12 research outputs found

    Comparative Structural Analysis of Human DEAD-Box RNA Helicases

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    DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members

    The three-loop form factor in N=4 super Yang-Mills

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    In this paper we study the Sudakov form factor in {N} = {4} super Yang-Mills theory to the three-loop order. The latter is expressed in terms of planar and non-planar loop integrals. We show that it is possible to choose a representation in which each loop integral has uniform transcendentality. We verify analytically the expected exponentiation of the infrared divergences with the correct values of the three-loop cusp and collinear anomalous dimensions in dimensional regularisation. We find that the form factor in {N} = {4} super Yang-Mills can be related to the leading transcendentality part of the quark and gluon form factors in QCD. We also study the ultraviolet properties of the form factor in D > 4 dimensions, and find unexpected cancellations, resulting in an improved ultraviolet behaviour

    Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature

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    Background!#!Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates.!##!Methods!#!We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia.!##!Results!#!With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever.!##!Conclusions!#!Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question. Trial registration The original trial whose dataset was analyzed was registered at ClinicalTrials.gov (NCT01187134) on August 23, 2010, the first patient was included on July 1, 2011
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