bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home-EEG assessment of possible compensatory mechanisms for sleep disruption in highly irregular shift workers – The ANCHOR study
Authors: Mentink Lara J. , Thomas Jana , Melis René J.F. , Olde Rikkert Marcel G.M. , Overeem Sebastiaan , Claassen Jurgen A.H.R. 
Published: August 2020

AbstractStudy objectivesWhile poor sleep quality has been related to increased risk of Alzheimer’s disease, long-time shift workers (maritime pilots) did not manifest evidence of early Alzheimer’s disease in a recent study. We explored two hypotheses of possible compensatory mechanisms for sleep disruption: Increased efficiency in generating deep sleep during workweeks (model 1) and rebound sleep during rest weeks (model 2).MethodsWe used data from ten male maritime pilots (mean age: 51.6±2.4 years) with a history of approximately 18 years of irregular shift work. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). A single lead EEG-device was used to investigate sleep in the home/work environment, quantifying total sleep time (TST), deep sleep time (DST), and deep sleep time percentage (DST%). Using multilevel models, we studied the sleep architecture of maritime pilots over time, at the transition of a workweek to a rest week.ResultsMaritime pilots reported worse sleep quality in workweeks compared to rest weeks (PSQI=8.2±2.2 vs. 3.9±2.0; p<0.001). Model 1 showed a trend towards an increase in DST% of 0.6% per day during the workweek (p=0.08). Model 2 did not display an increase in DST% in the rest week (p=0.87).ConclusionsOur findings indicated that increased efficiency in generating deep sleep during workweeks is a more likely compensatory mechanism for sleep disruption in the maritime pilot cohort than rebound sleep during rest weeks. Compensatory mechanisms for poor sleep quality might mitigate sleep disruption-related risk of developing Alzheimer’s disease. These results should be used as a starting point for future studies including larger, more diverse populations of shift workers.
How the Motor Aspect of Speaking Influences the Blink Rate
Authors: Brych Mareike , Murali Supriya , Händel Barbara 
Published: August 2020

AbstractThe blink rate increases if a person indulges in a conversation compared to quiet rest. Since various factors were suggested to explain this increase, the present study tested the influence of motor activity, cognitive processes and auditory input on the blink rate but at the same time excluding any social interaction. While the cognitive and auditory factors only showed a minor influence, mere mouth movements during speaking highly increased the blink rate. Even more specific, lip movements, but less jaw movements, are likely responsible for the increase during a conversation. Such purely motor related influences on the blink rate advise caution when using blinks as neurological indicators during patient interviews.
Genome-wide RNAi screen for regulators of UPRmtinCaenorhabditis elegansmutants with defects in mitochondrial fusion
Authors: Haeussler Simon , Yeroslaviz Assa , Rolland Stéphane G. , Luehr Sebastian , Conradt Barbara 
Published: August 2020

ABSTRACTThe disruption of mitochondrial dynamics has detrimental consequences for mitochondrial and cellular homeostasis and leads to the activation of the mitochondrial unfolded protein response (UPRmt), a quality control mechanism that adjusts cellular metabolism and restores homeostasis. To identify genes involved in the induction of UPRmtin response to a block in mitochondrial fusion, we performed a genome-wide RNAi screen inCaenorhabditis elegansmutants lacking the genefzo-1, which encodes the ortholog of mammalian Mitofusin. We find that approximately 90% of the 299 suppressors and 86 enhancers identified are conserved in humans and that one third of the conserved genes have been implicated in human disease. Furthermore, many of the 385 genes have roles in developmental processes, which suggests that mitochondrial function and the response to stress are defined during development and maintained throughout life. In addition, we find that enhancers are predominantly ‘mitochondrial’ genes and suppressors ‘non-mitochondrial’ genes, which indicates that the maintenance of mitochondrial homeostasis has evolved as a critical cellular function that when disrupted can be compensated for by a variety of cellular processes. Our analysis of ‘non-mitochondrial’ enhancers and ‘mitochondrial’ suppressors suggests that organellar contact sites, especially between ER and mitochondria, are of importance for mitochondrial homeostasis. Finally, we uncovered several genes involved in IP3signaling that modulate UPRmtinfzo-1mutants, found a potential link between pre-mRNA splicing and UPRmtactivation and identified theMiga-1/2orthologK01D12.6as required for mitochondrial dynamics inC. elegans.
Inoculation with highly-related mycorrhizal fungal siblings, and their interaction with plant genoptypes, strongly shapes tropical mycorrhizal fungal community structure
Authors: Ordoñez Yuli Marcela , Villard Lucas , Ceballos Isabel , Masclaux Frédéric G. , Rodriguez Alia , Sanders Ian R. 
Published: August 2020

