DNA recombination: the replication connection.

Chromosomal double-strand breaks (DSBs) arise after exposure to ionizing radiation or enzymatic cleavage, but especially during the process of DNA replication itself. Homologous recombination plays a critical role in repair of such DSBs. There has been significant progress in our understanding of two processes that occur in DSB repair: gene conversion and recombination-dependent DNA replication. Recent evidence suggests that gene conversion and break-induced replication are related processes that both begin with the establishment of a replication fork in which both leading- and lagging-strand synthesis occur. There has also been much progress in characterization of the biochemical roles of recombination proteins that are highly conserved from yeast to humans.     

The justification for providing dietary guidance for the nutritional intake of boron

Because a biochemical function has not been defined for boron (B), its nutritional essentiality has not been firmly established. Nonetheless, dietary guidance should be formulated for B, because it has demonstrated beneficial, if not essential, effects in both animals and humans. Intakes of B commonly found with diets abundant in fruits, vegetables, legumes, pulses, and nuts have effects construed to be beneficial in macromineral, energy, nitrogen, and reactive oxygen metabolism, in addition to enhancing the response to estrogen therapy and improving psychomotor skills and cognitive processes of attention and memory. Perhaps the best-documented beneficial effect of B is on calcium (Ca) metabolism or utilization, and thus, bone calcification and maintenance. The paradigm emerging for the provision of dietary guidance that includes consideration of the total health effects of a nutrient, not just the prevention of a deficiency disease, has resulted in dietary guidance for chromium (Cr) and fluoride; both of these elements have beneficial effects in humans, but neither has a defined biochemical function. Knowledge of B nutritional effects in humans equals or is superior to that of Cr and fluoride; thus, establishing a dietary reference intake for B is justified. An analysis of both human and animal data suggests that an acceptable safe range of population mean intakes of B for adults could well be 1–13 mg/d. Recent findings indicate that a significant number of people do not consistently consume more than 1 mg B/d; this suggests that B could be a practical nutritional or clinical concern.     

Evolutionary,structural and biochemical evidence for a new interaction site of the leptin obesity protein

The Leptin protein is central to the regulation of energy metabolism in mammals. By integrating evolutionary, structural, and biochemical information, a surface segment, outside of its known receptor contacts, is predicted as a second interaction site that may help to further define its roles in energy balance and its functional differences between humans and other mammals.     

Genome-wide identification of genes that play a role in boron stress response in yeast

Boron is an essential micronutrient for plants and it is either necessary or beneficial for animals. Studies identified only few genes related to boron metabolism thus far and details of how boron is imported into cells and used in cell metabolism are largely unknown. In order to identify genes that play roles in boron metabolism, we screened the entire set of yeast haploid deletion mutants and identified 6 mutants that were resistant to toxic levels of boron, and 21 mutants that were highly sensitive to boron treatment. Furthermore, we performed a proteomic approach to identify additional proteins that are significantly up-regulated by boron treatment. Our results revealed many genes and pathways related to boron stress response and suggest a possible link between boron toxicity and translational control.     

小型猪糖尿病模型研究进展

小型猪的生理解剖结构、糖脂代谢、血液生化指标和疾病发生机制与人类都很相似,而且价格也相对适中,所以小型猪是诱导糖尿病模型的理想动物,本文就近年来用小型猪来诱导糖尿病模型的研究做一综述。     

Root Growth Inhibition in Boron-Deficient or Aluminum-Stressed Squash May Be a Result of Impaired Ascorbate Metabolism

Although cessation of growth is the most apparent symptom of boron deficiency, the biochemical function of boron in growth processes is not well understood. We propose that the action of boron in root meristems is associated with ascorbate metabolism. Total inhibition of root growth in squash (Cucurbita pepo L.) plants transferred to boron-free medium coincided with a major decrease (up to 98%) in the ascorbate concentration of root apices. Under low-boron conditions, in which root growth was partially inhibited, ascorbate concentration declined in proportion to growth rate. The decline in ascorbate concentration in boron-deficient root tips was not related to ascorbate oxidation. Ascorbate added to the medium improved root growth in plants supplied with insufficient boron. Increasing concentrations of aluminum in the nutrient medium caused progressive inhibition of root growth and a parallel reduction in ascorbate concentration of root apices. Elevated boron levels improved root growth under toxic aluminum conditions and produced root apices with higher ascorbate concentrations. To our knowledge, this is the first report of a correlation between boron nutrition, ascorbate concentration in root apices, and growth. These findings show that root growth inhibition resulting from either boron deficiency or aluminum toxicity may be a consequence of disrupted ascorbate metabolism.     

High spatial resolution analysis of fungal cell biochemistry--bridging the analytical gap using synchrotron FTIR spectromicroscopy.

