Genetic Variants in Arhgef11 Are Associated With Kidney Injury in the Dahl Salt-Sensitive Rat

A previous genetic analysis comparing the Dahl salt-sensitive (S) rat to the spontaneously hypertensive rat (SHR) identified a major locus on chromosome 2 that influences proteinuria in the S rat. In the present study, blood pressure, proteinuria, and renal hemodynamics were evaluated in congenic strains with small segments of the protective SHR genome on the S background. Proteinuria and renal function were significantly improved in the congenic strains compared to the S. The causative locus interval was narrowed to Arhgef11, Pear1, and Sh2d2 were identified as important candidate genes that may be linked to kidney injury in the S rat. In particular, Arhgef11 plays an important role in the activation of the Rho-ROCK signaling pathway. Inhibition of this pathway using fasudil resulted in a significant reduction of proteinuria in treated S rats (compared to untreated S). However, no difference was observed between treated or untreated SHR or congenic strains. The homologous region in humans was found to be associated with estimated glomerular filtration rate (eGFR) in the Candidate Gene Association Resource (CARe) population. In summary, these findings demonstrate that allelic variants in Arhgef11, acting through the Rho-ROCK pathway, could influence kidney injury in the S as well as provide insight into human kidney disease

Transverse-momentum-dependent Multiplicities of Charged Hadrons in Muon-Deuteron Deep Inelastic Scattering

A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality $Q^{2}>1$ (GeV/$c$)$^2$, invariant mass of the hadronic system $W > 5$ GeV/$c^2$, Bjorken scaling variable in the range $0.003 < x < 0.4$, fraction of the virtual photon energy carried by the hadron in the range $0.2 < z < 0.8$, square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/$c)^2 < P_{\rm{hT}}^{2} < 3$ (GeV/$c$)$^2$. The multiplicities are presented as a function of $P_{\rm{hT}}^{2}$ in three-dimensional bins of $x$, $Q^2$, $z$ and compared to previous semi-inclusive measurements. We explore the small-$P_{\rm{hT}}^{2}$ region, i.e. $P_{\rm{hT}}^{2} < 1$ (GeV/$c$)$^2$, where hadron transverse momenta are expected to arise from non-perturbative effects, and also the domain of larger $P_{\rm{hT}}^{2}$, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small $P_{\rm{hT}}^{2}$ to study the dependence of the average transverse momentum $\langle P_{\rm{hT}}^{2}\rangle$ on $x$, $Q^2$ and $z$. The power-law behaviour of the multiplicities at large $P_{\rm{hT}}^{2}$ is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.Comment: 28 pages, 20 figure

Single-Trait and Multi-Trait Genome-Wide Association Analyses Identify Novel Loci for Blood Pressure in African-Ancestry Populations

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P \u3c 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension

Using Interviews in CER Projects: Options, Considerations, and Limitations

Interviews can be a powerful chemistry education research tool. Different from an assessment score or Likert-scale survey number, interviews can provide the researcher with a way to examine and describe what we cannot see, aspects such as feelings, thoughts, or explanations of thinking or behavior. Most people have no doubt seen countless interviews on TV news and talk shows. These sessions might convey interviewing as a spontaneous, easy, and straightforward process. However, using interviews as a meaningful research tool requires considerable thought, preparation, and practice. This chapter provides a general introduction to the use of interviews as a tool within a chemistry education research context. The chapter provides a general introduction to the use of interviews as a research tool including how to plan, conduct, and analyze interviews. It highlights important considerations for designing and conducting fruitful interviews, provides examples of different ways in which interviews have been used effectively in chemistry education research, and supplies additional references for the reader who wants to delve more deeply into particular topics

Randomized Dose-Ranging Controlled Trial of AQ-13, a Candidate Antimalarial, and Chloroquine in Healthy Volunteers

OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. SETTING: Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS: 126 healthy adults 21–45 years of age. INTERVENTIONS: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics

Collins and Sivers transverse-spin asymmetries in inclusive muoproduction of ρ0\rho^0 mesons

