Correct regionalization of a tissue primordium is essential for coordinated morphogenesis.

During organ development, tubular organs often form from flat epithelial primordia. In the placodes of the forming tubes of the salivary glands in the Drosophila embryo, we previously identified spatially defined cell behaviors of cell wedging, tilting, and cell intercalation that are key to the initial stages of tube formation. Here, we address what the requirements are that ensure the continuous formation of a narrow symmetrical tube from an initially asymmetrical primordium whilst overall tissue geometry is constantly changing. We are using live-imaging and quantitative methods to compare wild-type placodes and mutants that either show disrupted cell behaviors or an initial symmetrical placode organization, with both resulting in severe impairment of the invagination. We find that early transcriptional patterning of key morphogenetic transcription factors drives the selective activation of downstream morphogenetic modules, such as GPCR signaling that activates apical-medial actomyosin activity to drive cell wedging at the future asymmetrically placed invagination point. Over time, transcription of key factors expands across the rest of the placode and cells switch their behavior from predominantly intercalating to predominantly apically constricting as their position approaches the invagination pit. Misplacement or enlargement of the initial invagination pit leads to early problems in cell behaviors that eventually result in a defective organ shape. Our work illustrates that the dynamic patterning of the expression of transcription factors and downstream morphogenetic effectors ensures positionally fixed areas of cell behavior with regards to the invagination point. This patterning in combination with the asymmetric geometrical setup ensures functional organ formation

A dynamic microtubule cytoskeleton directs medial actomyosin function during tube formation

The cytoskeleton is a major determinant of cell-shape changes that drive the formation of complex tissues during development. Important roles for actomyosin during tissue morphogenesis have been identified, but the role of the microtubule cytoskeleton is less clear. Here, we show that during tubulogenesis of the salivary glands in the fly embryo, the microtubule cytoskeleton undergoes major rearrangements, including a 90° change in alignment relative to the apicobasal axis, loss of centrosomal attachment, and apical stabilization. Disruption of the microtubule cytoskeleton leads to failure of apical constriction in placodal cells fated to invaginate. We show that this failure is due to loss of an apical medial actomyosin network whose pulsatile behavior in wild-type embryos drives the apical constriction of the cells. The medial actomyosin network interacts with the minus ends of acentrosomal microtubule bundles through the cytolinker protein Shot, and disruption of Shot also impairs apical constriction

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

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

Stereotactic or conformal radiotherapy for adrenal metastases: patient characteristics and outcomes in a multicenter analysis

To report outcome (freedom from local progression: FFLP, overall survival: OS, and toxicity) after stereotactic, palliative, or highly conformal fractionated (&gt; 12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤ 12 fractions, biologically effective dose, (BED10) ≥ 50 Gy), 3DCRT/IMRT (&gt; 12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 &lt; 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/Log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). 326 patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT, and Pall-RT in 260, 27, and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%), and melanoma (6.7%). Unadjusted FFLP was higher after SBRT v. Pall-RT (p&nbsp;=&nbsp;0.026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4%, and 27.7%). OS was longer after SBRT v. other groups (p &lt; 0.05) and increased in patients with locally-controlled metastases in a landmark analysis (p &lt; 0.0001). Toxicity was mostly mild; notably, 4 cases of adrenal insufficiency occurred, 2 of which were likely caused by immunotherapy or tumor progression. RT for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. 1-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway

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