bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stochastic survival of the densest and mitochondrial DNA clonal expansion in ageing
Authors: Insalata Ferdinando , Hoitzing Hanne , Aryaman Juvid , Jones Nick S. 
Published: September 2020

AbstractThe expansion of deleted mitochondrial DNA molecules has been associated with ageing1,2, particularly in skeletal muscle fibres3–5; its mechanism has remained unclear for three decades. Previous accounts have assigned a replicative advantage to the deletions6–8, but there is evidence that cells can, instead, selectively remove defective mitochondrial DNA9. Here we present a spatial model that, without a replicative advantage, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with speeds consistent with experimental data10. A standard model based on replicative advantage yields waves that are too fast. We provide a formula that predicts that wave-speed drops with copy number, consonant with experimental data. Crucially, our model yields travelling waves of mutants even if mutants are preferentially eliminated. Additionally, we predict that experimentally observed mutant loads can be produced byde novomutation rates that are drastically lower than previously thought for neutral models11. Given this exemplar of how noise, density and spatial structure affect muscle age-ing, we introduce the mechanism of stochastic survival of the densest, an alternative to replicative advantage, that may underpin other evolutionary phenomena.
Genomic signatures of the unjamming transition in compressed human bronchial epithelial cells
Authors: De Marzio Margherita , Kılıç Ayşe , Maiorino Enrico , Mitchel Jennifer , McGill Maureen , Chase Robert , Fredberg Jeffrey J. , Park Jin-Ah , Glass Kimberly , Weiss Scott T. 
Published: September 2020

AbstractEpithelial tissue has the capacity to switch from a collective phase that is quiescent, solidlike and non-migratory to one that is dynamic, fluid-like and migratory. In certain physiological and pathophysiological contexts this phenotypic switch has been attributed not to the well-known epithelial-to-mesenchymal transition, EMT, but rather to the recently discovered unjamming transition, UJT. UJT has been characterized thus far mainly at functional and morphological levels whereas underlying genome-wide molecular events remain largely unexplored. Using primary human bronchial epithelial cells and one well-defined trigger of UJT –mechanical compression– here we combine temporal RNA-Seq data and Protein-Protein Interaction networks to provide the first genome-wide analysis of UJT. Our results show that compression induces a multiphasic transcriptional response characterized by an early activation of genes regulating the membrane and actomyosin structure, and a delayed activation of genes regulating the extracellular matrix and cellmatrix interactions. This biphasic response is mediated by a cascade of signaling processes that promotes actin polymerization through the recruitment of integrin-ECM adhesive complexes and promotes increased cellular motility through activation of AP-1 transcription factors via ERK and JNK pathways. These findings, taken together, show that the UJT program is not the result of any single signaling pathway but rather comprises a coordinated interplay of downstream pathways including development, fate selection, energy metabolism, cytoskeletal reorganization, and adhesive interaction with extracellular matrix.
In Silico Analysis of Effect of Non-synonymous SNPs associated with Permanent Neonatal Diabetes Mellitus on Stability and Structure of Human Insulin
Authors: Tabassum Nishat 
Published: September 2020

AbstractMotivationProteins are the building-blocks of life. However with the deluge of data on protein sequences and their association with diseases, it is imperative to use computational tools to aid experimental analysis. Determination of the impact of disease-causing SNPs on protein’s structure is crucial in discovering how a disease affects the functions on a fundamental level and thereafter, determining potential drug targets.ResultsSNPs associated with the genetic disease permanent neonatal diabetus mellitus (PNDM) were studied to determine their impact on human insulin. Out of 16 missense variants, eight were predicted to be deleterious. 6 of the SNPs resulted in high structural differences (RMSD > 0.9, H bonds > 35). Stability changes were also determined.
RecT recombinase expression enables efficient gene editing inEnterococcus
Authors: Chen Victor , Griffin Matthew E. , Hang Howard C. 
Published: September 2020

