julilili42/papers huggingface dataset:
The MazEF Toxin-Antitoxin System Alters the β-Lactam Susceptibility of Staphylococcus aureus
2015-05-12

Toxin-antitoxin (TA) systems are genetic elements of prokaryotes which encode a stable toxin and an unstable antitoxin that can counteract toxicity. TA systems residing on plasmids are often involved in episomal maintenance whereas those on chromosomes can have multiple functions. The opportunistic pathogen Staphylococcus aureus possesses at least four different families of TA systems but their physiological roles are elusive. The chromosomal mazEF system encodes the RNase toxin MazF and the antitoxin MazE. In the light of ambiguity regarding the cleavage activity, we here verify that MazF specifically targets UACAU sequences in S. aureus in vivo. In a native strain background and under non-stress conditions, cleavage was observed in the absence or presence of mazE. Transcripts of spa (staphylococcal protein A) and rsbW (anti-σB factor) were cut, but translational reporter fusions indicated that protein levels of the encoded products were unaffected. Despite a comparable growth rate as the wild-type, an S. aureus mazEF deletion mutant was more susceptible to β-lactam antibiotics, which suggests that further genes, putatively involved in the antibiotic stress response or cell wall synthesis or turnover, are controlled by this TA system.
Identifying spatial variations in glacial catchment erosion with detrital thermochronology
2015-05-12

Understanding the spatial distribution of glacial catchment erosion during glaciation has previously proven difficult due to limited access to the glacier bed. Recent advances in detrital thermochronology provide a new technique to quantify the source elevation of sediment. This approach utilizes the tendency of thermochronometer cooling ages to increase with elevation and provides a sediment tracer for the elevation of erosion. We apply this technique to the Tiedeman Glacier in the heavily glaciated Mount Waddington region, British Columbia. A total of 106 detrital apatite (U‐Th)/He (AHe) and 100 apatite fission track (AFT) single‐grain ages was presented from the modern outwash of the Tiedemann Glacier with catchment elevations between 530 and 3960 m. These data are combined with nine AHe and nine AFT bedrock ages collected from a ~2400 m vertical transect to test the hypotheses that erosion is uniformly or nonuniformly distributed in the catchment. A Monte Carlo sampling model and Kuiper statistical test are used to quantify the elevation range where outwash sediment is sourced. Model results from the AHe data suggest nearly uniform erosion in the catchment, with a preference for sediment being sourced from ~2900 to 2700 m elevation. Ages indicated that the largest source of sediment is near the present‐day ELA. These results demonstrate the utility of AHe detrital thermochronology (and to a lesser degree AFT data) to quantify the distribution of erosion by individual geomorphic processes, as well as some of the limitations of the technique.Key PointsDetrital thermochronometers record spatial pattern of erosionNearly uniform erosion under the present‐day glacierThe largest observed source area of erosion is near the ELA
An eye movement pre-training fosters the comprehension of processes and functions in technical systems
2015-05-12

The main research goal of the present study was to investigate in how far pre-training eye movements can facilitate knowledge acquisition in multimedia (pre-training principle). We combined considerations from research on eye movement modeling and pre-training to design and test a non-verbal eye movement-based pre-training. Participants in the experimental condition watched an animated circle moving in close spatial resemblance to a static visualization of a solar plant accompanied by a narration in a subsequently presented learning environment. This training was expected to foster top-down processes as reflected in gaze behavior during the learning process and enhance knowledge acquisition. We compared two groups (N = 45): participants in the experimental condition received pre-training in a first step and processed the learning material in a second step, whereas the control group underwent the second step without any pre-training. The pre-training group outperformed the control group in their learning outcomes, particularly in knowledge about processes and functions of the solar plant. However, the superior learning outcomes in the pre-training group could not be explained by eye-movement patterns. Furthermore, the pre-training moderated the relationship between experienced stress and learning outcomes. In the control group, high stress levels hindered learning, which was not found for the pre-training group. On a delayed posttest participants were requested to draw a picture of the learning content. Despite a non-significant effect of training on the quality of drawings, the pre-training showed associations between learning outcomes at the first testing time and process-related aspects in the quality of their drawings. Overall, non-verbal pre-training is a successful instructional intervention to promote learning processes in novices although these processes did not directly reflect in learners' eye movement behavior during learning.
A review on functional and structural brain connectivity in numerical cognition
2015-05-13

