A genome-wide association study implicates the pleiotropic effect of NMUR2 on asthma and COPD

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that are associated with chronic inflammation. They share common features in terms of their advanced stages and genetic factors. This study aimed to identify novel genes underlying both asthma and COPD using genome-wide association study (GWAS) to differentiate between the two diseases. We performed a GWAS of asthma and COPD in 7828 Koreans from three hospitals. In addition, we investigated genetic correlations. The UK Biobank dataset was used for the replication studies. We found that rs2961757, located near neuromedin U receptor 2 (NMUR2) on chromosome 5, was genome-wide significant ([Formula: see text] = 0.44, P-valueAsthma-COPD = 3.41 × 10-8), and significant results were replicated with the UK Biobank data ([Formula: see text] = 0.04, P-valueAsthma-COPD = 0.0431). A positive genetic correlation was observed between asthma and COPD (39.8% in the Korean dataset and 49.8% in the UK Biobank dataset). In this study, 40-45% of the genetic effects were common to asthma and COPD. Moreover, NMUR2 increases the risk of asthma development and suppresses COPD development. This indicates that NMUR2 allows for better differentiation of both diseases, which can facilitate tailored medical therapy

Gate-tuned normal and superconducting transport at the surface of a topological insulator

Three-dimensional topological insulators are characterized by the presence of a bandgap in their bulk and gapless Dirac fermions at their surfaces. New physical phenomena originating from the presence of the Dirac fermions are predicted to occur, and to be experimentally accessible via transport measurements in suitably designed electronic devices. Here we study transport through superconducting junctions fabricated on thin Bi2Se3 single crystals, equipped with a gate electrode. In the presence of perpendicular magnetic field B, sweeping the gate voltage enables us to observe the filling of the Dirac fermion Landau levels, whose character evolves continuously from electron- to hole-like. When B=0, a supercurrent appears, whose magnitude can be gate tuned, and is minimum at the charge neutrality point determined from the Landau level filling. Our results demonstrate how gated nano-electronic devices give control over normal and superconducting transport of Dirac fermions at an individual surface of a three-dimensional topological insulator.Comment: 28 pages, 5 figure

On reminder effects, drop-outs and dominance: evidence from an online experiment on charitable giving

We present the results of an experiment that (a) shows the usefulness of screening out drop-outs and (b) tests whether different methods of payment and reminder intervals affect charitable giving. Following a lab session, participants could make online donations to charity for a total duration of three months. Our procedure justifying the exclusion of drop-outs consists in requiring participants to collect payments in person flexibly and as known in advance and as highlighted to them later. Our interpretation is that participants who failed to collect their positive payments under these circumstances are likely not to satisfy dominance. If we restrict the sample to subjects who did not drop out, but not otherwise, reminders significantly increase the overall amount of charitable giving. We also find that weekly reminders are no more effective than monthly reminders in increasing charitable giving, and that, in our three months duration experiment, standing orders do not increase giving relative to one-off donations

Publishing and sharing multi-dimensional image data with OMERO

Imaging data are used in the life and biomedical sciences to measure the molecular and structural composition and dynamics of cells, tissues, and organisms. Datasets range in size from megabytes to terabytes and usually contain a combination of binary pixel data and metadata that describe the acquisition process and any derived results. The OMERO image data management platform allows users to securely share image datasets according to specific permissions levels: data can be held privately, shared with a set of colleagues, or made available via a public URL. Users control access by assigning data to specific Groups with defined membership and access rights. OMERO’s Permission system supports simple data sharing in a lab, collaborative data analysis, and even teaching environments. OMERO software is open source and released by the OME Consortium at www.openmicroscopy.org

