Bartonella spp. in Bats, Guatemala

To better understand the role of bats as reservoirs of Bartonella spp., we estimated Bartonella spp. prevalence and genetic diversity in bats in Guatemala during 2009. We found prevalence of 33% and identified 21 genetic variants of 13 phylogroups. Vampire bat–associated Bartonella spp. may cause undiagnosed illnesses in humans

Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor

Background and Purpose Flecainide is a use-dependent blocker of cardiac Na+ channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na+ channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca2+-release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na+ and/or RyR2 channels. Experimental Approach We compared the ability of fully charged (QX-FL) and neutral (NU-FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca2+ sparks in intact adult rat cardiac myocytes. Key Results Both QX-FL and NU-FL were partial blockers of the non-physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX-FL, but not NU-FL, reduced Ca2+ spark frequency. Conclusions and Implications Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic-to-luminal current, the effect of QX-FL on Ca2+ sparks is likely, by analogy with flecainide, to result from Na+ channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na+ and RyR2 channels

Chance and necessity in the genome evolution of endosymbiotic bacteria of insects

[EN] An open question in evolutionary biology is how does the selection¿drift balance determine the fates of biological interactions. We searched for signatures of selection and drift in genomes of five endosymbiotic bacterial groups known to evolve under strong genetic drift. Although most genes in endosymbiotic bacteria showed evidence of relaxed purifying selection, many genes in these bacteria exhibited stronger selective constraints than their orthologs in free-living bacterial relatives. Remarkably, most of these highly constrained genes had no role in the host¿symbiont interactions but were involved in either buffering the deleterious consequences of drift or other host-unrelated functions, suggesting that they have either acquired new roles or their role became more central in endosymbiotic bacteria. Experimental evolution of Escherichia coli under strong genetic drift revealed remarkable similarities in the mutational spectrum, genome reduction patterns and gene losses to endosymbiotic bacteria of insects. Interestingly, the transcriptome of the experimentally evolved lines showed a generalized deregulation of the genome that affected genes encoding proteins involved in mutational buffering, regulation and amino acid biosynthesis, patterns identical to those found in endosymbiotic bacteria. Our results indicate that drift has shaped endosymbiotic associations through a change in the functional landscape of bacterial genes and that the host had only a small role in such a shiftThis work was supported by Science Foundation Ireland (12/IP/1637) and grants from the Spanish Ministerio de Economia y Competitividad (MINECO-FEDER; BFU2012-36346 and BFU2015-66073-P) to MAF. 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oPOSSUM: integrated tools for analysis of regulatory motif over-representation

The identification of over-represented transcription factor binding sites from sets of co-expressed genes provides insights into the mechanisms of regulation for diverse biological contexts. oPOSSUM, an internet-based system for such studies of regulation, has been improved and expanded in this new release. New features include a worm-specific version for investigating binding sites conserved between Caenorhabditis elegans and C. briggsae, as well as a yeast-specific version for the analysis of co-expressed sets of Saccharomyces cerevisiae genes. The human and mouse applications feature improvements in ortholog mapping, sequence alignments and the delineation of multiple alternative promoters. oPOSSUM2, introduced for the analysis of over-represented combinations of motifs in human and mouse genes, has been integrated with the original oPOSSUM system. Analysis using user-defined background gene sets is now supported. The transcription factor binding site models have been updated to include new profiles from the JASPAR database. oPOSSUM is available at http://www.cisreg.ca/oPOSSUM

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS

Observation of associated production of a ZZ boson with a DD meson in the~forward region

A search for associated production of a $Z$ boson with an open charm meson is presented using a data sample, corresponding to an integrated luminosity of $1.0\,\mathrm{fb}^{-`}$ of proton--proton collisions at a centre-of-mass energy of 7\,TeV, collected by the LHCb experiment. %% Seven candidate events for associated production of a $Z$ boson with a $D^0$ meson and four candidate events for a $Z$ boson with a $D^+$ meson are observed with a combined significance of 5.1standard deviations. The production cross-sections in the forward region are measured to be $$\sigma_{Z\rightarrow\mu^+\mu^-\!,D^0} = 2.50\pm1.12\pm0.22pb$$ $$\sigma_{Z\rightarrow\mu^+\mu^-\!,D^+} = 0.44\pm0.23\pm0.03pb,$$ where the first uncertainty is statistical and the second systematic.Comment: 18 pages, 2 figure

Search for CP violation in D+→K−K+π+D^{+} \to K^{-}K^{+}\pi^{+} decays

A model-independent search for direct CP violation in the Cabibbo suppressed decay $D^+ \to K^- K^+\pi^+$ in a sample of approximately 370,000 decays is carried out. The data were collected by the LHCb experiment in 2010 and correspond to an integrated luminosity of 35 pb$^{-1}$. The normalized Dalitz plot distributions for $D^+$ and $D^-$ are compared using four different binning schemes that are sensitive to different manifestations of CP violation. No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.

Measurements of the B+B^+, B0B^0, Bs0B_s^0 meson and Λb0\Lambda_b^0 baryon lifetimes

Measurements of $b$-hadron lifetimes are reported using $pp$ collision data, corresponding to an integrated luminosity of 1.0fb$^{-1}$, collected by the LHCb detector at a centre-of-mass energy of $7$Tev. Using the exclusive decays $B^+\to J/\psi K^+$, $B^0\to J/\psi K^*(892)^0$, $B^0\to J/\psi K^0_{\rm S}$, $\Lambda_b^0\to J/\psi \Lambda$ and $B^0_s\to J/\psi \phi$ the average decay times in these modes are measured to be $\tau_{B^+\to J/\psi K^+}$ = $1.637 \pm$ 0.004 $\pm$ 0.003 ps, $\tau_{B^0\to J/\psi K^*(892)^0}$ = $1.524 \pm$ 0.006 $\pm$ 0.004 ps, $\tau_{B^0\to J/\psi K^0_{\rm S}}$ = $1.499 \pm$ 0.013 $\pm$ 0.005 ps, $\tau_{\Lambda_b^0\to J/\psi \Lambda}$ = $1.415 \pm$ 0.027 $\pm$ 0.006 ps and $\tau_{B^0_s\to J/\psi \phi}$ = $1.480 \pm$ 0.011 $\pm$ 0.005 ps, where the first uncertainty is statistical and the second is systematic. These represent the most precise lifetime measurements in these decay modes. In addition, ratios of these lifetimes, and the ratio of the decay-width difference, $\Delta\Gamma_d$, to the average width, $\Gamma_d$, in the $B^0$ system, $\Delta \Gamma_d/\Gamma_d = -0.044 \pm 0.025 \pm 0.011$, are reported. All quantities are found to be consistent with Standard Model expectations.Comment: 28 pages, 4 figures. Updated reference