Catálogo de publicaciones - revistas

<jats:p> The conservation of large carnivores is a formidable challenge for biodiversity conservation. Using a data set on the past and current status of brown bears ( <jats:italic>Ursus arctos</jats:italic> ), Eurasian lynx ( <jats:italic>Lynx lynx</jats:italic> ), gray wolves ( <jats:italic>Canis lupus</jats:italic> ), and wolverines ( <jats:italic>Gulo gulo</jats:italic> ) in European countries, we show that roughly one-third of mainland Europe hosts at least one large carnivore species, with stable or increasing abundance in most cases in 21st-century records. The reasons for this overall conservation success include protective legislation, supportive public opinion, and a variety of practices making coexistence between large carnivores and people possible. The European situation reveals that large carnivores and people can share the same landscape. </jats:p>

<jats:p> The design of functional membrane proteins from first principles represents a grand challenge in chemistry and structural biology. Here, we report the design of a membrane-spanning, four-helical bundle that transports first-row transition metal ions Zn <jats:sup>2+</jats:sup> and Co <jats:sup>2+</jats:sup> , but not Ca <jats:sup>2+</jats:sup> , across membranes. The conduction path was designed to contain two di-metal binding sites that bind with negative cooperativity. X-ray crystallography and solid-state and solution nuclear magnetic resonance indicate that the overall helical bundle is formed from two tightly interacting pairs of helices, which form individual domains that interact weakly along a more dynamic interface. Vesicle flux experiments show that as Zn <jats:sup>2+</jats:sup> ions diffuse down their concentration gradients, protons are antiported. These experiments illustrate the feasibility of designing membrane proteins with predefined structural and dynamic properties. </jats:p>

<jats:p> The generation of new enzymatic activities has mainly relied on repurposing the interiors of preexisting protein folds because of the challenge in designing functional, three-dimensional protein structures from first principles. Here we report an artificial metallo-β-lactamase, constructed via the self-assembly of a structurally and functionally unrelated, monomeric redox protein into a tetrameric assembly that possesses catalytic zinc sites in its interfaces. The designed metallo-β-lactamase is functional in the <jats:italic>Escherichia coli</jats:italic> periplasm and enables the bacteria to survive treatment with ampicillin. In vivo screening of libraries has yielded a variant that displays a catalytic proficiency [( <jats:italic>k</jats:italic> <jats:sub>cat</jats:sub> / <jats:italic>K</jats:italic> <jats:sub>m</jats:sub> )/ <jats:italic>k</jats:italic> <jats:sub>uncat</jats:sub> ] for ampicillin hydrolysis of 2.3 × 10 <jats:sup>6</jats:sup> and features the emergence of a highly mobile loop near the active site, a key component of natural β-lactamases to enable substrate interactions. </jats:p>

<jats:p>Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3. The role of the H3.3K27M mutation in tumorigenesis is not fully understood. Here, we use a human embryonic stem cell system to model this tumor. We show that H3.3K27M expression synergizes with p53 loss and PDGFRA activation in neural progenitor cells derived from human embryonic stem cells, resulting in neoplastic transformation. Genome-wide analyses indicate a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Drug screening assays identified a compound targeting the protein menin as an inhibitor of tumor cell growth in vitro and in mice.</jats:p>

<jats:p> Variability in gene expression among genetically identical cells has emerged as a central preoccupation in the study of gene regulation; however, a divide exists between the predictions of molecular models of prokaryotic transcriptional regulation and genome-wide experimental studies suggesting that this variability is indifferent to the underlying regulatory architecture. We constructed a set of promoters in <jats:italic>Escherichia coli</jats:italic> in which promoter strength, transcription factor binding strength, and transcription factor copy numbers are systematically varied, and used messenger RNA (mRNA) fluorescence in situ hybridization to observe how these changes affected variability in gene expression. Our parameter-free models predicted the observed variability; hence, the molecular details of transcription dictate variability in mRNA expression, and transcriptional noise is specifically tunable and thus represents an evolutionarily accessible phenotypic parameter. </jats:p>

<jats:p> Immunological tolerance to self requires naturally occurring regulatory T (T <jats:sub>reg</jats:sub> ) cells. Yet how they stably control autoimmune T cells remains obscure. Here, we show that T <jats:sub>reg</jats:sub> cells can render self-reactive human CD8 <jats:sup>+</jats:sup> T cells anergic (i.e., hypoproliferative and cytokine hypoproducing upon antigen restimulation) in vitro, likely by controlling the costimulatory function of antigen-presenting cells. Anergic T cells were naïve in phenotype, lower than activated T cells in T cell receptor affinity for cognate antigen, and expressed several coinhibitory molecules, including cytotoxic T lymphocyte–associated antigen-4 (CTLA-4). Using these criteria, we detected in healthy individuals anergic T cells reactive with a skin antigen targeted in the autoimmune disease vitiligo. Collectively, our results suggest that T <jats:sub>reg</jats:sub> cell–mediated induction of anergy in autoimmune T cells is important for maintaining self-tolerance. </jats:p>

<jats:p>On this week's show: Breakthrough of the year and a yearly news roundup.</jats:p>

<jats:p>In this first installment of a three part series, "The Art and Science of Traditional Medicine," we present a series of articles making a case for the integration of traditional Chinese medicine (TCM) into modern medical practice. From the new WHO Traditional Medicine Strategy to the application of systems biology in studying TCM, we aim to highlight the potential for creating an integrated, network-based health care system. The next two issues will cover herbal genomics and highlight the importance of quality control, standardization, regulation, and safety for traditional therapies. An overview of indigenous medicines in Europe, Africa, the Middle East, India, and the Americas will also be provided.</jats:p> <jats:p> This special supplement brought to you by the <jats:bold>Science</jats:bold> /AAAS Custom Publishing Office. </jats:p>

<jats:p>In this first installment of a three part series, "The Art and Science of Traditional Medicine," we present a series of articles making a case for the integration of traditional Chinese medicine (TCM) into modern medical practice. From the new WHO Traditional Medicine Strategy to the application of systems biology in studying TCM, we aim to highlight the potential for creating an integrated, network-based health care system. The next two issues will cover herbal genomics and highlight the importance of quality control, standardization, regulation, and safety for traditional therapies. An overview of indigenous medicines in Europe, Africa, the Middle East, India, and the Americas will also be provided.</jats:p> <jats:p> This special supplement brought to you by the <jats:bold>Science</jats:bold> /AAAS Custom Publishing Office. </jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>