AbstractEnterococcus faeciumis a ubiquitous Gram-positive bacterium that has been recovered from the environment, food, and microbiota of mammals. Commensal strains ofE. faeciumcan confer beneficial effects on host physiology and immunity, but antibiotic usage has afforded antibiotic-resistant and pathogenic isolates from livestock and humans. However, the dissection ofE. faeciumfunctions and mechanisms has been restricted by inefficient gene editing methods. To address these limitations, here we report the expression ofE. faeciumRecT recombinase significantly improves the efficiency of recombineering technologies in both commensal and antibiotic-resistant strains ofE. faeciumand otherEnterococcusspecies such asE. duransandE. hirae. Notably, the expression of RecT in combination with clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 and guide RNAs (gRNAs) enabled highly efficient scar-less single-stranded DNA recombineering to generate specific gene editing mutants inE. faecium. Moreover, we demonstrate thatE. faeciumRecT expression facilitated chromosomal insertions of double-stranded DNA templates encoding antibiotic selectable markers to generate gene deletion mutants. As further proof-of-principle, we use CRISPR-Cas9 mediated recombineering to knock out both sortase A genes inE. faeciumfor downstream functional characterization. The general RecT-mediated recombineering methods described here should significantly enhance genetic studies ofE. faeciumand other closely related species for functional and mechanistic studies.ImportanceEnterococcus faeciumis widely recognized as an emerging public health threat with the rise of drug resistance and nosocomial infections. Nevertheless, commensalEnterococcusstrains possess beneficial health functions in mammals to upregulate host immunity and prevent microbial infections. This functional dichotomy ofEnterococcusspecies and strains highlights the need for in-depth studies to discover and characterize the genetic components underlining its diverse activities. However, current genetic engineering methods inE. faeciumstill require passive homologous recombination from plasmid DNA. This involves the successful cloning of multiple homologous fragments into a plasmid, introducing the plasmid intoE. faecium, and screening for double-crossover events that can collectively take up to multiple weeks to perform. To alleviate these challenges, we show that RecT recombinase enables rapid and efficient integration of mutagenic DNA templates to generate substitutions, deletions, and insertions in genomic DNA ofE. faecium. These improved recombineering methods should facilitate functional and mechanistic studies ofEnterococcus.
The activity of yeast Apn2 AP endonuclease at uracil-derived AP sites is dependent on the major carbon source
Authors: Stokdyk Kasey , Berroyer Alexandra , Grami Zacharia A. , Kim Nayun 
Published: September 2020

ABSTRACTYeast Apn2 is an AP endonuclease and DNA 3’-diesterase that belongs to the Exo III family with homology to theE. coliexonuclease III,Schizosaccharomyces pombeeth1, and human AP endonucleases APEX1 and APEX2. In the absence of Apn1, the major AP endonuclease in yeast, Apn2 can cleave the DNA backbone at an AP lesion initiating the base excision repair pathway. In order to study the role and relative contribution of Apn2, we took advantage of a reporter system that was previously used to delineate how uracil-derived AP sites are repaired. At this reporter, disruption of the Apn1-initiated base excision repair pathway led to a significant elevation of A:T to C:G transversions. Here we show that such highly elevated A:T to C:G transversion mutations associated with uracil residues in DNA are abolished whenapn1Δ yeast cells are grown in glucose as the primary carbon source. We also show that the disruption of Apn2, either by the complete gene deletion or by the mutation of a catalytic residue, results in a similarly reduced rate of the uracil-associated mutations. Overall, our results indicate that Apn2 activity is regulated by the glucose repression pathway in yeast.
Spindle alignment is uncoupled with Kar9 symmetry breaking
Authors: Meziane Miram , Genthial Rachel , Vogel Jackie 
Published: September 2020

