Diverging evolution of anti-GAD and anti-IA-2 antibodies in long-standing diabetes mellitus as a function of age at onset: no association with complications

Three short, respectively promising self-rating scales used for the assessment of emotional states, especially depression, were examined: a visual analogue scale with only five items, a short version of the so-called "adjectives list" and a differentiated scale for recording current emotions, possible susceptibility to them and the ability to express them. We checked statistical parameters of item analysis, reliability, validity and time course measurement. This study was carried out with depressive inpatients (n = 35) at the time of admission and 4 weeks later in beginning remission. All three scales proved to be reliable (Cronbach-alpha between 0.48 and 0.97) and partially very valid instruments (concurrent validity between 0.04 and 0.87). In order to improve the documentation of a beginning response to therapeutic efforts, separate recordings of depressive subsyndromes such as "impetus" or "positive emotionality" seem to be quite promising approaches.     

Kinetic analysis of the interaction of actin-depolymerizing factor (ADF)/cofilin with G- and F-actins. Comparison of plant and human ADFs and effect of phosphorylation

The thermodynamics and kinetics of actin interaction with Arabidopsis thaliana actin-depolymerizing factor (ADF)1, human ADF, and S6D mutant ADF1 protein mimicking phosphorylated (inactive) ADF are examined comparatively. ADFs interact with ADP.G-actin in rapid equilibrium (k+ = 155 microM-1.s-1 and k- = 16 s-1 at 4 degreesC under physiological ionic conditions). The kinetics of interaction of plant and human ADFs with F-actin are slower and exhibit kinetic cooperativity, consistent with a scheme in which the initial binding of ADF to two adjacent subunits of the filament nucleates a structural change that propagates along the filament, allowing faster binding of ADF in a "zipper" mode. ADF binds in a non-cooperative faster process to gelsolin-capped filaments or to subtilisin-cleaved F-actin, which are structurally different from standard filaments (Orlova, A., Prochniewicz, E., and Egelman, E. H. (1995) J. Mol. Biol. 245, 598-607). In contrast, the binding of phalloidin to F-actin cooperatively inhibits its interaction with ADF. The ADF-facilitated nucleation of ADP.actin self-assembly indicates that ADF stabilizes lateral interactions in the filament. Plant and human ADFs cause only partial depolymerization of F-actin at pH 8, consistent with identical functions in enhancing F-actin dynamics. Phosphorylation does not affect ADF activity per se, but decreases its affinity for actin by 20-fold.     

An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse

Wallerian degeneration is the degeneration of the distal stump of an injured axon. It normally occurs over a time course of around 24 hr but it is delayed in the slow Wallerian degeneration mutant mouse (C57BL/Wlds) for up to 3 weeks. The gene, which protects from rapid Wallerian degeneration, Wld, previously has been mapped to distal chromosome 4. This paper reports the fine genetic mapping of the Wld locus, the generation of a 1.4-Mb bacterial artificial chromosome and P1 artificial chromosome contig, and the identification of an 85-kb tandem triplication mapping within the candidate region. The mutation is unique to C57BL/Wlds among 36 strains tested and therefore is a strong candidate for the mutation that leads to delayed Wallerian degeneration. There are very few reports of tandem triplications in a vertebrate and no evidence for a mutation mechanism so this unusual mutation was characterized in more detail. Sequence analysis of the boundaries of the repeat unit revealed a minisatellite array at the distal boundary and a matching 8-bp sequence at the proximal boundary. This finding suggests that recombination between short homologous sequences ("illegitimate" or "nonhomologous" recombination) was involved in the rearrangement. In addition, a duplication allele was identified in two Wlds mice, indicating some instability in the repeat copy number and suggesting that the triplication arose from a duplication by unequal crossing over.     

