or all of their life cycle submerged in water. Although these insects vary in their reliance on atmospheric oxygen, with many having the ability to extract dissolved oxygen directly from the water, all retain an internal air-filled respiratory system, their tracheal system, due to their terrestrial origins. However, carrying air within their tracheal system, and even augmenting this volume with additional air bubbles carried on their body, dramatically increases their buoyancy, which can make it challenging to remain submerged. But by manipulating this air volume a few aquatic insects can deliberately alter or regulate their position in the water column. Unlike cephalopods and teleost fish that control the volume of gas within their hydrostatic organs by either using osmosis to pull liquid from a rigid chamber or secreting oxygen at high pressure to inflate a flexible chamber, insects have evolved hydrostatic control mechanisms that rely either on the temporary stabilization of a compressible air bubble volume with O₂ unloaded from hemoglobin or on the mechanical expansion and contraction of a gas-filled volume with rigid, gas-permeable walls. The ability to increase their buoyancy while submerged separates aquatic insects from the buoyancy compensation achieved by other air-breathing aquatic animals that also use air within their respiratory systems to offset their submerged weight. The mechanisms they have evolved to achieve this are unique and provide new insights into the function and evolution of mechanochemical systems.