julilili42/papers huggingface dataset:
Electrophysiological properties of mouse and epitope-tagged human cardiac sodium channel Nav1.5 expressed in HEK293 cells
2013-04-05

<ns4:p><ns4:bold>Background: </ns4:bold>The pore-forming subunit of the cardiac sodium channel, Na<ns4:sub>v</ns4:sub>1.5, has been previously found to be mutated in genetically determined arrhythmias. Na<ns4:sub>v</ns4:sub>1.5 associates with many proteins that regulate its function and cellular localisation. In order to identify more <ns4:italic>in situ</ns4:italic> Na<ns4:sub>v</ns4:sub>1.5 interacting proteins, genetically-modified mice with a high-affinity epitope in the sequence of Na<ns4:sub>v</ns4:sub>1.5 can be generated.</ns4:p><ns4:p><ns4:bold>Methods:</ns4:bold> In this short study, we (1) compared the biophysical properties of the sodium current (I<ns4:sub>Na</ns4:sub>) generated by the mouse Na<ns4:sub>v</ns4:sub>1.5 (mNa<ns4:sub>v</ns4:sub>1.5) and human Na<ns4:sub>v</ns4:sub>1.5 (hNa<ns4:sub>v</ns4:sub>1.5) constructs that were expressed in HEK293 cells, and (2) investigated the possible alterations of the biophysical properties of the human Na<ns4:sub>v</ns4:sub>1.5 construct that was modified with specific epitopes.</ns4:p><ns4:p><ns4:bold>Results: </ns4:bold>The biophysical properties of mNa<ns4:sub>v</ns4:sub>1.5 were similar to the human homolog. Addition of epitopes either up-stream of the N-terminus of hNa<ns4:sub>v</ns4:sub>1.5 or in the extracellular loop between the S5 and S6 transmembrane segments of domain 1, significantly decreased the amount of I<ns4:sub>Na</ns4:sub> and slightly altered its biophysical properties. Adding green fluorescent protein (GFP) to the N-terminus did not modify any of the measured biophysical properties of hNa<ns4:sub>v</ns4:sub>1.5.</ns4:p><ns4:p><ns4:bold>Conclusions:</ns4:bold> These findings have to be taken into account when planning to generate genetically-modified mouse models that harbour specific epitopes in the gene encoding mNa<ns4:sub>v</ns4:sub>1.5.</ns4:p>
Endothelial SRF/MRTF ablation causes vascular disease phenotypes in murine retinae
2013-04-07

Retinal vessel homeostasis ensures normal ocular functions. Consequently, retinal hypovascularization and neovascularization, causing a lack and an excess of vessels, respectively, are hallmarks of human retinal pathology. We provide evidence that EC-specific genetic ablation of either the transcription factor SRF or its cofactors MRTF-A and MRTF-B, but not the SRF cofactors ELK1 or ELK4, cause retinal hypovascularization in the postnatal mouse eye. Inducible, EC-specific deficiency of SRF or MRTF-A/MRTF-B during postnatal angiogenesis impaired endothelial tip cell filopodia protrusion, resulting in incomplete formation of the retinal primary vascular plexus, absence of the deep plexi, and persistence of hyaloid vessels. All of these features are typical of human hypovascularization-related vitreoretinopathies, such as familial exudative vitreoretinopathies including Norrie disease. In contrast, conditional EC deletion of Srf in adult murine vessels elicited intraretinal neovascularization that was reminiscent of the age-related human pathologies retinal angiomatous proliferation and macular telangiectasia. These results indicate that angiogenic homeostasis is ensured by differential stage-specific functions of SRF target gene products in the developing versus the mature retinal vasculature and suggest that the actin-directed MRTF-SRF signaling axis could serve as a therapeutic target in the treatment of human vascular retinal diseases.
Laughing at a saint? Miracle and irony in the Vita Gangulfi prima
2013-04-07

