julilili42/papers huggingface dataset:
Structure Analysis of the Major Capsid Proteins of Human Polyomaviruses 6 and 7 Reveals an Obstructed Sialic Acid Binding Site
2014-07-10

ABSTRACT Human polyomavirus 6 (HPyV6) and HPyV7 are commonly found on human skin. We have determined the X-ray structures of their major capsid protein, VP1, at resolutions of 1.8 and 1.7 Å, respectively. In polyomaviruses, VP1 commonly determines antigenicity as well as cell-surface receptor specificity, and the protein is therefore linked to attachment, tropism, and ultimately, viral pathogenicity. The structures of HPyV6 and HPyV7 VP1 reveal uniquely elongated loops that cover the bulk of the outer virion surfaces, obstructing a groove that binds sialylated glycan receptors in many other polyomaviruses. In support of this structural observation, interactions of VP1 with α2,3- and α2,6-linked sialic acids could not be detected in solution by nuclear magnetic resonance spectroscopy. Single-cell binding studies indicate that sialylated glycans are likely not required for initial attachment to cultured human cells. Our findings establish distinct antigenic properties of HPyV6 and HPyV7 capsids and indicate that these two viruses engage nonsialylated receptors. IMPORTANCE Eleven new human polyomaviruses, including the skin viruses HPyV6 and HPyV7, have been identified during the last decade. In contrast to better-studied polyomaviruses, the routes of infection, cell tropism, and entry pathways of many of these new viruses remain largely mysterious. Our high-resolution X-ray structures of major capsid proteins VP1 from HPyV6 and from HPyV7 reveal critical differences in surface morphology from those of all other known polyomavirus structures. A groove that engages specific sialic acid-containing glycan receptors in related polyomaviruses is obstructed, and VP1 of HPyV6 and HPyV7 does not interact with sialylated compounds in solution or on cultured human cells. A comprehensive comparison with other structurally characterized polyomavirus VP1 proteins enhances our understanding of molecular determinants that underlie receptor specificity, antigenicity, and, ultimately, pathogenicity within the polyomavirus family and highlight the need for structure-based analysis to better define phylogenetic relationships within the growing polyomavirus family and perhaps also for other viruses.
The Structure ofEurope: International Input–Output Analysis with Trade in Intermediate Inputs and Capital Flows
2014-07-10

Abstract In this paper we theoretically derive an international R ybczynski matrix. Its elements indicate the aggregate output change in a country when endowment with one or more factors in the same or another country is increased. This allows us to characterize the production structure in 11 countries of the E uropean U nion. Starting from a baseline case with free trade in final goods only, we analyze two types of interaction between countries: international trade of intermediate inputs and internationally mobile capital.
10.1063/1.4885464.3
2014-07-10

The imaging speed of the wide-spread force mapping mode for quantitative mechanical measurements on soft samples in liquid with the atomic force microscope (AFM) is limited by the bandwidth of the z-scanner and viscous drag forces on the cantilever. Here, we applied high-speed, large scan-range atomic force microscopy and small cantilevers to increase the speed of force mapping by ≈10−100 times. This allowed resolving dynamic processes on living mouse embryonic fibroblasts. Cytoskeleton reorganization during cell locomotion, growth of individual cytoskeleton fibers, cell blebbing, and the formation of endocytic pits in the cell membrane were observed. Increasing the force curve rate from 2 to 300 Hz increased the measured apparent Young's modulus of the cells by about 10 times, which facilitated force mapping measurements at high speed.
10.1063/1.4885464.1
2014-07-10

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Christoph Braunsmann, Jan Seifert, Johannes Rheinlaender, Tilman E. Schäffer; High-speed force mapping on living cells with a small cantilever atomic force microscope. Rev. Sci. Instrum. 1 July 2014; 85 (7): 073703. https://doi.org/10.1063/1.4885464 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioReview of Scientific Instruments Search Advanced Search |Citation Search
10.1063/1.4885464.4
2014-07-10

The imaging speed of the wide-spread force mapping mode for quantitative mechanical measurements on soft samples in liquid with the atomic force microscope (AFM) is limited by the bandwidth of the z-scanner and viscous drag forces on the cantilever. Here, we applied high-speed, large scan-range atomic force microscopy and small cantilevers to increase the speed of force mapping by ≈10−100 times. This allowed resolving dynamic processes on living mouse embryonic fibroblasts. Cytoskeleton reorganization during cell locomotion, growth of individual cytoskeleton fibers, cell blebbing, and the formation of endocytic pits in the cell membrane were observed. Increasing the force curve rate from 2 to 300 Hz increased the measured apparent Young's modulus of the cells by about 10 times, which facilitated force mapping measurements at high speed.
Definition, Classification and Diagnosis of Diabetes Mellitus
2014-07-11

Diabetes mellitus is a general term for heterogeneous disturbances of metabolism for which the main finding is chronic hyperglycaemia. The cause is either impaired insulin secretion or impaired insulin action or both.
Health in Elite Sports from a Salutogenetic Perspective: Athletes' Sense of Coherence
2014-07-11

The identification of contrast groups with varying SOC scores contributes to the development of more targeted salutogenetic health promotion programs. Such programs would ideally include learning modules pertaining to coping with overuse injuries, as well as social support systems aiming to effectively combine education and elite sport.
Measurement of the effect of non ionising energy losses on the leakage current of silicon drift detector prototypes for the LOFT satellite
2014-07-11

The silicon drift detectors are at the basis of the instrumentation aboard\\nthe Large Observatory For x-ray Timing (LOFT) satellite mission, which\\nunderwent a three year assessment phase within the "Cosmic Vision 2015 - 2025"\\nlong-term science plan of the European Space Agency. Silicon detectors are\\nespecially sensitive to the displacement damage, produced by the non ionising\\nenergy losses of charged and neutral particles, leading to an increase of the\\ndevice leakage current and thus worsening the spectral resolution.\\n During the LOFT assessment phase, we irradiated two silicon drift detectors\\nwith a proton beam at the Proton Irradiation Facility in the accelerator of the\\nPaul Scherrer Institute and we measured the increase in leakage current. In\\nthis paper we report the results of the irradiation and we discuss the impact\\nof the radiation damage on the LOFT scientific performance.\\n
Deep layer neurons in the rat medial entorhinal cortex fire sparsely irrespective of spatial novelty
2014-07-11

Extracellular recordings in medial entorhinal cortex have revealed the existence of spatially-modulated firing patterns, which are thought to contribute to a cognitive map of external space. Previous work indicated that during exploration of novel environments, spiking activity in deep entorhinal layers is much sparser than in superficial layers. In the present report, we ask whether this laminar activity profile is a consequence of environmental novelty. We report on a large dataset of juxtacellularly-recorded neurons (n = 70) whose spiking activity was monitored while rats explored either a novel or a familiar environment, or both within the same session. Irrespective of previous knowledge of the environment, deep layer activity was very low during exploration (median firing rate 0.4 Hz for non-silent cells), with a large fraction of silent cells (n = 19 of a total 37), while superficial layer activity was several times higher (median firing rate 2.4 Hz; n = 33). The persistence of laminar differences in firing activity both under environmental novelty and familiarity, and even in head-restrained stationary animals, suggests that sparse coding might be a constitutive feature of deep entorhinal layers.
The effects of hyper-velocity dust-particle impacts on the LOFT Silicon Drift Detectors
2014-07-11

Solid-state detectors that operate in orbit are required to withstand harsh space environment conditions. Among the various phenomena able to damage the sensors, X-ray detectors are subjected to impacts of orbital debris and micrometeoroids whenever, to be sensitive to low energy photons, they need to be ``directly'' exposed to the sky. The LOFT mission, proposed for the M3 class opportunity of the ESA Cosmic Vision, has a very-large sensitive area (greater than 10 m2) made of Silicon Drift Detectors (SDD). Moreover, the satellite includes an X-ray Wide-Field Monitor based on the same SDD detectors. Here we present the results of a test campaign at the Cosmic Dust Accelerator Facility at MPIK in Heidelberg aimed at the space qualification of the detectors with respect to this phenomenon.
Liposome Reconstitution and Modulation of Recombinant Prenylated Human Rac1 by GEFs, GDI1 and Pak1
2014-07-11

Small Rho GTPases are well known to regulate a variety of cellular processes by acting as molecular switches. The regulatory function of Rho GTPases is critically dependent on their posttranslational modification at the carboxyl terminus by isoprenylation and association with proper cellular membranes. Despite numerous studies, the mechanisms of recycling and functional integration of Rho GTPases at the biological membranes are largely unclear. In this study, prenylated human Rac1, a prominent member of the Rho family, was purified in large amount from baculovirus-infected Spodoptera frugiperda insect cells using a systematic detergent screening. In contrast to non-prenylated human Rac1 purified from Escherichia coli, prenylated Rac1 from insect cells was able to associate with synthetic liposomes and to bind Rho-specific guanine nucleotide dissociation inhibitor 1 (GDI1). Subsequent liposome reconstitution experiments revealed that GDI1 efficiently extracts Rac1 from liposomes preferentially in the inactive GDP-bound state. The extraction was prevented when Rac1 was activated to its GTP-bound state by Rac-specific guanine nucleotide exchange factors (GEFs), such as Vav2, Dbl, Tiam1, P-Rex1 and TrioN, and bound by the downstream effector Pak1. We found that dissociation of Rac1-GDP from its complex with GDI1 strongly correlated with two distinct activities of especially Dbl and Tiam1, including liposome association and the GDP/GTP exchange. Taken together, our results provided first detailed insights into the advantages of the in vitro liposome-based reconstitution system to study both the integration of the signal transducing protein complexes and the mechanisms of regulation and signaling of small GTPases at biological membranes.
Personality and prosocial behavior: Linking basic traits and social value orientations.
2014-07-14

Concerning the dispositional determinants of prosocial behavior and cooperation, work based on the classic 5 personality factors, and especially Agreeableness, has turned out somewhat inconsistent. A clearer picture has emerged from consideration of the HEXACO model of personality--though supported entirely by hypothetical behavior as criterion, so far. Thus, in 2 studies and a reanalysis, we investigated "actual behavior" in the form of individually and socially consequential distribution decisions. As expected, HEXACO Honesty-Humility consistently predicted prosocial behavior, including a theory-consistent pattern on the facet level. Importantly, this pattern might explain why five-factor Agreeableness has only sometimes been found to account for prosocial behavior. Indeed, further results indicate that five-factor Agreeableness comprises some aspects that are predictive of prosocial behavior--aspects well covered by HEXACO Honesty-Humility--but also others that play no role for this criterion. As such, the links between five-factor Agreeableness and prosocial behavior are well-covered by HEXACO Honesty-Humility, but not vice versa. Taken together, these findings hint that especially HEXACO Honesty-Humility (and certain aspects of five-factor Agreeableness) account for prosocial behavior--thus explaining previous inconsistencies and providing a more nuanced understanding of the links between basic personality and prosocial or cooperative behavior.
Human (Clovis)–gomphothere (Cuvieroniussp.) association ∼13,390 calibrated yBP in Sonora, Mexico
2014-07-14

Significance Archaeological evidence from Sonora, Mexico, indicates that the earliest widespread and recognizable group of hunter-gatherers (“Clovis”) were in place ∼13,390 y ago in southwestern North America. This is the earliest well-documented population on the continent and suggests that the unique Clovis artifact style originated in the southwest or south central part of the continent, well south of the Arctic gateways into the continent. These hunters targeted gomphotheres, an elephant common in south and central North America, but unknown in association with humans or at this late age in North America.
Synergistic Effects of Antimicrobial Peptides and Antibiotics against Clostridium difficile
2014-07-15

ABSTRACT Accelerating rates of health care-associated infections caused by Clostridium difficile , with increasing recurrence and rising antibiotic resistance rates, have become a serious problem in recent years. This study was conducted to explore whether a combination of antibiotics with human antimicrobial peptides may lead to an increase in antibacterial activity. The in vitro activities of the antimicrobial peptides HBD1 to HBD3, HNP1, HD5, and LL-37 and the antibiotics tigecycline, moxifloxacin, piperacillin-tazobactam, and meropenem alone or in combination against 10 toxinogenic and 10 nontoxinogenic C. difficile strains were investigated. Bacterial viability was determined by flow cytometry and toxin production by enzyme-linked immunosorbent assay (ELISA). When combined at subinhibitory concentrations, antimicrobial peptides and antibiotics generally led to an additive killing effect against toxinogenic and nontoxinogenic C. difficile strains. However, LL-37 and HBD3 acted in synergism with all the antibiotics that were tested. Electron microscopy revealed membrane perturbation in bacterial cell walls by HBD3. In 3 out of 10 toxinogenic strains, HBD3, LL-37, piperacillin-tazobactam, and meropenem administration led to an increased toxin release which was not neutralized by the addition of HNP1. Antimicrobial peptides increase the bacterial killing of antibiotics against C. difficile regardless of the antibiotics' mode of action. Membrane perturbation in or pore formation on the bacterial cell wall may enhance the uptake of antibiotics and increase their antibacterial effect. Therefore, a combination of antibiotics with antimicrobial peptides may represent a promising novel approach to the treatment of C. difficile infections.
Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial
2014-07-15

G-CIMP and 1p/19q codeletion are reliably detectable by HM450 analysis and are associated with prognosis in the NOA-04 trial. For MGMT, HM450 suggests promoter methylation in the vast majority of G-CIMP tumors, which is supported by pyrosequencing.
BN‐Phenanthryne: Cyclotetramerization of an 1,2‐Azaborine Derivative
2014-07-15

Abstract Thermolysis of 9‐azido‐9‐borafluorene in heptane solution produces the tetramer of a BN‐phenanthryne. The isolation of the self‐trapping product provides evidence for the involvement of the BN‐aryne in the thermolysis reaction. Its formation may be rationalized by denitrogenation of the azide and ring enlargement.
High spatial resolution of distribution and interconnections between F e‐ and N ‐redox processes in profundal lake sediments
2014-07-15

Summary The F e and N biogeochemical cycles play key roles in freshwater environments. We aimed to determine the spatial positioning and interconnections of the N and F e cycles in profundal lake sediments. The gradients of O 2 , NO 3 − , NH 4 + , pH , E h , F e( II ) and F e( III ) were determined and the distribution of microorganisms was assessed by most probable numbers and quantitative polymerase chain reaction. The redox zones could be divided into an oxic zone (0–8 mm), where microaerophiles ( G allionellaceae ) were most abundant at a depth of 7 mm. This was followed by a denitrification zone (6–12 mm), where NO 3 − ‐dependent F e( II ) oxidizers and organoheterotrophic denitrifiers both reduce nitrate. Lastly, an iron redox transition zone was identified at 12.5–22.5 mm. F e( III ) was most abundant above this zone while F e( II ) was most abundant beneath. The high abundance of poorly crystalline iron suggested iron cycling. The F e and N cycles are biologically connected through nitrate‐reducing F e( II ) oxidizers and chemically by NO x − species formed during denitrification, which can chemically oxidize F e( II ). This study combines high resolution chemical, molecular and microbiological data to pinpoint sedimentary redox zones in which F e is cycled between F e( II ) and F e( III ) and where F e and N ‐redox processes interact.
Real-time functional MRI neurofeedback
2014-07-15

The promising results in clinical application indicate that rtfMRI-nf and other metabolic neurofeedback, such as near-infrared spectroscopy, might become a potential therapeutic tool. Further research is still required to examine whether rtfMRI-nf is a useful tool for psychiatry because there is still lack of knowledge about the neural function of certain brain systems and about neuronal markers for specific mental illnesses.
Efficacy of Imiquimod-Based Transcutaneous Immunization Using a Nano-Dispersed Emulsion Gel Formulation
2014-07-15

In summary, we developed a novel imiquimod formulation with feasible pharmaceutical properties and immunological efficacy that fosters the rational design of a next generation transcutaneous vaccination platform suitable for the treatment of cancer or persistent virus infections.
Constraints on Donkey Pronouns
2014-07-15

This article reports on an experimental study of donkey pronouns , pronouns (e.g. it ) whose meaning covaries with that of a non-pronominal noun phrase (e.g. a donkey ) even though they are not in a structural relationship that is suitable for quantifier-variable binding. We investigate three constraints, (i) the preference for the presence of an overt NP antecedent that is not part of another word, (ii) the salience of the position of an antecedent that is part of another word, and (iii) the uniqueness of an intended antecedent (in terms of world knowledge). We compare constructions in which intended antecedents occur in a context such as who owns an N / who is an N-owner with constructions of the type who was without an N / who was N-less . Our findings corroborate the existence of the overt NP antecedent constraint, and also show that the salience of an unsuitable antecedent’s position matters. Furthermore, our findings show that uniqueness only matters in the N-less type construction and not in the N-owner type construction; we conclude that this supports a potential approach in terms of dynamic semantics over a competing e-type approach .
Common Genetic Variation in the Human CTF1 Locus, Encoding Cardiotrophin-1, Determines Insulin Sensitivity
2014-07-15

&lt;div&gt;&lt;p&gt;Aims/Hypothesis&lt;/p&gt;&lt;p&gt;Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs) in the &lt;i&gt;CTF1&lt;/i&gt; locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans.&lt;/p&gt;&lt;p&gt;Methods&lt;/p&gt;&lt;p&gt;We genotyped 1,771 German subjects for three &lt;i&gt;CTF1&lt;/i&gt; tagging SNPs (rs1046276, rs1458201, and rs8046707). The subjects were metabolically characterized by an oral glucose tolerance test. Subgroups underwent magnetic resonance (MR) imaging/spectroscopy and hyperinsulinaemic-euglycaemic clamps.&lt;/p&gt;&lt;p&gt;Results&lt;/p&gt;&lt;p&gt;After appropriate adjustment, the minor allele of &lt;i&gt;CTF1&lt;/i&gt; SNP rs8046707 was significantly associated with decreased &lt;i&gt;in vivo&lt;/i&gt; measures of insulin sensitivity. The other tested SNPs were not associated with OGTT-derived sensitivity parameters, nor did the three tested SNPs show any association with OGTT-derived parameters of insulin release. In the MR subgroup, SNP rs8046707 was nominally associated with lower visceral adipose tissue. Furthermore, the SNP rs1458201 showed a nominal association with increased VLDL levels.&lt;/p&gt;&lt;p&gt;Conclusions&lt;/p&gt;&lt;p&gt;In conclusion, this study, even though preliminary and awaiting further confirmation by independent replication, provides first evidence that common genetic variation in &lt;i&gt;CTF1&lt;/i&gt; could contribute to insulin sensitivity in humans. Our SNP data indicate an insulin-desensitizing effect of cardiotrophin-1 and underline that cardiotrophin-1 represents an interesting target to influence insulin sensitivity.&lt;/p&gt;&lt;/div&gt;
Central Insulin Administration Improves Whole-Body Insulin Sensitivity via Hypothalamus and Parasympathetic Outputs in Men
2014-07-16

Animal studies suggest that insulin action in the brain is involved in the regulation of peripheral insulin sensitivity. Whether this holds true in humans is unknown. Using intranasal application of insulin to the human brain, we studied the impacts of brain insulin action on whole-body insulin sensitivity and the mechanisms involved in this process. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic glucose clamp before and after intranasal application of insulin and placebo in randomized order in lean and obese men. After insulin spray application in lean subjects, a higher glucose infusion rate was necessary to maintain euglycemia compared with placebo. Accordingly, clamp-derived insulin sensitivity index improved after insulin spray. In obese subjects, this insulin-sensitizing effect could not be detected. Change in the high-frequency band of heart rate variability, an estimate of parasympathetic output, correlated positively with change in whole-body insulin sensitivity after intranasal insulin. Improvement in whole-body insulin sensitivity correlated with the change in hypothalamic activity as assessed by functional magnetic resonance imaging. Intranasal insulin improves peripheral insulin sensitivity in lean but not in obese men. Furthermore, brain-derived peripheral insulin sensitization is associated with hypothalamic activity and parasympathetic outputs. Thus, the findings provide novel insights into the regulation of insulin sensitivity and the pathogenesis of insulin resistance in humans.