Transduction peptides: from technology to physiology

During the past fifteen years, a variety of peptides have been characterized for their ability to translocate into live cells. Most are efficient vectors that can internalize hydrophilic cargoes, and so provide a valuable biological (and potentially therapeutic) tool for targeting proteins into cells. Furthermore, translocation of cell-permeable peptides across the plasma membrane and their subsequent access to the cytosol, even when fused to large hydrophilic proteins, is challenging the perception of the plasma membrane as an impermeable barrier.     

Digestive lipases: from three-dimensional structure to physiology

Human gastric lipase (HGL) is a lipolytic enzyme that is secreted by the chief cells located in the fundic part of the stomach. HGL plays an important role in lipid digestion, since it promotes the subsequent hydrolytic action of pancreatic lipase in duodenal lumen. Physiological studies have shown that HGL is able of acting not only in the highly acid stomach environment but also in the duodenum in synergy with human pancreatic lipase (HPL). Recombinant HGL (r-HGL) was expressed in the baculovirus/insect cell system in the form of an active protein with a molecular mass of 45 kDa. The specific activities of r-HGL were found to be similar to that of the native enzyme when tested on various triacylglycerol (TG) substrates. The 3-D structure of r-HGL was the first solved within the mammalian acid lipase family. This globular enzyme (379 residues) shows a new feature, different from the other known lipases structures, which consists of a core domain having the alpha/beta hydrolase fold and a cap domain including a putative 'lid' of 30 residues covering the active site of the lipase (closed conformation). HPL is the major lipolytic enzyme involved in the digestion of dietary TG. HPL is a 50 kDa glycoprotein which is directly secreted as an active enzyme. HPL was the first mammalian lipase to be solved structurally, and it revealed the presence of two structural domains: a large N-terminal domain (residues 1-336) and a smaller C-terminal domain (residues 337-449). The large N-terminal domain belongs to the alpha/beta hydrolase fold and contains the active site. A surface loop called the lid domain (C237-C261) covers the active site in the closed conformation of the lipase. The 3-D structure of the lipase-procolipase complex illustrates how the procolipase might anchor the lipase at the interface in the presence of bile salts: procolipase binds to the C-terminal domain of HPL and exposes the hydrophobic tips of its fingers at the opposite site of its lipase-binding domain. These hydrophobic tips help to bring N-terminal domain into close conformation with the interface where the opening of the lid domain probably occurs. As a result of all these conformational changes, the open lid and the extremities of the procolipase form an impressive continuous hydrophobic plateau, extending over more than 50 A. This surface might able to interact strongly with a lipid-water interface. The biochemical, histochemical and clinical studies as well as the 3-D structures obtained will be a great help for a better understanding of the structure-function relationships of digestive lipases.     

Anhydrobiosis in bacteria: from physiology to applications

Anhydrobiosis is a phenomenon related to the partial or total desiccation of living organisms, keeping their vital functions after rehydration. The desiccated state in prokaryotes has been widely studied, mainly due to the broad spectrum of the anhydrobiosis applications. In this review, we present the basic theoretical concepts related to anhydrobiosis, focusing on bacterial species. An update about desiccation tolerance in bacteria is given; and the general mechanisms of desiccation tolerance and desiccation damage are described. In addition, we show how the study of anhydrobiosis in prokaryotes has established the theoretical and practical basis for the development of the drying technologies. With regard to the desiccation tolerance in bacteria, although many mechanisms remain undiscovered at the molecular level, important research about the physiology of the anhydrobiotic state and its applications has been performed, and here we provide the most recent information about this subject. On the other hand, the most widely used drying technologies and their particular applications in several fields are described (e.g. medicine, agriculture and food industry). Finally, topics on the stability of desiccated bacterial cells are treated, concluding with the necessity of focusing the research on the mathematical modelling of the desiccated state in bacteria.     

NMR and microbiology: from physiology to metabolomics

Recent advances in the application of NMR to microbiology are reviewed. Instrumental and methodological developments are described. The advantages and the constraints of NMR are illustrated with examples from the literature. Recent work from the authors' laboratories, taken as representative of current research in the field, is described in more detail.     

Brown adipose tissue: from thermal physiology to bioenergetics

Brown adipose tissue is an organ in mammals specialized for the generation of heat. The tissue plays an important role in thermoregulatory heat production (nonshivering thermogenesis), and in nutritional energetics (through the process of diet-induced thermogenesis). Much of the current interest in brown adipose tissue has been catalysed by the postulate (1970’s) that a reduced capacity for thermogenesis underlies the development of obesity. Heat is generated in brown fat by a controlled uncoupling of oxidative phosphorylation, a process regulated by a tissue-specific mitochondrial uncoupling protein,M _r 32–33,000. The immunological identification of uncoupling protein is now used as a biochemical criterion for distinguishing brown fat from white adipose tissue. The gene coding for uncoupling protein has been cloned in several species, and a number of factors regulating the expression of the gene, as well as the amount and activity of the protein itself, have been documented. In addition to its direct role in heat production, brown adipose tissue has some notable general metabolic properties, such as in the conversion of thyroxine to triiodothyronine. An overview of the biology of brown adipose tissue is presented in this article, with an emphasis on some recent developments.     