Only recently has the complex anatomo-functional system underlying numerical cognition become accessible to evaluation in the living brain. We identified 27 studies investigating brain connectivity in numerical cognition. Despite considerable heterogeneity regarding methodological approaches, populations investigated, and assessment procedures implemented, the results provided largely converging evidence regarding the underlying brain connectivity involved in numerical cognition. Analyses of both functional/effective as well as structural connectivity have consistently corroborated the assumption that numerical cognition is subserved by a fronto-parietal network including (intra)parietal as well as (pre)frontal cortex sites. Evaluation of structural connectivity has indicated the involvement of fronto-parietal association fibers encompassing the superior longitudinal fasciculus dorsally and the external capsule/extreme capsule system ventrally. Additionally, commissural fibers seem to connect the bilateral intraparietal sulci when number magnitude information is processed. Finally, the identification of projection fibers such as the superior corona radiata indicates connections between cortex and basal ganglia as well as the thalamus in numerical cognition. Studies on functional/effective connectivity further indicated a specific role of the hippocampus. These specifications of brain connectivity augment the triple-code model of number processing and calculation with respect to how gray matter areas associated with specific number-related representations may work together.
Binary 2in1 Vectors Improve in Planta (Co)localization and Dynamic Protein Interaction Studies
2015-05-13

Fluorescence-based protein-protein interaction techniques are vital tools for understanding in vivo cellular functions on a mechanistic level. However, only under the condition of highly efficient (co)transformation and accumulation can techniques such as Förster resonance energy transfer (FRET) realize their potential for providing highly accurate and quantitative interaction data. FRET as a fluorescence-based method unifies several advantages, such as measuring in an in vivo environment, real-time context, and the ability to include transient interactions as well as detecting the mere proximity of proteins. Here, we introduce a novel vector set that incorporates the benefit of the recombination-based 2in1 cloning system with the latest state-of-the-art fluorescent proteins for optimal coaccumulation and FRET output studies. We demonstrate its utility across a range of methods. Merging the 2in1 cloning system with new-generation FRET fluorophore pairs allows for enhanced detection, speeds up the preparation of clones, and enables colocalization studies and the identification of meaningful protein-protein interactions in vivo.
The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a retrospective study in 107 patients
2015-05-13

HER2 status can change during the course of breast cancer. CTC phenotyping may serve as an easy-to-perform "liquid biopsy" to reevaluate HER2 status and potentially guide treatment decisions. Further, prospective studies are needed.
Scale-up of the production of highly reactive biogenic magnetite nanoparticles using Geobacter sulfurreducens
2015-05-13

Although there are numerous examples of large-scale commercial microbial synthesis routes for organic bioproducts, few studies have addressed the obvious potential for microbial systems to produce inorganic functional biomaterials at scale. Here we address this by focusing on the production of nanoscale biomagnetite particles by the Fe(III)-reducing bacterium Geobacter sulfurreducens , which was scaled up successfully from laboratory- to pilot plant-scale production, while maintaining the surface reactivity and magnetic properties which make this material well suited to commercial exploitation. At the largest scale tested, the bacterium was grown in a 50 l bioreactor, harvested and then inoculated into a buffer solution containing Fe(III)-oxyhydroxide and an electron donor and mediator, which promoted the formation of magnetite in under 24 h. This procedure was capable of producing up to 120 g of biomagnetite. The particle size distribution was maintained between 10 and 15 nm during scale-up of this second step from 10 ml to 10 l, with conserved magnetic properties and surface reactivity; the latter demonstrated by the reduction of Cr(VI). The process presented provides an environmentally benign route to magnetite production and serves as an alternative to harsher synthetic techniques, with the clear potential to be used to produce kilogram to tonne quantities.
Weight‐sparing effect of insulin detemir: a consequence of central nervous system‐mediated reduced energy intake?
2015-05-13

Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight‐sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system ( CNS ); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter‐regulatory response to insulin through restoration of the hepatic–peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight‐sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.
Analysis of incomplete excisions of basal‐cell carcinomas after breadloaf microscopy compared with 3D‐microscopy: a prospective randomized and blinded study
2015-05-13

Basal‐cell carcinomas may show irregular, asymmetric subclinical growth. This study analyzed the efficacy of ‘breadloaf’ microscopy (serial sectioning) and three‐dimensional ( 3D ) microscopy in detecting positive tumor margins. Two hundred eighty‐three (283) tumors (51.2%) were put into the breadloaf microscopy group; 270 tumors (48.8%) into the 3D microscopy group. The position of any detected tumor outgrowths was identified in clock face fashion. The time required for cutting and embedding the specimens and the examination of the microscopic slides was measured. Patient/tumor characteristics and surgical margins did not differ significantly. Tumor outgrowths at the excision margin were found in 62 of 283 cases (21.9%) in the breadloaf microscopy group and in 115 of 270 cases (42.6%) in the 3D microscopy group, constituting a highly significant difference (p &lt; 0.001). This difference held true with incomplete excision of fibrosing (infiltrative/sclerosing/morpheaform) tumors [32.9% in the breadloaf microscopy group and 57.5% in the 3D microscopy group (p = 0.003)] and also with solid (nodular) tumors [16.1 and 34.2%, respectively (p &lt; 0.001)]. The mean overall examination time required showed no important difference. In summary, for detection of tumor outgrowths, 3D microscopy has almost twice the sensitivity of breadloaf microscopy, particularly in the situation of aggressive/infiltrative carcinomas.
Function of human WIPI proteins in autophagosomal rejuvenation of endomembranes?
2015-05-13

Despite the availability of a large pool of experimental approaches and hypothetical considerations, the hunt for the enigmatic membrane origin of autophagosomes is still on. In mammalian cells proposed scenarios for the formation of the autophagosomal membrane include both de novo assembly, and rearrangements plus maturation of pre‐existing membrane sections from the endoplasmic reticulum (ER), plasma membrane, Golgi or mitochondria. Earlier, we identified the human WD‐repeat protein interacting with phosphoinositides (WIPI) family and showed that WIPI proteins function as essential phosphatidylinositol 3‐phosphate (PtdIns3 P ) effectors at the nascent autophagosome. Interestingly, WIPI proteins localize to both pre‐existing endomembranes and nascent autophagosomes. In this context, and on the basis of historical records on the formation of autophagosomes, we discuss with appropriate modesty an alternative perspective on the membrane origin of autophagosomes.
Neuropeptide S receptor gene variation and neural correlates of cognitive emotion regulation
2015-05-13

The neuropeptide S (NPS) and its receptor NPSR have captured attention in the pathogenesis of anxiety disorders. Here, a functional polymorphism in the NPSR1 gene has been linked to deviant cortico-limbic interactions in response to negative stimuli. While healthy T allele carriers exhibited increased amygdala and prefrontal cortex activity, panic disorder patients carrying the T risk allele displayed hypofrontality possibly reflecting insufficient prefrontal inhibition of limbic reactivity. In order to study multi-level effects of genotype and anxiety, prefrontal cortex activity during an emotional n-back task was measured in 66 volunteers genotyped for the NPSR1 rs324981 A/T variant (AA homozygotes vs. T allele carriers) by means of functional near-infrared spectroscopy. For a high working memory load (3-back), T allele carriers showed a signal increase to negative pictures in the dorsolateral and medial prefrontal cortex while AA homozygotes displayed a signal decrease. Since groups did not differ on skin conductance level and behavioral parameters, this effect in the risk group in line with results from fMRI studies is speculated to represent an adaptive mechanism to compensate for presumably increased subcortical activity driven by an overactive NPS system. However, anxiety sensitivity correlated negatively with prefrontal activity in T allele carriers possibly suggesting a decompensation of the adaptive compensatory upregulation.
Frontline Learning Research
2015-05-13

This study expands the discussion on teacher competence by investigating the relevance of teachers’ combined cognitive resources and emotional resources for effective classroom management. While research on teacher qualification stresses the importance of knowledge for effective teaching, research on teacher stress focuses on their emotional functioning, often without connection to their in-class behaviour. Drawing on findings from health psychology showing that high levels of emotional exhaustion can impair cognitive performance, we hypothesised that teachers’ pedagogical/psychological knowledge would predict their classroom management behaviour only when their level of emotional exhaustion was low. We administered a test to assess the pedagogical/psychological knowledge of 205 secondary school teachers, measured their emotional exhaustion, and assessed their classroom management using ratings of their 4,672 students obtained one year later. Data were analysed using latent moderation analyses, a novel statistical approach that rarely has been employed in research on learning and instruction. Our findings confirmed our hypotheses and indicated an interaction between teachers’ cognitive resources and emotional resources, which together predict their classroom management behaviour. Thus, the new theoretical and empirical integration of two distinct areas of teacher quality broadens our understanding of teacher resources necessary for effective instruction. We argue that teacher education should acknowledge the interplay of the different resources teachers have and help them develop their emotional resources to ensure effective instruction.
ADAMTSL4‐associated isolated ectopia lentis: Further patients, novel mutations and a detailed phenotype description
2015-05-14

ADAMTSL4 mutations seem to be the most common cause of isolated ectoplia lentis (EL) and thus are important concerning the differential diagnosis of connective tissue syndromes with EL as main feature. In this study, we describe an additional cohort of patients with apparently isolated EL. All underwent a detailed clinical exam with cardiac evaluation combined with ADAMTSL4 mutation analysis. Mutations were identified in 12/15 patients with EL. Besides the European founder mutation p. (Gln256Profs*38) we identified five further mutations not yet described in the literature: p. (Leu249Tyrfs*21), p. (Ala388Glyfs*8), p. (Arg746His), p. (Gly592Ser), and p. (Arg865His). Clinical evaluation showed common additional ocular features such as high myopia, but no major systemic findings. In particular: no dilatation of the aortic root was reported on. This report increases the total number of patients with ADAMTSL4 mutations reported on today and reviews in detail the clinical findings in all patients reported on to date demonstrate, that these patients have a mainly ocular phenotype. There are no consistent systemic findings. The differentiation between syndromic and isolated EL is crucial for the further surveillance, treatment, and counseling of these patients, especially in young children. © 2015 Wiley Periodicals, Inc.
Fundamental measure theory for the inhomogeneous hard-sphere system based on Santos' consistent free energy
2015-05-14

Based on Santos' general solution for the scaled-particle differential equation [Phys. Rev. E 86, 040102(R) (2012)], we construct a free-energy functional for the hard-sphere system. The functional is obtained by a suitable generalization and extension of the set of scaled-particle variables using the weighted densities from Rosenfeld's fundamental measure theory for the hard-sphere mixture [Phys. Rev. Lett. 63, 980 (1989)]. While our general result applies to the hard-sphere mixture, we specify remaining degrees of freedom by requiring the functional to comply with known properties of the pure hard-sphere system. Both for mixtures and pure systems, the functional can be systematically extended following the lines of our derivation. We test the resulting functionals regarding their behavior upon dimensional reduction of the fluid as well as their ability to accurately describe the hard-sphere crystal and the liquid-solid transition.
Expression of stage-specific embryonic antigen-4 (SSEA-4) defines spontaneous loss of epithelial phenotype in human solid tumor cells
2015-05-15

Stage-specific embryonic antigen-4 (SSEA-4) is a glycosphingolipid, which is overexpressed in some cancers and has been linked to disease progression. However, little is known about the functions of SSEA-4 and the characteristics of SSEA-4 expressing tumor cells. Our studies identified SSEA-4 expression on a subpopulation of cells in many solid tumor cell lines but not in leukemic cell lines. Fluorescence-activated cell sorting-sorted SSEA-4(+) prostate cancer cells formed fibroblast-like colonies with limited cell-cell contacts, whereas SSEA-4(-) cells formed cobblestone-like epithelial colonies. Only colonies derived from SSEA-4(+) cells were enriched for pluripotent embryonic stem cell markers. Moreover, major epithelial cell-associated markers Claudin-7, E-cadherin, ESRP1 and GRHL2 were down-regulated in the SSEA-4(+) fraction of DU145 and HCT-116 cells. Similar to cell lines, SSEA-4(+) primary prostate tumor cells also showed down-regulation of epithelial cell-associated markers. In addition, they showed up-regulation of epithelial-to-mesenchymal transition as well as mesenchymal markers. Furthermore, SSEA-4(+) cells escape from adhesive colonies spontaneously and form invadopodia-like migratory structures, in which SSEA-4, cortactin as well as active pPI3K, pAkt and pSrc are enriched and colocalized. Finally, SSEA-4(+) cells displayed strong tumorigenic ability and stable knockdown of SSEA-4 synthesis resulted in decreased cellular adhesion to different extracellular matrices. In conclusion, we introduce SSEA-4 as a novel marker to identify heterogeneous, invasive subpopulations of tumor cells. Moreover, increased cell-surface SSEA-4 expression is associated with the loss of cell-cell interactions and the gain of a migratory phenotype, suggesting an important role of SSEA-4 in cancer invasion by influencing cellular adhesion to the extracellular matrix.
Increased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse models
2015-05-15

Abnormalities in brains of Alzheimer's disease (AD) patients are thought to start long before the first clinical symptoms emerge. The identification of affected individuals at this 'preclinical AD' stage relies on biomarkers such as decreased levels of the amyloid-β peptide (Aβ) in the cerebrospinal fluid (CSF) and positive amyloid positron emission tomography scans. However, there is little information on the longitudinal dynamics of CSF biomarkers, especially in the earliest disease stages when therapeutic interventions are likely most effective. To this end, we have studied CSF Aβ changes in three Aβ precursor protein transgenic mouse models, focusing our analysis on the initial Aβ deposition, which differs significantly among the models studied. Remarkably, while we confirmed the CSF Aβ decrease during the extended course of brain Aβ deposition, a 20-30% increase in CSF Aβ40 and Aβ42 was found around the time of the first Aβ plaque appearance in all models. The biphasic nature of this observed biomarker changes stresses the need for longitudinal biomarker studies in the clinical setting and the search for new 'preclinical AD' biomarkers at even earlier disease stages, by using both mice and human samples. Ultimately, our findings may open new perspectives in identifying subjects at risk for AD significantly earlier, and in improving the stratification of patients for preventive treatment strategies.