julilili42/papers huggingface dataset:
Staphylococcus epidermidis SrrAB Regulates Bacterial Growth and Biofilm Formation Differently under Oxic and Microaerobic Conditions
2014-11-18

ABSTRACT SrrAB expression in Staphylococcus epidermidis strain 1457 (SE1457) was upregulated during a shift from oxic to microaerobic conditions. An srrA deletion (Δ srrA ) mutant was constructed for studying the regulatory function of SrrAB. The deletion resulted in retarded growth and abolished biofilm formation both in vitro and in vivo and under both oxic and microaerobic conditions. Associated with the reduced biofilm formation, the Δ srrA mutant produced much less polysaccharide intercellular adhesion (PIA) and showed decreased initial adherence capacity. Microarray analysis showed that the srrA mutation affected transcription of 230 genes under microaerobic conditions, and 51 genes under oxic conditions. Quantitative real-time PCR confirmed this observation and showed downregulation of genes involved in maintaining the electron transport chain by supporting cytochrome and quinol-oxidase assembly (e.g., qoxB and ctaA ) and in anaerobic metabolism (e.g., pflBA and nrdD ). In the Δ srrA mutant, the expression of the biofilm formation-related gene icaR was upregulated under oxic conditions and downregulated under microaerobic conditions, whereas icaA was downregulated under both conditions. An electrophoretic mobility shift assay further revealed that phosphorylated SrrA bound to the promoter regions of icaR , icaA , qoxB , and pflBA , as well as its own promoter region. These findings demonstrate that in S. epidermidis SrrAB is an autoregulator and regulates biofilm formation in an ica -dependent manner. Under oxic conditions, SrrAB modulates electron transport chain activity by positively regulating qoxBACD transcription. Under microaerobic conditions, it regulates fermentation processes and DNA synthesis by modulating the expression of both the pfl operon and nrdDG .
Human Eye Development Is Characterized by Coordinated Expression of Fibrillin Isoforms
2014-11-18

Fibrillin-1, -2, and, unique to humans, fibrillin-3 are found in various ocular structures during human embryonic eye development, whereas fibrillin-1 dominates the postnatal zonule. We speculate that vasculature spanning the ciliary body and lens, which elaborates fibrillin-2 and -3, may provide an initial scaffold for fibrillin assembly and zonule formation.
Discovery of the VHE gamma-ray source HESS J1832-093 in the vicinity of SNR G22.7-0.2
2014-11-18

The region around the supernova remnant (SNR) W41 contains several TeV sources and has prompted the HESS Collaboration to perform deep observations of this field of view. This resulted in the discovery of the new very high energy (VHE) source HESS J1832−093, at the position RA=18h32m50s±3sstat±2ssyst,Dec=−9∘22′36′′±32′′stat±20′′syst(J2000), spatially coincident with a part of the radio shell of the neighbouring remnant G22.7−0.2. The photon spectrum is well described by a power law of index Γ = 2.6 ± 0.3stat ± 0.1syst and a normalization at 1 TeV of Φ0=(4.8±0.8stat±1.0syst)×10−13cm−2s−1TeV−1. The location of the gamma-ray emission on the edge of the SNR rim first suggested a signature of escaping cosmic rays illuminating a nearby molecular cloud. Then a dedicated XMM–Newton observation led to the discovery of a new X-ray point source spatially coincident with the TeV excess. Two other scenarios were hence proposed to identify the nature of HESS J1832−093. Gamma-rays from inverse Compton radiation in the framework of a pulsar wind nebula scenario or the possibility of gamma-ray production within a binary system are therefore also considered. Deeper multiwavelength observations will help to shed new light on this intriguing VHE source.
Overall survival of relapsed and refractory multiple myeloma patients after adjusting for crossover in the MM‐003 trial for pomalidomide plus low‐dose dexamethasone
2014-11-18

Summary In the phase III MM ‐003 trial, pomalidomide plus low‐dose dexamethasone ( POM +Lo DEX ) improved overall survival ( OS ) versus high‐dose dexamethasone (Hi DEX ) in 455 patients with relapsed and refractory multiple myeloma ( RRMM ) after treatment with bortezomib and lenalidomide. Here, a two‐stage Weibull method was used to adjust for the crossover of patients in the Hi DEX arm to pomalidomide‐based therapy. The adjusted difference in median OS between patients in the POM +Lo DEX and Hi DEX arms was 7·0 months (12·7 vs. 5·7 months, respectively). These findings provide important evidence for understanding the clinical efficacy of pomalidomide on OS benefits seen in RRMM patients.
Solution-Phase Parallel Synthesis of Ruxolitinib-Derived Janus Kinase Inhibitors via Copper-Catalyzed Azide–Alkyne Cycloaddition
2014-11-18

A solution-phase parallel synthesis of triazole-derived ruxolitinib analogues was developed in the current study. The method employs copper-catalyzed azide-alkyne cycloaddition to build up the central triazole template. Product isolation by precipitation and centrifugation is straightforward and yields high purity compounds suited for biological profiling. A simple protocol for accessing the terminal alkyne precursors in high yields was established and a library of ruxolitinib-like triazoles featuring diverse functional groups was prepared. In addition, a model for the binding mode of ruxolitinib to Janus kinase (JAK) 2 is proposed. In contrast to previous models, the pose explains the compound selectivity for JAK1/JAK2 and is in accordance with published structure-activity data. On this basis, a structure-based design hypothesis for inverting the selectivity profile of ruxolitinib is deduced. Application of this strategy identified a moderately potent JAK3 inhibitor (35 nM) with high selectivity against other JAKs, potentially exploiting a covalent binding mode.
Majoring in Selection, and Minoring in Socialization: The Role of the College Experience in Goal Change Post–High School
2014-11-18

Abstract Though it is frequently assumed that the college experience can influence our life goals, this claim has been relatively understudied. The current study examined the role of goals in college major selection, as well as whether major selection influences later goal change. In addition, we examined whether a person's perceptions of his or her peers' goals influence goal setting. Using a sample of German students ( M age = 19 years; n = 3,023 at W ave 1), we assessed life goal levels and changes from high school into college across three assessment occasions. Participants reported their current aspirations, along with the perceived goals of their peers during the college assessments. Using latent growth curve models, findings suggest that life goals upon entering college significantly predict the majors students select. However, this major selection had limited influence on later changes in life goals. Stronger effects were found with respect to perceptions of peers' goals, with students tending to change their goals to better align with their peers. The current study provides evidence that life goals are relatively stable and yet can change during the emerging adult years, in ways that demonstrate the potential influence of the college experience.
Fine Tuning of CaV1.3 Ca2+ Channel Properties in Adult Inner Hair Cells Positioned in the Most Sensitive Region of the Gerbil Cochlea
2014-11-19

Hearing relies on faithful signal transmission by cochlear inner hair cells (IHCs) onto auditory fibres over a wide frequency and intensity range. Exocytosis at IHC ribbon synapses is triggered by Ca(2+) inflow through Ca(V)1.3 (L-type) Ca(2+) channels. We investigated the macroscopic (whole-cell) and elementary (cell-attached) properties of Ca(2+) currents in IHCs positioned at the middle turn (frequency ∼ 2 kHz) of the adult gerbil cochlea, which is their most sensitive hearing region. Using near physiological recordings conditions (body temperature and a Na(+) based extracellular solution), we found that the macroscopic Ca(2+) current activates and deactivates very rapidly (time constant below 1 ms) and inactivates slowly and only partially. Single-channel recordings showed an elementary conductance of 15 pS, a sub-ms latency to first opening, and a very low steady-state open probability (Po: 0.024 in response to 500-ms depolarizing steps at ∼-18 mV). The value of Po was significantly larger (0.06) in the first 40 ms of membrane depolarization, which corresponds to the time when most Ca(2+) channel openings occurred clustered in bursts (mean burst duration: 19 ms). Both the Po and the mean burst duration were smaller than those previously reported in high-frequency basal IHCs. Finally, we found that middle turn IHCs are likely to express about 4 times more Ca(2+) channels per ribbon than basal cells. We propose that middle-turn IHCs finely-tune Ca(V)1.3 Ca(2+) channel gating in order to provide reliable information upon timing and intensity of lower-frequency sounds.
View-Based Organization and Interplay of Spatial Working and Long-Term Memories
2014-11-19