ABSTRACTSpindle positioning must be tightly regulated to ensure asymmetric cell divisions are successful. In budding yeast, spindle positioning is mediated by the asymmetric localization of microtubule +end tracking protein Kar9. Kar9 asymmetry is believed to be essential for spindle alignment. However, the temporal correlation between symmetry breaking and spindle alignment has not been measured. Here, we establish a method of quantifying Kar9 symmetry breaking and find that Kar9 asymmetry is not well coupled with early spindle alignment. We report the majority of asymmetric cells are not stably aligned. Rather, stable alignment, a state we define as perfect alignment, is correlated with Kar9 localization to the bud compartment, regardless of symmetry state. Our findings suggest that Kar9 asymmetry alone is insufficient for perfect alignment and reveal a possible role for Swe1 in regulating spindle alignment efficiency.
Insulin-Induced Conformational Changes in the Full-Length Insulin Receptor: Structural Insights Gained from Molecular Modeling Analyses
Authors: Yang Yong Xiao , Li Peng , Wang Pan , Zhu Bao Ting 
Published: September 2020

ABSTRACTInsulin receptor plays an important role in regulation of energy metabolism. Dysfunction of insulin receptor (IR) can lead to many disease states, such as diabetes mellitus. Deciphering the complex dynamic structure of human IR and its mechanism of activation would greatly aid in understanding IR-mediated signaling pathways and in particular, in designing new drugs (including nonpeptidal insulin analogs) to treat diabetes mellitus. Experimental evidence about IR structure has been gradually obtained by biologists over the past three decades. Based on the available experimental structures of IR in different states, here we employ molecular modeling approach to construct the full-length IR structures in different states and model its structural and conformational changes during insulin-induced IR activation. Several key possible intermediate states are constructed based on structural alignment, rotation and computational modeling. Based on the structures of the full-length IR in different states, it appears that there are two possible conformational transition pathways: one is symmetric, and the other one is asymmetric. Structural changes and motions of different domains of the full-length IR along the pathways are analyzed. The role of insulin binding to IR in facilitating the conformational transition of the receptor is modeled. Information and insights derived from our present structural modeling analyses may aid in understanding the complex dynamic, structural and conformational changes during the process of IR activation.
Deep-learning convolutional neural networks with transfer learning accurately classify COVID19 lung infection on portable chest radiographs
Authors: Kikkisetti Shreeja , Zhu Jocelyn , Shen Beiyi , Li Haifang , Duong Tim Q 
Published: September 2020

ABSTRACTPortable chest x-ray (pCXR) has become an indispensable tool in the management of Coronavirus Disease 2019 (COVID-19) lung infection. This study employed deep-learning convolutional neural networks to classify COVID-19 lung infections on pCXR from normal and related lung infections to potentially enable more timely and accurate diagnosis. This retrospect study employed deep-learning convolutional neural network (CNN) with transfer learning to classify based on pCXRs COVID-19 pneumonia (N=455) on pCXR from normal (N=532), bacterial pneumonia (N=492), and non-COVID viral pneumonia (N=552). The data was split into 75% training and 25% testing. A five-fold cross-validation was used. Performance was evaluated using receiver-operating curve analysis. Comparison was made with CNN operated on the whole pCXR and segmented lungs. CNN accurately classified COVID-19 pCXR from those of normal, bacterial pneumonia, and non-COVID-19 viral pneumonia patients in a multiclass model. The overall sensitivity, specificity, accuracy, and AUC were 0.79, 0.93, and 0.79, 0.85 respectively (whole pCXR), and were 0.91, 0.93, 0.88, and 0.89 (CXR of segmented lung). The performance was generally better using segmented lungs. Heatmaps showed that CNN accurately localized areas of hazy appearance, ground glass opacity and/or consolidation on the pCXR. Deep-learning convolutional neural network with transfer learning accurately classifies COVID-19 on portable chest x-ray against normal, bacterial pneumonia or non-COVID viral pneumonia. This approach has the potential to help radiologists and frontline physicians by providing more timely and accurate diagnosis.
Electrophysiological Phenotype Characterization of Human iPSC-Derived Neuronal Cell Lines by Means of High-Density Microelectrode Arrays
Authors: Ronchi Silvia , Buccino Alessio Paolo , Prack Gustavo , Kumar Sreedhar Saseendran , Schröter Manuel , Fiscella Michele , Hierlemann Andreas 
Published: September 2020

