The polarized distribution of poly(A+)-mRNA-induced functional ion channels in the Xenopus oocyte plasma membrane is prevented by anticytoskeletal drugs

Foreign mRNA was expressed in Xenopus laevis oocytes. Newly expressed ion currents localized in defined plasma membrane areas were measured using the two-electrode voltage clamp technique in combination with a specially designed chamber, that exposed only part of the surface on the oocytes to channel agonists or inhibitors. Newly expressed currents were found to be unequally distributed in the surface membrane of the oocyte. This asymmetry was most pronounced during the early phase of expression, when channels could almost exclusively be detected in the animal hemisphere of the oocyte. 4 d after injection of the mRNA, or later, channels could be found at a threefold higher density at the animal than at the vegetal pole area. The pattern of distribution was observed to be similar with various ion channels expressed from crude tissue mRNA and from cRNAs coding for rat GABAA receptor channel subunits. Electron microscopical analysis revealed very similar microvilli patterns at both oocyte pole areas. Thus, the asymmetric current distribution is not due to asymmetric surface structure. Upon incubation during the expression period in either colchicine or cytochalasin D, the current density was found to be equal in both pole areas. The inactive control substance beta-lumicolchicine had no effect on the asymmetry of distribution. Colchicine was without effect on the amplitude of the expressed whole cell current. Our measurements reveal a pathway for plasma membrane protein expression endogenous to the Xenopus oocyte, that may contribute to the formation and maintenance of polarity of this highly organized cell.

Higher Risk of Incident HCV-Coinfections in MSM with a Wide HIV Transmission Bottleneck

BACKGROUND  High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually-transmitted HCV among HIV-infected men who have sex with men(MSM). METHODS  We assessed the association between the HIV-transmission-bottleneck and the prevalence and incidence of HCV-coinfections in HIV-infected MSM from the Swiss-HIV-Cohort-Study(SHCS). As a proxy for the width of the transmission bottleneck we used the fraction of ambiguous nucleotides in Genotypic-Resistance-Tests(GRTs) from recent HIV-infections. We defined a broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously-established threshold(0.5%). RESULTS  From the SHCS, we identified 671 MSMs with available HCV-serologies and with a HIV-GRT sampled during recent infection. Of those, 161(24.0%) exhibited a broad HIV-transmission-bottleneck, 38(5.7%) had at least one positive HCV test, and 26(3.9%) had an incident HCV infection. Individuals with broad HIV-transmission bottlenecks exhibited a twofold-higher odds of having ever experienced an HCV coinfection(OR[95%CI]=2.2[1.1, 4.3]) and a threefold-higher hazard of an incident HCV infection(HR[95%CI]= 3.0[1.4, 6.6]) than individuals with narrow HIV-transmission-bottlenecks. CONCLUSIONS  Our results indicate that the currently occurring sexual spread of HCV is focused on those MSMs that are prone to exhibit broad HIV-transmission-bottlenecks. This is consistent with an important role of high-risk behavior and mucosal-barrier-impairment in the transmission of HCV among MSM.

Exercise-associated glucose metabolism in individuals with type 1 diabetes mellitus.

PURPOSE OF REVIEW The primary focus of this review is threefold: first, to summarize available knowledge on exercise-associated glucose metabolism in individuals with type 1 diabetes mellitus (T1DM); second, to elucidate physiological mechanisms predisposing to glycemic variations in patients in T1DM; and third, to describe novel approaches derived from physiological perceptions applicable to stabilize exercise-related glycemia in individuals with T1DM. RECENT FINDINGS Recent studies corroborate the concept that despite partial differences in counter-regulatory mechanisms individuals with T1DM do not fundamentally differ in their glucose response to exercise when compared with healthy individuals if studies are performed under standardized conditions with insulin and glucose levels held close to physiological ranges. Novel approaches derived from a better understanding of exercise-associated glucose metabolism (e.g., the concept of intermittent high-intensity exercise) may provide alternative ways to master the challenges imposed by exercise to individuals with T1DM. SUMMARY Exercise still imposes high demands on patients with T1DM and increases risks for hypoglycemia and hyperglycemia. Deeper insight into the associated metabolic pathways has revealed novel options to stabilize exercise-associated glucose levels in these patients.

Probing the moduli dependence of refined topological amplitudes

With the aim of providing a worldsheet description of the refined topological string, we continue the study of a particular class of higher derivative couplings Fg,n in the type II string effective action compactified on a Calabi–Yau threefold. We analyse first order differential equations in the anti-holomorphic moduli of the theory, which relate the Fg,n to other component couplings. From the point of view of the topological theory, these equations describe the contribution of non-physical states to twisted correlation functions and encode an obstruction for interpreting the Fg,n as the free energy of the refined topological string theory. We investigate possibilities of lifting this obstruction by formulating conditions on the moduli dependence under which the differential equations simplify and take the form of generalised holomorphic anomaly equations. We further test this approach against explicit calculations in the dual heterotic theory.

Accelerated magnetic resonance diffusion tensor imaging of the median nerve using simultaneous multi-slice echo planar imaging with blipped CAIPIRINHA.

PURPOSE To investigate the feasibility of MR diffusion tensor imaging (DTI) of the median nerve using simultaneous multi-slice echo planar imaging (EPI) with blipped CAIPIRINHA. MATERIALS AND METHODS After federal ethics board approval, MR imaging of the median nerves of eight healthy volunteers (mean age, 29.4 years; range, 25-32) was performed at 3 T using a 16-channel hand/wrist coil. An EPI sequence (b-value, 1,000 s/mm(2); 20 gradient directions) was acquired without acceleration as well as with twofold and threefold slice acceleration. Fractional anisotropy (FA), mean diffusivity (MD) and quality of nerve tractography (number of tracks, average track length, track homogeneity, anatomical accuracy) were compared between the acquisitions using multivariate ANOVA and the Kruskal-Wallis test. RESULTS Acquisition time was 6:08 min for standard DTI, 3:38 min for twofold and 2:31 min for threefold acceleration. No differences were found regarding FA (standard DTI: 0.620 ± 0.058; twofold acceleration: 0.642 ± 0.058; threefold acceleration: 0.644 ± 0.061; p ≥ 0.217) and MD (standard DTI: 1.076 ± 0.080 mm(2)/s; twofold acceleration: 1.016 ± 0.123 mm(2)/s; threefold acceleration: 0.979 ± 0.153 mm(2)/s; p ≥ 0.074). Twofold acceleration yielded similar tractography quality compared to standard DTI (p > 0.05). With threefold acceleration, however, average track length and track homogeneity decreased (p = 0.004-0.021). CONCLUSION Accelerated DTI of the median nerve is feasible. Twofold acceleration yields similar results to standard DTI. KEY POINTS • Standard DTI of the median nerve is limited by its long acquisition time. • Simultaneous multi-slice acquisition is a new technique for accelerated DTI. • Accelerated DTI of the median nerve yields similar results to standard DTI.