Amino-acid sequence and three-dimensional structure of the Staphylococcus aureus metalloproteinase at 1.72 å resolution

AbstractBackground: Aureolysin is an extracellular zinc-dependent metalloproteinase from the pathogenic bacterium Staphylococcus aureus. This enzyme exhibits in vitro activity against several molecules of biological significance for the host, indicating that it is involved in the pathology of staphylococcal diseases.Results: Here we report the amino-acid sequence and inhibitor-free X-ray crystal structure of aureolysin, a member of the thermolysin family of zinc-dependent metalloproteinases. This enzyme, which binds one zinc and three calcium ions, comprises a single chain of 301 amino acids that consists of a β-strand-rich upper domain and an α-helix-rich lower domain.Conclusions: The overall structure of aureolysin is very similar to that of the other three members of this family whose structures are known – thermolysin (TLN) from Bacillus thermoproteolyticus, neutral protease (NP) from Bacillus cereus and elastase (PAE) from Pseudomonas aeruginosa. But an important difference has been encountered: in contrast to what has been observed in the other three members of this family (TLN, NP and PAE), inhibitor-free aureolysin displays a ‘closed’ active site cleft conformation. This new structure therefore raises questions about the universality of the hinge-bending motion model for the neutral metalloproteinases

Linear Estimation of Location and Scale Parameters Using Partial Maxima

Consider an i.i.d. sample X^*_1,X^*_2,...,X^*_n from a location-scale family, and assume that the only available observations consist of the partial maxima (or minima)sequence, X^*_{1:1},X^*_{2:2},...,X^*_{n:n}, where X^*_{j:j}=max{X^*_1,...,X^*_j}. This kind of truncation appears in several circumstances, including best performances in athletics events. In the case of partial maxima, the form of the BLUEs (best linear unbiased estimators) is quite similar to the form of the well-known Lloyd's (1952, Least-squares estimation of location and scale parameters using order statistics, Biometrika, vol. 39, pp. 88-95) BLUEs, based on (the sufficient sample of) order statistics, but, in contrast to the classical case, their consistency is no longer obvious. The present paper is mainly concerned with the scale parameter, showing that the variance of the partial maxima BLUE is at most of order O(1/log n), for a wide class of distributions.Comment: This article is devoted to the memory of my six-years-old, little daughter, Dionyssia, who leaved us on August 25, 2010, at Cephalonia isl. (26 pages, to appear in Metrika

Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes

Wellcome Trust. Grant Number: 098882/Z/12/Z National Institute for Health Research (NIHR

Shaping black holes with free fields

Starting from a metric Ansatz permitting a weak version of Birkhoff's theorem we find static black hole solutions including matter in the form of free scalar and p-form fields, with and without a cosmological constant \Lambda. Single p-form matter fields permit multiple possibilities, including dyonic solutions, self-dual instantons and metrics with Einstein-Kaelher horizons. The inclusion of multiple p-forms on the other hand, arranged in a homogeneous fashion with respect to the horizon geometry, permits the construction of higher dimensional dyonic p-form black holes and four dimensional axionic black holes with flat horizons, when \Lambda<0. It is found that axionic fields regularize black hole solutions in the sense, for example, of permitting regular -- rather than singular -- small mass Reissner-Nordstrom type black holes. Their cosmic string and Vaidya versions are also obtained.Comment: 38 pages. v2: minor changes, published versio

Diverse histologic appearances in pulmonary mucinous cystic neoplasia: A case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Testing matter effects in propagation of atmospheric and long-baseline neutrinos

