A Spectraplakin Is Enriched on the Fusome and Organizes Microtubules during Oocyte Specification in Drosophila

AbstractBackground: During Drosophila oogenesis a membranous organelle called the fusome has a key function in the establishment of oocyte fate and polarity, ultimately leading to the establishment of the major body axes of the animal. The fusome is necessary for the microtubule-driven restriction of markers of oocyte fate to the oocyte, but the mechanism by which the fusome organizes the microtubules is not known.Results: We have identified the spectraplakin Short stop (Shot) as a new component of the fusome. Spectraplakins are giant cytoskeletal linker proteins, with multiple isoforms produced from each gene. Shot is the sole spectraplakin in Drosophila. The phenotype caused by the absence of Shot is not similar to that of other components of the fusome but instead is similar to the absence of the downstream components that interact with microtubules: the dynein/dynactin-complex-associated proteins Egalitarian and BicaudalD. Shot is required for the association of microtubules with the fusome and the subsequent specification of the oocyte in 16-cell cysts. Shot is also required for the concentration of centrosomes into the oocyte, a process thought to be independent of microtubules because it still occurs in the presence of microtubule depolymerizing drugs. This suggests that Shot may protect some microtubules from depolymerization and that these microtubules are sufficient for this process.Conclusions: Shot provides the missing link between the fusome and microtubules within meiotic cysts, which is essential for the establishment of the oocyte. Shot associates with the fusome and is required for microtubule organization. We suggest that it does this directly, via its microtubule binding GAS2 domain

Maintaining epithelial integrity: a function for gigantic spectraplakin isoforms in adherens junctions

The Short stop (Shot/Kakapo) spectraplakin is a giant cytoskeletal protein, which exists in multiple isoforms with characteristics of both spectrin and plakin superfamilies. Previously characterized Shot isoforms are similar to spectrin and dystrophin, with an actin-binding domain followed by spectrin repeats. We describe a new large exon within the shot locus, which encodes a series of plakin repeats similar to the COOH terminus of plakins such as plectin and BPAG1e. We find that the plakin repeats are inserted between the actin-binding domain and spectrin repeats, generating isoforms as large as 8,846 residues, which could span 400 nm. These novel isoforms localized to adherens junctions of embryonic and follicular epithelia. Loss of Shot within the follicle epithelium leads to double layering and accumulation of actin and ZO-1 in between, and a reduction of Armadillo and Discs lost within, mutant cells, indicative of a disruption of adherens junction integrity. Thus, we identify a new role for spectraplakins in mediating cell–cell adhesion

Der frühe Beginn der Zwangsstörung

Einleitung: Die vorliegende Untersuchung geht der Fragestellung nach, ob sich eine Zwangsstörung, die bereits im Kindes- bzw. Jugendalter beginnt, von einer Zwangsstörung, die erst im Erwachsenenalter beginnt, hinsichtlich Schweregrad und Symptomatik unterscheidet. Patienten und Methoden: Eine Stichprobe von 370 Patienten mit Zwangsstörung (ICD-10 F42), die sich zwischen 1998 und 2002 stationär in der Psychosomatischen Klinik Windach befanden, wurde in eine Early-Onset-Gruppe (Störungsbeginn ≤15 Jahre) und in eine Late-Onset-Gruppe (Störungsbeginn ≥16 Jahre) aufgeteilt. Die Gruppen wurden über ICD-10-Diagnosen und Y-BOCSWerte verglichen. Ergebnisse: Beim Schweregrad zeigte sich, dass 20,5% der Early-Onset-Gruppe, aber lediglich 8,7% der Late-Onset-Gruppe unter einer «massiven Zwangsstörung» leiden. Bei der Symptomatik zeigte sich, dass die Early-Onset-Gruppe häufiger die Diagnose «Zwangsgedanken und -handlungen gemischt» (76,9%)erhält als die Late-Onset-Gruppe (61,8%). Außerdem nennt die Early-Onset-Gruppe sowohl für die Gegenwart als auch für die Vergangenheit mehr Symptome als die Late-Onset-Gruppe (Gegenwart 8,2 vs. 7,0; Vergangenheit 5,5 vs. 3,9 Symptomgruppen). Weiter ergaben sich inhaltliche Unterschiede der Zwangsgedanken und Zwangshandlungen. Schlussfolgerungen: Early-Onset-Patienten scheinen häufiger von einer massiven Form der Zwangsstörung und einer größeren Symptomvielfalt betroffen zu sein als Late-Onset-Patienten. Ob es sich bei der Zwangsstörung mit Beginn im Kindes- und Jugendalter um einen abgrenzbaren Subtypus handelt, konnte jedoch in dieser Untersuchung nicht eindeutig geklärt werden und bedarf weiterer Forschungen.Introduction: This study investigates if obsessive compulsive disorder with early onset differs in severity and symptomatology from that with late onset. Patients and Methods: A sample of 370 patients with obsessive compulsive disorder (OCD; ICD 10 F42) who received in-patient treatment at the psychosomatic clinic of Windach between 1998 and 2002 were divided into an early-onset group (onset ≤15 years) and a late-onset group (onset ≥16 years). Groups were compared regarding ICD-10 diagnosis and Y-BOCS scores. Results: Considering severity of the disorder 20.5% of the early-onset group but merely 8.7% of the late-onset group suffered from an extreme form of OCD. With respect to symptomatology, the early-onset group was diagnosed with ‘obsessions and compulsions, mixed’ (76.9%) more often than the lateonset group (61.8%). Also, the early-onset group reported a wider variety of symptoms both for the present and for the past than the late-onset group (present 8,2 vs 7.0; past 5.5 vs 3.9 types of symptoms). There were also differences in the content of rumination and types of compulsive rituals. Conclusions: Patients with early-onset OCD seem to be more frequently affected by an extreme form of OCD and to experience a higher variety of symptoms than patients with late-onset OCD. If early-onset OCD can be considered a distinct subtype could not be answered unequivocally by the results of this study. This question needs additional research