This article examines the Vita Gangulfi prima , a text which was frequently copied and widely circulated in the Middle Ages. It argues that the text can be understood as an ironic discourse on miracle stories in hagiographical texts: the central message of the Vita is that meek and penitential living leads to sanctity, and not the enjoyment of stories about miracles. At the same time, the Vita presents the reader to some extent with a performance of this idea. The reader who sees through to the Vita's ironic intent is encouraged to laugh at the saint and thereby comes to comprehend the very sin for which the various characters in the Vita are punished, while the text simultaneously depicts penitence as the way out of this sinfulness. The Vita's critique of miracle stories made an eccentric contribution to a discourse which was also carried on in a number of other hagiographical texts of the early tenth century.
Microbiological processes in banded iron formation deposition
2013-04-08

Abstract Banded iron formations have been studied for decades, particularly regarding their potential as archives of the Precambrian environment. In spite of this effort, the mechanism of their deposition and, specifically, the role that microbes played in the precipitation of banded iron formation minerals, remains unresolved. Evidence of an anoxic Earth with only localized oxic areas until the Great Oxidation Event ca 2·45 to 2·32 Ga makes the investigation of O 2 ‐independent mechanisms for banded iron formation deposition relevant. Recent studies have explored the long‐standing proposition that Archean banded iron formations may have been formed, and diagenetically modified, by anaerobic microbial metabolisms. These efforts encompass a wide array of approaches including isotope, ecophysiological and phylogeny studies, molecular and mineral marker analysis, and sedimentological reconstructions. Herein, the current theories of microbial processes in banded iron formation mineral deposition with particular regard to the mechanisms of chemical sedimentation and post‐depositional alteration are described. The main findings of recent years are summarized and compared here, and suggestions are made regarding cross‐disciplinary information still required to constrain the role of the biosphere in banded iron formation deposition.
Overcoming drug-resistant herpes simplex virus (HSV) infection by a humanized antibody
2013-04-08

Despite the availability of antiviral chemotherapy, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections remain a severe global health problem. Of particular concern is the growing incidence of drug resistance in immunocompromised patients, which stresses the urgency to develop new effective treatment alternatives. We have developed a humanized monoclonal antibody (mAb hu2c) that completely abrogates viral cell-to-cell spread, a key mechanism by which HSV-1/2 escapes humoral immune surveillance. Moreover, mAb hu2c neutralized HSV fully independent of complement and/or immune effector cell recruitment in a highly efficient manner. Prophylactic and therapeutic administration of mAb hu2c completely prevented infection-related mortality of severely immunodeficient mice being challenged with a lethal dose of HSV-1. The high neutralization capacity of mAb hu2c was fully maintained toward clinical HSV isolates being multiresistant to standard antiviral drugs, and infection was fully resolved in 7/8 nonobese diabetic/SCID mice being infected with a multidrug resistant HSV-1 patient isolate. Immunohistochemical studies revealed no significant cross-reactivity of the antibody toward human tissues. These features warrant further clinical development of mAb hu2c as an immunotherapeutic compound for the management of severe and particularly drug-resistant HSV infections.
Plant Core Environmental Stress Response Genes Are Systemically Coordinated during Abiotic Stresses
2013-04-08

Studying plant stress responses is an important issue in a world threatened by global warming. Unfortunately, comparative analyses are hampered by varying experimental setups. In contrast, the AtGenExpress abiotic stress experiment displays intercomparability. Importantly, six of the nine stresses (wounding, genotoxic, oxidative, UV-B light, osmotic and salt) can be examined for their capacity to generate systemic signals between the shoot and root, which might be essential to regain homeostasis in Arabidopsis thaliana. We classified the systemic responses into two groups: genes that are regulated in the non-treated tissue only are defined as type I responsive and, accordingly, genes that react in both tissues are termed type II responsive. Analysis of type I and II systemic responses suggest distinct functionalities, but also significant overlap between different stresses. Comparison with salicylic acid (SA) and methyl-jasmonate (MeJA) responsive genes implies that MeJA is involved in the systemic stress response. Certain genes are predominantly responding in only one of the categories, e.g., WRKY genes respond mainly non-systemically. Instead, genes of the plant core environmental stress response (PCESR), e.g., ZAT10, ZAT12, ERD9 or MES9, are part of different response types. Moreover, several PCESR genes switch between the categories in a stress-specific manner.
Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes
2013-04-08

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing.
Chorein sensitivity of cytoskeletal organization and degranulation of platelets
2013-04-08

