N-imidazolebenzyl-histidine substitution in somatostatin and in its octapeptide analogue modulates receptor selectivity and function

Despite 3 decades of focused chemical, biological, structural, and clinical developments, unusual properties of somatostatin (SRIF, 1) analogues are still being uncovered. Here we report the unexpected functional properties of 1 and the octapeptide cyclo(3-14)H-Cys-Phe-Phe-Trp(8)-Lys-Thr-Phe-Cys-OH (somatostatin numbering; OLT-8, 9) substituted by imBzl-l- or -d-His at position 8. These analogues were tested for their binding affinity to the five human somatostatin receptors (sst(1-5)), as well as for their functional properties (or functionalities) in an sst(3) internalization assay and in an sst(3) luciferase reporter gene assay. While substitution of Trp(8) in somatostatin by imBzl-l- or -d-His(8) results in sst(3) selectivity, substitution of Trp(8) in the octapeptide 9 by imBzl-l- or -d-His(8) results in loss of binding affinity for sst(1,2,4,5) and a radical functional switch from agonist to antagonist.

Effects of training and melodic features on mode perception

The two modes most widely used in Western music today convey opposite moods—a distinction that nonmusicians and even young children are able to make. However, the current studies provide evidence that, despite a strong link between mode and affect, mode perception is problematic. Nonmusicians found mode discrimination to be harder than discrimination of other melodic features, and they were not able to accurately classify major and minor melodies with these labels. Although nonmusicians were able to classify major and minor melodies using affective labels, they performed at chance in mode discrimination. Training, in the form of short lessons given to nonmusicians and the natural musical experience of musicians, improved performance, but not to ceiling levels. Tunes with high note density were classified as major, and tunes with low note density as minor, even though these features were actually unrelated in the experimental material. Although these findings provide support for the importance of mode in the perception of emotion, they clearly indicate that these mode perceptions are inaccurate, even in trained individuals, without the assistance of affective labeling.

Abandoned Coal Mine Drainage and Its Remediation: Impacts on Stream Ecosystem Structure and Function

The effects of abandoned mine drainage (AMD) on streams and responses to remediation efforts were studied using three streams (AMD-impacted, remediated, reference) in both the anthracite and the bituminous coal mining regions of Pennsylvania (USA). Response variables included ecosystem function as well as water chemistry and macroinvertebrate community composition. The bituminous AMD stream was extremely acidic with high dissolved metals concentrations, a prolific mid-summer growth of the filamentous alga, Mougeotia, and .10-fold more chlorophyll than the reference stream. The anthracite AMD stream had a higher pH, substrata coated with iron hydroxide(s), and negligible chlorophyll. Macroinvertebrate communities in the AMD streams were different from the reference streams, the remediated streams, and each other. Relative to the reference stream, the AMD stream(s) had (1) greater gross primary productivity (GPP) in the bituminous region and undetectable GPP in the anthracite region, (2) greater ecosystem respiration in both regions, (3) greatly reduced ammonium uptake and nitrification in both regions, (4) lower nitrate uptake in the bituminous (but not the anthracite) region, (5) more rapid phosphorus removal from the water column in both regions, (6) activities of phosphorus-acquiring, nitrogenacquiring, and hydrolytic-carbon-acquiring enzymes that indicated extreme phosphorus limitation in both regions, and (7) slower oak and maple leaf decomposition in the bituminous region and slower oak decomposition in the anthracite region. Remediation brought chlorophyll concentrations and GPP nearer to values for respective reference streams, depressed ecosystem respiration, restored ammonium uptake, and partially restored nitrification in the bituminous (but not the anthracite) region, reduced nitrate uptake to an undetectable level, restored phosphorus uptake to near normal rates, and brought enzyme activities more in line with the reference stream in the bituminous (but not the anthracite) region. Denitrification was not detected in any stream. Water chemistry and macroinvertebrate community structure analyses capture the impact of AMD at the local reach scale, but functional measures revealed that AMD has ramifications that can cascade to downstream reaches and perhaps to receiving estuaries.

Pesiqta Rabbati: a text-linguistic and form-analytical analysis of the rabbinic homily

Pesiqta Rabbati is a unique homiletic midrash that follows the liturgical calendar in its presentation of homilies for festivals and special Sabbaths. This article attempts to utilize Pesiqta Rabbati in order to present a global theory of the literary production of rabbinic/homiletic literature. In respect to Pesiqta Rabbati it explores such areas as dating, textual witnesses, integrative apocalyptic meta-narrative, describing and mapping the structure of the text, internal and external constraints that impacted upon the text, text linguistic analysis, form-analysis: problems in the texts and linguistic gap-filling, transmission of text, strict formalization of a homiletic unit, deconstructing and reconstructing homiletic midrashim based upon form-analytic units of the homily, Neusner’s documentary hypothesis, surface structures of the homiletic unit, and textual variants. The suggested methodology may assist scholars in their production of editions of midrashic works by eliminating superfluous material and in their decoding and defining of ancient texts.