Measurement of the Neutron Spin Structure Function g1ng_1^n with a Polarized ^3He Target

Results are reported from the HERMES experiment at HERA on a measurement of the neutron spin structure function $g_1^n(x,Q^2)$ in deep inelastic scattering using 27.5 GeV longitudinally polarized positrons incident on a polarized $^3$He internal gas target. The data cover the kinematic range $0.023<x<0.6$ and $1 (GeV/c)^2 < Q^2 <15 (GeV/c)^2$. The integral $\int_{0.023}^{0.6} g_1^n(x) dx$ evaluated at a fixed $Q^2$ of $2.5 (GeV/c)^2$ is $-0.034\pm 0.013(stat.)\pm 0.005(syst.)$. Assuming Regge behavior at low $x$, the first moment $\Gamma_1^n=\int_0^1 g_1^n(x) dx$ is $-0.037\pm 0.013(stat.)\pm 0.005(syst.)\pm 0.006(extrapol.)$.Comment: 4 pages TEX, text available at http://www.krl.caltech.edu/preprints/OAP.htm

Frequency and predictors of relapses following SARS-CoV-2 vaccination in patients with multiple sclerosis: interim results from a longitudinal observational study

Despite protection from severe COVID-19 courses through vaccinations, some people with multiple sclerosis (PwMS) are vaccination-hesitant due to fear of post-vaccination side effects/increased disease activity. The aim was to reveal the frequency and predictors of post-SARS-CoV-2-vaccination relapses in PwMS. This prospective, observational study was conducted as a longitudinal Germany-wide online survey (baseline survey and two follow-ups). Inclusion criteria were age ≥18 years, MS diagnosis, and ≥1 SARS-CoV-2 vaccination. Patient-reported data included socio-demographics, MS-related data, and post-vaccination phenomena. Annualized relapse rates (ARRs) of the study cohort and reference cohorts from the German MS Registry were compared pre- and post-vaccination. Post-vaccination relapses were reported by 9.3% PwMS (247/2661). The study cohort’s post-vaccination ARR was 0.189 (95% CI: 0.167–0.213). The ARR of a matched unvaccinated reference group from 2020 was 0.147 (0.129–0.167). Another reference cohort of vaccinated PwMS showed no indication of increased post-vaccination relapse activity (0.116; 0.088–0.151) compared to pre-vaccination (0.109; 0.084–0.138). Predictors of post-vaccination relapses (study cohort) were missing immunotherapy (OR = 2.09; 1.55–2.79; p < 0.001) and shorter time from the last pre-vaccination relapse to the first vaccination (OR = 0.87; 0.83–0.91; p < 0.001). Data on disease activity of the study cohort in the temporal context are expected for the third follow-up

Flavor Decomposition of the Polarized Quark Distributions in the Nucleon from Inclusive and Semi-inclusive Deep-inelastic Scattering