Chorea‐acanthocytosis (ChAc), a lethal disease caused by defective chorein, is characterized by neurodegeneration and erythrocyte acanthocytosis. The functional significance of chorein in other cell types remained ill‐defined. The present study revealed chorein expression in blood platelets. As compared to platelets from healthy volunteers, platelets from patients with ChAc displayed a 47% increased globular/ filamentous actin ratio, indicating actin depolymerization. Moreover, phosphoinositide‐3‐kinase subunit p85 phosphorylation, p21 protein‐activated kinase (PAK1) phosphorylation, as well as vesicle‐associated membrane protein 8 (VAMP8) expression were significantly reduced in platelets from patients with ChAc (by 17, 22, and 39%, respectively) and in megakaryocytic (MEG‐01) cells following chorein silencing (by 16, 54, and 11%, respectively). Activation‐induced platelet secretion from dense granules (ATP release) and α granules (P‐selectin exposure) were significantly less (by 55% after stimulation with 1 μg/ml CRP and by 33% after stimulation with 5 μM TRAP, respectively) in ChAc platelets than in control platelets. Furthermore, platelet aggregation following stimulation with different platelet agonists was significantly impaired. These observations reveal a completely novel function of chorein, i.e. , regulation of secretion and aggregation of blood platelets.—Schmidt, E.‐M., Schmid, E., Münzer, P., Hermann, A., Eyrich, A.‐K., Russo, A., Walker, B., Gu, S., Müller vom Hagen, J., Faggio, C., Schaller, M., Föller, M., Schöls, L., Gawaz, M., Borst, O., Storch, A., Stournaras, C., Lang, F. Chorein sensitivity of cytoskeletal organization and degranulation of platelets. FASEB J. 27, 2799‐2806 (2013). www.fasebj.org
Scanning Behavior in Echolocating Common Pipistrelle Bats (Pipistrellus pipistrellus)
2013-04-08

Echolocating bats construct an auditory world sequentially by analyzing successive pulse-echo pairs. Many other mammals rely upon a visual world, acquired by sequential foveal fixations connected by visual gaze saccades. We investigated the scanning behavior of bats and compared it to visual scanning. We assumed that each pulse-echo pair evaluation corresponds to a foveal fixation and that sonar beam movements between pulses can be seen as acoustic gaze saccades. We used a two-dimensional 16 microphone array to determine the sonar beam direction of succeeding pulses and to characterize the three dimensional scanning behavior in the common pipistrelle bat (Pipistrellus pipistrellus) flying in the field. We also used variations of signal amplitude of single microphone recordings as indicator for scanning behavior in open space. We analyzed 33 flight sequences containing more than 700 echolocation calls to determine bat positions, source levels, and beam aiming. When searching for prey and orienting in space, bats moved their sonar beam in all directions, often alternately back and forth. They also produced sequences with irregular or no scanning movements. When approaching the array, the scanning movements were much smaller and the beam was moved over the array in small steps. Differences in the scanning pattern at various recording sites indicated that the scanning behavior depended on the echolocation task that was being performed. The scanning angles varied over a wide range and were often larger than the maximum angle measurable by our array. We found that echolocating bats use a "saccade and fixate" strategy similar to vision. Through the use of scanning movements, bats are capable of finding and exploring targets in a wide search cone centered along flight direction.
Automated transcription start site prediction for comparative Transcriptomics using the SuperGenome
2013-04-08

RNA deep-sequencing (RNA-seq) has been revolutionizing transcriptome analyses. Despite the high-throughput nature of this technology, very often transcriptome features such as transcription start sites (TSS) are still manually annotated. The problem is compounded for comparative transcriptomics of several species. We developed the SuperGenome algorithm, a novel general approach to comparative and integrative analysis of RNA-seq data. The SuperGenome can be utilized for comparative analyses of gene expression data, promoter sequences or SNPs in several species. Furthermore, it can be used for the comparative detection of TSS, for which we developed an automated TSS prediction method for differential RNA-seq experiments.
Quantum stabilization of a closed Nielsen-Olesen string
2013-04-08

