Development of atopy and asthma: candidate environmental influences and important periods of exposure.

Atopy is a major risk factor for the development of asthma. Immune processes that lead to the development of antigen-specific IgE are essential to the development of atopy. This review examines the immune processes that are candidate targets for modulation by environmental agents; environmental and lifestyle factors that have been suggested as modulators of the development of atopy; and the impact of known environmental agents on atopic processes in the airway. The most important periods of immune development with regard to expression of atopy are likely during gestation and early childhood. A better understanding of which environmental agents are important, as well as the period of life during which these agents may exert an important effect, is essential to devising rational environmental avoidance strategies for at-risk populations

Identification and analysis of seven effector protein families with different adaptive and evolutionary histories in plant-associated members of the Xanthomonadaceae.

The Xanthomonadaceae family consists of species of non-pathogenic and pathogenic γ-proteobacteria that infect different hosts, including humans and plants. In this study, we performed a comparative analysis using 69 fully sequenced genomes belonging to this family, with a focus on identifying proteins enriched in phytopathogens that could explain the lifestyle and the ability to infect plants. Using a computational approach, we identified seven phytopathogen-enriched protein families putatively secreted by type II secretory system: PheA (CM-sec), LipA/LesA, VirK, and four families involved in N-glycan degradation, NixE, NixF, NixL, and FucA1. In silico and phylogenetic analyses of these protein families revealed they all have orthologs in other phytopathogenic or symbiotic bacteria, and are involved in the modulation and evasion of the immune system. As a proof of concept, we performed a biochemical characterization of LipA from Xac306 and verified that the mutant strain lost most of its lipase and esterase activities and displayed reduced virulence in citrus. Since this study includes closely related organisms with distinct lifestyles and highlights proteins directly related to adaptation inside plant tissues, novel approaches might use these proteins as biotechnological targets for disease control, and contribute to our understanding of the coevolution of plant-associated bacteria

Single-day therapy: an expert opinion on a recent development for the episodic treatment of recurrent genital herpes

One common method for treating recurrent genital herpes outbreaks is 3–5 day episodic therapy with nucleoside analogues. However, since maximum viral replication occurs within 24 h after the onset of symptoms, short-term patient-initiated episodic therapy started at prodromal onset or at the first appearance of lesions in patients without a prodrome may represent an important option. In a recent randomized trial, single-day famciclovir treatment decreased lesion healing time and the duration of pain and other symptoms by approximately 2 days compared to placebo, and prevented progression to a full outbreak in almost one in four patients. Because single-day treatment is more convenient than traditional therapies, it may lead to improved patient compliance and better overall management of recurrent genital herpes outbreaks

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Prevention of noncommunicable diseases by interventions in the preconception period: A FIGO position paper for action by healthcare practitioners

With the increase in obesity prevalence among women of reproductive age globally, the risks of type 2 diabetes, gestational diabetes, pre‐eclampsia, and other conditions are rising, with detrimental effects on maternal and newborn health. The period before pregnancy is increasingly recognized as crucial for addressing weight management and reducing malnutrition (both under‐ and overnutrition) in both parents to reduce the risk of noncommunicable diseases (NCDs) in the mother as well as the passage of risk to her offspring. Healthcare practitioners, including obstetricians, gynecologists, midwives, and general practitioners, have an important role to play in supporting women in planning a pregnancy and achieving healthy nutrition and weight before pregnancy. In this position paper, the FIGO Pregnancy Obesity and Nutrition Initiative provides an overview of the evidence for preconception clinical guidelines to reduce the risk of NCDs in mothers and their offspring. It encourages healthcare practitioners to initiate a dialogue on women’s health, nutrition, and weight management before conception. While acknowledging the fundamental importance of the wider social and environmental determinants of health, this paper focuses on a simple set of recommendations for clinical practice that can be used even in short consultations. The recommendations can be contextualized based on local cultural and dietary practices as part of a system‐wide public health approach to influence the wider determinants as well as individual factors influencing preconception health

R-parity violation in SU(5)

We show that judiciously chosen R-parity violating terms in the minimal renormalizable supersymmetric SU(5) are able to correct all the phenomenologically wrong mass relations between down quarks and charged leptons. The model can accommodate neutrino masses as well. One of the most striking consequences is a large mixing between the electron and the Higgsino. We show that this can still be in accord with data in some regions of the parameter space and possibly falsified in future experiments.Comment: 30 pages, 1 figure. Revised version. To appear in JHE

Serratamolide is a hemolytic factor produced by Serratia marcescens

Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use. © 2012 Shanks et al

Anomalous tqγtq\gamma coupling effects in exclusive radiative B-meson decays

The top-quark FCNC processes will be searched for at the CERN LHC, which are correlated with the B-meson decays. In this paper, we study the effects of top-quark anomalous interactions $tq\gamma$ in the exclusive radiative $B\to K^*\gamma$ and $B\to\rho\gamma$ decays. With the current experimental data of the branching ratios, the direct CP and the isospin asymmetries, bounds on the coupling $\kappa_{tcR}^{\gamma}$ from $B\to K^*\gamma$ and $\kappa_{tuR}^{\gamma}$ from $B\to \rho\gamma$ decays are derived, respectively. The bound on $|\kappa_{tcR}^{\gamma}|$ from ${\mathcal B}(B\to K^{*}\gamma)$ is generally compatible with that from ${\mathcal B}(B\to X_{s}\gamma)$. However, the isospin asymmetry $\Delta(K^{*}\gamma)$ further restrict the phase of $\kappa_{tcR}^{\gamma}$, and the combined bound results in the upper limit, $\mathcal B(t\to c\gamma)<0.21$, which is lower than the CDF result. For real $\kappa_{tcR}^{\gamma}$, the upper bound on $\mathcal B(t\to c\gamma)$ is about of the same order as the $5\sigma$ discovery potential of ATLAS with an integrated luminosity of $10 {\rm fb}^{-1}$. For $B\to\rho\gamma$ decays, the NP contribution is enhanced by a large CKM factor $|V_{ud}/V_{td}|$, and the constraint on $tu\gamma$ coupling is rather restrictive, $\mathcal B(t\to u\gamma)<1.44\times 10^{-5}$. With refined measurements to be available at the LHCb and the future super-B factories, we can get close correlations between $B\to V \gamma$ and the rare $t\to q\gamma$ decays, which will be studied directly at the LHC ATLAS and CMS.Comment: 25 pages, 15 figures, pdflate

Neutrinoless double beta decay in seesaw models

We study the general phenomenology of neutrinoless double beta decay in seesaw models. In particular, we focus on the dependence of the neutrinoless double beta decay rate on the mass of the extra states introduced to account for the Majorana masses of light neutrinos. For this purpose, we compute the nuclear matrix elements as functions of the mass of the mediating fermions and estimate the associated uncertainties. We then discuss what can be inferred on the seesaw model parameters in the different mass regimes and clarify how the contribution of the light neutrinos should always be taken into account when deriving bounds on the extra parameters. Conversely, the extra states can also have a significant impact, cancelling the Standard Model neutrino contribution for masses lighter than the nuclear scale and leading to vanishing neutrinoless double beta decay amplitudes even if neutrinos are Majorana particles. We also discuss how seesaw models could reconcile large rates of neutrinoless double beta decay with more stringent cosmological bounds on neutrino masses.Comment: 34 pages, 5 eps figures and 1 axodraw figure. Final version published in JHEP. NME results available in Appendi