bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensorineural hearing loss degrades behavioral and physiological measures of human spatial selective auditory attention
Authors: Dai Lengshi , Best Virginia , Shinn-Cunningham Barbara G. 
Published: March 2018

Significance
Listeners with hearing loss have trouble communicating in many social settings. In such situations, listeners with normal hearing suppress the neural representation of competing sounds, a process known as auditory selective attention. We compared hearing-impaired (HI) and normal-hearing (NH) listeners on a spatial selective attention task while measuring neural responses using electroencephalography. Compared with NH listeners, HI listeners have poorer sensitivity to spatial cues, perform more poorly on the selective attention task, and show weaker neural suppression of competing sounds. Moreover, these different measures are correlated both for HI and for NH listeners. These results suggest that poor spatial acuity produces problems with selective attention. These findings have implications both for basic science and for development of next-generation hearing aids.
Monoclonal antibody targeting the β-barrel assembly machine of
Escherichia coli
is bactericidal
Authors: Storek Kelly M. , Auerbach Marcy R. , Shi Handuo , Garcia Natalie K. , Sun Dawei , Nickerson Nicholas N. , Vij Rajesh , Lin Zhonghua , Chiang Nancy , Schneider Kellen , Wecksler Aaron T. , Skippington Elizabeth , Nakamura Gerald , Seshasayee Dhaya , Koerber James T. , Payandeh Jian , Smith Peter A. , Rutherford Steven T. 
Published: March 2018

Significance
The outer membrane of Gram-negative bacteria presents a formidable barrier to the discovery of new antibiotics needed to combat infections by multidrug-resistant bacteria. Targeting essential proteins or processes directly exposed to the environment could bypass this obstacle. Here, we describe a monoclonal antibody that selectively and potently antagonizes BamA, which folds and inserts integral outer membrane β-barrel proteins, by binding to a surface-exposed BamA epitope and, as a result, inhibits bacterial cell growth. Mechanisms of resistance to the antibody reveal that membrane fluidity affects BamA activity. This antibody validates the potential therapeutic strategy of targeting essential, exposed functions and provides a powerful tool for dissecting the fundamental process of folding integral membrane β-barrel proteins in vivo.
Agricultural origins on the Anatolian plateau
Authors: Baird Douglas , Fairbairn Andrew , Jenkins Emma , Martin Louise , Middleton Caroline , Pearson Jessica , Asouti Eleni , Edwards Yvonne , Kabukcu Ceren , Mustafaoğlu Gökhan , Russell Nerissa , Bar-Yosef Ofer , Jacobsen Geraldine , Wu Xiaohong , Baker Ambroise , Elliott Sarah 
Published: March 2018

Significance
We demonstrate that the initial spread of farming outside of the area of its first appearance in the Fertile Crescent of Southwest Asia, into Central Anatolia, involved adoption of cultivars by indigenous foragers and contemporary experimentation in animal herding of local species. This represents a rare clear-cut instance of forager adoption and sustained low-level food production. We have also demonstrated that farming uptake was not uniform, with some forager communities rejecting it despite proximity to early farming communities. We also show that adoption of small-scale cultivation could still have significant social consequences for the communities concerned. The evidence suggests forager adoption of cultivation and initiation of herding was not necessarily motivated by simple economic concerns of increasing levels of food production and security.
Frictional lubricity enhanced by quantum mechanics
Authors: Zanca Tommaso , Pellegrini Franco , Santoro Giuseppe E. , Tosatti Erio 
Published: March 2018

Significance
Sliding friction, a corner of physics still under debate after centuries, is currently studied in nanosystems such as optical lattice emulators, where parameters are easy to control but where applicability of classical mechanics is no longer guaranteed. The quantum effects on friction being largely unexplored, we show here that even a basic theoretical model predicts important novelties. For a particle dragged over large barriers, whose classical stick–slip friction would be large, Landau–Zener tunneling through the barrier can avert stick–slip, with an increase of lubricity. This and related forms of quantum lubricity should be observable for cold ions sliding in optical lattices.
Interaction of laser beams with magnetized substance in a strong magnetic field
Authors: Kuzenov V V 
Published: March 2018

Abstract
Laser-driven magneto-inertial fusion assumed plasma and magnetic flux compression by quasisymmetric laser-driven implosion of magnetized target. We develop a 2D radiation magnetohydrodynamic code and a formulation for the one-fluid two-temperature equations for simulating compressible non-equilibrium magnetized target plasma. Laser system with pulse radiation with 10 ns duration is considered for numerical experiments. A numerical study of a scheme of magnetized laser-driven implosion in the external magnetic field is carried out.
What’s New in Pediatric Hip?
Authors: Schmitz Matthew R. , Blumberg Todd J. , Nelson Susan E. , Sees Julieanne P. , Sankar Wudbhav N. 
Published: March 2018

Background:
Developmental dysplasia of the hip (DDH), which encompasses a wide spectrum of disease from mild dysplasia to frank dislocation, is one of the most common developmental deformities of the lower extremities and one of the leading causes of future osteoarthritis and hip arthroplasty. Legg-Calvé-Perthes disease (LCPD) results from a vascular insult to the growing femoral epiphysis, which in turn can create permanent morphologic changes to the hip joint. Slipped capital femoral epiphysis (SCFE) occurs when the proximal femoral physis fails allowing the epiphysis to displace in relation to the metaphysis. Infections about the hip also create significant morbidity in the pediatric hip.

Methods:
We searched the PubMed database for all studies related to DDH, LCPD, SCFE, and pediatric hip infections that were published between July 1, 2014 and August 31, 2017. The search was limited to English articles and yielded 839 papers. This project was initiated by the Pediatric Orthopaedic Society of North America Publications Committee and was reviewed and approved by the Pediatric Orthopaedic Society of North America Presidential Line.

Results:
A total of 40 papers were selected for review based upon new and significant findings. Select historical manuscripts are also included to provide sufficient background information.

Conclusions:
DDH, LCPD, SCFE, and infections about the hip continue to be important topics in pediatric orthopaedics and areas of vital research. This manuscript reviews the most important recent literature on the diagnosis and treatment of these pediatric hip conditions.

Level of Evidence:
Level V.
MORPHOLOGIC CHARACTERISTICS OF MACULAR HOLE AND MACULAR HOLE RETINAL DETACHMENT ASSOCIATED WITH EXTREME MYOPIA
Authors: Ohsugi Hideharu , Ikuno Yasushi , Matsuba Shinji , Ohsugi Eiko , Nagasato Daisuke , Shoujou Tomohiro , Tabuchi Hitoshi 
Published: March 2018

Purpose:
To investigate the surgical results and morphologic characteristics of macular hole (MH) and macular hole retinal detachment (MHRD) associated with extreme myopia.

Methods:
We retrospectively reviewed consecutive cases with axial length ≥28 mm who were treated with pars plana vitrectomy for MH or MHRD. The choroidal and scleral thickness at the fovea, presence of dome-shaped macula, and the height of posterior staphyloma 3 mm from the fovea were measured from postoperative optical coherence tomography images.

Results:
Significant improvement in visual acuity was obtained postoperatively in both MH (16 eyes; 15 patients) and MHRD (19 eyes; 18 patients) groups (P < 0.05). Final MH closure rate was not significantly different between the groups (MH: 15/16, MHRD: 14/19, P = 0.19). Axial length was not significantly different between the groups (MH: 30.5 ± 1.5 mm, MHRD: 29.6 ± 1.3 mm, P = 0.098). Eyes with MH had significantly greater choroidal thickness (MH: 61.9 ± 66.0 μm, MHRD: 24.1 ± 19.8 μm, P = 0.045), greater scleral thickness (MH: 294 ± 77 μm, MHRD: 232 ± 89 μm, P = 0.008), higher frequency of dome-shaped macula (MH: 6/16, MHRD: 1/19, P = 0.032), and lower staphyloma height (MH: 190 ± 113 μm, MHRD: 401 ± 156 μm, P < 0.001).

Conclusion:
Surgical outcomes were generally favorable. The pathogenetic differences between the two conditions may be attributable to differences with respect to eye morphology.
Rapid Paediatric Sequencing (RaPS): Comprehensive real-life workflow for rapid diagnosis of critically ill children
Authors: Boukhibar Lamia , Clement Emma , Jones Wendy , Drury Suzanne , Ocaka Louise , Gagunashvili Andrey , Le Quesne Stabej Polona , Bacchelli Chiara , Jani Nital , Rahman Shamima , Jenkins Lucy , Hurst Jane , Bitner-Glindzicz Maria , Peters Mark , Beales Philip , Williams Hywel J 
Published: March 2018

AbstractBackgroundRare genetic conditions are frequent risk factors for, or direct causes of, organ failure requiring paediatric intensive care unit (PICU) support. Such conditions are frequently suspected but unidentified at PICU admission. Compassionate and effective care is greatly assisted by definitive diagnostic information. There is therefore a need to provide a rapid genetic diagnosis to inform clinical management.To date, Whole Genome Sequencing (WGS) approaches have proved successful in diagnosing a proportion of children with rare diseases, but results may take months to report or require the use of equipment and practices not compatible with a clinical diagnostic setting. We describe an end-to-end workflow for the use of rapid WGS for diagnosis in critically ill children in a UK National Health Service (NHS) diagnostic setting.MethodsWe sought to establish a multidisciplinary Rapid Paediatric Sequencing (RaPS) team for case selection, trio WGS, a rapid bioinformatics pipeline for sequence analysis and a phased analysis and reporting system to prioritise genes with a high likelihood of being causal. Our workflow was iteratively developed prospectively during the analysis of the first 10 children and applied to the following 14 to assess its utility.FindingsTrio WGS in 24 critically ill children led to a molecular diagnosis in ten (42%) through the identification of causative genetic variants. In three of these ten individuals (30%) the diagnostic result had an immediate impact on the individual’s clinical management. For the last 14 trios, the shortest time taken to reach a provisional diagnosis was four days (median 7 days).InterpretationRapid WGS can be used to diagnose and inform management of critically ill children using widely available off the shelf products within the constraints of an NHS clinical diagnostic setting. We provide a robust workflow that will inform and facilitate the rollout of rapid genome sequencing in the NHS and other healthcare systems globally.FundingThe study was funded by NIHR GOSH/UCL BRC: ormbrc-2012-1
External and Internally Generated Task Predictions are Integrated in Prefrontal Cortex to Jointly Guide Cognitive Control
Authors: Jiang Jiefeng , Wagner Anthony D. , Egner Tobias 
Published: March 2018

AbstractCognitive control proactively configures information processing to suit expected task demands. Predictions of forthcoming demand can be driven by explicit external cues or be generated internally, based on past experience (cognitive history). However, it is not known whether and how the brain reconciles these two sources of information to guide control. Pairing a probabilistic task-switching paradigm with computational modeling, we found that external and internally generated predictions jointly guide task preparation, with a bias for internal predictions. Using model-based neuroimaging, we then show that the two sources of task prediction are integrated in dorsolateral prefrontal cortex, and jointly inform a representation of the likelihood of a change in task demand, encoded in frontoparietal cortex. Upon task-stimulus onset, dorsomedial prefrontal cortex encoded the need for reactive task-set adjustment. These data reveal, for the first time, how the human brain integrates external cues and cognitive history to prepare for an upcoming task.
A benchmarking study on virtual ligand screening against homology models of human GPCRs
Authors: Lim Victor Jun Yu , Du Weina , Chen Yu Zong , Fan Hao 
Published: March 2018

AbstractG-protein-coupled receptor (GPCR) is an important target class of proteins for drug discovery, with over 27% of FDA-approved drugs targeting GPCRs. However, being a membrane protein, it is difficult to obtain the 3D crystal structures of GPCRs for virtual screening of ligands by molecular docking. Thus, we evaluated the virtual screening performance of homology models of human GPCRs with respect to the corresponding crystal structures. Among the 19 GPCRs involved in this study, we observed that 10 GPCRs have homology models that have better or comparable performance with respect to the corresponding X-ray structures, making homology models a viable choice for virtual screening. For a small subset of GPCRs, we also explored how certain methods like consensus enrichment and sidechain perturbation affect the utility of homology models in virtual screening, as well as the selectivity between agonists and antagonists. Most notably, consensus enrichment across multiple homology models often yields results comparable to the best performing model, suggesting that ligand candidates predicted with consensus scores from multiple models can be the optimal option in practical applications where the performance of each model cannot be estimated.
Antibiotic-induced cell chaining triggers pneumococcal competence by reshaping quorum sensing to autocrine signaling
Authors: Domenech Arnau , Slager Jelle , Veening Jan-Willem 
Published: March 2018

AbstractStreptococcus pneumoniaecan acquire antibiotic resistance by activation of competence and subsequent DNA uptake. Several antibiotics induce competence by disrupting protein-quality control or perturbing DNA replication. Here, we demonstrate that aztreonam (AZT) and clavulanic acid (CLA) also promote competence. We show that both compounds induce cell chain formation by targeting the D,D-carboxypeptidase PBP3. In support of the hypothesis that chain formation promotes competence, we demonstrate that an autolysin mutant (lytB) is hypercompetent. As competence is initiated by the binding of a small extracellular peptide (CSP) to a membrane-anchored receptor (ComD), we wondered if chain formation alters CSP diffusion and thereby sensing by ComD. Indeed, the presence of AZT or CLA affects competence synchronization by switching CSP-based quorum sensing to autocrine-like signaling, as CSP is retained to chained cells and no longer shared in a common pool. Together, these insights demonstrate the versatility of quorum sensing in integrating different stresses and highlight that certain antibiotics should be prescribed with care not to drive the spread of antibiotic resistance.
Refactoring the upper sugar metabolism ofPseudomonas putidafor co-utilization of disaccharides, pentoses, and hexoses
Authors: Dvořák Pavel , de Lorenzo Víctor 
Published: March 2018

AbstractGiven its capacity to tolerate stress, NAD(P)H/ NAD(P) balance, and increased ATP levels, the platform strainPseudomonas putidaEM42, a genome-edited derivative of the soil bacteriumP. putidaKT2440, can efficiently host a suite of harsh reactions of biotechnological interest. Because of the lifestyle of the original isolate, however, the nutritional repertoire ofP. putidaEM42 is centered largely on organic acids, aromatic compounds and some hexoses (glucose and fructose). To enlarge the biochemical network ofP. putidaEM42 to include disaccharides and pentoses, we implanted heterologous genetic modules for D-cellobiose and D-xylose metabolism into the enzymatic complement of this strain. Cellobiose was actively transported into the cells through the ABC complex formed by native proteins PP1015-PP1018. The knocked-in β-glucosidase BglC fromThermobifida fuscacatalyzed intracellular cleavage of the disaccharide to D-glucose, which was then channelled to the default central metabolism. Xylose oxidation to the dead end product D-xylonate was prevented by by deleting thegcdgene that encodes the broad substrate range quinone-dependent glucose dehydrogenase. Intracellular intake was then engineered by expressing theEscherichia coliproton-coupled symporter XylE. The sugar was further metabolized by the products ofE. coli xylA(xylose isomerase) andxylB(xylulokinase) towards the pentose phosphate pathway. The resultingP. putidastrain co-utilized xylose with glucose or cellobiose to complete depletion of the sugars. These results not only show the broadening of the metabolic capacity of a soil bacterium towards new substrates, but also promoteP. putidaEM42 as a platform for plug-in of new biochemical pathways for utilization and valorization of carbohydrate mixtures from lignocellulose processing.
Auxin-Mediated Sterility Induction System for Longevity and Mating Studies inCaenorhabditis elegans
Authors: Kasimatis Katja R. , Moerdyk-Schauecker Megan J. , Phillips Patrick C. 
Published: March 2018

ABSTRACTThe ability to control both the means and timing of sexual reproduction provides a powerful tool to understand not only fertilization, but also life history trade-offs resulting from sexual reproduction. However, precisely controlling fertilization has proved a major challenge across model systems. An ideal sterility induction system should be external, non-toxic, and reversible. Using the auxin-inducible degradation system targeting thespe-44gene within the nematodeCaenorhabditis elegans, we designed a means of externally inducing spermatogenesis arrest. We show that exposure to auxin during larval development induces both hermaphrodite self-sterility and male sterility. Moreover, male sterility can be reversed upon cessation of auxin exposure. The sterility induction system developed here has multiple applications in the fields of spermatogenesis and mating systems evolution. Importantly, this system is also a highly applicable tool for aging studies. We show that auxin-induced self-sterility is comparable to the commonly used chemically-induced FUdR sterility, while offering multiple benefits, including being less labor intensive, being non-toxic, and avoiding compound interactions with other experimental treatments.
6mer Seed Toxicity Determines Strand Selection in miRNAs
Authors: Gao Quan Q. , Putzbach William E. , Murmann Andrea E. , Chen Siquan , Ambrosini Giovanna , Peter Johannes M. , Bartom Elizabeth T. , Peter Marcus E. 
Published: March 2018

