julilili42/papers huggingface dataset:
The Effect of 6-Weeks of Aerobic Exercise Training on Serum Fetuin-A levels in Non-Diabetic Obese Women
2010-05-21

Emerging evidence suggests that fetuin-A, a liver-derived glycoprotein, represents an important factor in the pathophysiology of the metabolic syndrome, type 2 diabetes and cardiovascular disease. So far circulating fetuin-A was found to be increased in fatty liver disease, however, the precise mechanisms regulating fetuin-A expression and secretion are largely unknown. Here we assessed serum fetuin-A levels in 14 non-diabetic, obese women (BMI 36.5 ± 1.5 kg/m (2)) before and after a 6-week aerobic exercise program. Despite decreasing waist circumference (from 114.9 ± 3.5 to 112.3 ± 3.2 cm; P = 0.006) and body fat content (from 44.1 ± 1.5% to 43.4 ± 1.5%; P = 0.022) regular exercise 3-times per week over a 6-week period did not affect serum fetuin-A levels (before vs. after: 0.440 ± 0.018 vs. 0.440 ± 0.014 μg/ml; P = 0.767). Thus, our data provide evidence against a major role of exercise in the regulation of serum fetuin-A levels in non-diabetic obese women.
Coactive Processing of Dimensionally Redundant Targets Within the Auditory Modality?
2010-05-22

Previous reaction time studies have demonstrated coactivation processes within the visual modality for redundant stimuli that differ in two dimensions (e.g., shape and color). The present study provides novel results of analogous processes within the auditory modality. A redundant-target effect (RTE) was obtained in a Go/NoGo experiment using tones that differed in location and/or frequency. Participants were asked to respond to a specific tone location (e.g., left) and/or tone frequency (e.g., 200 Hz) of auditory stimuli. For redundant targets (e.g., a 200 Hz tone presented to the left), an RTE was observed which was too large to be explained by mere statistical facilitation. Therefore, responses to redundant targets were triggered by a combined activation of the target dimensions. The results are consistent with the modular hybrid account of Mordkoff and Yantis (1993) .
cGMP‐dependent cone photoreceptor degeneration in the cpfl1 mouse retina
2010-05-23

Abstract Inherited retinal degeneration affecting both rod and cone photoreceptors constitutes one of the leading causes of blindness in the developed world. Such degeneration is at present untreatable, and the underlying neurodegenerative mechanisms are unknown, even though certain genetic causes have been established. The rd1 mouse is one of the best characterized animal models for rod photoreceptor degeneration, whereas the cpfl1 mouse is a recently discovered model for cone cell death. Because both animal models are affected by functionally similar mutations in the rod and cone phosphodiesterase 6 genes, respectively, we asked whether the mechanisms of photoreceptor degeneration in these two mouse lines share common pathways. In the present study, we followed the temporal progression of photoreceptor degeneration in the cpfl1 retina, correlated it with specific metabolic markers, and compared it with the wild‐type and the rd1 situation. Similar to corresponding rd1 observations, cpfl1 cone photoreceptor cell death was associated with an accumulation of cyclic guanosine monophosphate (cGMP), activity of calpains, and phosphorylation of vasodilator‐stimulated protein (VASP). Cone degeneration progressed rapidly, with a peak in cell death around postnatal day 24. Furthermore, cpfl1 cone photoreceptor migration during early postnatal development was delayed significantly compared with the corresponding wild‐type retina. The finding that rod and cone photoreceptor degeneration was associated with the same metabolic markers suggests that in both cell types similar degenerative mechanisms are active. This raises the possibility that equivalent neuroprotective strategies may be used to prevent both rod and cone photoreceptor degeneration. J. Comp. Neurol. 518:3604–3617, 2010. © 2010 Wiley‐Liss, Inc.
DIALIGN-TX and multiple protein alignment using secondary structure information at GOBICS
2010-05-23

We introduce web interfaces for two recent extensions of the multiple-alignment program DIALIGN. DIALIGN-TX combines the greedy heuristic previously used in DIALIGN with a more traditional 'progressive' approach for improved performance on locally and globally related sequence sets. In addition, we offer a version of DIALIGN that uses predicted protein secondary structures together with primary sequence information to construct multiple protein alignments. Both programs are available through 'Göttingen Bioinformatics Compute Server' (GOBICS).
Arabidopsis PIS1 encodes the ABCG37 transporter of auxinic compounds including the auxin precursor indole-3-butyric acid
2010-05-24

Differential distribution of the plant hormone auxin within tissues mediates a variety of developmental processes. Cellular auxin levels are determined by metabolic processes including synthesis, degradation, and (de)conjugation, as well as by auxin transport across the plasma membrane. Whereas transport of free auxins such as naturally occurring indole-3-acetic acid (IAA) is well characterized, little is known about the transport of auxin precursors and metabolites. Here, we identify a mutation in the ABCG37 gene of Arabidopsis that causes the polar auxin transport inhibitor sensitive1 ( pis1 ) phenotype manifested by hypersensitivity to auxinic compounds. ABCG37 encodes the pleiotropic drug resistance transporter that transports a range of synthetic auxinic compounds as well as the endogenous auxin precursor indole-3-butyric acid (IBA), but not free IAA. ABCG37 and its homolog ABCG36 act redundantly at outermost root plasma membranes and, unlike established IAA transporters from the PIN and ABCB families, transport IBA out of the cells. Our findings explore possible novel modes of regulating auxin homeostasis and plant development by means of directional transport of the auxin precursor IBA and presumably also other auxin metabolites.
Early tumor dissemination, but late metastasis: insights into tumor dormancy
2010-05-24

The classical model of metastasis is that tumor cell dissemination occurs late in tumor development, after the primary tumor has grown, and that only then will tumor cells invade the local tissue, enter the blood or lymphatic vessels, and colonize new sites to cause metastases. However, evidence increasingly indicates that single tumor cells spread to distant sites much earlier than previously believed. In this issue of the JCI, Eyles and colleagues provide new insight into the mechanisms underlying early tumor cell dissemination, formation of metastases, and tumor immunosurveillance using transgenic mice that spontaneously develop melanomas of the uvea. The authors provide striking evidence that tumor cells start to disseminate during the initial steps of tumor development, that late appearing metastases arise from these early disseminated tumor cells, and that CD8+ T cells inhibit the growth of disseminated tumor cells, surprisingly, not by cytotoxic effects, but through cytostatic effects.
Trafficking through COPII Stabilises Cell Polarity and Drives Secretion during Drosophila Epidermal Differentiation
2010-05-24

Taken together, epithelial differentiation during Drosophila embryogenesis is a concerted action of ECM formation, plasma membrane remodelling and maintenance of cell polarity that all three rely mainly, if not absolutely, on the canonical secretory pathway from the ER over the Golgi apparatus to the plasma membrane. Our results indicate that COPII vesicles constitute a central hub for these processes.
Reply to Kass and Takimoto: Cardiac hypertrophy without cGKI and PDE5 in cardiac myocytes
2010-05-24

Concerning the letter by Kass and Takimoto (1) in PNAS regarding our recent publication (2), we would like to make the following comments. First, we agree that our results showing a “lack of importance” for cGMP-dependent protein kinase I (cGKI) as a modulator of cardiac hypertrophy only refers to the “basal” condition as we clearly stated in the manuscript (1, 2). We purposely did not use guanylyl cyclase stimulators or phosphodiesterase (PDE) inhibitors in these studies. However, we do note that, particularly under the stress conditions of isoproterenol infusion or aortic constriction, atrial natriuretic peptide is substantially increased. This provides substantial drive on cGMP synthesis. It is possible that cGKI needs to be induced by very high cGMP to have protective effects, although induction is not a requirement for the importance of this kinase in other tissues. The point here is that ablation of cGKI from cardiomyocytes and most other tissues (except vasculature) does not potentiate the ability of transverse aortic constriction (TAC) or isoproterenol (ISO) to cause hypertrophy. To us, this is an observation that needs to be reconciled with current dogma. The degrees of hypertrophy obtained in our studies were equal to or even higher than those obtained in many other studies.
Multicenter, Double-Blind, Randomized, Intraindividual Crossover Comparison of Gadobenate Dimeglumine and Gadopentetate Dimeglumine for MR Angiography of Peripheral Arteries
2010-05-25

Higher-quality vessel visualization, greater contrast enhancement, fewer technical failures, and improved diagnostic performance are obtained with gadobenate dimeglumine, relative to gadopentetate dimeglumine, when compared intraindividually at 0.1-mmol/kg doses in patients undergoing contrast-enhanced MR angiography for suspected peripheral arterial occlusive disease.
Policy benchmarking report on neonatal health and social policies in 13 European countries
2010-05-25

Abstract Background and aim: Preterm birth is the major cause of infant mortality and morbidity in both developed and developing countries. In Europe, the prevalence rate of premature birth ranges from 5.5 to 11.4% ‐ an average of 7.1% of all live births. In this report, we aim to compare the current health and social policies, as well as practices in 13 EU member states. Materials and methods: Using desk research, relevant information was gathered from each of the 13 European countries with regard to the prevalence of preterm birth, the cost of preterm birth to healthcare budgets, and the relevant policies, guidelines and practices in place at the national and, in some cases, regional level. The information comes from a range of sources, including government and parent association websites, published scientific literature and media reports. Results: Despite the growing prevalence and increasing costs, neonatal and preterm infant health rank low on the policy agendas of EU member states. Conclusion: Based on the findings, there are a number of recommendations that should be considered. The European Union should (i) recognize the growing challenge of prematurity in Europe and its significant impact on infant morbidity and mortality, (ii) improve neonatal health through the development and implementation of coordinated EU health and social policies, (iii) address the lack of comparable European data on prematurity, including prevalence, mortality, acute morbidity and long‐term impairment, (iv) also increase the standard of neonatal care across Europe by supporting the development and implementation of European medical guidelines and quality standards, (v) support the development of European postgraduate training programmes in Peri‐ and Neonatology in order to increase the quality and availability of trained healthcare professionals.
GABA receptors and prepulse inhibition of acoustic startle in mice and rats
2010-05-26

Abstract The acoustic startle reflex is strongly inhibited by a moderate‐intensity acoustic stimulus that precedes the startling stimulus by roughly 10–1000 ms (prepulse inhibition, PPI). At long interstimulus intervals (ISIs) of 100–1000 ms, PPI in rats is reduced by the muscarinic receptor antagonist scopolamine. Here, we studied the role of GABA receptors in PPI at full ISI ranges in both mice and rats. In B6 mice, PPI begins and ends at shorter ISIs (4 and 1000 ms, respectively) than in Wistar rats (8 and 5000 ms). The GABA A antagonist bicuculline (1 mg/kg i.p.) reduced PPI at ISIs near the peak of PPI in both rats and mice. The GABA B antagonist phaclofen (10 or 30 mg/kg i.p. in rats or mice, respectively) reduced PPI only at long ISIs, similar to the effects of the muscarinic antagonist scopolamine (1 mg/kg i.p.). The effects of phaclofen and scopolamine were additive in rats, suggesting independent effects of GABA B and muscarinic receptors. Patch‐clamp recordings of startle‐mediating PnC (nucleus reticularis pontis caudalis) giant neurons in rat slices show that EPSCs evoked by either trigeminal or auditory fiber stimulation were inhibited by the GABA A/C agonist muscimol or the GABA B agonist baclofen via postsynaptic mechanisms. Hyperpolarization of PnC neurons by muscimol was reversed with bicuculline, indicating that postsynaptic GABA A receptors strongly inhibit PnC giant neurons needed for startle. Therefore, GABA receptors on PnC giant neurons mediate a substantial part of PPI, with GABA A receptors contributing at the peak of PPI, and GABA B receptors adding to muscarinic effects on PPI at long ISIs.
Permanent Genetic Resources added to the Molecular Ecology Resources Database 1 February 2010–31 March 2010
2010-05-26

Abstract This article documents the addition of 228 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Anser cygnoides, Apodemus flavicollis, Athene noctua, Cercis canadensis, Glis glis, Gubernatrix cristata, Haliotis tuberculata, Helianthus maximiliani, Laricobius nigrinus, Laricobius rubidus, Neoheligmonella granjoni, Nephrops norvegicus, Oenanthe javanica, Paramuricea clavata, Pyrrhura orcesi and Samanea saman. These loci were cross‐tested on the following species: Apodemus sylvaticus, Laricobius laticollis and Laricobius osakensis (a proposed new species currently being described).
Design, Synthesis, and Biological Evaluation of a Novel Class of γ-Secretase Modulators with PPARγ Activity
2010-05-26

We present a novel class of dual modulators of gamma-secretase and peroxisome proliferator-activated receptor gamma (PPARgamma) based on the structure of 2-(bis(phenethoxy)pyrimidine-2-ylthio)hexanoic acid 8 (IC(50)(Abeta42) = 22.8 microM, EC(50)(PPARgamma) = 8.3 microM). The modulation of both targets with approved drugs (i.e., amyloid-beta 42 (Abeta42)-lowering NSAIDs for gamma-secretase and glitazones for PPARgamma) has demonstrated beneficial effects in in vitro and in vivo models of Alzheimer's disease (AD). However, although NSAIDs and PPARgamma agonists share similar structural features, no druglike compounds with dual activities as gamma-secretase modulators (GSMs) and PPARgamma agonists have been designed so far. On the basis of our initial lead structure 8, we present the structure-activity relationships (SARs) of broad structural variations. A significant improvement was reached by the introduction of p-trifluoromethyl substituents at the phenyl residues yielding compound 16 (IC(50)(Abeta42) = 6.0 microM, EC(50)(PPARgamma) = 11.0 microM) and the replacement of the two phenyl residues of 8 by cyclohexyl yielding compound 22 (IC(50)(Abeta42) = 5.1 microM, EC(50)(PPARgamma) = 6.6 microM).
Diagnosis of cutaneous tumors with in vivo confocal laser scanning microscopy
2010-05-26

Summary In recent years, in vivo confocal laser scanning microscopy (CLSM) has become an established method for the non‐invasive examination of the skin. In vivo CLSM allows for real‐time imaging of micro‐anatomic cutaneous structures. It has been used to diagnose ambiguous skin tumors and to measure subclinical tumor spread prior to surgery. By additionally providing high power morphologic information, in vivo CLSM helps to reduce unnecessary biopsies. A multitude of diagnostic features for skin tumors has been published. Here we review published diagnostic in vivo CLSM features, and compare them to our own experience in 100 tumors. In combination with clinical examination and dermatoscopy, in vivo CLSM is a valuable additional tool for non‐invasive skin tumor diagnosis.
Neutrino propagation in the nuclear ‘pasta phase’ of neutron stars
2010-05-26

Abstract\\nThe mean free path of neutrino in charged and neutral current reactions is calculated for inhomogeneous nuclear matter which is expected to appear in the inner crust of neutron stars. The relevant cross section depends on Fermi and Gamow-Teller strength distributions, which are derived from the self-consistent Skyrme-Hartree-Fock and a relativistic mean-field calculations. The inhomogeneous nuclear matter, which appears at the boundary between the inner crust and outer core is described in terms of cubic Wigner-Seitz cells. It allows for a microscopic description of the structures in the so-called pasta phase of nuclear configurations and provides a smooth transition to the limit of homogeneous matter. The influence of the pasta phase, its microscopical structure and geometrical shapes on neutrino propagation are consid- ered.
YLoc—an interpretable web server for predicting subcellular localization
2010-05-27

