Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

Neutrinoless double beta decay within Self-consistent Renormalized Quasiparticle Random Phase Approximation and inclusion of induced nucleon currents

The first, to our knowledge, calculation of neutrinoless double beta decay ($0\nu\beta\beta$-decay) matrix elements within the self-consistent renormalised Quasiparticle Random Phase Approximation (SRQRPA) is presented. The contribution from the momentum-dependent induced nucleon currents to $0\nu\beta\beta$-decay amplitude is taken into account. A detailed nuclear structure study includes the discussion of the sensitivity of the obtained SRQRPA results for $0\nu\beta\beta$-decay of $^{76}$Ge to the parameters of nuclear Hamiltonian, two-nucleon short-range correlations and the truncation of the model space. A comparision with the standard and renormalized QRPA is presented. We have found a considerable reduction of the SRQRPA nuclear matrix elements, resulting in less stringent limits for the effective neutrino mass.Comment: 13 pages, 3 figures, 1 tabl

Complex Pharmacology of Free Fatty Acid Receptors

G protein-coupled receptors (GPCRs) are historically the most successful family of drug targets. In recent times it has become clear that the pharmacology of these receptors is far more complex than previously imagined. Understanding of the pharmacological regulation of GPCRs now extends beyond simple competitive agonism or antagonism by ligands interacting with the orthosteric binding site of the receptor to incorporate concepts of allosteric agonism, allosteric modulation, signaling bias, constitutive activity, and inverse agonism. Herein, we consider how evolving concepts of GPCR pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or “free” fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets for the treatment of metabolic and inflammatory diseases. Further understanding of the complex pharmacology of these receptors will be critical to unlocking their ultimate therapeutic potential

Different Types of Door-Opening Motions as Contributing Factors to Containment Failures in Hospital Isolation Rooms

10.1371/journal.pone.0066663PLoS ONE86-POLN

Status of four-neutrino mass schemes: a global and unified approach to current neutrino oscillation data

We present a unified global analysis of neutrino oscillation data within the framework of the four-neutrino mass schemes (3+1) and (2+2). We include all data from solar and atmospheric neutrino experiments, as well as information from short-baseline experiments including LSND. If we combine only solar and atmospheric neutrino data, (3+1) schemes are clearly preferred, whereas short-baseline data in combination with atmospheric data prefers (2+2) models. When combining all data in a global analysis the (3+1) mass scheme gives a slightly better fit than the (2+2) case, though all four-neutrino schemes are presently acceptable. The LSND result disfavors the three-active neutrino scenario with only $\Delta m^2_{sol}$ and $\Delta m^2_{atm}$ at 99.9% CL with respect to the four-neutrino best fit model. We perform a detailed analysis of the goodness of fit to identify which sub-set of the data is in disagreement with the best fit solution in a given mass scheme.Comment: 32 pages, 8 Figures included, REVTeX4.Improved discussion in sec. XI, references added, version accepted by Phys. Rev.

The role of Probiotics in allergic diseases

Allergic disorders are very common in the pediatric age group. While the exact etiology is unclear, evidence is mounting to incriminate environmental factors and an aberrant gut microbiota with a shift of the Th1/Th2 balance towards a Th2 response. Probiotics have been shown to modulate the immune system back to a Th1 response. Several in vitro studies suggest a role for probiotics in treating allergic disorders. Human trials demonstrate a limited benefit for the use of probiotics in atopic dermatitis in a preventive as well as a therapeutic capacity. Data supporting their use in allergic rhinitis are less robust. Currently, there is no role for probiotic therapy in the treatment of bronchial asthma. Future studies will be critical in determining the exact role of probiotics in allergic disorders

Can R-parity violation explain the LSND data as well?

