bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple adjoining word- and face-selective regions in ventral temporal cortex exhibit distinct dynamics
Authors: Boring Matthew J. , Silson Edward H. , Ward Michael J. , Richardson R. Mark , Fiez Julie A. , Baker Chris I. , Ghuman Avniel Singh 
Published: December 2020

AbstractThe map of category-selectivity in human ventral temporal cortex (VTC) provides organizational constraints to models of object recognition. One important principle is lateral-medial response biases to stimuli that are typically viewed in the center or periphery of the visual field. However, little is known about the relative temporal dynamics and location of regions that respond preferentially to stimulus classes that are centrally viewed, like the face- and word-processing networks. Here, word- and face-selective regions within VTC were mapped using intracranial recordings from 36 patients. Partially overlapping, but also anatomically dissociable patches of face- and word-selectivity were found in VTC. In addition to canonical word-selective regions along the left posterior occipitotemporal sulcus, selectivity was also located medial and anterior to face-selective regions on the fusiform gyrus at the group level and within individual subjects. These regions were replicated using 7 Tesla fMRI in healthy subjects. Left hemisphere word-selective regions preceded right hemisphere responses by 125 ms, potentially reflecting the left hemisphere bias for language; with no hemispheric difference in face-selective response latency. Word-selective regions along the posterior fusiform responded first, then spread medially and laterally, then anteriorally. Face-selective responses were first seen in posterior fusiform regions bilaterally, then proceeded anteriorally from there. For both words and faces, the relative delay between regions was longer than would be predicted by purely feedforward models of visual processing. The distinct time-courses of responses across these regions, and between hemispheres, suggest a complex and dynamic functional circuit supports face and word perception.Significance StatementRepresentations of visual objects in the human brain have been shown to be organized by several principles, including whether those objects tend to be viewed centrally or peripherally in the visual field. However, it remains unclear how regions that process objects that are viewed centrally, like words and faces, are organized relative to one another. Here, invasive and non-invasive neuroimaging suggests there is a mosaic of regions in ventral temporal cortex that respond selectively to either words or faces. These regions display differences in the strength and timing of their responses, both within and between brain hemispheres, suggesting they play different roles in perception. These results illuminate extended, bilateral, and dynamic brain pathways that support face perception and reading.
Comparison of everting sutures and the lateral tarsal strip with or without everting sutures for involutional lower eyelid entropion: A meta-analysis
Authors: Hwang Gyudeok , Kim Hyo Sin , Lee Jiyoung , Paik Ji-Sun 
Published: December 2020

AbstractThere are three pathophysiologies of involutional entropion, vertical laxity (VL), horizontal laxity (HL), and overriding of the preseptal orbicularis. The effects of methods to correct VL only, HL only, or both VL and HL in patients with involutional entropion were compared using the published results of randomized controlled trials (RCTs).To find RCT studies that investigated methods to correct involutional entropion, a systematic search was performed from database inception to April 2020 in the Medline, EMBASE, and Cochrane databases. Two independent researchers conducted the literature selection and data extraction. Evaluation of the quality of the reports was performed using the Cochrane Collaboration tool for assessing the risk of bias (ROB 2.0). The data analysis was conducted according to the PRISMA guidelines using Review Manager 5.3.Two RCT studies were included in this meta-analysis. Surgery for involutional entropion was performed on a total of 109 eyes. Everting sutures (ES) were used on 57 eyes and lateral tarsal strips (LTS) or combined procedures (LTS + ES) were performed on 52 eyes. At the end of the follow-up periods, involutional entropion recurred in 18 eyes (31.6%) in the ES group and three eyes (5.8%) in the LTS +/- ES group. Analysis of the risk ratio showed that the LTS +/- ES method significantly lowered the recurrence rate compared to using ES only (P = 0.007).Performing LTS +/- ES effectively lowered the recurrence rate of involutional entropion compared to ES alone. However, some patients cannot tolerate more invasive corrections such as LTS. Therefore, sequential procedures, in which ES is performed first and then when entropion recurs LTS +/- ES is performed, or another methods depending upon the degree of HL may be used.
Female Dispersion Is Necessary, But Not Sufficient, For The Evolution of Monogamy in Mammals
Authors: Dunbar R.I.M. 
Published: December 2020

