The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Application of Jain and Munczek's bound-state approach to gamma gamma-processes of pi0, eta_c and eta_b

We point out the problems affecting most quark--antiquark bound state approaches when they are faced with the electromagnetic processes dominated by Abelian axial anomaly. However, these problems are resolved in the consistently coupled Schwinger-Dyson and Bethe-Salpeter approach. Using one of the most successful variants of this approach, we find the dynamically dressed propagators of the light u and d quarks, as well as the heavy c and b quarks, and find the Bethe-Salpeter amplitudes for their bound states pi0, eta_c and \eta_b. Thanks to incorporating the dynamical chiral symmetry breaking, the pion simultaneously appears as the (pseudo)Goldstone boson. We give the theoretical predictions for the gamma-gamma decay widths of pi0, eta_c and eta_b, and for the pi0 gamma* -> gamma transition form factor, and compare them with experiment. In the chiral limit, the axial-anomaly result for pi0->gamma-gamma is reproduced analytically in the consistently coupled Schwinger-Dyson and Bethe-Salpeter approach, provided that the quark-photon vertex is dressed consistently with the quark propagator, so that the vector Ward-Takahashi identity of QED is obeyed. On the other hand, the present approach is also capable of quantitatively describing systems of heavy quarks, concretely eta_c and possibly eta_b, and their gamma-gamma decays. We discuss the reasons for the broad phenomenological success of the bound-state approach of Jain and Munczek.Comment: RevTeX, 37 pages, 7 eps figures, submitted to Int. J. Mod. Phys.

Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular ( RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng center dot kg(-1) center dot min(-1)) and, consecutively, ILO (60 ng center dot kg(-1) center dot min(-1)) for 20 min each. We measured pulmonary artery pressure ( PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E-es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E-es was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function. Copyright (C) 2005 S. Karger AG, Basel

Decomposition of semigroup algebras

Let A \subseteq B be cancellative abelian semigroups, and let R be an integral domain. We show that the semigroup ring R[B] can be decomposed, as an R[A]-module, into a direct sum of R[A]-submodules of the quotient ring of R[A]. In the case of a finite extension of positive affine semigroup rings we obtain an algorithm computing the decomposition. When R[A] is a polynomial ring over a field we explain how to compute many ring-theoretic properties of R[B] in terms of this decomposition. In particular we obtain a fast algorithm to compute the Castelnuovo-Mumford regularity of homogeneous semigroup rings. As an application we confirm the Eisenbud-Goto conjecture in a range of new cases. Our algorithms are implemented in the Macaulay2 package MonomialAlgebras.Comment: 12 pages, 2 figures, minor revisions. Package may be downloaded at http://www.math.uni-sb.de/ag/schreyer/jb/Macaulay2/MonomialAlgebras/html

Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and non-canonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Turbulent Diffusion and Turbulent Thermal Diffusion of Aerosols in Stratified Atmospheric Flows

The paper analyzes the phenomenon of turbulent thermal diffusion in the Earth atmosphere, its relation to the turbulent diffusion and its potential impact on aerosol distribution. This phenomenon was predicted theoretically more than 10 years ago and detected recently in the laboratory experiments. This effect causes a non-diffusive flux of aerosols in the direction of the heat flux and results in formation of long-living aerosol layers in the vicinity of temperature inversions. We demonstrated that the theory of turbulent thermal diffusion explains the GOMOS aerosol observations near the tropopause (i.e., the observed shape of aerosol vertical profiles with elevated concentrations located almost symmetrically with respect to temperature profile). In combination with the derived expression for the dependence of the turbulent thermal diffusion ratio on the turbulent diffusion, these measurements yield an independent method for determining the coefficient of turbulent diffusion at the tropopause. We evaluated the impact of turbulent thermal diffusion to the lower-troposphere vertical profiles of aerosol concentration by means of numerical dispersion modelling, and found a regular upward forcing of aerosols with coarse particles affected stronger than fine aerosols.Comment: 19 pages, 10 figure

Free-ocean CO2 enrichment (FOCE) systems: present status and future developments

Free-ocean CO2 enrichment (FOCE) systems are designed to assess the impact of ocean acidification on biological communities in situ for extended periods of time (weeks to months). They overcome some of the drawbacks of laboratory experiments and field observations by enabling (1) precise control of CO2 enrichment by monitoring pH as an offset of ambient pH, (2) consideration of indirect effects such as those mediated through interspecific relationships and food webs, and (3) relatively long experiments with intact communities. Bringing perturbation experiments from the laboratory to the field is, however, extremely challenging. The main goal of this paper is to provide guidelines on the general design, engineering, and sensor options required to conduct FOCE experiments. Another goal is to introduce xFOCE, a community-led initiative to promote awareness, provide resources for in situ perturbation experiments, and build a user community. Present and existing FOCE systems are briefly described and examples of data collected presented. Future developments are also addressed as it is anticipated that the next generation of FOCE systems will include, in addition to pH, options for oxygen and/or temperature control. FOCE systems should become an important experimental approach for projecting the future response of marine ecosystems to environmental change

In-depth study of moderately young but extremely red, very dusty substellar companion HD206893B

Accepted for publication in Astronomy & Astrophysics. Reproduced with permission from Astronomy & Astrophysics. © 2018 ESO.The substellar companion HD206893b has recently been discovered by direct imaging of its disc-bearing host star with the SPHERE instrument. We investigate the atypical properties of the companion, which has the reddest near-infrared colours among all known substellar objects, either orbiting a star or isolated, and we provide a comprehensive characterisation of the host star-disc-companion system. We conducted a follow-up of the companion with adaptive optics imaging and spectro-imaging with SPHERE, and a multiinstrument follow-up of its host star. We obtain a R=30 spectrum from 0.95 to 1.64 micron of the companion and additional photometry at 2.11 and 2.25 micron. We carried out extensive atmosphere model fitting for the companions and the host star in order to derive their age, mass, and metallicity. We found no additional companion in the system in spite of exquisite observing conditions resulting in sensitivity to 6MJup (2MJup) at 0.5" for an age of 300 Myr (50 Myr). We detect orbital motion over more than one year and characterise the possible Keplerian orbits. We constrain the age of the system to a minimum of 50 Myr and a maximum of 700 Myr, and determine that the host-star metallicity is nearly solar. The comparison of the companion spectrum and photometry to model atmospheres indicates that the companion is an extremely dusty late L dwarf, with an intermediate gravity (log g 4.5-5.0) which is compatible with the independent age estimate of the system. Though our best fit corresponds to a brown dwarf of 15-30 MJup aged 100-300 Myr, our analysis is also compatible with a range of masses and ages going from a 50 Myr 12MJup planetary-mass object to a 50 MJup Hyades-age brown dwarf...Peer reviewedFinal Accepted Versio