Space perception provides egocentric, oriented views of the environment from which working and long-term memories are constructed. "Allocentric" (i.e. position-independent) long-term memories may be organized as graphs of recognized places or views but the interaction of such cognitive graphs with egocentric working memories is unclear. Here we present a simple coherent model of view-based working and long-term memories, together with supporting evidence from behavioral experiments. The model predicts (i) that within a given place, memories for some views may be more salient than others, (ii) that imagery of a target square should depend on the location where the recall takes place, and (iii) that recall favors views of the target square that would be obtained when approaching it from the current recall location. In two separate experiments in an outdoor urban environment, pedestrians were approached at various interview locations and asked to draw sketch maps of one of two well-known squares. Orientations of the sketch map productions depended significantly on distance and direction of the interview location from the target square, i.e. different views were recalled at different locations. Further analysis showed that location-dependent recall is related to the respective approach direction when imagining a walk from the interview location to the target square. The results are consistent with a view-based model of spatial long-term and working memories and their interplay.
“How Much Is Too Much?” The Social Construction of Elite Youth Athlete Exercise Tolerances From the Coaches’ Perspective
2014-11-19

Coaches are key actors in youth elite sport. As such, they are regularly confronted with professional problems that are both complex and highly consequential. Herein, we address one fundamental coaching problem: the definition of athletes’ exercise tolerance levels. Drawing on the sociology of knowledge, we focus on coaches’ conceptions of exercise tolerance and the sociocultural framing of their reflections. The qualitative analyses of 16 interviews with German youth elite sport coaches reveal that the coaches’ understanding of exercise tolerances is changed by a variety of aspects (e.g., athletes’ injury status, up-coming events, coaching philosophy). Furthermore, the coaches rely heavily on socioculturally shaped experiential knowledge. This results in subjective and flexible definitions of exercise tolerance, which are functional, but bear risks of inappropriate loading.
Female transcriptomic response to male genetic and nongenetic ejaculate variation
2014-11-19

Postcopulatory variation in reproductive success is fundamental for sexual selection. Because evolutionary change is impossible without a heritable basis for variation, the study of postcopulatory variation has mainly focused on genetic differences between males, that is, the effect of sperm competition or differential female responses toward male genotypes (cryptic female choice). The role of environmental components in shaping postcopulatory variation in reproductive success is well known, for example, in the form of damaging lifestyle effects on sperm, but their effect on eliciting female responses has rarely been tested, as has its relative significance compared with male genotypic effects. Here we provide such a test in bedbugs, a species where cryptic female choice has been hypothesized to be directed toward specific sperm genotypes. We measured female transcriptomic responses after experimentally controlling the male genetic and environmental component of the ejaculate. For identical female genetic background and identical male age at mating, we analyzed female gene expression in response to insemination with sperm of 3 different inbred populations (genotypes), each exposed to 1 of 2 environmental treatments (sperm storage duration in the male). Females responded mainly to environmental variation: &gt;15 times more genes were differentially expressed, including stress response genes, compared with male genotypic variation. Our results suggest that postcopulatory natural selection exists and plays a significant role in the evolution and diversification of reproductive traits. Our results add complexity to testing the cryptic female choice hypothesis and show that nongenetic ejaculate effects are an important but underappreciated source of variation in biology.
Reply: PRKAR1B mutations are a rare cause of FUS negative neuronal intermediate filament inclusion disease
2014-11-19

Sir, We thank Pottier et al. , 2014 for their interest in our recent study, reporting the identification of a novel mutation in the PRKAR1B gene in a family with cases of FUS-negative neuronal intermediate filament inclusion disease (NIFID) ...
Cell type-specific transcriptome analysis in the early Arabidopsis thaliana embryo
2014-11-20

In multicellular organisms, cellular differences in gene activity are a prerequisite for differentiation and establishment of cell types. In order to study transcriptome profiles, specific cell types have to be isolated from a given tissue or even the whole organism. However, whole-transcriptome analysis of early embryos in flowering plants has been hampered by their size and inaccessibility. Here, we describe the purification of nuclear RNA from early stage Arabidopsis thaliana embryos using fluorescence-activated nuclear sorting (FANS) to generate expression profiles of early stages of the whole embryo, the proembryo and the suspensor. We validated our datasets of differentially expressed candidate genes by promoter-reporter gene fusions and in situ hybridization. Our study revealed that different classes of genes with respect to biological processes and molecular functions are preferentially expressed either in the proembryo or in the suspensor. This method can be used especially for tissues with a limited cell population and inaccessible tissue types. Furthermore, we provide a valuable resource for research on Arabidopsis early embryogenesis.
mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity
2014-11-20

The epithelial Na+ channel (ENaC) is essential for Na+ homeostasis, and dysregulation of this channel underlies many forms of hypertension. Recent studies suggest that mTOR regulates phosphorylation and activation of serum/glucocorticoid regulated kinase 1 (SGK1), which is known to inhibit ENaC internalization and degradation; however, it is not clear whether mTOR contributes to the regulation of renal tubule ion transport. Here, we evaluated the effect of selective mTOR inhibitors on kidney tubule Na+ and K+ transport in WT and Sgk1-/- mice, as well as in isolated collecting tubules. We found that 2 structurally distinct competitive inhibitors (PP242 and AZD8055), both of which prevent all mTOR-dependent phosphorylation, including that of SGK1, caused substantial natriuresis, but not kaliuresis, in WT mice, which indicates that mTOR preferentially influences ENaC function. PP242 also substantially inhibited Na+ currents in isolated perfused cortical collecting tubules. Accordingly, patch clamp studies on cortical tubule apical membranes revealed that mTOR inhibition markedly reduces ENaC activity, but does not alter activity of K+ inwardly rectifying channels (ROMK channels). Together, these results demonstrate that mTOR regulates kidney tubule ion handling and suggest that mTOR regulates Na+ homeostasis through SGK1-dependent modulation of ENaC activity.
Molecular characterization of Shigella spp. from patients in Gabon 2011-2013
2014-11-20

There is a strong link of Gabonese Shigella spp. isolates with pandemic lineages as they cluster with major global clones and frequently carry atypical class 1 integrons which are frequently reported in Shigella spp. from Asia.
Better Know When (Not) to Think Twice
2014-11-20

Before approaching situations, individuals frequently imagine “what would happen, if . . . .” Such prefactual thought can promote confidence and facilitate behavior preparation when the upcoming situation can benefit from forethought, but it also delays action. The present research tested how social power predicts prefactual thought when its benefits are clear versus ambiguous. Power enhances flexible behavior adaptation and action tendencies—presumably without much forethought. We therefore proposed that power diminishes prefactual thought, unless the situation suggests that such thought is adaptive (i.e., could benefit performance). Power-holders indeed generated less prefactuals than the powerless (Experiments 1 and 2), but only if benefits for performance were ambiguous rather than clear (Experiment 3). These findings indicate that social context factors related to confidence affect prefactual thought, and that power-holders’ flexible adaptation to the situation sometimes elicits inaction (i.e., prefactual thought) rather than spontaneous action.
Recent developments and emerging challenges in international human resource management
2014-11-20

Whereas a comprehensive review of the current state and trends of research in International Human Resource Management (IHRM) is clearly beyond the scope of this introduction (for this, see, for exa...
Inhibitors of c-Jun N-Terminal Kinases: An Update
2014-11-21

The c-Jun N-terminal kinases (JNKs) are serine/threonine kinases implicated in the pathogenesis of various diseases. Recent advances in the development of novel inhibitors of JNKs will be reviewed. Significant progress in the design of JNK inhibitors displaying selectivity versus other kinases has been achieved within the past 4 years. However, the development of isoform selective JNK inhibitors is still an open task.
Quantifying Traces of Tool Use: A Novel Morphometric Analysis of Damage Patterns on Percussive Tools
2014-11-21