Spin asymmetries of semi-inclusive cross sections for the production of positively and negatively charged hadrons have been measured in deep-inelastic scattering of polarized positrons on polarized hydrogen and 3He targets, in the kinematic range 0.023<x<0.6 and 1 GeV^2<Q^2<10 GeV^2. Polarized quark distributions are extracted as a function of x for up $(u+u_bar) and down (d+d_bar) flavors. The up quark polarization is positive and the down quark polarization is negative in the measured range. The polarization of the sea is compatible with zero. The first moments of the polarized quark distributions are presented. The isospin non-singlet combination Delta_q_3 is consistent with the prediction based on the Bjorken sum rule. The moments of the polarized quark distributions are compared to predictions based on SU(3)_f flavor symmetry and to a prediction from lattice QCD.Comment: 14 pages, 6 figures (eps format), 10 tables in Latex New version contains tables of asymmetries and correlation matri

Occurrence and risk factors of relapse activity after vaccination against COVID-19 in people with multiple sclerosis: 1-year follow-up results from a nationwide longitudinal observational study

Several studies reported post-SARS-CoV-2-vaccination (PV) symptoms. Even people with multiple sclerosis (PwMS) have concerns about disease activity following the SARS-CoV-2 vaccination. We aimed to determine the proportion of PwMS with PV relapses, the PV annualized relapse rate (ARR), the time from vaccination to subsequent relapses, and identify sociodemographic/clinical risk factors for PV relapses. PwMS were surveyed several times at baseline and four follow-ups as part of a longitudinal observational study regarding the safety and tolerability of the SARS-CoV-2 vaccination. The inclusion criteria for this analysis were age ≥18 years, ≥1 SARS-CoV-2 vaccination, and ≥1-year observation period since initial vaccination. Of 2466 PwMS, 13.8% reported PV relapses (mostly after second [N = 147] or booster vaccination [N = 145]) at a median of 8.0 (first/third quantile: 3.55/18.1) weeks PV, with the shortest period following initial vaccination (3.95 weeks). The ARR was 0.153 (95% confidence interval: 0.138-0.168), with a median observation period since initial vaccination of 1.2 years. Risk factors for PV relapses were younger age, female gender, moderate-severe disability levels, concurrent autoimmune diseases, relapsing-remitting MS courses, no DMT, and relapses within the year prior to the first vaccination. Patients' health conditions before/during initial vaccination may play a more important role in PV relapse occurrence than vaccination per se

The HERMES Spectrometer

The HERMES experiment is collecting data on inclusive and semi-inclusive deep inelastic scattering of polarised positrons from polarised targets of Il, D, and He-3. These data give information on the spin structure of the nucleon. This paper describes the forward angle spectrometer built for this purpose. The spectrometer includes numerous tracking chambers (micro-strip gas chambers, drift and proportional chambers) in front of and behind a 1.3 T.m magnetic field, as well as an extensive set of detectors for particle identification (a lead-glass calorimeter, a pre-shower detector, a transition radiation detector, and a threshold Cherenkov detector). Two of the main features of the spectrometer are its good acceptance and identification of both positrons and hadrons, in particular pions. These characteristics, together with the purity of the targets, are allowing HERMES to make unique contributions to the understanding of how the spins of the quarks contribute to the spin of the nucleon. (C) 1998 Elsevier Science B.V. All rights reserved

Conformation and self-association of peptide amphiphiles based on the KTTKS collagen sequence

Studying peptide amphiphiles (PAs), we investigate the influence of alkyl chain length on the aggregation behavior of the collagen-derived peptide KTTKS with applications ranging from antiwrinkle cosmetic creams to potential uses in regenerative medicine. We have studied synthetic peptides amphiphiles C14− KTTKS (myristoyl Lys-Thr-Thr-Lys-Ser) and C18−KTTKS(stearoyl-Lys-Thr Thr-Lys-Ser) to investigate in detail their physicochemical properties. It is presumed that the hydrophobic chain in these self-assembling peptide amphiphiles enhances peptide permeation across the skin compared to KTTKS alone. Subsequently Cn−KTTKS should act as a prodrug and release the peptide by enzymatic cleavage. Our results should be useful in the further development of molecules with collagen-stimulating activity

Observation of a coherence length effect in exclusive ρ(0) electroproduction

Exclusive incoherent electroproduction of the ρ0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q^2>0.4 GeV^2 and positron energy loss ν from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark-antiquark fluctuations with the nuclear medium