Predicting subcellular localization has become a valuable alternative to time-consuming experimental methods. Major drawbacks of many of these predictors is their lack of interpretability and the fact that they do not provide an estimate of the confidence of an individual prediction. We present YLoc, an interpretable web server for predicting subcellular localization. YLoc uses natural language to explain why a prediction was made and which biological property of the protein was mainly responsible for it. In addition, YLoc estimates the reliability of its own predictions. YLoc can, thus, assist in understanding protein localization and in location engineering of proteins. The YLoc web server is available online at www.multiloc.org/YLoc.
A new chlorophyll d-containing cyanobacterium: evidence for niche adaptation in the genus Acaryochloris
2010-05-27

Abstract Chlorophyll d is a photosynthetic pigment that, based on chemical analyses, has only recently been recognized to be widespread in oceanic and lacustrine environments. However, the diversity of organisms harbouring this pigment is not known. Until now, the unicellular cyanobacterium Acaryochloris marina is the only characterized organism that uses chlorophyll d as a major photopigment. In this study we describe a new cyanobacterium possessing a high amount of chlorophyll d, which was isolated from waters around Heron Island, Great Barrier Reef (23° 26′ 31.2′′ S, 151° 54′ 50.4′′ E). The 16S ribosomal RNA is 2% divergent from the two previously described isolates of A. marina, which were isolated from waters around the Palau islands (Pacific Ocean) and the Salton Sea lake (California), suggesting that it belongs to a different clade within the genus Acaryochloris. An overview sequence analysis of its genome based on Illumina technology yielded 871 contigs with an accumulated length of 8 371 965 nt. Their analysis revealed typical features associated with Acaryochloris, such as an extended gene family for chlorophyll-binding proteins. However, compared with A. marina MBIC11017, distinct genetic, morphological and physiological differences were observed. Light saturation is reached at lower light intensities, Chl d/a ratios are less variable with light intensity and the phycobiliprotein phycocyanin is lacking, suggesting that cyanobacteria of the genus Acaryochloris occur in distinct ecotypes. These data characterize Acaryochloris as a niche-adapted cyanobacterium and show that more rigorous attempts are worthwhile to isolate, cultivate and analyse chlorophyll d-containing cyanobacteria for understanding the ecophysiology of these organisms.
Bacillus subtilis BY‐kinase PtkA controls enzyme activity and localization of its protein substrates
2010-05-27

Summary Bacillus subtilis BY‐kinase PtkA was previously shown to phosphorylate, and thereby regulate the activity of two classes of protein substrates: UDP‐glucose dehydrogenases and single‐stranded DNA‐binding proteins. Our recent phosphoproteome study identified nine new tyrosine‐phosphorylated proteins in B. subtilis . We found that the majority of these proteins could be phosphorylated by PtkA in vitro . Among these new substrates, single‐stranded DNA exonuclease YorK, and aspartate semialdehyde dehydrogenase Asd were activated by PtkA‐dependent phosphorylation. Because enzyme activity was not affected in other cases, we used fluorescent protein tags to study the impact of PtkA on localization of these proteins in vivo . For several substrates colocalization with PtkA was observed, and more importantly, the localization pattern of the proteins enolase, YjoA, YnfE, YvyG, Ugd and SsbA was dramatically altered in Δ ptkA background. Our results confirm that PtkA can control enzyme activity of its substrates in some cases, but also reveal a new mode of action for PtkA, namely ensuring correct cellular localization of its targets.
EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders
2010-05-27

Objectives: These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work‐up is indicated. Search strategy: To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta‐analyses, review papers and guideline recommendations reviewed. Results: The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot‐Marie‐Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders, a precise description of the phenotype, including the use of immunologic methods in the case of myopathies, is considered as good clinical practice to guide molecular genetic testing. Conclusion: These guidelines are provisional and the future availability of molecular‐genetic epidemiological data about the neurogenetic disorders under discussion in this article will allow improved recommendation with an increased level of evidence.