The recent Super-Kamiokande data now admit only one type of mass hierarchy in a framework with three active and one sterile neutrinos. We show that neutrino masses and mixings generated by R-parity-violating couplings, with values within their experimental upper limits, are capable of reproducing this hierarchy, explaining all neutrino data particularly after including the LSND results.Comment: 7 pages, Latex, 3 PS figures; in v2 a few clarifying remarks included and two references added (to appear in Physical Review D

Lactobacillus rhamnosus HN001 Attenuates Allergy Development in a Pig Model

HN001 (HN001) supplementation decreased the prevalence of eczema and IgE associated eczema. However, the influence of HN001 on the incidence of wheeze, asthma, and/or other allergic manifestations has yet to be reported.This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model. allergen (ASA) during a six week time frame in post-weanling pigs supplemented daily with HN001, or without supplementation. One week following final sensitization intradermal skin tests and respiratory challenges were conducted.In response to intradermal and respiratory challenges, ASA-sensitized pigs fed HN001 had less severe skin flare reactions, smaller increases in pleural pressure, and trends towards lower changes in arterial oxygen and carbon dioxide partial pressure levels compared to control pigs. The frequency of ASA-specific IFN-γ-secreting peripheral blood mononuclear cells, as well as the amount of IL-10 produced by ASA-specific cells, was of greater magnitude in probiotic-fed pigs compared to control animals. These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression.Probiotic supplementation decreased the severity of allergic skin and lung responses in allergen-sensitized pigs with a corresponding increase in IFN-γ expression. A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans

Spherical Lactic Acid Bacteria Activate Plasmacytoid Dendritic Cells Immunomodulatory Function via TLR9-Dependent Crosstalk with Myeloid Dendritic Cells

Plasmacytoid dendritic cells (pDC) are a specialized sensor of viral and bacterial nucleic acids and a major producer of IFN-α that promotes host defense by priming both innate and acquired immune responses. Although synthetic Toll-like receptor (TLR) ligands, pathogenic bacteria and viruses activate pDC, there is limited investigation of non-pathogenic microbiota that are in wide industrial dietary use, such as lactic acid bacteria (LAB). In this study, we screened for LAB strains, which induce pDC activation and IFN-α production using murine bone marrow (BM)-derived Flt-3L induced dendritic cell culture. Microbial strains with such activity on pDC were absent in a diversity of bacillary strains, but were observed in certain spherical species (Lactococcus, Leuconostoc, Streptococcus and Pediococcus), which was correlated with their capacity for uptake by pDC. Detailed study of Lactococcus lactis subsp. lactis JCM5805 and JCM20101 revealed that the major type I and type III interferons were induced (IFN-α, -β, and λ). IFN-α induction was TLR9 and MyD88-dependent; a slight impairment was also observed in TLR4-/- cells. While these responses occurred with purified pDC, IFN-α production was synergistic upon co-culture with myeloid dendritic cells (mDC), an interaction that required direct mDC-pDC contact. L. lactis strains also stimulated expression of immunoregulatory receptors on pDC (ICOS-L and PD-L1), and accordingly augmented pDC induction of CD4+CD25+FoxP3+ Treg compared to the Lactobacillus strain. Oral administration of L. lactis JCM5805 induced significant activation of pDC resident in the intestinal draining mesenteric lymph nodes, but not in a remote lymphoid site (spleen). Taken together, certain non-pathogenic spherical LAB in wide dietary use has potent and diverse immunomodulatory effects on pDC potentially relevant to anti-viral immunity and chronic inflammatory disease

Neutrinoless Double Beta Decay of Ge76, Se82, Mo100 and Xe136 to excited 0^+ states

The neutrinoless double beta decay transition to the first excited 0^+ collective final state is examined for A=76, 82, 100 and 136 nuclei by assuming light and heavy Majorana neutrino exchange mechanisms as well as the trilinear R-parity violating contributions. Realistic calculations of nuclear matrix elements have been performed within the renormalized quasiparticle random phase approximation. Transitions to the first excited two-quadrupole phonon 0^+ state are described within a boson expansion formalism and alternatively by using the operator recoupling method. We present the sensitivity parameters to different lepton number violating signals, which can be used in planning the neutrinoless double beta decay experiments. The half-life of neutrinoless double beta decay to the first excited state 0^+_1 is by a factor of 10 to 100 larger than that of the transition to the ground state.Comment: 31 pages, RevTex, 1 Postscript figures, to appear in Phys. Rev.