Drug scene roles and HIV risk

AIMS: Drug scenes (social and spatial drug-using and drug-selling environments) have complex role structures. Many drug injectors earn money or drugs as drug or syringe sellers, hit doctors (people who help others to inject) commercial sex workers, or in other roles. This paper aims to measure "role behaviors" of drug injectors; describe which drug injectors are more likely to engage in such role behaviors; and to determine whether roles are related to elements of HIV risk. DESIGN: Cross-sectional study of drug injectors. SETTING: Bushwick, a section of Brooklyn, New York, a major location for injection drug use and drug sales. PARTICIPANTS: Seven hundred and sixty-seven street-recruited drug injectors. MEASUREMENTS: Participants were interviewed about their roles, behaviors, socio-demographics and risk networks; sera were collected and assayed for HIV and hepatitis B core antibody. FINDINGS: Socio-demographic variables are related to role-holding in complex ways. Economic need is generally associated with engaging in drug-scene role behaviors. Holders of these roles are at greater behavioral and network risk for HIV and other blood-borne infections than are other drug injectors. They also engage in extensive communication with other drug users, including discussion of HIV risk reduction. CONCLUSION: Role behaviors can be measured in quantitative studies, and seem to be related to HIV risk. Role-holders may be strategic targets for risk-reduction campaigns. It seems feasible and advisable to measure drug scene role-holding in research on drug users.     

The TempEval challenge: identifying temporal relations in text

TempEval is a framework for evaluating systems that automatically annotate texts with temporal relations. It was created in the context of the SemEval 2007 workshop and uses the TimeML annotation language. The evaluation consists of three subtasks of temporal annotation: anchoring an event to a time expression in the same sentence, anchoring an event to the document creation time, and ordering main events in consecutive sentences. In this paper we describe the TempEval task and the systems that participated in the evaluation. In addition, we describe how further task decomposition can bring even more structure to the evaluation of temporal relations.

Analysing the Combined Health,Social and Economic Impacts of the Corovanvirus Pandemic Using Agent-Based Social Simulation

Minds and Machines - During the COVID-19 crisis there have been many difficult decisions governments and other decision makers had to make. E.g. do we go for a total lock down or keep schools open?...     

Neuropsychological performance and CD4 levels in HIV-1 asymptomatic infection

The performance of 68 HIV-1 seropositive asymptomatic (HIV+) subjects stratified on CD4 levels were compared with 82 HIV-1 seronegative (HIV-) subjects on a battery of neuropsychological, mood state, and perceived health status measures. The neuropsychological test battery included measures of attention, reaction time, memory, intellectual ability, psychomotor speed, frontal lobe or "executive" function, and decision time. None of the HIV+ subjects were taking antiviral agents. The groups did not differ for age, mood state, or WAIS-R Verbal and Performance IQ scores. Due to group differences for education and weekly ethanol consumption, both variables were used as covariates in multivariate analyses of variance. Relatively few differences were observed between subgroups of HIV+ patients or between these subgroups and control subjects. These data suggest that factors other than absolute levels of immunosuppression as expressed by CD4 levels alone, appear to be responsible for the deficits observed in HIV+ asymptomatic patients.     

Substrate requirements of bacterial phosphatidylinositol-specific phospholipase C

A series of symmetric short-chain phosphatidylinositols (PI), including dihexanoyl-PI, diheptanoyl-PI (racemic as well as D and L forms), and 2-methoxy inositol-substituted diheptanoyl-PI, have been synthesized, characterized, and used to investigate key mechanistic questions about phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis. Key results include the following: (i) bacterial PI-PLC exhibits a 5-6-fold "interfacial activation" when its substrate is present in an interface as opposed to existing as a monomer in solution (in fact, the similarity to the activation observed with nonspecific PLC enzymes suggests a similarity in activation mechanisms); (ii) the 2-OH must be free since the enzyme cannot hydrolyze diheptanoyl-2-O-methyl-PI (this is most consistent with the formation of inositol cyclic 1,2-phosphate as a necessary step in catalysis); (iii) the inositol ring must have the D stereochemistry (the L-inositol attached to the lipid moiety is neither a substrate nor an inhibitor); and (iv) the presence of noninhibitory L-PI with the D-PI substrate relieves the diacylglycerol product inhibition detected at approximately 30% hydrolysis.     

Blood and serum substances for markers of prostate cancer

Serummarkers for prostate carcinoma are widely applied for the purpose of early detection of cancer and the differentiation between benign and malignant disease, for the pre-treatment staging of detected prostatic cancers, and for the monitoring of prostate cancer after curative or palliative therapies. This review illustrates the limitations of current markers for prostatic disease in blood en serum. It gives an overview of what is known about PSA and its isoforms, hK2, PSMA, and PSCA, and discusses, based on this information, in what direction current research is developing in order to improve these markers.