AbstractArbuscular mycorrhizal fungi (AMF) have the potential to increase crop yields and all globally important crops form the mycorrhizal symbiosis. Only a few studies have investigated the impact of introduced AMF on local AMF communities and most studies have only investigated effects of one isolate. We studied the impact on AMF community structure of inoculating roots of the globally important crop cassava with highly genetically-related clonal siblings of two genetically differentRhizophagus irregularisisolates. We hypothesized that inoculation withR. irregularissiblings differentially influences the structure and the diversity of the pre-existing AMF community colonizing cassava. Alpha and beta taxonomic and phylogenetic AMF diversity were strongly and significantly altered differentially following inoculation with sibling AMF progeny. In most cases, the effects were also cassava-genotype specific. Although biomass production and AMF colonization were also both differentially affected by inoculation with siblingR. irregularisprogeny these variables were not correlated with changes in the AMF community structure. The results highlight that investigations on the impact of an introduced AMF species, that use only one isolate, are unlikely to be representative of the overall effects of that AMF species and that the genetic identity of the host must be considered. The amount of inoculum added was very small and effects were observed 12 months following inoculation. That such a small amount of almost genetically identical fungal inoculum can strongly differentially influence AMF community structure 12 months following inoculation, indicates that AMF communities in tropical soils are not very resistant to perturbation.
Neural repetition suppression modulates time perception: Evidence from electrophysiology and pupillometry
Authors: Kruijne Wouter , Olivers Christian N. L. , van Rijn Hedderik 
Published: August 2020

AbstractHuman time perception is malleable and subject to many biases. For example, it has repeatedly been shown that stimuli that are physically intense or that are unexpected seem to last longer. Two hypotheses have been proposed to account for such biases: one states that these temporal illusions are the result of heightened arousal which speeds up neural clock dynamics, whereas the alternative ‘magnitude coding’ account states that the magnitude of sensory responses causally modulates perceived durations. Common experimental paradigms used to study temporal biases can not dissociate between these accounts, as arousal and sensory magnitude covary and modulate each other. Here, we present two temporal discrimination experiments where flashing stimuli demarcated the start and end of a to-be-timed interval. These stimuli could either be in the same or in a different location, which led to different sensory responses due to neural repetition suppression. Crucially, changes and repetitions were fully predictable, allowing us to explore effects of sensory response magnitude without changes in arousal or surprise. Intervals with changing markers were perceived as lasting longer than those with repeating markers. We measured EEG (Experiment 1) and pupil size (Experiment 2), and found that temporal perception related to changes in event-related potentials (P2) and pupil constriction, both of which have been related to responses in the sensory cortex. Conversely, correlates of surprise and arousal (P3 amplitude and pupil dilation) were unaffected by stimulus repetitions and changes. These results demonstrate that sensory magnitude affects time perception even under constant levels of arousal.
Biochemical and mathematical lessons from the evolution of the SARS-CoV-2 virus: paths for novel antiviral warfare
Authors: Cluzel Nicolas , Lambert Amaury , Maday Yvon , Turinici Gabriel , Danchin Antoine 
Published: August 2020

AbstractIn the fight against the spread of COVID-19 the emphasis is on vaccination or on reactivating existing drugs used for other purposes. The tight links that necessarily exist between the virus as it multiplies and the metabolism of its host are systematically ignored. Here we show that the metabolism of all cells is coordinated by the availability of a core building block of the cell’s genome, cytidine triphosphate (CTP). This metabolite is also the key to the synthesis of the viral envelope and to the translation of its genome into proteins. This unique role explains why evolution has led to the early emergence in animals of an antiviral immunity enzyme, viperin, that synthesizes a toxic analogue of CTP. The constraints arising from this dependency guide the evolution of the virus. With this in mind, we explored the real-time experiment taking place before our eyes using probabilistic modelling approaches to the molecular evolution of the virus. We have thus followed, almost on a daily basis, the evolution of the composition of the viral genome to link it to the progeny produced over time, particularly in the form of blooms that sparked a firework of viral mutations. Some of those certainly increase the propagation of the virus. This led us to make out the critical role in this evolution of several proteins of the virus, such as its nucleocapsid N, and more generally to begin to understand how the virus ties up the host metabolism to its own benefit. A way for the virus to escape CTP-dependent control in cells would be to infect cells that are not expected to grow, such as neurons. This may account for unexpected body sites of viral development in the present epidemic.
Distinguishing between recent balancing selection and incomplete sweep using deep neural networks
Authors: Isildak Ulas , Stella Alessandro , Fumagalli Matteo 
Published: August 2020