AbstractExplanations for the evolution of monogamy in mammals typically emphasise one of two possibilities: monogamy evolves when females are overdispersed (such that males cannot defend more than one female at a time) or when males provide a service to the female. However, the first claim has never been directly tested. I test it directly at three levels using data from primates and ungulates. First, I show that the females of monogamous genera do not have territories that are significantly larger, either absolutely or relatively, than those of polygamous genera. Second, using both the Mitani-Rodman and Lowen-Dunbar inequalities, I show that, given their typical day journey lengths, males of most monogamous species could easily defend an area large enough to allow them to monopolise as many as 5-10 females if these ranged solitarily. Finally, I use a model of male mate searching strategies to show that, unlike the males of socially-living polygamous species, the opportunity cost that monogamous males incur is typically more than five times the reproductive success they have by being obligately monogamous. This suggests that the selection pressure dissuading them from pursuing a roving male strategy must be very considerable.
5-Deoxyadenosine Salvage by Promiscuous Enzyme Activity leads to Bioactive Deoxy-Sugar Synthesis inSynechococcus elongatus
Authors: Rapp Johanna , Rath Pascal , Kilian Joachim , Brilisauer Klaus , Grond Stephanie , Forchhammer Karl 
Published: December 2020

Abstract7-Deoxysedoheptulose is an unusual deoxy-sugar, which acts as antimetabolite of the shikimate pathway thereby exhibiting antimicrobial and herbicidal activity. It is produced by the unicellular cyanobacteriumSynechococcus elongatusPCC 7942, which has a small, stream-lined genome, assumed to be free from gene clusters for secondary metabolite synthesis. In this study, we identified the pathway for the synthesis of 7-deoxysedoheptulose. It originates from 5-deoxyadenosine, a toxic byproduct of radicalS-adenosylmethionine (SAM) enzymes, present in all domains of life. Thereby we identified a novel 5-deoxyadenosine salvage pathway, which first leads to the synthesis and excretion of 5-deoxyribose and subsequently of 7-deoxysedoheptulose. Remarkably, all reaction steps are conducted by promiscuous enzymes. This is a unique example for the synthesis of a bioactive compound without involving a specific gene cluster. This challenges the view on bioactive molecule synthesis by extending the range of possible compounds beyond the options predicted from secondary metabolite gene clusters.
Restoring Glutamate receptosome dynamics at synapses rescues Autism-like deficits in Shank3-deficient mice
Authors: Moutin Enora , Sakkaki Sophie , Compan Vincent , Bouquier Nathalie , Giona Federica , Areias Julie , Goyet Elise , Hemonnot-Girard Anne-Laure , Seube Vincent , Benac Nathan , Chastagnier Yan , Raynaud Fabrice , Audinat Etienne , Groc Laurent , Maurice Tangui , Sala Carlo , Verpelli Chiara , Perroy Julie 
Published: December 2020