Percussive technology continues to play an increasingly important role in understanding the evolution of tool use. Comparing the archaeological record with extractive foraging behaviors in nonhuman primates has focused on percussive implements as a key to investigating the origins of lithic technology. Despite this, archaeological approaches towards percussive tools have been obscured by a lack of standardized methodologies. Central to this issue have been the use of qualitative, non-diagnostic techniques to identify percussive tools from archaeological contexts. Here we describe a new morphometric method for distinguishing anthropogenically-generated damage patterns on percussive tools from naturally damaged river cobbles. We employ a geomatic approach through the use of three-dimensional scanning and geographical information systems software to statistically quantify the identification process in percussive technology research. This will strengthen current technological analyses of percussive tools in archaeological frameworks and open new avenues for translating behavioral inferences of early hominins from percussive damage patterns.
MetaProSIP: Automated Inference of Stable Isotope Incorporation Rates in Proteins for Functional Metaproteomics
2014-11-21

We propose a joint experimental and theoretical approach to the automated reconstruction of elemental fluxes in microbial communities. While stable isotope probing of proteins (protein-SIP) has been successfully applied to study interactions and elemental carbon and nitrogen fluxes, the volume and complexity of mass spectrometric data in protein-SIP experiments pose new challenges for data analysis. Together with a flexible experimental setup, the novel bioinformatics tool MetaProSIP offers an automated high-throughput solution for a wide range of (13)C or (15)N protein-SIP experiments with special emphasis on the analysis of metaproteomic experiments where differential labeling of organisms can occur. The information calculated in MetaProSIP includes the determination of multiple relative isotopic abundances, the labeling ratio between old and new synthesized proteins, and the shape of the isotopic distribution. These parameters define the metabolic capacities and dynamics within the investigated microbial culture. MetaProSIP features a high degree of reproducibility, reliability, and quality control reporting. The ability to embed into the OpenMS framework allows for flexible construction of custom-tailored workflows. Software and documentation are available under an open-source license at www.openms.de/MetaProSIP.
Arbitrary mass Majorana neutrinos in neutrinoless double beta decay
2014-11-21

We revisit the mechanism of neutrinoless double beta (NLDBD) decay mediated\\nby the exchange with the heavy Majorana neutrino N of arbitrary mass mN,\\nslightly mixed with the electron neutrino. By assuming the dominance of this\\nmechanism, we update the well-known NLDBD-decay exclusion plot in the\\nmass-mixing angle plane taking into account recent progress in the calculation\\nof nuclear matrix elements within quasiparticle random phase approximation and\\nimproved experimental bounds on the NLDBD-decay half-life of Ge-76 and Xe-136.\\nWe also consider the known formula approximating the mN dependence of the\\nNLDBD-decay nuclear matrix element in a simple explicit form. We analyze its\\naccuracy and specify the corresponding parameters, allowing one to easily\\ncalculate the NLDBD-decay half-life for arbitrary mN for all the experimentally\\ninteresting isotopes without resorting to real nuclear structure calculations.\\n
The Longest Acenes
2014-11-21

Abstract For a long time, the largest known member of the acene series was hexacene, consisting of six linearly fused benzene rings. The next higher member, heptacene, is so highly reactive that either stabilization using substituents is required or matrix isolation techniques need to be employed for the detection of the parent hydrocarbon. This Record Review summarizes recent research that culminated in the synthesis of substituted and parent nonacene.
Tetra-Substituted Pyridinylimidazoles As Dual Inhibitors of p38α Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase 3 for Potential Treatment of Neurodegenerative Diseases
2014-11-21

Tetra-substituted imidazoles were designed as dual inhibitors of c-Jun N-terminal kinase (JNK) 3 and p38α mitogen-activated protein (MAP) kinase. A library of 45 derivatives was prepared and evaluated in a kinase activity assay for their ability to inhibit both kinases, JNK3 and p38α MAP kinase. Dual inhibitors with IC50 values down to the low double-digit nanomolar range at both enzymes were identified. The best balanced dual JNK3/p38α MAP kinase inhibitors are 6m (IC50: JNK3, 18 nM; p38α, 30 nM) and 14d (IC50: JNK3, 26 nM; p38α, 34 nM) featuring both excellent solubility and metabolic stability. They may serve as useful tool compounds for preclinical proof-of-principle studies in order to validate the synergistic role of both kinases in the progression of Huntington's disease.