Howard Hughes Medical Institute

About: Howard Hughes Medical Institute is a nonprofit organization based out in Chevy Chase, Maryland, United States. It is known for research contribution in the topics: Gene & RNA. The organization has 20371 authors who have published 34677 publications receiving 5247143 citations. The organization is also known as: HHMI & hhmi.org.

UniFrac: an effective distance metric for microbial community comparison

Abstract: UniFrac is a β-diversity measure that uses phylogenetic information to compare environmental samples. UniFrac, coupled with standard multivariate statistical techniques including principal coordinates analysis (PCoA), identifies factors explaining differences among microbial communities. A recent simulation study concluded that UniFrac is unsuitable as a distance metric and should not be used for multivariate analysis (Schloss, 2008). We counter this argument by reassessing the data that led to this conclusion and by providing a mathematical proof showing that UniFrac is a distance metric. However, we confirm with actual sequence data that UniFrac values can be influenced by the number of sequences/sample, and recommend sequence jackknifing (that is, determining how often the cluster results are recovered using random subsets of the data) to avoid this issue.

Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.

Abstract: The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that beclin 1-/- mutant mice die early in embryogenesis and beclin 1+/- mutant mice suffer from a high incidence of spontaneous tumors. These tumors continue to express wild-type beclin 1 mRNA and protein, establishing that beclin 1 is a haploinsufficient tumor suppressor gene. Beclin 1-/- embryonic stem cells have a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal. These results demonstrate that beclin 1 is a critical component of mammalian autophagy and establish a role for autophagy in tumor suppression. They both provide a biological explanation for recent evidence implicating beclin 1 in human cancer and suggest that mutations in other genes operating in this pathway may contribute to tumor formation through deregulation of autophagy.

p63 is a p53 homologue required for limb and epidermal morphogenesis.

Abstract: The p53 tumour suppressor is a transcription factor that regulates the progression of the cell through its cycle and cell death (apoptosis) in response to environmental stimuli such as DNA damage and hypoxia1,2. Even though p53 modulates these critical cellular processes, mice that lack p53 are developmentally normal3, suggesting that p53-related proteins might compensate for the functions of p53 during embryogenesis. Two p53 homologues, p63 and p73, are known4,5 and here we describe the function of p63 in vivo. Mice lacking p63 are born alive but have striking developmental defects. Their limbs are absent or truncated, defects that are caused by a failure of the apical ectodermal ridge to differentiate. The skin of p63-deficient mice does not progress past an early developmental stage: it lacks stratification and does not express differentiation markers. Structures dependent upon epidermal–mesenchymal interactions during embryonic development, such as hair follicles, teeth and mammary glands, are absent in p63-deficient mice. Thus, in contrast to p53, p63 is essential for several aspects of ectodermal differentiation during embryogenesis.

Protein S-nitrosylation: purview and parameters.

Abstract: S-nitrosylation, the covalent attachment of a nitrogen monoxide group to the thiol side chain of cysteine, has emerged as an important mechanism for dynamic, post-translational regulation of most or all main classes of protein. S-nitrosylation thereby conveys a large part of the ubiquitous influence of nitric oxide (NO) on cellular signal transduction, and provides a mechanism for redox-based physiological regulation.

Regulation of Adaptive Immunity by the Innate Immune System

Abstract: Twenty years after the proposal that pattern recognition receptors detect invasion by microbial pathogens, the field of immunology has witnessed several discoveries that have elucidated receptors and signaling pathways of microbial recognition systems and how they control the generation of T and B lymphocyte-mediated immune responses. However, there are still many fundamental questions that remain poorly understood, even though sometimes the answers are assumed to be known. Here, we discuss some of these questions, including the mechanisms by which pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury.