bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing microRNA-mediated modulation of gene expression noise and its effect on synthetic gene circuits
Authors: Wei Lei , Li Shuailin , Hu Tao , Zhang Michael Q. , Xie Zhen , Wang Xiaowo 
Published: July 2020

AbstractGene expression noise plays an important role in many biological processes, such as cell differentiation and reprogramming. It can also dramatically influence the behavior of synthetic gene circuits. MicroRNAs (miRNAs) have been shown to reduce the noise of lowly expressed genes and increase the noise of highly expressed genes, but less is known about how miRNAs with different properties may regulate gene expression noise differently. Here, by quantifying gene expression noise using mathematical modeling and experimental measurements, we showed that competing RNAs and the composition of miRNA response elements (MREs) play important roles in modulating gene expression noise. We found that genes targeted by miRNAs with weak competing RNAs show lower noise than those targeted by miRNAs with strong competing RNAs. In addition, in comparison with a single MRE, repetitive MREs targeted by the same miRNA suppress the noise of lowly expressed genes but increase the noise of highly expressed genes. Additionally, MREs composed of different miRNA targets could cause similar repression levels but lower noise compared with repetitive MREs. We further observed the influence of miRNA-mediated noise modulation in synthetic gene circuits which could be applied to classify cell types using miRNAs as sensors. We found that miRNA sensors that introduce higher noise could lead to better classification performance. Our results provide a systematic and quantitative understanding of the function of miRNAs in controlling gene expression noise and how we can utilize miRNAs to modulate the behavior of synthetic gene circuits.
Gain-of-function CRISPR screens identify tumor-promoting genes conferring melanoma cell plasticity and therapy-resistance
Authors: Gautron Arthur , Bachelot Laura , Quéméner Anaïs M. , Corre Sébastien , Aubry Marc , Rambow Florian , Paris Anaïs , Tardif Nina , Leclair Héloïse M. , Coulouarn Cédric , Marine Jean-Christophe , Galibert Marie-Dominique , Gilot David 
Published: July 2020

ABSTRACTMost genetic alterations that drive melanoma development and resistance to targeted therapy have been uncovered. In contrast, and despite their increasingly recognized contribution, little is known about the non-genetic mechanisms that drive these processes. Here, we performedin vivogain-of-function CRISPR screens and identifiedSMAD3,BIRC3andSLC9A5as key actors of BRAFi-resistance and these genes promote the tumor growth capability of persister cells. We show that their expression levels increase during acquisition of BRAFi-resistance, and remain high in persister cells and during relapse. The upregulation of the SMAD3 transcriptional activity (SMAD3-signature) promotes a mesenchymal-like phenotype and BRAFi-resistance by acting as an upstream transcriptional regulator of potent BRAFi-resistance genes such as EGFR and AXL. This SMAD3-signature predicts resistance to both current melanoma therapies in different cohorts. Critically, chemical inhibition of SMAD3 may constitute amenable target for melanoma since it efficiently abrogates persister cells survival. Interestingly, decrease of SMAD3 activity can also be reached by inhibiting the aryl hydrocarbon receptor (AhR), another druggable transcription factor governing SMAD3 expression level. Our work expands our understanding of the biology of persister cells and highlight novel drug vulnerabilities that can be exploited to develop long-lasting antimelanoma therapies.
Honeybees optimize their foraging behaviour in relation to spatio-temporal changes in nectar and pollen availability
Authors: Kreider Jan J. , Nehrkorn Anna , Bänsch Svenja , Kirsch Carmen , Westphal Catrin 
Published: July 2020

AbstractIntensified agriculture increasingly threatens wild and managed bees by promoting landscape uniformity and reducing floral resource availability whereas urban areas can provide continuous floral resources within green spaces and private gardens. Mass-flowering events of crops and trees, such as lime trees (Tiliaspp.), can provide ample floral resources but only for short time periods. Using waggle dance decoding, pollen analysis and bee abundance recordings, we investigated the temporal shift in honeybee foraging behaviour in response to lime tree mass-flowering. Honeybees in urban areas extended their foraging range during lime tree flowering. Foraging behaviour of honeybees in rural areas did not change to such an extent and honeybees foraged in sown flower strips. Our results suggest that honeybees optimize their foraging behaviour to exploit highly rewarding resources instead of extending foraging ranges in times of floral resource scarcity.
Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase)
Authors: Fenn Gareth D. , Waller-Evans Helen , Atack John R. , Bax Benjamin D. 
Published: July 2020