We quantify our current knowledge of the size and flavor structure of the matter effects in the evolution of atmospheric and long-baseline neutrinos based solely on the analysis of the corresponding neutrino data. To this aim we generalize the matter potential of the Standard Model by rescaling its strength, rotating it away from the e-e sector, and rephasing it with respect to the vacuum term. This phenomenological parametrization can be easily translated in terms of non-standard neutrino interactions in matter. We show that in the most general case, the strength of the potential cannot be determined solely by atmospheric and long-baseline data. However its flavor composition is very much constrained and the present determination of the neutrino masses and mixing is robust under its presence. We also present an update of the constraints arising from this analysis in the particular case in which no potential is present in the e-mu and e-tau sectors. Finally we quantify to what degree in this scenario it is possible to alleviate the tension between the oscillation results for neutrinos and antineutrinos in the MINOS experiment and show the relevance of the high energy part of the spectrum measured at MINOS.Comment: PDFLaTeX file using JHEP3 class, 25 pages, 7 figures included. Accepted for publication in JHE

Multi-Scale Motility Amplitude Associated with Suicidal Thoughts in Major Depression

Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI]) derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n = 36) monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n = 12 of each type). VI was associated inversely with suicidal thinking (r =  –0.61 with all subjects and r =  –0.73 with bipolar disorder subjects; both p<0.0001) and distinguished patients with bipolar versus unipolar major depression with a sensitivity of 91.7% and a specificity of 79.2%. VI may be a useful biomarker of characteristic features of major depression, contribute to differentiating bipolar and unipolar depression, and help to detect risk of suicide. An objective biomarker of suicide-risk could be advantageous when patients are unwilling or unable to share suicidal thinking with clinicians

Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter

PEP was a Wellcome Trust Clinical Research Training Fellow and this research was supported by the Wellcome Trust (Grant 098882/Z/12/Z). This research was also supported by the National Institute for Health Research (NIHR) Clinical Research Facility at Guy’s & St Thomas’ NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London

Learners' decisions for attending Pediatric Grand Rounds: a qualitative and quantitative study

BACKGROUND: Although grand rounds plays a major educational role at academic medical centers, there has been little investigation into the factors influencing the learners' decision to attend. Greater awareness of attendees' expectations may allow grand rounds planners to better accommodate the learners' perspective, potentially making continuing education activities more attractive and inviting. METHODS: We used both qualitative (part A) and quantitative (part B) techniques to investigate the motivators and barriers to grand rounds attendance. Part A investigated contextual factors influencing attendance as expressed through attendee interviews. Transcripts of the interviews were analyzed using grounded theory techniques. We created a concept map linking key factors and their relationships. In part B we quantified the motivators and barriers identified during the initial interviews through a survey of the grand rounds audience. RESULTS: Sixteen persons voluntarily took part in the qualitative study (part A) by participating in one of seven group interview sessions. Of the 14 themes that emerged from these sessions, the most frequent factors motivating attendance involved competent practice and the need to know. All sessions discussed intellectual stimulation, social interaction, time constraints and convenience, licensure, content and format, and absence of cost for attending sessions. The 59 respondents to the survey (part B) identified clinically-useful topics (85%), continuing education credit (46%), cutting-edge research (27%), networking (22%), and refreshments (8%) as motivators and non-relevant topics (44%) and too busy to attend (56%) as barriers. CONCLUSION: Greater understanding of the consumers' perspective can allow planners to tailor the style, content, and logistics to make grand rounds more attractive and inviting

Charged hadrons in local finite-volume QED+QCD with C⋆ boundary conditions

In order to calculate QED corrections to hadronic physical quantities by means of lattice simulations, a coherent description of electrically-charged states in finite volume is needed. In the usual periodic setup, Gauss's law and large gauge transformations forbid the propagation of electrically-charged states. A possible solution to this problem, which does not violate the axioms of local quantum field theory, has been proposed by Wiese and Polley, and is based on the use of C* boundary conditions. We present a thorough analysis of the properties and symmetries of QED in isolation and QED coupled to QCD, with C* boundary conditions. In particular we learn that a certain class of electrically-charged states can be constructed in this setup in a fully consistent fashion, without relying on gauge fixing. We argue that this class of states covers most of the interesting phenomenological applications in the framework of numerical simulations. We also calculate finite-volume corrections to the mass of stable charged particles and show that these are much smaller than in non-local formulations of QED