Fungi impact humans and the environment in many ways, for good and ill. Some fungi support the growth of terrestrial plants or are used in biotechnology, and yet others are established or emerging pathogens. In some cases, the same organism may play different roles depending on the context or the circumstance. A better understanding of the relationship between fungal biochemical composition as related to the fungal growth environment is essential if we are to support or control their activities. Synchrotron FTIR (sFTIR) spectromicroscopy of fungal hyphae is a major new tool for exploring cell composition at a high spatial resolution. Brilliant synchrotron light is essential for this analysis due to the small size of fungal hyphae. sFTIR biochemical characterization of subcellular variation in hyphal composition will allow detailed exploration of fungal responses to experimental treatments and to environmental factors.     

High spatial resolution analysis of fungal cell biochemistry – bridging the analytical gap using synchrotron FTIR spectromicroscopy

Fungi impact humans and the environment in many ways, for good and ill. Some fungi support the growth of terrestrial plants or are used in biotechnology, and yet others are established or emerging pathogens. In some cases, the same organism may play different roles depending on the context or the circumstance. A better understanding of the relationship between fungal biochemical composition as related to the fungal growth environment is essential if we are to support or control their activities. Synchrotron FTIR (sFTIR) spectromicroscopy of fungal hyphae is a major new tool for exploring cell composition at a high spatial resolution. Brilliant synchrotron light is essential for this analysis due to the small size of fungal hyphae. sFTIR biochemical characterization of subcellular variation in hyphal composition will allow detailed exploration of fungal responses to experimental treatments and to environmental factors.     

Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A2 in activated cells

Mammalian cells contain several calcium-independent phospholipase A2 (PLA2) enzymes. The best studied of them is the so-called Group VIA PLA2 (iPLA2-VIA), which is an 85-88 kDa enzyme with unique structural features among the PLA2 superfamily of enzymes, and has been found to play a key role in homeostatic membrane phospholipid metabolism in various cell types. Growing evidence suggests that, in addition to its homeostatic function, iPLA2-VIA may also play distinct roles in cellular signaling. This review focuses on the biochemical mechanisms that regulate the activity of iPLA2-VIA in activated cells, and the biological functions proposed for this enzyme during stimulus-response coupling.     

Influence of boron toxicity on single phenols of tomato leaves

Summary Leaves of tomato plants grown in a hydroponic culture using a boron toxic solution present a different single phenols composition than those grown using an optimized nutrient solution. The absence of caffeic acid and aesculetin in boron toxic plants at flowering suggests that these compounds can be used as markers for the biochemical diagnosis of boron toxicity in tomato plants.     

Borate Transport and Cell Growth and Proliferation: Not Only in Plants

Boron is an abundant mineral essential for the life cycle of plants and may play a role in animal development and growth. Very little is known about boron homeostasis in plant and animal cells and the physiological roles of boron in animals. The recent identification of boron transporters, BOR1 in plants and NaBC1 in mammals, and that NaBC1 functions as an electrogenic Na+-coupled borate transporter essential for cell growth and proliferation open the way to probe the roles of boron in cellular function and physiology.     

Sphingolipids in cancer: regulation of pathogenesis and therapy

Sphingolipids are known to play important roles in the regulation of cell proliferation, response to chemotherapeutic agents, and/or prevention of cancer. Recently, significant progress has been made in the identification of the enzymes and their biochemical functions involved in sphingolipid metabolism. In addition, development of new techniques for the quantitative analysis of sphingolipids at their physiological levels has facilitated studies to examine distinct functions of these bioactive sphingolipids in cancer pathogenesis and therapy. This review will focus on the recent developments regarding the roles of bioactive sphingolipids in the regulation of cell growth/proliferation, and anti-cancer therapeutics.     

The role of lipins in innate immunity and inflammation

Lipins are phosphatidic acid phosphatase enzymes whose cellular function in regulating lipid metabolism has been known for decades, particularly in metabolically active tissues such as adipose tissue or liver. In recent years evidence is accumulating for key regulatory roles of the lipin family in innate immune cells. Lipins may help regulate signaling through relevant immune receptors such as Toll-like receptors, and are also integral part of the cellular machinery for lipid storage in these cells, thereby modulating certain inflammatory processes. Mutations in genes that encode for members of this family produce autoinflammatory hereditary diseases or diseases with an important inflammatory component in humans. In this review we summarize recent findings on the role of lipins in cells of the innate immune system and in the onset and progress of inflammatory processes.     

Family C1 cysteine proteases: biological diversity or redundancy?

Recent progress in the identification and partial characterization of novel genes encoding cysteine proteases of the papain family has considerably increased our knowledge of this family of enzymes. Kinetic data available to date for this large family indicate relatively broad, overlapping specificities for most enzymes, thus inspiring a growing conviction that they may exhibit functional redundancy. This is also supported in part by phenotypes of cathepsin knockout mice and suggests that several proteases can substitute for each other to degrade or process a given substrate. On the other hand, specific functions of one particular protease have also been documented. In addition, differences in cellular distribution and intracellular localization may contribute to defining specific functional roles for some of these proteases.     

Ascorbate as a biosynthetic precursor in plants

BACKGROUND AND AIMS: l-Ascorbate (vitamin C) has well-documented roles in many aspects of redox control and anti-oxidant activity in plant cells. This Botanical Briefing highlights recent developments in another aspect of l-ascorbate metabolism: its function as a precursor for specific processes in the biosynthesis of organic acids. SCOPE: The Briefing provides a summary of recent advances in our understanding of l-ascorbate metabolism, covering biosynthesis, translocation and functional aspects. The role of l-ascorbate as a biosynthetic precursor in the formation of oxalic acid, l-threonic acid and l-tartaric acid is described, and progress in elaborating the mechanisms of the formation of these acids is reviewed. The potential conflict between the two roles of l-ascorbate in plant cells, functional and biosynthetic, is highlighted. CONCLUSIONS: Recent advances in the understanding of l-ascorbate catabolism and the formation of oxalic and l-tartaric acids provide compelling evidence for a major role of l-ascorbate in plant metabolism. Combined experimental approaches, using classic biochemical and emerging 'omics' technologies, have provided recent insight to previously under-investigated areas.     

Regulation of plant glucosinolate metabolism

Glucosinolates and their degradation products are known to play important roles in plant interaction with herbivores and micro-organisms. In addition, they are important for human life. For example, some degradation products are flavor compounds and some exhibit anticarcinogenic properties. Recent years have seen great progress made in the understanding of glucosinolate biosynthesis in Arabidopsis thaliana. The core glucosinolate biosynthetic pathway has been revealed using biochemical and reverse genetics approaches. Future research needs to focus on questions related to regulation and control of glucosinolate metabolism. Here we review current status of studies on the regulation of glucosinolate metabolism at different levels, and highlight future research towards elucidating the signaling and metabolic network that control glucosinolate metabolism.     

Poly(A) and translation: development control

The stage-specific translational control of maternal mRNAs is determined by their differential polyadenylation and deadenylation. In the past year, a growing number of cis-acting elements that both positively and negatively regulate polyadenylation and deadenylation have been delineated. Considerable progress has been made on the biochemical characterization and regulation of trans-acting polyadenylation and deadenylation factors. This review summarizes these advances and their relevance to the roles of polyadenylation and deadenylation in translational control.     

The roles of iron in health and disease

Iron is vital for almost all living organisms by participating in a wide variety of metabolic processes, including oxygen transport, DNA synthesis, and electron transport. However, iron concentrations in body tissues must be tightly regulated because excessive iron leads to tissue damage, as a result of formation of free radicals. Disorders of iron metabolism are among the most common diseases of humans and encompass a broad spectrum of diseases with diverse clinical manifestations, ranging from anemia to iron overload and, possibly, to neurodegenerative diseases. The molecular understanding of iron regulation in the body is critical in identifying the underlying causes for each disease and in providing proper diagnosis and treatments. Recent advances in genetics, molecular biology and biochemistry of iron metabolism have assisted in elucidating the molecular mechanisms of iron homeostasis. The coordinate control of iron uptake and storage is tightly regulated by the feedback system of iron responsive element-containing gene products and iron regulatory proteins that modulate the expression levels of the genes involved in iron metabolism. Recent identification and characterization of the hemochromatosis protein HFE, the iron importer Nramp2, the iron exporter ferroportin1, and the second transferrin-binding and -transport protein transferrin receptor 2, have demonstrated their important roles in maintaining body's iron homeostasis. Functional studies of these gene products have expanded our knowledge at the molecular level about the pathways of iron metabolism and have provided valuable insight into the defects of iron metabolism disorders. In addition, a variety of animal models have implemented the identification of many genetic defects that lead to abnormal iron homeostasis and have provided crucial clinical information about the pathophysiology of iron disorders. In this review, we discuss the latest progress in studies of iron metabolism and our current understanding of the molecular mechanisms of iron absorption, transport, utilization, and storage. Finally, we will discuss the clinical presentations of iron metabolism disorders, including secondary iron disorders that are either associated with or the result of abnormal iron accumulation.     

Yeast models of human mitochondrial diseases

The yeast Saccharomyces cerevisiae is an excellent model for gaining insights into the molecular basis of human mitochondrial disorders, particularly those resulting from impaired mitochondrial metabolism. Yeast is a very well characterized system and most of our current knowledge about mitochondrial biogenesis in humans derives from yeast genetics and biochemistry. Systematic yeast genome-wide approaches have allowed for the identification of human disease genes. In addition, the functional characterization of a large number of yeast gene products resident in mitochondria has been instrumental for the later identification and characterization of their human orthologs. Here I will review the molecular and biochemical characterization of several mitochondrial diseases that have been ascribed to mutations in genes that were first found in yeast to be necessary for the assembly of the mitochondrial respiratory chain. The usefulness of yeast as a model system for human mitochondrial disorders is evaluated.     

The second messenger cascade in olfactory receptor neurons.

The molecular cloning of components involved in the cAMP second messenger cascade has allowed their biochemical characterization and revealed properties that are important for their role in sensory transduction. Recent evidence suggests inositol 1,4,5-trisphosphate functions as an additional second messenger in olfactory signalling. The interaction of these two pathways may contribute to the sensitivity of the olfactory system.