Digestive physiology: a view from molecules to ecosystem

Digestive physiology links physiology to applications valued by society, such as understanding ecology and ecological toxicology and managing and conserving species. Here I illustrate this applied and integrative perspective with several avian case studies. The match between digestive features and diet provides evidence of tradeoffs that preclude doing well on all possible substrates with a single digestive design, and this influences ecological niche partitioning. But some birds, such as wild house sparrow (Passer domesticus) nestlings, are digestively very flexible. Their intestinal maltase activity and mRNA for intestinal maltase glucoamylase specifically and reversibly change when they switch among foods with different starch content. Houses sparrows and many other birds absorb hydrolyzed water-soluble monomers, such as glucose, mainly passively via tight junctions between enterocytes (i.e., paracellular absorption). Such species might be good models for studying this process, which is important biomedically for absorption of drugs. High paracellular absorption may enhance absorption of low molecular weight, natural water-soluble toxins. Also, reliance of American robins (Turdus migratorius) on passive absorption makes them less sensitive to types of plant toxins that inhibit mediated glucose absorption, such as phlorizin or the flavanoid isoquercetrin. Determining absorption of environmental contaminants is another important ecological application. Common loon (Gavia immer) chicks absorbed 83% of methyl mercury in fish meals, eliminate the mercury slowly, and consequently are predicted in the wild to bioaccumulate mercury to higher concentrations than in their foods. The quantitative details can be used to set regulatory levels for mercury that will protect wildlife.     

Synaptic physiology: plenty of models to choose from

Do graded potential synapses work the same way as action potential synapses? Recent work emphasizes the differences and suggests that graded potential synapses are not all the same either.     

Animal reproduction and physiology: from basis to application

<正>Animal reproduction and physiology is one of the traditional subjects in biology, and also one of the most rapidly developing fields because it is related to human food     

Methylotrophy in a lake: from metagenomics to single-organism physiology

This review provides a brief summary of ongoing studies in Lake Washington (Seattle, WA) directed at an understanding of the content and activities of microbial communities involved in methylotrophy. One of the findings from culture-independent approaches, including functional metagenomics, is the prominent presence of Methylotenera species in the site and their inferred activity in C(1) metabolism, highlighting the local environmental importance of this group. Comparative analyses of individual genomes of Methylophilaceae from Lake Washington provide insights into their genomic divergence and suggest significant metabolic flexibility.     

二氧化硫生物学研究进展:从毒理学到生理学

本文以作者20余年的系列研究为基础,对二氧化硫(SO2)生物学研究进展进行了综述.首先,总结近年来SO2的毒理学作用及其机制的研究;其次,评述SO2作为一种新型气体信号分子的生理学作用及SO2供体方面的最新研究进展;最后介绍SO2的病理生理学作用的研究进展.     

Stem cell research: from molecular physiology to therapeutic applications

Stem cell research promises remedies to many devastating diseases that are currently incurable, ranging from diabetes and Parkinson’s disease to paralysis. Totipotent embryonic stem cells have great potential for generating a wide     

The hypothalamus for whole-body physiology: from metabolism to aging

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.     

Mechanotransduction at focal adhesions: from physiology to cancer development

Living cells are continuously exposed to mechanical cues, and can translate these signals into biochemical information (e.g. mechanotransduction). This process is crucial in many normal cellular functions, e.g. cell adhesion, migration, proliferation, and survival, as well as the progression of diseases such as cancer. Focal adhesions are the major sites of interactions between extracellular mechanical environments and intracellular biochemical signalling molecules/cytoskeleton, and hence focal adhesion proteins have been suggested to play important roles in mechanotransduction. Here, we overview the current molecular understanding in mechanotransduction occurring at focal adhesions. We also introduce recent studies on how extracellular matrix and mechanical microenvironments contribute to the development of cancer.     

Scaling-up from nutrient physiology to the size-structure of phytoplankton communities

In many community assemblages, the abundance of organisms isa power-law function of organism size. In phytoplankton communities,changes in size structure associated with increases in resourceavailability and total biomass have often been interpreted asa release from grazer control. A metapopulation-like approachis used to scale up from the individual physiological responsesto environmental conditions to community size structure assumingthe community taxonomic composition reflects the species pool.We show that the size scaling of cellular nutrient requirementsand growth can cause (1) the power-law relationship betweencell size and abundance, (2) dominance of small phytoplanktoncells under oligotrophic conditions, and (3) relative increasein abundance of larger phytoplankton cells under eutrophic conditions.If physiological differences associated with the taxonomic compositionof different community size fractions are considered, then themodel can replicate detailed field observations such as theabsence of small, slow-growing Prochlorococcus spp. and therelative dominance of large diatom species in nutrient-rich,upwelling regions of the ocean. This paper was presented in a session on "Size Structure ofPlankton Communities", at the ASLO Summer International Meeting,held in Santiago de Compostela, Spain, between 19 and 24 June,and coordinated by Xabier Irigoien, Roger Harris and Angel Lopez-Urrutia.     

An approach to primary prevention from the aspect of applied physiology

The main reason for our decreasing population number--a most remarkable indicator of the inadequacy of our health culture--is the high rate of overall mortality. In its background one finds a number of risk factors of high prevalence, such as hypertension disease, addiction pathology, reduced stress tolerance as well as physical and psychic inactivity. Patterns of life that are positive are scarce and as yet not attractive or efficient. The spirit of primary prevention is yet far from permeating medicine; the most the clinical side did realize has been a recognition of the population's need for regular medical screenings. A completely new approach that involves prevention programs embracing the whole of society, and an elaboration of new strategies are badly needed to achieve a desirable change in the present set of values. One of the already available remedies is to give full and science-based support to the positive life patterns in our culture, for instance by demonstrating how physiology can be applied to human life, by putting the latter within a broader scope, namely that of psychophysiology and social psychology. In this framework the elements to be discussed are such aspects of culture as dietary habits, physical exercise, and mental and sexual hygiene. Placing greater emphasis on sports and intense habitual physical exercise can promote a healthier lifestyle, above all in our youth.