The production of vector mesons in deep inelastic scattering is an interesting yet scarsely explored channel to study the transverse spin structure of the nucleon and the related phenomena. The COMPASS collaboration has performed the first measurement of the Collins and Sivers asymmetries for inclusively produced $\rho^0$ mesons. The analysis is based on the data set collected in deep inelastic scattering in $2010$ using a $160\,\,\rm{GeV}/c$ $\mu^+$ beam impinging on a transversely polarized $\rm{NH}_3$ target. The $\rho^{0}$ mesons are selected from oppositely charged hadron pairs, and the asymmetries are extracted as a function of the Bjorken-$x$ variable, the transverse momentum of the pair and the fraction of the energy $z$ carried by the pair. Indications for positive Collins and Sivers asymmetries are observed

Spin Density Matrix Elements in Exclusive ρ0\rho ^0 Meson Muoproduction

We report on a measurement of Spin Density Matrix Elements (SDMEs) in hard exclusive $\rho ^0$ meson muoproduction at COMPASS using 160~GeV/$c$ polarised $\mu ^{+}$ and $\mu ^{-}$ beams impinging on a liquid hydrogen target. The measurement covers the kinematic range 5.0~GeV/$c^2$ $< W <$ 17.0~GeV/$c^2$, 1.0 (GeV/$c$)$^2$ $< Q^2 <$ 10.0 (GeV/$c$)$^2$ and 0.01 (GeV/$c$)$^2$ $< p_{\rm{T}}^2 <$ 0.5 (GeV/$c$)$^2$. Here, $W$ denotes the mass of the final hadronic system, $Q^2$ the virtuality of the exchanged photon, and $p_{\rm{T}}$ the transverse momentum of the $\rho ^0$ meson with respect to the virtual-photon direction. The measured non-zero SDMEs for the transitions of transversely polarised virtual photons to longitudinally polarised vector mesons ($\gamma^*_T \to V^{ }_L$) indicate a violation of $s$-channel helicity conservation. Additionally, we observe a dominant contribution of natural-parity-exchange transitions and a very small contribution of unnatural-parity-exchange transitions, which is compatible with zero within experimental uncertainties. The results provide important input for modelling Generalised Parton Distributions (GPDs). In particular, they may allow one to evaluate in a model-dependent way the role of parton helicity-flip GPDs in exclusive $\rho ^0$ production

Identification of surface proteins in Enterococcus faecalis V583

<p>Abstract</p> <p>Background</p> <p>Surface proteins are a key to a deeper understanding of the behaviour of Gram-positive bacteria interacting with the human gastro-intestinal tract. Such proteins contribute to cell wall synthesis and maintenance and are important for interactions between the bacterial cell and the human host. Since they are exposed and may play roles in pathogenicity, surface proteins are interesting targets for drug design.</p> <p>Results</p> <p>Using methods based on proteolytic "shaving" of bacterial cells and subsequent mass spectrometry-based protein identification, we have identified surface-located proteins in <it>Enterococcus faecalis </it>V583. In total 69 unique proteins were identified, few of which have been identified and characterized previously. 33 of these proteins are predicted to be cytoplasmic, whereas the other 36 are predicted to have surface locations (31) or to be secreted (5). Lipid-anchored proteins were the most dominant among the identified surface proteins. The seemingly most abundant surface proteins included a membrane protein with a potentially shedded extracellular sulfatase domain that could act on the sulfate groups in mucin and a lipid-anchored fumarate reductase that could contribute to generation of reactive oxygen species.</p> <p>Conclusions</p> <p>The present proteome analysis gives an experimental impression of the protein landscape on the cell surface of the pathogenic bacterium <it>E. faecalis</it>. The 36 identified secreted (5) and surface (31) proteins included several proteins involved in cell wall synthesis, pheromone-regulated processes, and transport of solutes, as well as proteins with unknown function. These proteins stand out as interesting targets for further investigation of the interaction between <it>E. faecalis </it>and its environment.</p