SUMMARYMany siRNAs and shRNAs are toxic to cancer cells through a 6mer seed sequence (position 2-7 of the guide strand). A siRNA screen with all 4096 possible 6mer seed sequences in a neutral RNA backbone revealed a preference for guanine in positions 1-3 and a GC content of >80% of the 6mer seed in the most toxic siRNAs. These 6mer seed containing siRNAs exert their toxicity by targeting survival genes which contain GC-rich 3’UTRs. The master tumor suppressor miRNA miR-34a was found to be toxic through such a G-rich 6mer seed suggesting that certain tumor suppressive miRNAs use a toxic 6mer seed to kill cancer cells. An analysis of all mature miRNAs suggests that most miRNAs evolved to avoid guanine at the 5′ end of the 6mer seed sequence of the predominantly expressed arm. In contrast, for many tumor suppressive miRNAs the predominant arm contains a G-rich toxic 6mer seed, presumably to eliminate cancer cells.
NRG1 is required for the function of the TIR-NLR immune receptors Roq1 and RPP1 in Nicotiana. benthamiana
Authors: Qi Tiancong , Schultink Alex , Pham Julie , Cho Myeong-Je , Staskawicz Brian J. 
Published: March 2018

AbstractThe plant immune system involves a large family of nucleotide-binding leucine-rich repeat (NLR) intracellular immune receptors. These immune receptors often function to directly or indirectly mediate the perception of specific pathogen effector proteins secreted into the cell. Activation of these immune receptors typically results in activation of the immune system and subsequent suppression of pathogen proliferation. Although many examples of NLR receptors are known, a mechanistic understanding of how receptor activation ultimately leads to an immune response is not well understood. A subset of the NLR proteins contain a TIR domain at their N terminus (TNL). One such TNL, the N gene, was previously shown to depend on a non-TIR NLR protein, N requirement gene 1 (NRG1) for immune function. We tested additional NLR proteins in Nicotiana benthamiana for dependency on NRG1. We found that two additional TIR-NLR proteins, Roq1 and RPP1, also require NRG1 but that two coiled-coil NLR proteins, Bs2 and Rps2, do not. This finding suggests that NRG1 may be a conserved component of TNL signaling pathways.
A probabilistic interpretation of PID controllers using active inference
Authors: Baltieri Manuel , Buckley Christopher L. 
Published: March 2018

AbstractIn the past few decades, probabilistic interpretations of brain functions have become widespread in cognitive science and neuroscience. The Bayesian brain hypothesis, predictive coding, the free energy principle and active inference are increasingly popular theories of cognitive functions that claim to unify understandings of life and cognition within general mathematical frameworks derived from information theory, statistical physics and machine learning. Furthermore, it has been argued that one such proposal, active inference, combines both information and control theory and has its roots in cybernetics studies of the brain. The connections between information and control theory have been discussed since the 1950’s by scientists like Shannon and Kalman and have recently risen to prominence in modern stochastic optimal control theory. How-ever, the implications of the confluence of these two theoretical frame-works for the biological sciences have been slow to emerge. Here we argue that if the active inference proposal is to be taken as a general process theory for biological systems, we need to consider how existing control theoretical approaches to biological systems relate to it. In this work we will focus on PID (Proportional-Integral-Derivative) controllers, one of the most common types of regulators employed in engineering and more recently used to explain behaviour in biological systems, e.g. chemotaxis in bacteria and amoebae or robust adaptation in biochemical networks. Using active inference, we derive a probabilistic interpretation of PID controllers, showing how they can fit a more general theory of life and cognition under the principle of (variational) free energy minimisation once we use only simple linear generative models.