AbstractRecent advances in the field of cellular reprogramming have opened a route to study the fundamental mechanisms underlying common neurological disorders. High-density microelectrode-arrays (HD-MEAs) provide unprecedented means to study neuronal physiology at different scales, ranging from network through single-neuron to subcellular features. In this work, we used HD-MEAsin vitroto characterize and compare human induced-pluripotent-stem-cell (iPSC)-derived dopaminergic and motor neurons, including isogenic neuronal lines modeling Parkinson’s disease and amyotrophic lateral sclerosis. We established reproducible electrophysiological network, single-cell and subcellular metrics, which were used for phenotype characterization and drug testing. Metrics such as burst shapes and axonal velocity enabled the distinction of healthy and diseased neurons. The HD-MEA metrics could also be used to detect the effects of dosing the drug retigabine to human motor neurons. Finally, we showed that the ability to detect drug effects and the observed culture-to-culture variability critically depend on the number of available recording electrodes.
Examining the link among green human resource management practices, green supply chain management practices and performance
Authors: Acquah Innocent Senyo Kwasi , Agyabeng-Mensah Yaw , Afum Ebenezer 
Published: September 2020

PurposeThe increasing concern for the protection of the environment through pollution prevention, conservation of resources and less usage of energy has attracted several firms to align green practices with their supply chain and human resource policies and practices. This study explores the influence of green human resource management and green supply chain management practices on operational, market, financial, social and environmental performances.Design/methodology/approachThe study uses partial least square–structural equation modeling approach to analyze the data gathered through structured questionnaires from supply chain and human resource managers in manufacturing and hospitality firms in Ghana.FindingsIt is established that green supply chain management practices play complementary partial mediating role between green human resource management and operational, market, social and environmental performances, while it plays competitive partial mediating role between green human resource management and financial performance. Subsequently, the analysis reveals that the synergy between green human resource management and green supply chain management creates the highest value in operational performance, followed by market performance, environmental performance, financial performance and social performance.Originality/valueThe study proposes and tests a conceptual model that examines the synergistic influence of green human resource management and green supply chain management on operational, market, financial, social and environmental performances.
Energy sustainability in teaching and outreach initiatives and the contribution to the 2030 Agenda
Authors: Lange Salvia Amanda , Londero Brandli Luciana , Leal Filho Walter , Gasparetto Rebelatto Bianca , Reginatto Giovana 
Published: September 2020

Purpose
Considering the different roles universities can perform to contribute to sustainable development, it is through teaching and outreach that they might be able to connect to the academic and local communities the most. The purpose of this study is to investigate the extent to which energy sustainability is being considered in campus teaching and outreach activities of different higher education institutions worldwide. In this context, this exploratory study was developed.

Design/methodology/approach
Through an online survey, a group of 36 universities from all continents was inquired about the level of sustainability in energy aspects of teaching and outreach activities, including curriculum change, training courses for staff and the regularity of outreach projects.

Findings
The results allowed global analysis concerning challenges and opportunities of these educational activities. This study also touches upon the interconnection between these practices and the contribution of universities towards the 2030 Agenda, and how universities can expand their activities and contribute practically to society. In terms of practical contributions, this study provides recommendations for higher education institutions to develop further in the area of energy sustainability through teaching and outreach.

Originality/value
Energy is a sustainability aspect relatively well covered by actions on campus operations, but there is a paucity of studies connecting this topic to teaching and outreach activities. This study is an approach to not only fill this gap but also reinforce the university role and contribution to the Sustainable Development Goals.
Word‐of‐mouth communication and search
Authors: Campbell Arthur , Leister C. Matthew , Zenou Yves 
Published: September 2020

AbstractWe develop a word‐of‐mouth search model where information flows from the old to the new generation for an experience good with unknown quality. We study the features of the social network that determine product quality and welfare and characterize the demand‐side (under provision of search effort) and supply‐side (inefficient entry by firms) factors that result in inefficiencies. One striking result is to show that the more connected but also the less‐unequal a friendship network is (in the sense of second order stochastic dominance of the degree distribution), the less can disreputable (low‐quality) firms thrive in equilibrium.
The Neurophysiology of Implicit Alcohol Associations in Recently Abstinent Patients With Alcohol Use Disorder: An Event‐Related Potential Study Considering Gender Effects
Authors: Tschuemperlin Raphaela Martina , Batschelet Hallie Margareta , Moggi Franz , Koenig Thomas , Roesner Susanne , Keller Anne , Pfeifer Philippe , Soravia Leila Maria , Stein Maria 
Published: September 2020

BackgroundNeuroscientific models of alcohol use disorders (AUDs) postulate an imbalance between automatic, implicit, and controlled (conscious) processes. Implicit associations towards alcohol indicate the automatically attributed appeal of alcohol‐related stimuli. First, behavioral studies indicate that negative alcohol associations are less pronounced in patients compared to controls, but potential neurophysiological differences remain unexplored. This study investigates neurophysiological correlates of implicit alcohol associations in recently abstinent patients with AUD for the first time, including possible gender effects.MethodsA total of 62 patients (40 males and 22 females) and 21 controls performed an alcohol valence Implicit Association Test, combining alcohol‐related pictures with positive (incongruent condition) or negative (congruent condition) words, while brain activity was recorded using 64‐channel electroencephalography. Event‐related potentials (ERPs) for alcohol‐negative and alcohol‐positive trials were computed. Microstate analyses investigated the effects of group (patients, controls) and condition (incongruent, congruent); furthermore, possible gender effects in patients were analyzed. Significant effects were localized with standardized low‐resolution brain electromagnetic topography analysis.ResultsAlthough no behavioral group differences were found, ERPs of patients and controls were characterized by distinct microstates from 320 ms onwards. ERPs between conditions differed only in patients with higher signal strength during incongruent trials. Around 600 ms, controls displayed higher signal strength than patients. A gender effect mirrored this pattern with enhanced signal strength in females as opposed to male patients. Around 690 ms, a group‐by‐valence interaction indicated enhanced signal strength in congruent compared to incongruent trials, which was more pronounced in controls.ConclusionsFor patients with AUD, the pattern, timing, and source localization of effects suggest greater effort regarding semantic and self‐relevant integration around 400 ms during incongruent trials and attenuated emotional processing during the late positive potential timeframe. Interestingly, this emotional attenuation seemed reduced in female patients, thus corroborating the importance of gender‐sensitive research and potential treatment of AUD.
Artificial light may change flight patterns of bats near bridges along urban waterways
Authors: Barré K. , Spoelstra K. , Bas Y. , Challéat S. , Kiri Ing R. , Azam C. , Zissis G. , Lapostolle D. , Kerbiriou C. , Le Viol I. 
Published: September 2020

AbstractArtificial light at night (ALAN) is considered as a major threat to biodiversity, especially to nocturnal species, as it reduces availability, quality and functionality of habitats. However, its effects on the way species use landscape elements such as rivers are still largely understudied, especially the effect of crossing infrastructure lighting on bridges. These elements are nevertheless key commuting and foraging habitats in heavily urbanised landscapes for several taxa such as bats that are particularly affected by ALAN. We studied the effects of the illumination of facades and undersides of bridges on the relative abundance of pipistrelle bats, on their 3D distribution and their behavioural response (i.e. flight speed) close to bridges. We set‐up an innovative approach based on a microphone‐array to reconstruct positions and flight trajectories in 3D. We studied the effect of lighting on bats in the close proximity of six similar bridges, mostly differentiated by the presence or absence of lighting (3 lit and 3 unlit). All bridges cross the same waterway, within a uniformly and highly urbanized agglomeration (Toulouse, France). We found that bat activity was 1.7 times lower in lit sites. Bats tended to keep a larger distance, and to fly faster close to illuminated bridges. These results suggest that bridge lighting strongly reduces habitat availability and likely connectivity for bats. In that case, results call for switching off the illumination of such bridges crossing riverine ecosystems to preserve their functionality as habitats and corridors for bats.