The Design of XML-Based Model and Experiment Description Languages for Network Simulation

The Simulation Automation Framework for Experiments (SAFE) is a project created to raise the level of abstraction in network simulation tools and thereby address issues that undermine credibility. SAFE incorporates best practices in network simulationto automate the experimental process and to guide users in the development of sound scientific studies using the popular ns-3 network simulator. My contributions to the SAFE project: the design of two XML-based languages called NEDL (ns-3 Experiment Description Language) and NSTL (ns-3 Script Templating Language), which facilitate the description of experiments and network simulationmodels, respectively. The languages provide a foundation for the construction of better interfaces between the user and the ns-3 simulator. They also provide input to a mechanism which automates the execution of network simulation experiments. Additionally,this thesis demonstrates that one can develop tools to generate ns-3 scripts in Python or C++ automatically from NSTL model descriptions.

Type 2 diabetes is associated with reduced ATP-binding cassette transporter A1 gene expression, protein and function

Objective Increasing plasma glucose levels are associated with increasing risk of vascular disease. We tested the hypothesis that there is a glycaemia-mediated impairment of reverse cholesterol transport (RCT). We studied the influence of plasma glucose on expression and function of a key mediator in RCT, the ATP binding cassette transporter-A1 (ABCA1) and expression of its regulators, liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor–γ (PPARγ). Methods and Results Leukocyte ABCA1, LXRα and PPARγ expression was measured by polymerase chain reaction in 63 men with varying degrees of glucose homeostasis. ABCA1 protein concentrations were measured in leukocytes. In a sub-group of 25 men, ABCA1 function was quantified as apolipoprotein-A1-mediated cholesterol efflux from 2–3 week cultured skin fibroblasts. Leukocyte ABCA1 expression correlated negatively with circulating HbA1c and glucose (rho = −0.41, p<0.001; rho = −0.34, p = 0.006 respectively) and was reduced in Type 2 diabetes (T2DM) (p = 0.03). Leukocyte ABCA1 protein was lower in T2DM (p = 0.03) and positively associated with plasma HDL cholesterol (HDL-C) (rho = 0.34, p = 0.02). Apolipoprotein-A1-mediated cholesterol efflux correlated negatively with fasting glucose (rho = −0.50, p = 0.01) and positively with HDL-C (rho = 0.41, p = 0.02). It was reduced in T2DM compared with controls (p = 0.04). These relationships were independent of LXRα and PPARγ expression. Conclusions ABCA1 expression and protein concentrations in leukocytes, as well as function in cultured skin fibroblasts, are reduced in T2DM. ABCA1 protein concentration and function are associated with HDL-C levels. These findings indicate a glycaemia- related, persistent disruption of a key component of RCT.

Quantification of the carbonaceous matter origin in submicron marine aerosol by 13C and 14C isotope analysis

Dual carbon isotope anal. of marine aerosol samples has been performed for the first time demonstrating a potential in org. matter apportionment between three principal sources: marine, terrestrial (non-fossil) and fossil fuel due to unique isotopic signatures. The results presented here, utilizing combinations of dual carbon isotope anal., provides conclusive evidence of a dominant biogenic org. fraction to org. aerosol over biol. active oceans. In particular, the NE Atlantic, which is also subjected to notable anthropogenic influences via pollution transport processes, was found to contain 80 % org. aerosol matter of biogenic origin directly linked to plankton emissions. The remaining carbonaceous aerosol was of terrestrial origin. By contrast, for polluted air advected out from Europe into the NE Atlantic, the source apportionment is 30 % marine biogenic, 40 % fossil fuel, and 30 % continental non-fossil fuel. The dominant marine org. aerosol source in the atm. has significant implications for climate change feedback processes. [on SciFinder(R)]

Agrin is required for survival and function of monocytic cells

Agrin, an extracellular matrix protein belonging to the heterogeneous family of heparan sulfate proteoglycans (HSPGs), is expressed by cells of the hematopoietic system but its role in leukocyte biology is not yet clear. Here we demonstrate that agrin has a crucial, nonredundant role in myeloid cell development and functions. We have identified lineage-specific alterations that affect maturation, survival and properties of agrin-deficient monocytic cells, and occur at stages later than stem cell precursors. Our data indicate that the cell-autonomous signals delivered by agrin are sensed by macrophages through the α-DC (DG) receptor and lead to the activation of signaling pathways resulting in rearrangements of the actin cytoskeleton during the phagocytic synapse formation and phosphorylation of extracellular signal-regulated kinases (Erk 1/2). Altogether, these data identify agrin as a novel player of innate immunity.

Practice of ultrasound-guided arthrocentesis and joint injection, including training and implementation, in Europe: results of a survey of experts and scientific societies

To document the practice and training opportunities of US-guided arthrocentesis and joint injection (UGAJ) among rheumatologists in the member countries of the European League Against Rheumatism (EULAR).