AbstractShank3 monogenic mutations lead to Autism Spectrum Disorders (ASD). Shank3 is part of the glutamate receptosome that physically links ionotropic NMDA receptors to metabotropic mGlu5 receptors through interactions with scaffolding proteins PSD95-GKAP-Shank3-Homer. A main physiological function of the glutamate receptosome is to control NMDA synaptic function that is required for plasticity induction. Intact glutamate receptosome supports glutamate receptors activation and plasticity induction, while glutamate receptosome disruption blocks receptors activity, preventing the induction of subsequent plasticity. Despite possible impact on metaplasticity and cognitive behaviors, scaffold interaction dynamics and their consequences are poorly defined. Here we used mGlu5-Homer interaction as a biosensor of glutamate receptosome integrity to report changes of NMDA synaptic function. Combining BRET imaging and electrophysiology, we show that a transient neuronal depolarization inducing NMDA-dependent plasticity disrupts glutamate receptosome in a long-lasting manner at synapses and induces signaling required for the expression of the initiated neuronal plasticity such as ERK and mTOR pathways. Glutamate receptosome disruption also decreases NMDA/AMPA currents ratio, freezing the sensitivity of the synapse to subsequent changes of neuronal activity. These data show the importance of a fine-tuning of protein-protein interactions within glutamate receptosome, driven by changes of neuronal activity, to control plasticity. In a mouse model of ASD, a truncated mutant form of Shank3 prevents the integrity of the glutamate receptosome. These mice display altered plasticity, anxiety-like and stereotyped behaviors. Interestingly, repairing the integrity of glutamate receptosome and its sensitivity to the neuronal activity rescued synaptic transmission, plasticity and some behavioral traits of Shank3∆C mice. Altogether, our findings characterize mechanisms by which Shank3 mutations cause ASD and highlight scaffold dynamics as new therapeutic target.
ComEB protein is dispensable for transformation but must be translated for optimal synthesis of ComEC
Authors: De Santis Micaela , Hahn Jeanette , Dubnau David 
Published: December 2020

SummaryWe show that the ComEB protein is not required for transformation inBacillus subtilis,despite its expression from within thecomEoperon under competence control. We show further that the synthesis of the putative channel protein ComEC is translationally coupled to the upstreamcomEBopen reading frame, so that translation ofcomEBand a suboptimal ribosomal binding site embedded in its sequence are needed for propercomECexpression. Translational coupling appears to be a common mechanism in three major competence operons for the adjustment of protein amounts independent of transcriptional control, probably ensuring the correct stoichiometries for assembly of the transformation machinery.comEBandcomFCrespectively encode cytidine deaminase and a protein resembling type 1 phosphoribosyl transferases and we speculate that nucleotide scavenging proteins are produced under competence control for efficient reutilization of the products of degradation of the non-transforming strand during DNA uptake.
Dynamic Community Composition Unravels Allosteric Communication in PDZ3
Authors: Guclu Tandac F. , Atilgan Ali Rana , Atilgan Canan 
Published: December 2020

ABSTRACTThe third domain of PSD-95 (PDZ3) is a model for investigating allosteric communication in protein and ligand interactions. While motifs contributing to its binding specificity have been scrutinized, a conformational dynamical basis is yet to be established. Despite the miniscule structural changes due to point mutants, the observed significant binding affinity differences have previously been assessed with a focus on two α-helices located at the binding groove (α2) and the C-terminus (α3). Here, we employ a new computational approach to develop a generalized view on the molecular basis of PDZ3 binding selectivity and interaction communication for a set of point mutants of the protein (G330T, H372A, G330T-H372A) and its ligand (CRIPT named L1and its T-2F variant L2) along with the wild type (WT). To analyze the dynamical aspects hidden in the conformations that are produced by molecular dynamics simulations, we utilize variations in community composition calculated based on the betweenness centrality measure from graph theory. We find that the highly charged N-terminus which is located far from the ligand has the propensity to share the same community with the ligand in the biologically functional complexes, indicating a distal segment might mediate the binding dynamics. N- and C-termini of PDZ3 share communities, and α3acts as a hub for the whole protein by sustaining the communication with all structural segments, albeit being a trait not unique to the functional complexes. Moreover, α2which lines the binding cavity frequently parts communities with the ligand and is not a controller of the binding but is rather a slave to the overall dynamics coordinated by the N-terminus. Thus, ligand binding fate in PDZ3 is traced to the population of community compositions extracted from dynamics despite the lack of significant conformational changes.
Protein Docking Model Evaluation by Graph Neural Networks
Authors: Wang Xiao , Flannery Sean T , Kihara Daisuke 
Published: December 2020

AbstractPhysical interactions of proteins play key roles in many important cellular processes. Therefore, it is crucial to determine the structure of protein complexes to understand molecular mechanisms of interactions. To complement experimental approaches, which usually take a considerable amount of time and resources, various computational methods have been developed to predict the structures of protein complexes. In computational modeling, one of the challenges is to identify near-native structures from a large pool of generated models. Here, we developed a deep learning-based approach named Graph Neural Network-based DOcking decoy eValuation scorE (GNN-DOVE). To evaluate a protein docking model, GNN-DOVE extracts the interface area and represents it as a graph. The chemical properties of atoms and the inter-atom distances are used as features of nodes and edges in the graph. GNN-DOVE was trained and validated on docking models in the Dockground database. GNN-DOVE performed better than existing methods including DOVE, which is our previous development that uses convolutional neural network on voxelized structure models.
Screening a library of FDA-approved and bioactive compounds for antiviral activity against SARS-CoV-2
Authors: Biering Scott B. , Van Dis Erik , Wehri Eddie , Yamashiro Livia H. , Nguyenla Xammy , Dugast-Darzacq Claire , Graham Thomas G.W. , Stroumza Julien R. , Golovkine Guillaume R. , Roberts Allison W. , Fines Daniel M. , Spradlin Jessica N. , Ward Carl C. , Bajaj Teena , Dovala Dustin , Gahmen Ursula Schulze , Bajaj Ruchika , Fox Douglas M. , Ott Melanie , Murthy Niren , Nomura Daniel K. , Schaletzky Julia , Stanley Sarah A. 
Published: December 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has emerged as a major global health threat. The COVID-19 pandemic has resulted in over 80 million cases and 1.7 million deaths to date while the number of cases continues to rise. With limited therapeutic options, the identification of safe and effective therapeutics is urgently needed. The repurposing of known clinical compounds holds the potential for rapid identification of drugs effective against SARS-CoV-2. Here we utilized a library of FDA-approved and well-studied preclinical and clinical compounds to screen for antivirals against SARS-CoV-2 in human pulmonary epithelial cells. We identified 13 compounds that exhibit potent antiviral activity across multiple orthogonal assays. Hits include known antivirals, compounds with anti-inflammatory activity, and compounds targeting host pathways such as kinases and proteases critical for SARS-CoV-2 replication. We identified seven compounds not previously reported to have activity against SARS-CoV-2, including B02, a human RAD51 inhibitor. We further demonstrated that B02 exhibits synergy with remdesivir, the only antiviral approved by the FDA to treat COVID-19, highlighting the potential for combination therapy. Taken together, our comparative compound screening strategy highlights the potential of drug repurposing screens to identify novel starting points for development of effective antiviral mono- or combination therapies to treat COVID-19.
One step forward, two steps back: transcriptional advancements and fermentation phenomena inActinobacillus succinogenes130Z
Authors: Long Dianna S. , Immethun Cheryl M. , Vallecilla-Yepez Lisbeth , Wilkins Mark R. , Saha Rajib 
Published: December 2020