New surgical approach for late complications from spinal cord injury

BACKGROUND: The most frequent late complications in spinal cord injury result from arachnoiditis and consequent alterations in dynamics of cerebrospinal fluid flow. A surgical procedure carried out on patients with these alterations, resolved the various pathologies more efficiently in all cases. METHODS: From October 2000 to March 2006, 23 patients were selected for surgery: three showed signs of syringomyelia, three presented with microcystic lesions, three presented with arachnoid cysts in different locations but always confluent to the scar area, and 14 showed evidence of tethered cords. The surgery consisted of laminectomy at four levels, followed by dural opening in order to remove all the arachnoiditis at the level of the scar and to remove the altered arachnoid and its cysts, at least at two levels above and below the lesion. The dentate ligaments were cut at all exposed levels. RESULTS: The patients had no postoperative problems and not only retained all neurological functions but also showed neurological recovery. According to the motor and sensory scale of the American Spinal Injury Association, the recoveries were motor 20.6% (P < 0.001), touch 15.6% ((P < 0.001) and pinprick 14.4% (P < 0.001). These patients showed no signs of relapse at 4–66 month follow-up. CONCLUSION: This alternative surgery resolved the pathologies provoking neurological deterioration by releasing the complete spinal cord at the level of the scar and the levels above and below it. It thus avoids myelotomies and the use of shunts and stents, which have a high long-term failure rate and consequent relapses. Nevertheless, this surgical procedure allows patients the chance to opt for any further treatment that may evolve in the future

DPO multiplex PCR as an alternative to culture and susceptibility testing to detect Helicobacter pylori and its resistance to clarithromycin

<p>Abstract</p> <p>Background</p> <p>Macrolide resistance in <it>Helicobacter pylori </it>is the major risk factor for treatment failure when using a proton pump inhibitor-clarithromycin containing therapy. Macrolide resistance is due to a few mutations on the 23S ribomosal subunit encoded by the 23S rRNA gene. The present study aimed at investigating the performance of the dual priming oligonucleotide (DPO)-PCR kit named Seeplex^®ClaR-<it>H. pylori </it>ACE detection designed to detect <it>H. pylori </it>and two types of point mutations causing clarithromycin resistance in <it>H. pylori</it>.</p> <p>Methods</p> <p>The performance of Seeplex^®ClaR-<it>H. pylori </it>ACE detection was evaluated on 127 gastric biopsies in comparison to conventional bacterial culture followed by the determination of susceptibility to clarithromycin by E-test, as well as by an in-house real-time PCR using a fluorescence resonance energy transfer (FRET) technology.</p> <p>Results</p> <p>Considering culture as the reference test, the sensitivity of DPO-PCR and real-time FRET-PCR was 97.7% and 100% while specificity was 83.1% and 80.7%, respectively. However, both PCR were concordant in detecting 14 <it>H. pylori </it>positive cases which were negative by culture. Globally, E-test and DPO-PCR were concordant with regard to clarithromycin susceptibility in 95.3% of the cases (41/43), while real-time FRET-PCR and DPO-PCR were concordant in 95% (57/60).</p> <p>Conclusion</p> <p>The DPO-PCR is an interesting tool to detect <it>H. pylori </it>on gastric biopsies and to study its susceptibility to clarithromycin in laboratories that cannot perform real-time PCR assays.</p

Stability and inheritance of endosperm-specific expression of two transgenes in progeny from crossing independently transformed barley plants

To study stability and inheritance of two different transgenes in barley, we crossed a homozygous T8 plant, having uidA (or gus) driven by the barley endosperm-specific B1-hordein promoter (localized in the near centromeric region of chromosome 7H) with a second homozygous T4 plant, having sgfp(S65T) driven by the barley endosperm-specific D-hordein promoter (localized on the subtelomeric region of chromosome 2H). Both lines stably expressed the two transgenes in the generations prior to the cross. Three independently crossed F1 progeny were analyzed by PCR for both uidA and sgfp(S65T) in each plant and functional expression of GUS and GFP in F2 seeds followed a 3:1 Mendelian segregation ratio and transgenes were localized by FISH to the same location as in the parental plants. FISH was used to screen F2 plants for homozygosity of both transgenes; four homozygous plants were identified from the two crossed lines tested. FISH results showing presence of transgenes were consistent with segregation ratios of expression of both transgenes, indicating that the two transgenes were expressed without transgene silencing in homozygous progeny advanced to the F3 and F4 generations. Thus, even after crossing independently transformed, homozygous parental plants containing a single, stably expressed transgene, progeny were obtained that continued to express multiple transgenes through generation advance. Such stability of transgenes, following outcrossing, is an important attribute for trait modification and for gene flow studies

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe