julilili42/papers huggingface dataset:
The motor locus of no-go backward crosstalk.
2018-04-23

A frequent observation in dual-task studies is the backward crosstalk effect (BCE), meaning that aspects of a secondary Task 2 influence Task 1 performance. Up to this point, 2 major types of the BCE were investigated: a BCE based on dimensional overlap between both stimuli and/or responses (the compatibility-based BCE), and a BCE based on whether Task 2 is a go or no-go task (the no-go BCE). Recent evidence suggests that the compatibility-based BCE has its locus inside the response selection stage. The available evidence for the locus of the no-go BCE is still mixed, however. To this end, the 3 experiments reported in the present study used an extended psychological refractory period (PRP) paradigm with 3 subsequent tasks. Applying the locus of slack logic in Experiment 1, the no-go BCE was not absorbed into the cognitive slack and, thus, a locus before response selection could be ruled out. Subsequently applying the effect propagation logic in Experiment 2 and 3, the no-go BCE arising in Task 1 was even inverted in Task 3. Because no propagation of the no-go BCE was observed, a locus before or in response selection could be ruled out. Thus, we conclude that the no-go BCE has its locus during motor execution. Because the no-go BCE and the compatibility-based BCE are located in different stages, we suggest that both types of the BCE do not share a common underlying mechanism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
geno2pheno[ngs-freq]: a genotypic interpretation system for identifying viral drug resistance using next-generation sequencing data
2018-04-24

Identifying resistance to antiretroviral drugs is crucial for ensuring the successful treatment of patients infected with viruses such as human immunodeficiency virus (HIV) or hepatitis C virus (HCV). In contrast to Sanger sequencing, next-generation sequencing (NGS) can detect resistance mutations in minority populations. Thus, genotypic resistance testing based on NGS data can offer novel, treatment-relevant insights. Since existing web services for analyzing resistance in NGS samples are subject to long processing times and follow strictly rules-based approaches, we developed geno2pheno[ngs-freq], a web service for rapidly identifying drug resistance in HIV-1 and HCV samples. By relying on frequency files that provide the read counts of nucleotides or codons along a viral genome, the time-intensive step of processing raw NGS data is eliminated. Once a frequency file has been uploaded, consensus sequences are generated for a set of user-defined prevalence cutoffs, such that the constructed sequences contain only those nucleotides whose codon prevalence exceeds a given cutoff. After locally aligning the sequences to a set of references, resistance is predicted using the well-established approaches of geno2pheno[resistance] and geno2pheno[hcv]. geno2pheno[ngs-freq] can assist clinical decision making by enabling users to explore resistance in viral populations with different abundances and is freely available at http://ngs.geno2pheno.org.
Environmental Enrichment Prevents Transcriptional Disturbances Induced by Alpha-Synuclein Overexpression
2018-04-24

Onset and progression of neurodegenerative disorders, including synucleinopathies such as Parkinson's disease, have been associated with various environmental factors. A highly compelling association from a therapeutic point of view has been found between a physically active lifestyle and a significantly reduced risk for Parkinson's disease. Mimicking such conditions in animal models by promoting physical activity, social interactions, and novel surroundings yields in a so-called enriched environment known to enhance adult neurogenesis, increase synaptic plasticity, and decelerate neuronal loss. Yet, the genes that connect beneficial environmental cues to the genome and delay disease-related symptoms have remained largely unclear. To identify such mediator genes, we used a 2 × 2 factorial design opposing genotype and environment. Specifically, we compared wildtype to transgenic mice overexpressing human <i>SNCA</i>, a key gene in synucleinopathies encoding alpha-synuclein, and housed them in a standard and enriched environment from weaning to 12 months of age before profiling their hippocampal transcriptome using RNA-sequencing. Under standard environmental conditions, differentially expressed genes were overrepresented for calcium ion binding, membrane, synapse, and other Gene Ontology terms previously linked to alpha-synuclein biology. Upregulated genes were significantly enriched for genes attributed to astrocytes, microglia, and oligodendrocytes. These disturbances in gene activity were accompanied by reduced levels of several presynaptic proteins and the immediate early genes EGR1 and NURR1. Intriguingly, housing transgenic animals in the enriched environment prevented most of these perturbations in gene activity. In addition, a sustained activation specifically in transgenic animals housed in enriched conditions was observed for several immediate early genes including <i>Egr1, Nr4a2</i>/<i>Nurr1, Arc</i>, and <i>Homer1a</i>. These findings suggest a compensatory mechanism through an enriched environment-activated immediate early gene network that prevented most disturbances induced by alpha-synuclein overexpression. This regulatory framework might harbor attractive targets for novel therapeutic approaches that mimic beneficial environmental stimuli.
Structural and Functional Features of the Reovirus σ1 Tail
2018-04-24

ABSTRACT Mammalian orthoreovirus attachment to target cells is mediated by the outer capsid protein σ1, which projects from the virion surface. The σ1 protein is a homotrimer consisting of a filamentous tail, which is partly inserted into the virion; a body domain constructed from β-spiral repeats; and a globular head with receptor-binding properties. The σ1 tail is predicted to form an α-helical coiled coil. Although σ1 undergoes a conformational change during cell entry, the nature of this change and its contributions to viral replication are unknown. Electron micrographs of σ1 molecules released from virions identified three regions of flexibility, including one at the midpoint of the molecule, that may be involved in its structural rearrangement. To enable a detailed understanding of essential σ1 tail organization and properties, we determined high-resolution structures of the reovirus type 1 Lang (T1L) and type 3 Dearing (T3D) σ1 tail domains. Both molecules feature extended α-helical coiled coils, with T1L σ1 harboring central chloride ions. Each molecule displays a discontinuity (stutter) within the coiled coil and an unexpectedly seamless transition to the body domain. The transition region features conserved interdomain interactions and appears rigid rather than highly flexible. Functional analyses of reoviruses containing engineered σ1 mutations suggest that conserved residues predicted to stabilize the coiled-coil-to-body junction are essential for σ1 folding and encapsidation, whereas central chloride ion coordination and the stutter are dispensable for efficient replication. Together, these findings enable modeling of full-length reovirus σ1 and provide insight into the stabilization of a multidomain virus attachment protein. IMPORTANCE While it is established that different conformational states of attachment proteins of enveloped viruses mediate receptor binding and membrane fusion, less is understood about how such proteins mediate attachment and entry of nonenveloped viruses. The filamentous reovirus attachment protein σ1 binds cellular receptors; contains regions of predicted flexibility, including one at the fiber midpoint; and undergoes a conformational change during cell entry. Neither the nature of the structural change nor its contribution to viral infection is understood. We determined crystal structures of large σ1 fragments for two different reovirus serotypes. We observed an unexpectedly tight transition between two domains spanning the fiber midpoint, which allows for little flexibility. Studies of reoviruses with engineered changes near the σ1 midpoint suggest that the stabilization of this region is critical for function. Together with a previously determined structure, we now have a complete model of the full-length, elongated reovirus σ1 attachment protein.
Neural Food Reward Processing in Successful and Unsuccessful Weight Maintenance
2018-04-24

Objective Weight loss maintenance is one of the biggest challenges in behavioral weight loss programs. The present study aimed to examine metabolic influences on the mesolimbic reward system in people with successful and unsuccessful long‐term weight loss maintenance. Methods Thirty‐three women with obesity at least 6 months after the completion of a diet were recruited: seventeen women were able to maintain their weight loss, whereas sixteen showed weight regain. Using functional magnetic resonance imaging in combination with the assessment of appetite‐regulating hormones, neural reward processing during hunger and satiety was investigated. An incentive delay task was employed to investigate the expectation and receipt of both food‐related and monetary reward. Results Only participants with successful weight loss maintenance showed a satiety‐induced attenuation of brain activation during the receipt of a food‐related reward. Furthermore, in successful weight loss maintenance, the attenuation of active ghrelin levels was related to brain activation in response to food‐related reward anticipation during satiety. Conclusions The findings suggest that an attenuated influence of satiety signaling on the neural processing of food‐related reward contributes to unsuccessful weight loss maintenance. Thus, intact satiety signaling to the mesolimbic reward system may serve as a promising target for tackling weight cycling.
Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade
2018-04-24

Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP)-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, neurons in dorsal root ganglia (DRG) and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.
Using herbaria to study global environmental change
2018-04-24

During the last centuries, humans have transformed global ecosystems. With their temporal dimension, herbaria provide the otherwise scarce long-term data crucial to track ecological and evolutionary changes over these centuries of global change. The sheer size of herbaria, together with their increasing digitization and the possibility of sequencing DNA from the preserved plant material, makes them invaluable resources to understand ecological and evolutionary species responses to global environmental change. Following the chronology of global change, we highlight how herbaria can inform about long-term effects on plants of at least four of the main drivers of global change: pollution, habitat change, climate change, and invasive species. We summarize how herbarium specimens so far have been used in global change research, discuss future opportunities and challenges posed by the nature of these data, and advocate for an intensified use of these 'windows into the past' for global change research and beyond.
Preparation of Phosphonic Acid Analogues of Proline and Proline Analogues and Their Biological Evaluation as δ1-Pyrroline-5-carboxylate Reductase Inhibitors
2018-04-24

Racemic 1-hydroxy-3-butenyl-, 3-chloro-1-hydroxypropyl-, and 3-bromo-1-hydroxypropylphosphonate and the corresponding (<i>S</i>)-enantiomers obtained by lipase-catalyzed resolution of the respective racemic chloroacetates were subjected to functional group manipulations. These comprised ozonolysis, Mitsunobu reactions with hydrazoic acid and <i>N</i>-hydroxyphthalimide, alkylation of hydrazine derivative, removal of phthaloyl group followed by intramolecular substitution, and global deprotection to deliver the racemates and (<i>R</i>)-enantiomers (ee 92-99% by chiral high-performance liquid chromatography) of pyrrolidin-2-yl-, oxazolidin-3-yl-, oxazolidin-5-yl-, pyrazolidin-3-yl-, and 1,2-oxazinan-3-ylphosphonic acids. These phosphonic acids were evaluated as analogues of proline and proline analogues for the ability to inhibit γ-glutamyl kinase, δ<sup>1</sup>-pyrroline-5-carboxylate synthetase, and δ<sup>1</sup>-pyrroline-5-carboxylate reductase. Only the latter enzyme was inhibited by two of them at concentrations exceeding 1 mM.
Multimodal Chemosensor‐Based, Real‐Time Biomaterial/Cell Interface Monitoring
2018-04-24

Abstract Real‐time monitoring of the cell/biomaterial interface for biomedical applications can significantly improve the assessment of biomaterials. However, currently there are no multiparametric real‐time monitoring systems for the ex vivo assessment of biomaterials. This study presents a method for monitoring of cell and tissue response to biomaterials based on microsensor read‐outs of pH, O 2 , and impedance. In vitro, the sensors are compatible with cells implants. For ex vivo measurements, either a biodegradable polymer poly(lactic‐co‐glycolic acid) or a protein‐repellent plasma polymer nanofilm is coated onto sensor arrays and placed on the chorioallantoic membrane of avian embryo ex ovo cultures. Signals related to dissolved oxygen, pH, and electrical impedance are continuously acquired for up to 90 h. Optical observation, immunohistochemical examination of CD45, and Haematoxylin and Eosin (H&amp;E) staining show different unspecific immune responses. Tissue inflammation, capsule formation, and neovascularization are observed. These results correlate well with the type of coating material and the signal patterns acquired by the chemosensors. In addition, tissue death can be inferred from sensor signal patterns. This system is intended to enable continuous monitoring of biomaterials and is envisioned as a prescreening tool to provide real‐time monitoring of cell/biomaterial interface and also to reduce animal testing for biomaterial assessment purposes.
Axisymmetric black holes allowing for separation of variables in the Klein-Gordon and Hamilton-Jacobi equations
2018-04-25

We determine the class of axisymmetric and asymptotically flat black-hole\\nspacetimes for which the test Klein-Gordon and Hamilton-Jacobi equations allow\\nfor the separation of variables. The known Kerr, Kerr-Newman, Kerr-Sen and some\\nother black-hole metrics in various theories of gravity are within the class of\\nspacetimes described here. It is shown that although the black-hole metric in\\nthe Einstein-dilaton-Gauss-Bonnet theory does not allow for the separation of\\nvariables (at least in the considered coordinates), for a number of\\napplications it can be effectively approximated by a metric within the above\\nclass. This gives us some hope that the class of spacetimes described here may\\nbe not only generic for the known solutions allowing for the separation of\\nvariables, but also a good approximation for a broader class of metrics, which\\ndoes not admit such separation. Finally, the generic form of the axisymmetric\\nmetric is expanded in the radial direction in terms of the continued fractions\\nand the connection with other black-hole parametrizations is discussed.\\n
An immunological age index in bipolar disorder: A confirmatory factor analysis of putative immunosenescence markers and associations with clinical characteristics
2018-04-25

Abstract Objectives The study aims to generate an immunological age (IA) trait on the basis of immune cell differentiation parameters, and to test whether the IA is related to age and disease characteristics. Methods Forty‐four euthymic type I bipolar disorder patients were included in this study. Five immunosenescence‐related parameters were assessed: proportions of late‐differentiated cells (e.g., CD3+CD8+CD28‐CD27‐ and CD3‐CD19+IgD‐CD27‐), and the expression of CD69, CD71, and CD152 after stimulation. Confirmatory factor analysis was applied to generate an IA trait underling the 5 measures. Results The best‐fit model was constituted by 4 parameters that were each related to an underlying IA trait, with 1 cell population positively correlated (CD3+CD8+CD28‐CD27‐ [λ = 0.544, where λ represents the loading of the parameter onto the IA trait] and 3 markers negatively correlated (CD69 [λ = −0.488], CD71 [λ = −0.833], and CD152 [λ = −0.674]). The IA trait was associated with chronological age (β = 0.360, p = .013) and the number of previous mood episodes (β = 0.426, p = .006). In a mediation model, 84% of the effect between manic episodes, and IA was mediated by body mass index. Conclusion In bipolar disorder type I, premature aging of the immune system could be reliably measured using an index that validated against chronological age, which was related to adverse metabolic effects of the disease course.
Draft Genome Sequences of the Obligatory Marine Myxobacterial Strains Enhygromyxa salina SWB005 and SWB007
2018-04-25

ABSTRACT The two marine myxobacterial strains Enhygromyxa salina SWB005 and SWB007 were isolated from coastal soil samples using Escherichia coli as bait for these predatory strains. These strains produce unique specialized metabolites. Genomes were assembled into 312 contigs for E. salina SWB005 (9.0 Mbp) and 192 contigs for E. salina SWB007 (10.6 Mbp).
Enrichment of rare protein truncating variants in amyotrophic lateral sclerosis patients
2018-04-25

SUMMARY To discover novel genetic risk factors underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry matched controls. We observed a significant excess of ultra-rare and rare protein-truncating variants (PTV) among ALS cases, which was primarily concentrated in constrained genes; however, a significant enrichment in PTVs does persist in the remaining exome. Through gene level analyses, known ALS genes, SOD1, NEK1 , and FUS , were the most strongly associated with disease status. We also observed suggestive statistical evidence for multiple novel genes including DNAJC7 , which is a highly constrained gene and a member of the heat shock protein family (HSP40). HSP40 proteins, along with HSP70 proteins, facilitate protein homeostasis, such as folding of newly synthesized polypeptides, and clearance of degraded proteins. When these processes are not regulated, misfolding and accumulation of degraded proteins can occur leading to aberrant protein aggregation, one of the pathological hallmarks of neurodegeneration.
Tool Auctions
2018-04-25

We introduce tool auctions, a novel market mechanism for constructing a cost-efficient assembly line for producing a desired set of products from a given set of goods and tools. Such tools can be used to transform one type of good into a different one. We then study the computational complexity of tool auctions in detail, using methods from both classical and parameterized complexity theory. While solving such auctions is intractable in general, just as for the related frameworks of combinatorial and mixed auctions, we are able to identify several special cases of practical interest where designing efficient algorithms is possible.
First hydrodynamics simulations of radiation forces and photoionization feedback in massive star formation
2018-04-26

Aims . We present the first simulations of the formation and feedback of massive stars which account for radiation forces as well as photoionization feedback (along with protostellar outflows). In two different accretion scenarios modeled, we determine the relative strength of these feedback components and derive the size of the reservoir from which the forming stars gained their masses. Methods . We performed direct hydrodynamics simulations of the gravitational collapse of high-density mass reservoirs toward the formation of massive stars including self-gravity, stellar evolution, protostellar outflows, continuum radiation transport, photoionization, and the potential impact of ram pressure from large-scale gravitational infall. For direct comparison, we executed these simulations with and without the individual feedback components. Results . Protostellar outflows alone limit the stellar mass growth only in an accretion scenario with a finite mass reservoir; when including accretion and ram pressure from large scales (&gt;0.1 pc), protostellar outflows do not limit stellar mass growth at all. Photoionization and HII regions dominate the feedback ladder only at later times, after the star has already contracted down to the zero-age main sequence, and only on large scales. Specifically, photoionization yields a broadening of the bipolar outflow cavities and a reduction of the gravitational infall momentum by about 50%, but does not limit the stellar mass accretion. On the other hand, we find radiation forces restrain the gravitational infall toward the circumstellar disk, impact the gravito-centrifugal equilibrium at the outer edge of the disk, and eventually shut down stellar accretion completely. The most massive star formed in the simulations accreted 95 M ⊙ before disk destruction; this mass was drawn-in from an accretion reservoir of ≈240 M ⊙ and ≈0.24 pc in radius. Conclusions . In the regime of very massive stars, the final mass of these stars is controlled by their own radiation force feedback.
Isotopic insights on cave bear palaeodiet
2018-04-26

More than 300 cave bear bones from all over Europe have carbon and nitrogen isotopic composition that match overwhelmingly a diet based on plants, except for samples from two caves in Romania, for which high nitrogen-15 amounts have been interpreted as reflecting an omnivorous diet. This paper aims at deciphering the various factors influencing the carbon and nitrogen isotopic composition of a potential omnivorous species like cave bear, those linked to trophic levels and variations among plants and those caused by physiological factors. The comparison of European cave bears with coeval Late Pleistocene large mammals with different diets clearly shows that all the cave bear populations, including those from Romania, present isotopic values overlapping with herbivores, not with carnivores. Therefore omnivory is very unlikely for cave bears. Consumption of plants with high δ15N values, such as graminoids, forbs and possibly fungi, could explain in part the observed isotopic pattern. In addition, the variations in δ15N values through ontogeny support the hypothesis of a different hibernation pattern for the Romanian cave bears with high δ15N values. Future investigations using new isotopic approaches, especially nitrogen isotopic composition of collagen amino acids, should contribute to decipher the paleoecology of these Romanian cave bears.