We revisit the classical instability of closed strings in the Abelian Higgs\\nmodel. The instability is expressed by a vanishing energy as the torus-like\\nconfiguration shrinks to zero size. We treat the radius of the torus as a\\ncollective coordinate and demonstrate that a quantum mechanical treatment of\\nthis coordinate leads to a stabilization of the closed string at small radii.\\n
Rifampicin induced virulence determinants increase Candida albicans biofilm formation
2013-04-08

<ns4:p>Increased intravenous catheter use has been paralleled by increased bacterial and yeast bloodstream infection. Biofilm formation, which is associated with the cell surface hydrophobicity (CSH) phenotype, represents a major pathogenicity strategy of<ns4:italic>Candida albicans</ns4:italic>, becoming especially important in the colonization of intravascular medical devices. Increasing evidence shows the induction of virulence factors in<ns4:italic>C. albicans</ns4:italic>by diverse substances. Therefore, we investigated whether rifampicin, an antibiotic shown to be capable of inducing MDR1 expression in<ns4:italic>C. albicans</ns4:italic>may also promote the formation of a pathogenic biofilm. In response to 40 μg/mL rifampicin, an enhanced retention of<ns4:italic>C. albicans</ns4:italic>SC5314 cells on polystyrene culture plates was observed by measuring increased metabolic activity by XTT assay, indicating induction of biofilm formation. Rifampicin treatment also induced fibronectin binding, cell hydrophobicity and germ tube formation. Furthermore, increased RNA and protein expression of CSH1p, a major mediator of CSH, was demonstrated. We conclude that exposure to rifampicin may result in upregulation of key<ns4:italic>Candida</ns4:italic>virulence determinants, potentially boosting pathogenicity and supporting biofilm formation. This finding gains clinical significance from the increasing popularity of rifampicin-coated catheters, which might provide an advantageous gateway for<ns4:italic>Candida</ns4:italic>bloodstream infections.</ns4:p>
Use of illicit and prescription drugs for cognitive or mood enhancement among surgeons
2013-04-09

The use of illicit and prescription drugs for CE or ME is an underestimated phenomenon among surgeons which is generally attributable to high workload, perceived workload, and private stress. Such intake of drugs is associated with attempts to counteract fatigue and loss of concentration. However, drug use for CE may lead to addiction and to overestimation of one's own capabilities, which can put patients at risk. Coping strategies should be taught during medical education.
PSKR1 and PSY1R-mediated regulation of plant defense responses
2013-04-09

Plant peptide signaling is an upcoming topic in many areas of plant research. Our recent findings show that the tyrosine sulfated peptide receptors PSKR1 and PSY1R are not only involved in growth and development but also in plant defense. They modulate salicylate- and jasmonate-dependent defense pathways in an antagonistic manner and this phenomenon might be dependent on the age and developmental stage of the plant. Here we discuss how the endogenous peptides might integrate growth, wounding, senescence and the opposing defense pathways against biotrophic and necrotrophic pathogens for increased fitness of the plant.
Approach to the Core Structure of the Polycyclic Alkaloid Palhinine A
2013-04-09

A synthesis of the tricyclic partly substituted core structure of palhinine A was achieved. To reach the bicyclo[2.2.2]octane motif a domino Michael reaction was employed as a key step. After Arndt–Eistert homologation and intramolecular aldol reaction the isotwistane core could be obtained after simple functional-group manipulations.
Agree or Disagree?
2013-04-09

Consensus obtained in personality judgments based on thin slices of behavior was examined by manipulating the shared meaning of the traits being judged, the accountability for the judgments, and the amount of target information. 160 judges rated a total of 60 teachers on the Big Five personality dimensions. Consensus was approached from a judge and from a target perspective. A shared meaning had a negative effect on consensus in Extraversion ratings. Accountability had a consistently negative effect across consensus perspectives. A positive effect for amount of target information was found for Neuroticism. Additionally, it was shown that, under different conditions, judgments were based more or less on shared stereotypes. Results suggest that the degree to which we agree on our judgments of others can easily be manipulated by external influences, thus involving significant practical implication for various contexts.
A 0535+26 in the April 2010 outburst: probing the accretion regime at work
2013-04-10

