271 research outputs found

    Deforestation and CO 2 emissions in coastal Tanzania from 1990 to 2007

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    SUMMARY Conversion of forest to other land uses is a major Regional forest clearance in Tanzania is highly dynamic; while rates have slowed since 2000, forest habitat conversion has continued and there is no guarantee that future rates will remain low. A rigorous policy on reducing emissions from deforestation and degradation (REDD) should be implemented to avoid future increases in deforestation rates

    Structure and mechanism of acetolactate decarboxylase

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    Acetolactate decarboxylase catalyzes the conversion of both enantiomers of acetolactate to the (R)-enantiomer of acetoin, via a mechanism that has been shown to involve a prior rearrangement of the non-natural (R)-enantiomer substrate to the natural (S)-enantiomer. In this paper, a series of crystal structures of ALDC complex with designed transition state mimics are reported. These structures, coupled with inhibition studies and site-directed mutagenesis provide an improved understanding of the molecular processes involved in the stereoselective decarboxylation/protonation events. A mechanism for the transformation of each enantiomer of acetolactate is proposed

    QacR−Cation Recognition Is Mediated by a Redundancy of Residues Capable of Charge Neutralization

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    ABSTRACT: The Staphylococcus aureus multidrug binding protein QacR binds to a broad spectrum of structurally dissimilar cationic, lipophilic drugs. Our previous structural analyses suggested that five QacR glutamic acid residues are critical for charge neutralization and specification of certain drugs. For example, E57 and E58 interact with berberine and with one of the positively charged moieties of the bivalent drug dequalinium. Here we report the structural and biochemical effects of substituting E57 and E58 with alanine and glutamine. Unexpectedly, individual substitutions of these residues did not significantly affect QacR drug binding affinity. Structures of QacR(E57Q) and QacR(E58Q) bound to dequalinium indicated that E57 and E58 are redundant for charge neutralization. The most significant finding was that berberine was reoriented in the QacR multidrug binding pocket so that its positive charge was neutralized by side chain oxygen atoms and aromatic residues. Together, these data emphasize the remarkable versatility of the QacR multidrug binding pocket, illustrating that the capacity of QacR to bind myriad cationic drugs is largely governed by the presence in the pocket of a redundancy of polar, charged, and aromatic residues that are capable of electrostatic neutralization. Multidrug resistant bacteria represent a major global health threat that has in great part arisen through the action o

    Dynamical Supersymmetry Breaking

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    Supersymmetry is one of the most plausible and theoretically motivated frameworks for extending the Standard Model. However, any supersymmetry in Nature must be a broken symmetry. Dynamical supersymmetry breaking (DSB) is an attractive idea for incorporating supersymmetry into a successful description of Nature. The study of DSB has recently enjoyed dramatic progress, fueled by advances in our understanding of the dynamics of supersymmetric field theories. These advances have allowed for direct analysis of DSB in strongly coupled theories, and for the discovery of new DSB theories, some of which contradict early criteria for DSB. We review these criteria, emphasizing recently discovered exceptions. We also describe, through many examples, various techniques for directly establishing DSB by studying the infrared theory, including both older techniques in regions of weak coupling, and new techniques in regions of strong coupling. Finally, we present a list of representative DSB models, their main properties, and the relations between them.Comment: 113 pages, Revtex. Minor changes, references added and corrected. To appear in Reviews of Modern Physic

    Two Structures of a Thiazolinyl Imine Reductase from Yersinia enterocolitica Provide Insight into Catalysis and Binding to the Nonribosomal Peptide Synthetase Module of HMWP1

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    The thiazolinyl imine reductase from Yersinia enterocolitica (Irp3) catalyzes the NADPH-dependent reduction of a thiazoline ring in an intermediate for the formation of the siderophore yersiniabactin. Two structures of Irp3 were determined in the apo- (1.85 Å) and NADP+-bound (2.31 Å) forms. Irp3 shows structural homology to sugar oxidoreductases such as glucose-fructose oxidoreductase and 1,5-anhydro-D-fructose reductase, as well as to biliverdin reductase. A homology model of the thiazolinyl imine reductase from Pseudomonas aeruginosa (PchG) was generated. Extensive loop insertions are observed in the C-terminal domain that are unique to Irp3 and PchG and not found in the structural homologs that recognize small molecular substrates. These loops are hypothesized to be important for binding of the nonribosomal peptide synthetase modules (found in HMWP1 and PchF, respectively) to which the substrate of the reductase is covalently attached. A catalytic mechanism of proton donation from a general acid (either histidine-101 or tyrosine-128) and hydride donation from C4 of nicotinamide of the NADPH cofactor is proposed for reduction of the carbon-nitrogen double bond of the thiazoline

    Planck intermediate results I : Further validation of new Planck clusters with XMM-Newton

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    Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

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    <p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

    Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

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    The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

    Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

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    Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at sNN\sqrt{s_{_{\rm NN}}} = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in η<0.8|\eta|<0.8 and 0.3<pT<200.3 < p_T < 20 GeV/cc are compared to the expectation in pp collisions at the same sNN\sqrt{s_{\rm NN}}, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAAR_{\rm AA}. The result indicates only weak medium effects (RAAR_{\rm AA} \approx 0.7) in peripheral collisions. In central collisions, RAAR_{\rm AA} reaches a minimum of about 0.14 at pT=6p_{\rm T}=6-7GeV/cc and increases significantly at larger pTp_{\rm T}. The measured suppression of high-pTp_{\rm T} particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

    Chemical and structural analysis of an antibody folding intermediate trapped during glycan biosynthesis

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    Human IgG Fc glycosylation modulates immunological effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. Engineering of Fc glycans therefore enables fine-tuning of the therapeutic properties of monoclonal antibodies. The N-linked glycans of Fc are typically complex-type, forming a network of noncovalent interactions along the protein surface of the Cγ2 domain. Here, we manipulate the mammalian glycan-processing pathway to trap IgG1 Fc at sequential stages of maturation, from oligomannose- to hybrid- to complex-type glycans, and show that the Fc is structurally stabilized following the transition of glycans from their hybrid- to complex-type state. X-ray crystallographic analysis of this hybrid-type intermediate reveals that N-linked glycans undergo conformational changes upon maturation, including a flip within the trimannosyl core. Our crystal structure of this intermediate reveals a molecular basis for antibody biogenesis and provides a template for the structure-guided engineering of the protein-glycan interface of therapeutic antibodies
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