1AbstractBalancing selection is an important adaptive mechanism underpinning a wide range of phenotypes. Despite its relevance, the detection of recent balancing selection from genomic data is challenging as its signatures are qualitatively similar to those left by ongoing positive selection. In this study we developed and implemented two deep neural networks and tested their performance to predict loci under recent selection, either due to balancing selection or incomplete sweep, from population genomic data. Specifically, we generated forward-in-time simulations to train and test an artificial neural network (ANN) and a convolutional neural network (CNN). ANN received as input multiple summary statistics calculated on the locus of interest, while CNN was applied directly on the matrix of haplotypes. We found that both architectures have high accuracy to identify loci under recent selection. CNN generally outperformed ANN to distinguish between signals of balancing selection and incomplete sweep and was less affected by incorrect training data. We deployed both trained networks on neutral genomic regions in European populations and demonstrated a lower false positive rate for CNN than ANN. We finally deployed CNN within theMEFVgene region and identified several common variants predicted to be under incomplete sweep in a European population. Notably, two of these variants are functional changes and could modulate susceptibility to Familial Mediterranean Fever, possibly as a consequence of past adaptation to pathogens. In conclusion, deep neural networks were able to characterise signals of selection on intermediate-frequency variants, an analysis currently inaccessible by commonly used strategies.
Expression of Tim-3 drives naïve Treg to an effector-like state with enhanced suppressive activity
Authors: Banerjee Hridesh , Nieves-Rosado Hector , Kulkarni Aditi , Murter Benjamin , Chandran Uma R. , Chang Alexander , Szymczak-Workman Andrea L. , Vujanovic Lazar , Ferris Robert L. , Kane Lawrence P. 
Published: August 2020

AbstractRegulatory T cells (Treg) are critical mediators of self-tolerance but can also limit effective anti-tumor immunity. We and others previously reported that 40-60% percent of Treg-infiltrating head and neck cancer (HNC) and other tumors highly express Tim-3, compared with about 5% in lymphoid organs. Tumor-infiltrating Tim-3+Treg also have enhanced suppressive function and display a more effector-like phenotype. Using a novel mouse model with cell type-specific Tim-3 expression, we show here that expression of Tim-3 by Treg is sufficient to drive Treg to a more effector-like phenotype, resulting in enhanced suppressive activity and increased tumor growth. These findings may help to reconcile previous reports that some Tim-3 antibodies enhance T cell responsesin vivo, while expression of Tim-3 has a cell-intrinsic ability to enhance TCR signaling and T cell activation. Thus, we propose that Tim-3 regulates anti-tumor immunity at least in part through enhancement of Treg function. To our knowledge, this is the first example in which expression of a single co-stimulatory molecule is sufficient to drive differentiation of Treg in this manner.
Biomechanical Characterization of SARS-CoV-2 Spike RBD and Human ACE2 Protein-Protein Interaction
Authors: Cao W. , Dong C. , Kim S. , Hou D. , Tai W. , Du L. , Im W. , Zhang X.F. 
Published: August 2020

ABSTRACTThe current COVID-19 pandemic has led to a devastating impact across the world. SARS-CoV-2 (the virus causing COVID-19) is known to use receptor-binding domain (RBD) at viral surface spike (S) protein to interact with the angiotensin-converting enzyme 2 (ACE2) receptor expressed on many human cell types. The RBD–ACE2 interaction is a crucial step to mediate the host cell entry of SARS-CoV-2. Recent studies indicate that the ACE2 interaction with the SARS-CoV-2 S protein has higher affinity than its binding with the structurally identical S protein of SARS-CoV-1, the virus causing the 2002-2004 SARS outbreak. However, the biophysical mechanism behind such binding affinity difference is unclear. This study utilizes a combined single-molecule force spectroscopy and steered molecular dynamics (SMD) simulation approach to quantify the specific interactions between CoV-2 or CoV-1 RBD and ACE2. Depending on the loading rates, the unbinding forces between CoV-2 RBD and ACE2 range from 70 to 110 pN, and are 30-50% higher than those of CoV-1 RBD and ACE2 under similar loading rates. SMD results indicate that CoV-2 RBD interacts with the N-linked glycan on Asn90 of ACE2. This interaction is mostly absent in the CoV-1 RBD–ACE2 complex. During the SMD simulations, the extra RBD-N-glycan interaction contributes to a greater force and prolonged interaction lifetime. The observation is confirmed by our experimental force spectroscopy study. After the removal of N-linked glycans on ACE2, its mechanical binding strength with CoV-2 RBD decreases to a similar level of the CoV-1 RBD–ACE2 interaction. Together, the study uncovers the mechanism behind the difference in ACE2 binding between SARS-CoV-2 and SARS-CoV-1, and could aid in the development of new strategies to block SARS-CoV-2 entry.STATEMENT OF SIGNIFICANCEThis study utilizes a combined single-molecule force spectroscopy and steered molecular dynamics simulation approach to quantify the specific interactions between SARS-CoV-2 or SARS-CoV-1 receptor-binding domain and human ACE2. The study reveals the mechanism behind the difference in ACE2 binding between SARS-CoV-2 and SARS-CoV-1, and could aid in the development of new strategies to block SARS-CoV-2 entry.
The avian W chromosome is a refugium for endogenous retroviruses with likely effects on female-biased mutational load and genetic incompatibilities
Authors: Peona Valentina , Palacios-Gimenez Octavio M. , Blommaert Julie , Liu Jing , Haryoko Tri , Jønsson Knud A. , Irestedt Martin , Zhou Qi , Jern Patric , Suh Alexander 
Published: August 2020