Context. A number of accreting X-ray pulsars experience spectral changes, both on the long time scales and on the time scales of the neutron star spin period. The sources seem to form two distinct groups that differ by the type of the spectral variations with flux. Such a bimodality probably reflects two different regimes of accretion that may result in a particular pulsar depending on its luminosity – so-called sub- and super-critical regimes. Aims. We investigated the behavior of the spectral parameters of the Be/X-ray binary system A 0535+26, as a function of flux and pulse phase. Methods. We used the data collected with INTEGRAL and RXTE during the April 2010 outburst of the source. We analyzed the phase-averaged and phase-resolved spectra and performed pulse-to-pulse spectral analysis of the pulsar. Results. Our analysis reveals variability in the continuum parameters of the source’s pulse-averaged spectrum with flux. The pulse-averaged cyclotron line energy does not change with the source luminosity during the outburst, which is consistent with previous studies. Our pulse-phase resolved and pulse-to-pulse analyses reveal, however, indications for a positive correlation of the cyclotron line energy with flux, as well as a flux-dependence of the continuum parameters. Based on the observed behavior, we argue that A 0535+26 operates at the sub-critical accretion regime.
Discovery of a 168.8 s X-ray pulsar transiting in front of its Be companion star in the Large Magellanic Cloud
2013-04-11

\\n Aims. We report the discovery of LXP 169, a new high-mass X-ray binary in the Large Magellanic Cloud. The optical counterpart has been identified and appears to exhibit an eclipsing light curve. We performed follow-up observations to clarify the eclipsing nature of the system.\\n Methods. Energy spectra and time series were extracted from two XMM-Newton observations to search for pulsations, characterise the spectrum, and measure spectral and timing changes. Long-term X-ray variability was studied using archival ROSAT data. The XMM-Newton positions were used to identify the optical counterpart. We obtained ultraviolet to near-infrared photometry to characterise the companion, along with its 4000 d I-band light curve and colour–magnitude variability. We observed LXP 169 with Swift at two predicted eclipse times.\\n Results. We found a spin period of 168.8 s that did not change between two XMM-Newton observations. The X-ray spectrum, well characterised by a power law, was harder when the source was brighter. The X-ray flux of LXP 169 is found to be variable by a factor of at least 10. The counterpart is highly variable on short and long timescales, and its photometry is that of an early-type star with an ouflowing circumstellar disc producing a near-infrared excess. This classifies the source as a Be/X-ray binary pulsar. We observe a transit in the ultraviolet, thereby confirming that the companion star itself is eclipsed. We give an ephemeris for the transit of MJD \\n\\t\\t56 203.877-0.197+0.934 + N × (24.329±0.008). We propose and discuss the scenario where the matter captured from the companion’s equatorial disc creates an extended region of high density around the neutron star, which partially eclipses the companion as the neutron star transits in front of it.\\n Conclusions. This is most likely the first time the compact object in an X-ray binary is observed to eclipse its companion star. LXP 169 would be the first eclipsing Be/X-ray binary, and a wealth of important information might be gained from additional observations, such as a measure of the possible Be disc/orbital plane misalignment, or the mass of the neutron star.\\n
Comparison of abstract decision encoding in the monkey prefrontal cortex, the presupplementary, and cingulate motor areas
2013-04-11

Deciding between alternatives is a critical element of flexible behavior. Perceptual decisions have been studied extensively in an action-based framework. Recently, we have shown that abstract perceptual decisions are encoded in prefrontal cortex (PFC) neurons ( Merten and Nieder 2012 ). However, the role of other frontal cortex areas remained elusive. Here, we trained monkeys to perform a rule-based visual detection task that disentangled abstract perceptual decisions from motor preparation. We recorded the single-neuron activity in the presupplementary (preSMA) and the rostral part of the cingulate motor area (CMAr) and compared it to the results previously found in the PFC. Neurons in both areas traditionally identified with motor planning process the abstract decision independently of any motor preparatory activity by similar mechanisms as the PFC. A larger proportion of decision neurons and a higher strength of decision encoding was found in the preSMA than in the PFC. Neurons in both areas reliably predicted the monkeys' decisions. The fraction of CMAr decision neurons and their strength of the decision encoding were comparable to the PFC. Our findings highlight the role of both preSMA and CMAr in abstract cognitive processing and emphasize that both frontal areas encode decisions prior to the preparation of a motor output.