Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

Prenatal ultrasound and postmortem histologic evaluation of tooth germs: an observational, transversal study

Introduction: Hypodontia is the most frequent developmental anomaly of the orofacial complex, and its detection in prenatal ultrasound may indicate the presence of congenital malformations, genetic syndromes and chromosomal abnormalities.To date, only a few studies have evaluated the histological relationship of human tooth germs identified by two-dimensional (2D) ultrasonography. In order to analyze whether two-dimensional ultrasonography of tooth germs may be successfully used for identifying genetic syndromes, prenatal ultrasound images of fetal tooth germs obtained from a Portuguese population sample were compared with histological images obtained from fetal autopsies.Methods: Observational, descriptive, transversal study. The study protocol followed the ethical principles outlined by the Helsinki Declaration and was approved by the Ethics Committee of the School of Dental Medicine, University of Porto (FMDUP, Porto, Portugal) and of the Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/EPE, Porto, Portugal) as well as by the CGC Genetics Embryofetal Pathology Laboratory. Eighty-five fetuses examined by prenatal ultrasound screening from May 2011 to August 2012 had an indication for autopsy following spontaneous fetal death or medical termination of pregnancy. Of the 85 fetuses, 37 (43.5%) were randomly selected for tooth germ evaluation by routine histopathological analysis. Fetuses who were up to 30 weeks of gestation, and whose histological pieces were not representative of all maxillary tooth germs was excluded. Twenty four fetus between the 13th and 30th weeks of gestation fulfilled the parameters to autopsy.Results: Twenty four fetuses were submitted to histological evaluation and were determined the exact number, morphology, and mineralization of their tooth germs. All tooth germs were identifiable with ultrasonography as early as the 13th week of gestation. Of the fetuses autopsied, 41.7% had hypodontia (29.1% maxillary hypodontia and 20.9% mandibular hypodontia).Conclusions: This results indicateinfo:eu-repo/semantics/publishedVersio

Common Genetic Variants of the Human Steroid 21-Hydroxylase Gene (CYP21A2) Are Related to Differences in Circulating Hormone Levels

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Hungarian Scientific Research Fund (OTKA, PD100648 (AP)) Technology Innovation Fund, National Developmental Agency (KTIA-AIK-2012-12-1-0010). AP is the recipient of a “Lendület” grant from the Hungarian Academy of Sciences

Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.

Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11(+) and ACTA2(+)), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine

708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects:analysis for association with psychiatric disorder and cognitive traits

A balanced t(1;11) translocation that transects the Disrupted in schizophrenia 1 (DISC1) gene shows genome-wide significant linkage for schizophrenia and recurrent major depressive disorder (rMDD) in a single large Scottish family, but genome-wide and exome sequencing-based association studies have not supported a role for DISC1 in psychiatric illness. To explore DISC1 in more detail, we sequenced 528 kb of the DISC1 locus in 653 cases and 889 controls. We report 2718 validated single-nucleotide polymorphisms (SNPs) of which 2010 have a minor allele frequency of <1%. Only 38% of these variants are reported in the 1000 Genomes Project European subset. This suggests that many DISC1 SNPs remain undiscovered and are essentially private. Rare coding variants identified exclusively in patients were found in likely functional protein domains. Significant region-wide association was observed between rs16856199 and rMDD (P=0.026, unadjusted P=6.3 × 10-5, OR=3.48). This was not replicated in additional recurrent major depression samples (replication P=0.11). Combined analysis of both the original and replication set supported the original association (P=0.0058, OR=1.46). Evidence for segregation of this variant with disease in families was limited to those of rMDD individuals referred from primary care. Burden analysis for coding and non-coding variants gave nominal associations with diagnosis and measures of mood and cognition. Together, these observations are likely to generalise to other candidate genes for major mental illness and may thus provide guidelines for the design of future studies. © 2014 Macmillan Publishers Limited

Measurement of the running of the QED coupling in small-angle Bhabha scattering at LEP

Using the OPAL detector at LEP, the running of the effective QED coupling alpha(t) is measured for space-like momentum transfer from the angular distribution of small-angle Bhabha scattering. In an almost ideal QED framework, with very favourable experimental conditions, we obtain: Delta alpha(-6.07GeV^2) - Delta alpha(-1.81GeV^2) = (440 pm 58 pm 43 pm 30) X 10^-5, where the first error is statistical, the second is the experimental systematic and the third is the theoretical uncertainty. This agrees with current evaluations of alpha(t).The null hypothesis that alpha remains constant within the above interval of -t is excluded with a significance above 5sigma. Similarly, our results are inconsistent at the level of 3sigma with the hypothesis that only leptonic loops contribute to the running. This is currently the most significant direct measurment where the running alpha(t) is probed differentially within the measured t range.Comment: 43 pages, 12 figures, Submitted to Euro. Phys. J.

Landscape structure, human disturbance and crop management affect foraging ground selection by migrating geese

It is well known that agricultural intensification has caused severe population declines among bird species which use farmland for breeding and overwintering, while migrating bird species may benefit from intensive farming, but in turn damage crops. Knowledge of the habitat selection of migrating birds is important from both a conservation and agro-economic point of view. We investigated the habitat preferences of three common migrating goose species: White-fronted Goose Anser albifrons, Bean Goose A. fabalis and Greylag Goose A. anser during the autumn of 2009 in western Poland. A total of 24 flocks of these species were identified. Geese preferred large, elevated fields that were remote from forests and human settlements but in close proximity to a lake. Geese selected maize stubbles and avoided winter cereals. They selected sites in landscapes with a lower diversity of crops. Flock size was negatively correlated with the proportion of pastures in the landscape, but it increased with field size, distance to forest and distance to town. Our results are in contrast with the paradigm that less intensive farmland positively influences habitat use by birds during foraging. We advise the delayed ploughing of stubbles with the aim of creating appropriate foraging habitats for geese and minimizing damage to cereal crops

Synaptic-like axo-axonal transmission from striatal cholinergic interneurons onto dopaminergic fibers

\ua9 2022. Transmission from striatal cholinergic interneurons (CINs) controls dopamine release through nicotinic acetylcholine receptors (nAChRs) on dopaminergic axons. Anatomical studies suggest that cholinergic terminals signal predominantly through non-synaptic volume transmission. However, the influence of cholinergic transmission on electrical signaling in axons remains unclear. We examined axo-axonal transmission from CINs onto dopaminergic axons using perforated-patch recordings, which revealed rapid spontaneous EPSPs with properties characteristic of fast synapses. Pharmacology showed that axonal EPSPs (axEPSPs) were mediated primarily by high-affinity α6-containing receptors. Remarkably, axEPSPs triggered spontaneous action potentials, suggesting that these axons perform integration to convert synaptic input into spiking, a function associated with somatodendritic compartments. We investigated the cross-species validity of cholinergic axo-axonal transmission by recording dopaminergic axons in macaque putamen and found similar axEPSPs. Thus, we reveal that synaptic-like neurotransmission underlies cholinergic signaling onto dopaminergic axons, supporting the idea that striatal dopamine release can occur independently of somatic firing to provide distinct signaling