Protein topology of presenilin 1

Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.     

Conformations and folding of lysozyme ions in vacuo

Proton transfer reactivity of isolated charge states of the protein hen egg-white lysozyme shows that multiple distinct conformations of this protein are stable in the gas phase. The reactivities of the 9+ and 10+ charge state ions, formed by electrospray ionization of "native" (disulfide-intact) and "denatured" (disulfide-reduced) solutions, are consistent with values calculated for ions in their crystal structure and fully denatured conformations, respectively. Charge states below 8+ of both forms, formed by proton stripping, have similar or indistinguishable reactivities, indicating that the disulfide-reduced ions fold in the gas phase to a more compact conformation.     

HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.     

Insult, aggression, and the southern culture of honor: An "experimental ethnography."

Three experiments examined how norms characteristic of a "culture of honor" manifest themselves in the cognitions, emotions, behaviors, and physiological reactions of southern White males. Participants were University of Michigan students who grew up in the North or South. In 3 experiments, they were insulted by a confederate who bumped into the participant and called him an "asshole." Compared with northerners (who were relatively unaffected by the insult) southerners were more likely to think their masculine reputation was threatened, more upset (as shown by a rise in cortisol levels), more physiologically primed for aggression (as shown by a rise in testosterone levels), more cognitively primed for aggression, and more likely to engage in aggressive and dominant behavior. Findings highlight the insult–aggression cycle in cultures of honor, in which insults diminish a man's reputation and he tries to restore his status by aggressive or violent behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup

BACKGROUND & AIMS: Antineutrophil cytoplasmic antibodies (ANCA) have been consistently detected in a subgroup of patients with Crohn's disease (CD). This study was designed to determine whether serum ANCA expression in patients with CD characterizes an identifiable clinical subgroup. METHODS: The study population consisted of 69 consecutive patients with an established diagnosis of CD as determined by a combination of characteristic clinical, radiographic, endoscopic, and histopathologic criteria. Sera from the patients were analyzed for the presence of ANCAs using the fixed neutrophil enzyme-linked immunosorbent assay (ELISA) assay. Perinuclear ANCA (pANCA)-positive and cytoplasmic ANCA (cANCA)-positive results by ELISA were confirmed by indirect immunofluorescence staining. Clinical profiles of the ANCA-positive patients with CD were compared with those of patients with CD not expressing ANCA (ANCA-negative). RESULTS: pANCA-positive patients with CD have endoscopically and/or histopathologically documented left-sided colitis and symptoms of left-sided colonic inflammation, clinically reflected by rectal bleeding and mucus discharge, urgency, and treatment with topical agents. One hundred percent of patients with CD expressing pANCA had "UC-like" features. CONCLUSIONS: In patients with CD, serum pANCA expression characterizes a UC-like clinical phenotype. Stratification of CD by serum pANCA provides evidence of heterogeneity within CD and suggests a common intestinal mucosal inflammatory process among a definable subgroup of patients with CD and UC expressing this marker.     

Exploring indicators for quantifying surface urban heat islands of European cities with MODIS land surface temperatures

The term urban heat island describes the phenomenon of altered temperatures in urban areas compared to their rural hinterlands. A surface urban heat island encompasses the patterns of land surface temperatures in urban areas. The classical indicator to describe a surface urban heat island is the difference between urban and rural surface temperatures. However, several other indicators for this purpose have been suggested in the literature. In this study, we compared the eleven different indicators for quantifying surface urban heat islands that were most frequently used in recent publications on remote sensing-based urban heat island assessments. The dataset used here consists of 263 European cities with monthly mean temperatures from MODIS data products for July 2002, January 2003 and July 2003. We found that (i) the indicators individually reveal diurnal and seasonal patterns but show rather low correlations over time, and (ii) for single points in time, the different indicators show only weak correlations, although they are supposed to quantify the same phenomenon. Differentiating cities according to thermal climate zones increased the relationships between the indicators. Thus, we can identify temporal aspects and indicator selection as important factors determining the estimation of urban heat islands. We conclude that research should take into account the differences and instabilities of the indicators chosen for quantifying surface urban heat islands and should use several indicators in parallel for describing the surface urban heat island of a city.     

Solving Third Order Differential Equations with Maximal Symmetry Group

The largest group of Lie symmetries that a third-order ordinary differential equation (ode) may allow has seven parameters. Equations sharing this property belong to a single equivalence class with a canonical representative v ^′′′(u)=0. Due to this simple canonical form, any equation belonging to this equivalence class may be identified in terms of certain constraints for its coefficients. Furthermore a set of equations for the transformation functions to canonical form may be set up for which large classes of solutions may be determined algorithmically. Based on these steps a solution algorithm is described for any equation with this symmetry type which resembles a similar scheme for second order equations with projective symmetry group. Received March 9, 2000; revised June 8, 2000     

Fluid dynamics of a quantized vortex filament in a hole

The behavior of nucleated vortex loops and of remanent vortex filaments in idealized circular and slit-like orifices has been investigated by direct computation. It is found that such vortices can be stretched by the diverging flow on the exit side of the orifice. The energy needed to stretch the vortex is abstracted from the flow field and observed as dissipation. This occurs in the form of discrete phase-slip events in the case of nucleated vortex loops, and in the form of multiple-phase-slip cascades when a remanent vortex is involved.     

Analysis of temperature-dependent optical gain in GaN-InGaN quantum-well structures

The temperature dependent spectral gain in InGaN-GaN multiple quantum-well structures with 10% In content is investigated. Mode gain is measured in a temperature range between 239 K and 312 K using the Hakki-Paoli technique and compared to simulations. The simulation accounts for temperature-dependent polarization dephasing, and hence homogeneous broadening, in a rigorous fashion, without any fit parameter. It is found that the evolution of the gain spectrum with temperature at different drive currents can be modeled using a temperature-independent single value for inhomogeneous broadening. The resulting compositional fluctuations are compared to structural measurements.