AbstractWithin the field of bioproduction, non-model organisms offer promise as bio-platform candidates. Non-model organisms can possess natural abilities to consume complex feedstocks, produce industrially useful chemicals, and withstand extreme environments that can be ideal for product extraction. However, non-model organisms also come with unique challenges due to lack of characterization. As a consequence, developing synthetic biology tools, predicting growth behavior, and building computational models can be difficult. There have been many advancements that have improved work with non-model organisms to address broad limitations, however each organism can come with unique surprises. Here we share our work in the non-model bacteriumActinobacillus succinognes130Z, which includes both advancements in synthetic biology toolkit development and pitfalls in unpredictable fermentation behaviors. To develop a synthetic biology “tool kit” forA. succinogenes, information gleaned from a growth study and antibiotic screening was used to characterize 22 promoters which demonstrated a 260-fold range of fluorescence protein expression. The strongest of the promoters was incorporated into an inducible system for tunable gene control inA. succinogenesusing the promoter for thelacoperon as a template. This system flaunted a 481-fold range of expression and no significant basal expression. These findings were accompanied by unexpected changes in fermentation products characterized by a loss of succinic acid and increase in lactic acid after approximately 10 months in the lab. Contamination and mutation were ruled out as causes and further testing is needed to elucidate the driving factors. The significance of this work is to share tools developed inA. succinogeneswhile simultaneously serving as a cautionary tale. In sharing our findings, we seek to provide necessary information for further development ofA. succinogenesas a platform for bioproduction of succinic acid. Additionally, we hope to illustrate the importance of diligent and long-term observation when working with non-model bacteria.
Impacts of using wide bandgap transistors on electronics and motors
Authors: Gerber Mathieu , Callerant Guillaume , Espanet Christophe , Meibody-Tabar Farid , Takorabet Noureddine 
Published: December 2020

Purpose
The purpose of this paper is to study the high-frequency impacts of fast switching wide-bandgap transistors on electronic and motor designs. The high-frequency power converters, dedicated to driving high-speed motors, require specific models to design predictively electronic and motors.

Design/methodology/approach
From magnetic and electric models, the high-frequency parasitic elements for both electronics and motor are determined. Then, high-frequency circuit models accounting for of parasitic element extractions are built to study the wide bandgap transistors commutations and their impacts on motor windings.

Findings
The results of the models, for electronics and motors, are promising. The high-frequency commutation cell study is used to optimize the layouts and to improve the commutation behaviours and performances. The impact of the switching speed is highlighted on the winding voltage susceptibility. Then, the switching frequency and commutation rapidity can be both optimized to increase the performance of motor and electronics. The electronic model is validated by experimentations.

Research limitations/implications
The method can be only applied to the existing motor and electronic designs. It is not taken into account in an automized global high-frequency optimizer.

Originality/value
Helped by magnetic and electric FEA calculations where the parasitic element extractions are performed. The switching frequency and commutation rapidity can be both optimized to increase the performance of motor and electronics.
Adjoint-based topology optimization to reduce the energy consumption of a Hall effect thruster
Authors: Youness Rtimi , Messine Frederic 
Published: December 2020

Purpose
The presented study aims to minimize the energy consumed by a Hall effect thruster (HET) under a constraint which makes it possible to generate a specified magnetic field in a target region of the thruster.

Design/methodology/approach
Herein topology optimization (TO) is used to reduce the energy consumption of an HET while keeping its performance unchanged. The design variables are the current densities in the coils and the distribution of materials in the polar pieces of the thruster. Intermediate values of material distribution are penalized using the solid isotropic material with penalization method to favor binary solutions. By means of the adjoint method, this paper provides the derivatives of the objective and constraint functions with respect to material distribution and current density variables.

Findings
The TO-based design methodology is developed and validated on a design example involving 2,051 variables. The approach shows its interest and its effectiveness of on a large scale two-criteria problem.

Research limitations/implications
In this paper, TO is presented as a tool that has allowed to explore new and innovative designs. However, although the design presented is original, its fabrication is not feasible. Despite this, the designs found give a good idea of the starting points for shape and parametric optimization tools.

Practical implications
Through the HET design problem, TO shows the ability to explore more original design possibilities of a complex magnetostatic design problem and to discover designs that make a HET more efficient with respect to several criteria at the same time.

Originality/value
A new way to reduce the energy consumption of a HET is presented. To achieve this, an adjoint-based TO method is developed and then implemented in a simple way. This approach shows that, for efficiency purposes, TO is a key tool for extending the state of the art of HET designs.