Comparison of SIVmac239(352–382) and SIVsmmPBj41(360–390) enterotoxic synthetic peptides

AbstractTo characterize the active domain of the simian immunodeficiency virus (SIV) surface unit (SU) enterotoxin, peptides corresponding to the V3 loop of SIVmac239 (SIVmac) and SIVsmmPBj41 (SIVpbj) were synthesized and examined for enterotoxic activity, α-helical structure, and interaction(s) with model membranes. SIVmac and SIVpbj induced a dose-dependent diarrhea in 6–8-day-old mouse pups similar to full-length SU. The peptides mobilized [Ca2+]i in HT-29 cells with distinct oscillations and elevated inositol triphosphate levels. Circular dichroism analyses showed the peptides were predominantly random coil in buffer, but increased in α-helical content when placed in a hydrophobic environment or with cholesterol-containing membrane vesicles that are rich in anionic phospholipids. None of the peptides underwent significant secondary structural changes in the presence of neutral vesicles indicating ionic interactions were important. These data show that the SIV SU enterotoxic domain localizes in part to the V3 loop region and interacts with anionic membrane domains on the host cell surface

Penrose Matching Rules from Realistic Potentials in a Model System

We exhibit a toy model of a binary decagonal Al-Co quasicrystal -- closely related to actual structures -- in which realistic pair potentials yield a ground state which appears to perfectly implement Penrose's matching rules, for Hexagon-Boat-Star (HBS) tiles of edge 2.45 A. The second minimum of the potentials is crucial for this result.Comment: 7 pp, 2 figures; proc. "Quasicrystals: Silver Jubilee" (Tel Aviv, 2007), Phil. Mag. in pres

Who Are the Workers Who Never Joined a Union? : Empirical Evidence from Western and Eastern Germany

"Using representative data from the German social survey ALLBUS 2002 and the European Social Survey 2002/03, this paper provides the first empirical analysis of trade union ‘never-membership’ in Germany. We show that between 54 and 59 percent of all employees in Germany have never been members of a trade union. In western Germany, individuals’ probability of ‘never-membership’ is significantly affected by their personal characteristics, their political orientation and (to a lesser degree) their family background. In addition, the presence of a union at the workplace plays a significant role. While the latter factor is also important in eastern Germany, many of the variables which are relevant for ‘never-membership’ in the west prove to be irrelevant in the east. This difference probably reflects the fact that most employees in eastern Germany did not really have a choice not to become union members during the communist regime." (author's abstract)"Mit Daten des ALLBUS 2002 und des European Social Survey 2002/03 analysiert diese Arbeit erstmalig die ‚Nie-Mitgliedschaft’ in deutschen Gewerkschaften. Wir zeigen, dass 54 bis 59 Prozent aller Beschäftigten in Deutschland niemals Mitglied einer Gewerkschaft waren. Die individuelle Wahrscheinlichkeit einer ‚Nie-Mitgliedschaft’ hängt in Westdeutschland signifikant mit persönlichen Merkmalen, der politischen Ausrichtung und (in geringerem Maße) dem familiären Hintergrund zusammen. Darüber hinaus spielt das Vorhandensein einer Gewerkschaft am Arbeitsplatz eine signifikante Rolle. Während letzteres auch in Ostdeutschland von Bedeutung ist, erweisen sich viele der im Westen relevanten Erklärungsvariablen im Osten als irrelevant. Dieser Unterschied spiegelt wahrscheinlich wider, dass die meisten Arbeitnehmer in Ostdeutschland während des SED-Regimes kaum die Wahl hatten, auf eine Gewerkschaftsmitgliedschaft zu verzichten." (Autorenreferat

Can we detect Hot or Cold spots in the CMB with Minkowski Functionals?

In this paper, we investigate the utility of Minkowski Functionals as a probe of cold/hot disk-like structures in the CMB. In order to construct an accurate estimator, we resolve a long-standing issue with the use of Minkowski Functionals as probes of the CMB sky -- namely that of systematic differences ("residuals") when numerical and analytical MF are compared. We show that such residuals are in fact by-products of binning, and not caused by pixelation or masking as originally thought. We then derive a map-independent estimator that encodes the effects of binning, applicable to beyond our present work. Using this residual-free estimator, we show that small disk-like effects (as claimed by Vielva et al.) can be detected only when a large sample of such maps are averaged over. In other words, our estimator is noise-dominated for small disk sizes at WMAP resolution. To confirm our suspicion, we apply our estimator to the WMAP7 data to obtain a null result.Comment: 15 pages, 13 figure

Amyloid-Related memory decline in preclinical Alzheimer’s Disease is dependent on APOE ε4 and is detectable over 18-Months

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer’s disease

Jaw claudication and jaw stiffness in giant cell arteritis: secondary analysis of a qualitative research dataset

Objective Jaw symptoms can be a vital clue to the diagnosis of GCA. Guidelines recommend more intensive treatment if jaw claudication is present. We sought to explore how patients with GCA described their jaw symptoms. Methods We carried out a secondary, qualitative analysis of interview data from 36 participants from the UK (n = 25) and Australia (n = 11), originally collected in order to develop a patient-reported outcome measure for GCA. In all cases, GCA had been confirmed by biopsy/imaging. Interview transcripts were organized within QSR NVivo 12 software and analysed using template analysis. Themes were refined through discussion among the research team, including a patient partner. Results Twenty of 36 participants reported jaw symptoms associated with GCA. The median age of these 20 participants was 76.5 years; 60% were female. Five themes were identified: physical sensations; impact on function; impact on diet; symptom response with CSs; and attribution to other causes. Physical sensations included ache, cramp, stiffness and ‘lockjaw’. Functional impacts included difficulty in eating/chewing, cleaning teeth, speaking or opening the mouth. Dietary impacts included switching to softer food. Response to CSs was not always immediate. Jaw symptoms were initially mis-attributed by some participants to arthritis, age or viral illnesses; or by health-care professionals to a dental cavity, ear infection or teeth-grinding. Conclusion Jaw symptoms in GCA are diverse and can lead to diagnostic confusion with primary temporomandibular joint disorder, potentially contributing to delay in GCA diagnosis. Further research is needed to determine the relationship of jaw stiffness to jaw claudication

Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild cognitive impairment (MCI) participants at baseline and throughout the study, and progressors (N = 166); CN or MCI at baseline but progressing to either MCI or AD during the study. Significant KP changes in progressors included increased 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxyanthranilic acid/anthranilic acid (3-HAA/AA) ratio, the latter having the largest effect on the odds of an individual being a progressor (OR 35.3; 95% CI between 14 and 104). 3-HAA levels were hence surprisingly bi-phasic, high in progressors but low in non-progressors or participants who had already transitioned to MCI or dementia. This is a new, unexpected and interesting result, as most studies of the KP in neurodegenerative disease show reduced 3-HAA/AA ratio after diagnosis. The neuroprotective metabolite picolinic acid was also significantly decreased while the neurotoxic metabolite 3-hydroxykynurenine increased in progressors. These results were significant even after adjustment for confounders. Considering the magnitude of the OR to predict change in cognition, it is important that these findings are replicated in other populations. Independent validation of our findings may confirm the utility of 3-HAA/AA ratio to predict change in cognition leading to dementia in clinical settings