Vadim N. Gladyshev

Bio: Vadim N. Gladyshev is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Selenoprotein & Selenocysteine. The author has an hindex of 102, co-authored 490 publications receiving 34148 citations. Previous affiliations of Vadim N. Gladyshev include Pompeu Fabra University & Howard Hughes Medical Institute.

The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions

Abstract: Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.

Characterization of Mammalian Selenoproteomes

Abstract: In the genetic code, UGA serves as a stop signal and a selenocysteine codon, but no computational methods for identifying its coding function are available. Consequently, most selenoprotein genes are misannotated. We identified selenoprotein genes in sequenced mammalian genomes by methods that rely on identification of selenocysteine insertion RNA structures, the coding potential of UGA codons, and the presence of cysteine-containing homologs. The human selenoproteome consists of 25 selenoproteins.

Selenoproteins: molecular pathways and physiological roles.

Abstract: Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by se...

How selenium has altered our understanding of the genetic code.

Abstract: Selenium is an essential micronutrient in the diet of many life forms, including humans and other mammals. Significant health benefits have been attributed to this element. It is rapidly becoming recognized as one of the more promising cancer chemopreventive agents (19), and there are strong indications that it has a role in reducing viral expression (4), in preventing heart disease and other cardiovascular and muscle disorders (23), and in delaying the progression of AIDS in human immunodeficiency virus-infected patients (3). Additional evidence suggests that selenium may have a role in mammalian development (51), in immune function (70), in male reproduction (30), and in slowing the aging process (70). Despite the many potential health benefits of selenium, the means by which this element promotes better health are only just beginning to be elucidated (31, 91). There are about 20 known selenium-containing proteins in mammals (33), and it would seem very likely that several of these are mediators of health benefits of dietary selenium. Therefore, it is critical to understand how selenium is inserted into protein and the identities and functions of the resulting protein products. Selenium is present in naturally occurring selenium-containing proteins in two basic forms. It can be inserted posttranslationally as a dissociable cofactor (32). This rare form of protein-associated selenium has been found only in several bacterial molybdenum-containing enzymes and will not be discussed further in this review. Selenium is also cotranslationally inserted into protein as the amino acid selenocysteine (Sec). Such occurrence of this element in protein is widespread in all major domains of life and is responsible for the majority of biological effects of selenium. The elucidation of how Sec is incorporated into protein has progressed at a rapid pace in the last decade and has revealed some surprising results. In fact, unraveling this mystery has altered our understanding of the genetic code, as the code has now been expanded to include Sec as the 21st naturally occurring amino acid. When the code was deciphered in the mid-1960s (48, 79), 20 amino acids were assigned to 61 of the possible 64 codons within the triplet code and 3 codons were found to function as terminators for protein synthesis. Each of the 64 code words was therefore assigned a function, and there did not appear to be room for additional amino acids. Although it was recognized in the mid-1960s that one code word, AUG, had a dual role of initiating protein synthesis and inserting methionine at internal protein positions, the possibility that a second codon also had two functions was not considered at that time. We now know that UGA serves as both a termination codon and a Sec codon. The means by which UGA serves as a Sec codon and how Sec is biosynthesized and incorporated into protein have been examined in considerable detail with eubacteria (reviewed in reference 7) and with mammals (this review). While the fundamental mechanism of Sec insertion in these organisms appears to be similar, recent studies suggest that mammals evolved additional components that allow incorporation of multiple Secs into a single protein and provide stringent regulation of Sec biosynthesis. The present review discusses our current knowledge of these features in mammals. It should be noted that selenium can also be incorporated nonspecifically into protein (42). The nonspecific occurrence of this element in protein arises when selenium replaces sulfur in the biosynthesis of cysteine or methionine and the resulting selenoamino acid (Sec or selenomethionine) is inserted in place of the natural amino acid. Such misincorporation of selenium into protein may be toxic; this subject has been reviewed elsewhere (42).

Genome sequencing reveals insights into physiology and longevity of the naked mole rat

Abstract: The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

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