julilili42/papers huggingface dataset:
Histamine transport and metabolism are deranged in salivary glands in Sjogren's syndrome
2013-05-24

Ductal epithelial cells are non-professional histamine-producing cells able to release histamine via OCTs at the resting state up to ∼100 nM, enough to excite H3R/H4R(+) epithelial cells, but not H1R, which requires burst release from mast cells. At the stimulated phase, 50-60 μM histamine passes from the interstitial fluid through the acinar cells to saliva, whereas uptake by ductal cells leads to intracellular degradation by HNMT. OCT3/histamine/H4R-mediated cell maintenance and down-regulation of high histamine levels fail in SS SGs.
ABeppoSAXandXMM-Newtonspectral study of 4U 1735-44
2013-05-24

Low-mass X-ray binary systems consist of a neutron star and a main-sequence companion star. The compact object accretes matter via Roche-lobe overflow, which leads to an accretion disk. In addition to a broad-band continuum emission of a thermal component and a Comptonization part, evidence for a broad iron K{\\alpha} line is found in several sources. Some of them show an asymmetric line profile as well, which could originate from relativistic effects. To understand the spectral behavior of the system 4U 1735-44, we study the broad-band spectrum and especially the iron line feature between 6.4 and 6.97 keV. The shape of the line allows one to determine the region where the line is produced. Together with the continuum models, a geometrical model of the source can be proposed. Furthermore, the effects of pile-up in the XMM-Newton observation are investigated. We analyzed data obtained with the X-ray satellites BeppoSAX and XMM-Newton. The XMM-Newton data were analyzed, specifically taking into account pile-up effects. With the help of the data of these two satellites, we performed a detailed spectral study in an energy range from 0.2-24 keV. During the observations, the source was in the so-called banana state of an atoll source. Fitting the BeppoSAX data, we found line features that we were able to model with a reflection model, whereas the continuum was modeled with a combination of a thermal component and a Comptonization part. The analysis of the XMM-Newton data gave evidence for a broad but not asymmetric iron line. We found no broadening or asymmetry of the line because of pile-up.
Evaluation and Optimization of Virtual Screening Workflows with DEKOIS 2.0 – A Public Library of Challenging Docking Benchmark Sets
2013-05-25

The application of molecular benchmarking sets helps to assess the actual performance of virtual screening (VS) workflows. To improve the efficiency of structure-based VS approaches, the selection and optimization of various parameters can be guided by benchmarking. With the DEKOIS 2.0 library, we aim to further extend and complement the collection of publicly available decoy sets. Based on BindingDB bioactivity data, we provide 81 new and structurally diverse benchmark sets for a wide variety of different target classes. To ensure a meaningful selection of ligands, we address several issues that can be found in bioactivity data. We have improved our previously introduced DEKOIS methodology with enhanced physicochemical matching, now including the consideration of molecular charges, as well as a more sophisticated elimination of latent actives in the decoy set (LADS). We evaluate the docking performance of Glide, GOLD, and AutoDock Vina with our data sets and highlight existing challenges for VS tools. All DEKOIS 2.0 benchmark sets will be made accessible at http://www.dekois.com.
Direct Synthesis of 2,5-Disubstituted Oxazoles through an Iodine-Catalyzed Decarboxylative Domino Reaction
2013-05-27

An efficient iodine-catalyzed synthesis of highly substituted oxazoles is presented. Starting from readily available aryl methyl ketones, β-keto esters, or styrenes, in combination with α-amino acids as amine-containing coupling partners, the corresponding 2-alkyl-5-aryl- substituted oxazoles were obtained in up to 80% yield via a decarboxylative domino reaction.
Performance comparison of not-via addresses and maximally redundant trees (MRTs)
2013-05-27

Maximally redundant trees (MRTs) have been suggested in IETF as a new promising method for fast rerouting in IP networks. Unlike loop-free alternates (LFAs), they can protect against all link and node failures if topology allows. In this work, we compare MRTs and not-via addresses, which also guarantee full-failure coverage. We evaluate path lengths and relative link loads for single link and node failures in various test networks. The performance of MRTs significantly depends on the chosen root node so that the analysis presented in this paper should be performed before the roll-out of MRTs in operational networks.
The Phage Lytic Proteins from the Staphylococcus aureus Bacteriophage vB_SauS-phiIPLA88 Display Multiple Active Catalytic Domains and Do Not Trigger Staphylococcal Resistance
2013-05-28

The increase in antibiotic resistance world-wide revitalized the interest in the use of phage lysins to combat pathogenic bacteria. In this work, we analyzed the specific cleavage sites on the staphylococcal peptidoglycan produced by three phage lytic proteins. The investigated cell wall lytic enzymes were the endolysin LysH5 derived from the S. aureus bacteriophage vB_SauS-phi-IPLA88 (phi-IPLA88) and two fusion proteins between lysostaphin and the virion-associated peptidoglycan hydrolase HydH5 (HydH5SH3b and HydH5Lyso). We determined that all catalytic domains present in these proteins were active. Additionally, we tested for the emergence of resistant Staphylococcus aureus to any of the three phage lytic proteins constructs. Resistant S. aureus could not be identified after 10 cycles of bacterial exposure to phage lytic proteins either in liquid or plate cultures. However, a quick increase in lysostaphin resistance (up to 1000-fold in liquid culture) was observed. The lack of resistant development supports the use of phage lytic proteins as future therapeutics to treat staphylococcal infections.
Burst activity and ultrafast activation kinetics of CaV1.3 Ca2+ channels support presynaptic activity in adult gerbil hair cell ribbon synapses
2013-05-28

Key points The transfer of sound information to the brain relies on the precise release of neurotransmitter from sensory inner hair cell (IHC) ribbon synapses. Neurotransmitter release from IHCs is triggered by Ca 2+ entry mainly through one type of Ca 2+ channel (Ca V 1.3). In this study we show that in near‐physiological conditions Ca 2+ channels open very rapidly following a stimulus with a delay of about 50 μs. Despite the open probability of the Ca 2+ channels being very low, they can switch to a burst‐like mode during a stimulus, maximizing Ca 2+ influx into IHCs. These results help us to better understand how IHCs are able to accomplish high‐fidelity signal transfer at individual auditory ribbon synapses. Abstract Auditory information transfer to afferent neurons relies on precise triggering of neurotransmitter release at the inner hair cell (IHC) ribbon synapses by Ca 2+ entry through Ca V 1.3 Ca 2+ channels. Despite the crucial role of Ca V 1.3 Ca 2+ channels in governing synaptic vesicle fusion, their elementary properties in adult mammals remain unknown. Using near‐physiological recording conditions we investigated Ca 2+ channel activity in adult gerbil IHCs. We found that Ca 2+ channels are partially active at the IHC resting membrane potential (−60 mV). At −20 mV, the large majority (&gt;70%) of Ca 2+ channel first openings occurred with an estimated delay of about 50 μs in physiological conditions, with a mean open time of 0.5 ms. Similar to other ribbon synapses, Ca 2+ channels in IHCs showed a low mean open probability (0.21 at −20 mV), but this increased significantly (up to 0.91) when Ca 2+ channel activity switched to a bursting modality. We propose that IHC Ca 2+ channels are sufficiently rapid to transmit fast signals of sound onset and support phase‐locking. Short‐latency Ca 2+ channel opening coupled to multivesicular release would ensure precise and reliable signal transmission at the IHC ribbon synapse.
Interlayer structure in YBCO-coated conductors prepared by chemical solution deposition
2013-05-28

Abstract: The functionality of YBa2Cu3O7−δ (YBCO)-coated conductor technology depends on the reliability and microstructural properties of a given tape or wire architecture. Particularly, the interface to the metal tape is of interest since it determines the adhesion, mechanical stability of the film and thermal contact of the film to the substrate. A trifluoroacetate (TFA)metal organic deposition (MOD) prepared YBCO film deposited on a chemical solution-derived buffer layer architecture based on CeO2/La2Zr2O7 and grown on a flexible Ni5 at.%W substrate with a {100}〈001〉 biaxial texture was investigated. The YBCO film had a thickness was 440 nm and a jc of 1.02 MA cm−2 was determined at 77 K and zero external field. We present a sub-nanoscale analysis of a fully processed solution-derived YBCO-coated conductor by aberration-corrected scanning transmission electron microscopy (STEM) combined with electron energy-loss spectroscopy (EELS). For the first time, structural and chemical analysis of the valence has been carried out on the sub-nm scale. Intermixing of Ni, La, Ce, O and Ba takes place at these interfaces and gives rise to nanometer-sized interlayers which are a by-product of the sequential annealing process. Two distinct interfacial regions were analyzed in detail: (i) the YBCO/CeO2/La2Zr2O7 region (10 nm interlayer) and (ii) the La2Zr2O7/Ni5 at.%W substrate interface region (20 nm NiO). This is of particular significance for the functionality of these YBCO-coated conductor architectures grown by chemical solution deposition.
Faculty Opinions recommendation of Meta-analysis: peri-operative anti-TNFα treatment and post-operative complications in patients with inflammatory bowel disease.
2013-05-28

BACKGROUND: The impact of peri-operative use of TNFα antagonists on post-operative complications such as infection and wound healing is controversial.AIM: To conduct a systematic review and meta-analysis to assess the impact of peri-operative use of TNFα antagonists on post-operative complications such as infection and wound healing in patients with inflammatory bowel disease (IBD).METHODS: A literature search identified studies that investigated post-operative outcomes in patients with IBD using TNFα antagonists. The primary outcome was the rate of post-operative infectious complications. Secondary outcomes included the rates of non-infectious complications and total complications. Odds ratios (OR) with 95% confidence intervals (CI) are reported.RESULTS: Overall, 18 studies with 4659 participants were eligible for inclusion. Patients with IBD using preoperative anti-TNFα therapies had significant increases in post-operative infectious [OR 1.56 (95% CI, 1.09-2.24)], non-infectious [OR 1.57 (95% CI, 1.14-2.17)] and total complications [OR 1.73 (95% CI, 1.23-2.43)]. Studies limited to patients with Crohn's disease demonstrated a statistically significant increase in infectious (OR 1.93, 95% CI 1.28-2.89) and total (OR 2.19, 95% CI 1.69-2.84) complications, and a trend towards increase in non-infectious complications (OR 1.73, 95% CI 0.94-3.17). Studies of patients with ulcerative colitis did not demonstrate significant increases in infectious (OR 1.39, 95% CI 0.56-3.45), non-infectious (OR 1.40, 95% CI 0.68-2.85), or total complications (OR 1.10, 95% CI 0.81-1.47).CONCLUSION: Anti-TNFα therapies appear to increase the risk of post-operative complications. The increase in risk is small, and may well reflect residual confounding rather than a true biological effect. Nevertheless, physicians should exercise caution when continuing biological therapies during the peri-operative period.© 2013 Blackwell Publishing Ltd. PMID: 23581515
Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder
2013-05-29

Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline-corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.
Otoferlin Couples to Clathrin-Mediated Endocytosis in Mature Cochlear Inner Hair Cells
2013-05-29

The encoding of auditory information with indefatigable precision requires efficient resupply of vesicles at inner hair cell (IHC) ribbon synapses. Otoferlin, a transmembrane protein responsible for deafness in DFNB9 families, has been postulated to act as a calcium sensor for exocytosis as well as to be involved in rapid vesicle replenishment of IHCs. However, the molecular basis of vesicle recycling in IHCs is largely unknown. In the present study, we used high-resolution liquid chromatography coupled with mass spectrometry to copurify otoferlin interaction partners in the mammalian cochlea. We identified multiple subunits of the adaptor protein complex AP-2 (CLAP), an essential component of clathrin-mediated endocytosis, as binding partners of otoferlin in rats and mice. The interaction between otoferlin and AP-2 was confirmed by coimmunoprecipitation. We also found that AP-2 interacts with myosin VI, another otoferlin binding partner important for clathrin-mediated endocytosis (CME). The expression of AP-2 in IHCs was verified by reverse transcription PCR. Confocal microscopy experiments revealed that the expression of AP-2 and its colocalization with otoferlin is confined to mature IHCs. When CME was inhibited by blocking dynamin action, real-time changes in membrane capacitance showed impaired synaptic vesicle replenishment in mature but not immature IHCs. We suggest that an otoferlin-AP-2 interaction drives Ca 2+ - and stimulus-dependent compensating CME in mature IHCs.
Characterization of a Tumor-Associated Activating Mutation of the p110β PI 3-Kinase
2013-05-29

The PI3-kinase pathway is commonly activated in tumors, most often by loss of PTEN lipid phosphatase activity or the amplification or mutation of p110α. Oncogenic mutants have commonly been found in p110α, but rarely in any of the other catalytic subunits of class I PI3-kinases. We here characterize a p110β helical domain mutation, E633K, first identified in a Her2-positive breast cancer. The mutation increases basal p110β activity, but does not affect activation of p85/p110β dimers by phosphopeptides or Gβγ. Expression of the mutant causes increases in Akt and S6K1 activation, transformation, chemotaxis, proliferation and survival in low serum. E633 is conserved among class I PI3 Ks, and its mutation in p110β is also activating. Interestingly, the E633K mutant occurs near a region that interacts with membranes in activated PI 3-kinases, and its mutation abrogates the requirement for an intact Ras-binding domain in p110β-mediated transformation. We propose that the E633K mutant activates p110β by enhancing its basal association with membranes. This study presents the first analysis of an activating oncogenic mutation of p110β.
Bridge to Recovery or Permanent System Implantation: An Eight‐Year Single‐Center Experience in Transvenous Semipermanent Pacing
2013-05-29

Background To compare the risks, implications, and outcomes of transvenous semipermanent pacing as a bridge to permanent system implantation or recovery. Methods We investigated semipermanent transvenous pacing systems consisting of one (n = 57%) or two (n = 3%) bipolar active‐fixation pacing leads and an attached epicutaneous pulse generator implanted from 2000 to 2009. The study population comprised 60 patients aged 72.9 ± 10.5 years (44 [73.3%] male). Forty‐two (70%) were enrolled for complete system explantation for cardiac‐implanted electronic devices associated infection. Eighteen (30%) required temporary pacing in the context of a variety of mostly severe cardiac and noncardiac conditions. The semipermanent pacing systems were removed after implantation of permanent systems or recovery of a noncompromising heart rhythm, respectively. Results Transvenous semipermanent lead implantation was successful in 59 (98.3%) patients. Major and minor intraoperative complications occurred in one case (1.7%) each. The semipermanent systems were left in situ for a mean period of 14.6 ± 8.1 days). They served as a bridge to permanent system implantation in 68.3% (n = 41) and as a bridge to recovery of a noncompromising heart rhythm in 11.7% (n = 7). Four patients (8.3%) died with the semipermanent pacing system in situ, and seven (11.7%) were transferred to external hospitals with semipermanent pacing systems. Conclusions Transvenous semipermanent pacing with bipolar active‐fixation leads and epicutaneous pulse generators provide an important option for prolonged temporary pacing as a bridge to permanent system implantation or recovery.
Cluster Harvesting by Successive Reduction of a Metal Halide with a Nonconventional Reduction Agent: A Benefit for the Exploration of Metal-Rich Halide Systems
2013-05-29

The preparation of thermally labile compounds is a great temptation in chemistry which requires a careful selection of reaction media and reaction conditions. With a new scanning technique denoted here as Cluster Harvesting, a whole series of metal halide compounds is detected by differential thermal analysis (DTA) in fused silica tubes and structurally characterized by X-ray powder diffraction. Experiments of the reduction of tungsten hexahalides with elemental antimony and iron are presented. A cascade of six compounds is identified during the reduction with antimony, and five compounds or phases are monitored following the reduction with iron. The crystal structure of Fe2W2Cl10 is reported, and two other phases in the Fe-W-Cl system are discussed.
Tracking Effects Depend on Tracking Type
2013-05-30

The aim of the present study was to examine how different types of tracking— between-school streaming, within-school streaming, and course-by-course tracking—shape students’ mathematics self-concept. This was done in an internationally comparative framework using data from the Programme for International Student Assessment (PISA). After controlling for individual and track mean achievement, results indicated that generally for students in course-by-course tracking, high-track students had higher mathematics self-concepts and low-track students had lower mathematics self-concepts. For students in between-school and within-school streaming, the reverse pattern was found. These findings suggest a solution to the ongoing debate about the effects of tracking on students’ academic self-concept and suggest that the reference groups to which students compare themselves differ according to the type of tracking.
Spatial integration in mouse primary visual cortex
2013-05-30

Responses of many neurons in primary visual cortex (V1) are suppressed by stimuli exceeding the classical receptive field (RF), an important property that might underlie the computation of visual saliency. Traditionally, it has proven difficult to disentangle the underlying neural circuits, including feedforward, horizontal intracortical, and feedback connectivity. Since circuit-level analysis is particularly feasible in the mouse, we asked whether neural signatures of spatial integration in mouse V1 are similar to those of higher-order mammals and investigated the role of parvalbumin-expressing (PV+) inhibitory interneurons. Analogous to what is known from primates and carnivores, we demonstrate that, in awake mice, surround suppression is present in the majority of V1 neurons and is strongest in superficial cortical layers. Anesthesia with isoflurane-urethane, however, profoundly affects spatial integration: it reduces the laminar dependency, decreases overall suppression strength, and alters the temporal dynamics of responses. We show that these effects of brain state can be parsimoniously explained by assuming that anesthesia affects contrast normalization. Hence, the full impact of suppressive influences in mouse V1 cannot be studied under anesthesia with isoflurane-urethane. To assess the neural circuits of spatial integration, we targeted PV+ interneurons using optogenetics. Optogenetic depolarization of PV+ interneurons was associated with increased RF size and decreased suppression in the recorded population, similar to effects of lowering stimulus contrast, suggesting that PV+ interneurons contribute to spatial integration by affecting overall stimulus drive. We conclude that the mouse is a promising model for circuit-level mechanisms of spatial integration, which relies on the combined activity of different types of inhibitory interneurons.
SOX2 Expression and Prognostic Significance in Ovarian Carcinoma
2013-05-30

The transcription factor SOX2 has been extensively studied for its role in embryonic stem cell self-renewal and pluripotency. More recent data suggest oncogenic functions of SOX2 and demonstrate expression in several carcinoma types, predominantly of squamous cell origin. The gene SOX2 is located at chromosome 3q26, a region that is frequently amplified in ovarian high-grade serous carcinoma. In this study, we correlate SOX2 protein expression and gene-amplification status in ovarian carcinomas with histopathologic criteria and disease outcome. A total of 215 cases of ovarian carcinomas (154 serous, 39 endometrioid, 11 clear cell, 5 mucinous, and 6 transitional cell carcinomas) were analyzed by immunohistochemistry in a tissue microarray for nuclear expression of SOX2. A total of 60.5% of all carcinomas showed SOX2 expression with no significant difference between the major histologic types. Interestingly, SOX2 expression was predominantly a feature of high-grade tumors (G1: 36.4%, G2: 55.6%, G3: 64.0%, P=0.040). In 21.2% of these cases, fluorescence in situ hybridization analysis detected low-level SOX2 gene amplification which was not significantly associated with SOX2 protein expression. However, survival analysis of Stage II to IV high-grade serous carcinomas revealed a favorable effect of SOX2 expression (median disease-free survival 27 vs. 21 mo, P=0.041; median overall survival 39 vs. 25 mo, P=0.062). Further studies are needed to explore whether expression of SOX2 has a specific role in prognosis and therapy response.