SummaryIt is a broadly observed pattern that the non-recombining regions of sex-limited chromosomes (Y and W) accumulate more repeats than the rest of the genome, even in species like birds with a low genome-wide repeat content. Here we show that in birds with highly heteromorphic sex chromosomes, the W chromosome has a transposable element (TE) density of >55% compared to the genome-wide density of <10%, and contains over half of all full-length (thus potentially active) endogenous retroviruses (ERVs) of the entire genome. Using RNA-seq and protein mass spectrometry data, we were able to detect signatures of female-specific ERV expression. We hypothesise that the avian W chromosome acts as a refugium for active ERVs, likely leading to female-biased mutational load that may influence female physiology similar to the “toxic-Y” effect inDrosophila. Furthermore, Haldane’s rule predicts that the heterogametic sex has reduced fertility in hybrids. We propose that the excess of W-linked active ERVs over the rest of the genome may be an additional explanatory variable for Haldane’s rule, with consequences for genetic incompatibilities between species through TE/repressor mismatches in hybrids. Together, our results suggest that the sequence content of female-specific W chromosomes can have effects far beyond sex determination and gene dosage.
Understanding the evolution of multiple drug resistance in structured populations
Authors: McLeod David V. , Gandon Sylvain 
Published: August 2020

AbstractThe evolution of multidrug resistance (MDR) is a pressing public health concern. Yet many aspects, such as the role played by population structure, remain poorly understood. Here we argue that studying MDR evolution by focusing upon the dynamical equations for linkage disequilibrium (LD) can greatly simplify the calculations, generate more insight, and provide a unified framework for understanding the role of population structure. We demonstrate how a general epidemiological model of MDR evolution can be recast in terms of the LD equations. These equations reveal how the different forces generating and propagating LD operate in a dynamical setting at both the population and metapopulation levels. We then apply these insights to show how the LD perspective: (i) explains equilibrium patterns of MDR, (ii) provides a simple interpretative framework for transient evolutionary dynamics, and (iii) can be used to assess the consequences of different drug prescription strategies for MDR evolution.
VirPreNet: A weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all 8 segments
Authors: Yin Rui , Luo Zihan , Zhuang Pei , Lin Zhuoyi , Kwoh Chee Keong 
Published: August 2020

AbstractMotivationInfluenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics.ResultsIn this paper, we propose a weighted ensemble convolutional neural network for the virulence prediction of influenza A viruses named VirPreNet that uses all 8 segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the 8-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble convolutional neural network is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNet’s main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza virulence.Contactyinr0002@e.ntu.edu.sgAvailability and ImplementationCodes and data to generate the VirPreNet are publicly available athttps://github.com/Rayin-saber/VirPreNet
Independent Tryptophan pathway inTrichoderma asperellumandT koningiopsis: New insights with bioinformatic and molecular analysis
Authors: Mariana Uribe Bueno , Hernández-Mendoza JL , Armando García Carlos , Veronica Ancona , Larios-Serrato Violeta 
Published: August 2020

ABSTRACTThe synthesis of Indole Acetic Acid from tryptophan has been described in plants, fungi and bacteria; it is thus known as tryptophan-dependent indole acetic acid. Four possible pathways of IAA formation have been described, including the indole acetonitrile acid (IAN), indole acetamide (IAM), indole-pyruvic (IAP) and tryptamine (TRM) pathways. Of these, the indole acetonitrile pathway is particularly important because when this compound is transformed into IAA, a nitrogenated molecule is released. The microorganisms that have this pathway are thus called nitrogen fixers. There is another little-studied pathway called TRP-Independent, so-called because the IAA that is formed in it can have an exogenous origin, chorismic acid (CHA), and it enters the pathway through anthranilic acid (ANA). The TRP-Independent pathway is made up of three stages. The first from CHA to ANA, the second from AA to IAA and the third from TRP to ANA through Kynurenine (KYN). This work describes the different stages of the pathway, as well as the enzymes and the genes that control the production of IAA, using a bioinformatic analysis of the genes involved, which were identified by PCR. An expression analysis showed that onlyT asperellumhas the necessary genes to incorporate ANA into the TRP-I pathway and synthesize IAA through it. The analysis also detected the gene that regulates anthranilate phosphoribosyl transferase (AFT), an enzyme necessary for the synthesis of AIA from ANA; the presence of this gene was confirmed in the two species analyzed.