AbstractInositol monophosphatase (IMPase) is inhibited by lithium, the most efficacious treatment for bipolar disorder. Several therapies have been approved, or are going through clinical trials, aimed at the replacement of lithium in the treatment of bipolar disorder. One candidate small molecule is ebselen, a selenium-containing antioxidant, which has been demonstrated to produce lithium-like effects, both in a murine model and in clinical trials.Here we present the crystallization and first structure of human IMPase covalently complexed with ebselen, a 1.47Å crystal structure (PDB entry 6ZK0). In the human-IMPase-complex ebselen, in a ring opened conformation, is covalently attached to Cys141, a residue located away from the active site.IMPase is a dimeric enzyme and, in the crystal structure, two adjacent dimers share four ebselen molecules, creating a tetramer with ∼222 symmetry. In the crystal structure presented in this publication, the active site in the tetramer is still accessible, suggesting that ebselen may function as an allosteric inhibitor, or may block the binding of partner proteins.SynopsisHere we present a 1.47Å crystal structure of human inositol monophosphatase (IMPase) bound to the inhibitor ebselen (PDB entry 6ZK0). In the structure, ebselen forms a seleno-sulfide bond with cysteine 141 and ebselen-mediated contacts between two dimers give a ∼222 tetramer.
Sensing and seeing associated with overlapping occipitoparietal activation in simultaneous EEG-fMRI
Authors: Scrivener Catriona L. , Malik Asad , Lindner Michael , Roesch Etienne B. 
Published: July 2020

AbstractThe presence of a change in a visual scene can influence brain activity and behaviour, even in the absence of full conscious report. It may be possible for us to sense that such a change has occurred, even if we cannot specify exactly where or what it was. Despite existing evidence from electroencephalogram (EEG) and eye-tracking data, it is still unclear how this partial level of awareness relates to fMRI BOLD activation. Using EEG, functional magnetic resonance imaging (fMRI), and a change blindness paradigm, we found multi-modal evidence to suggest that sensing a change is distinguishable from being blind to it. Specifically, trials during which participants could detect the presence of a colour change but not identify the location of the change (sense trials), were compared to those where participants could both detect and localise the change (localise or see trials), as well as change blind trials. In EEG, late parietal positivity and N2 amplitudes were larger for localised changes only, when compared to change blindness. However, ERP-informed fMRI analysis found no voxels with activation that significantly co-varied with fluctuations in single-trial late positivity amplitudes. In fMRI, a range of visual (BA17,18), parietal (BA7,40), and midbrain (anterior cingulate, BA24) areas showed increased fMRI BOLD activation when a change was sensed, compared to change blindness. These visual and parietal areas are commonly implicated as the storage sites of visual working memory, and we therefore argue that sensing may not be explained by a lack of stored representation of the visual display. Both seeing and sensing a change were associated with an overlapping occipitoparietal network of activation when compared to blind trials, suggesting that the quality of the visual representation, rather than the lack of one, may result in partial awareness during the change blindness paradigm.
Optogenetic investigation into the role of the subthalamic nucleus in motor control
Authors: Guillaumin Adriane , Serra Gian Pietro , Georges François , Wallén-Mackenzie Åsa 
Published: July 2020

AbstractThe subthalamic nucleus is important achieve intended movements. Loss of its normal function is strongly associated with several movement disorders. Classical basal ganglia models postulate that two parallel pathways, the direct and indirect pathways, exert opposing control over movement, with the subthalamic nucleus part of the indirect pathway through which competing motor programs are prevented. The subthalamic nucleus is regulated by both inhibitory and excitatory projections but experimental evidence for its role in motor control has remained sparse. The objective here was to tease out the selective impact of the subthalamic nucleus on several motor parameters required to achieve intended movement, including locomotion, balance and motor coordination. Optogenetic excitation and inhibition using both bilateral and unilateral stimulations of the subthalamic nucleus were implemented in freely-moving mice. The results demonstrate that selective optogenetic inhibition of the subthalamic nucleus enhances locomotion while its excitation reduces locomotion. These findings lend experimental support to basal ganglia models in terms of locomotion. However, further analysis of subthalamic nucleus excitation revealed grooming and disturbed gait. Selective excitation also caused reduced motor coordination, independent of grooming, in advanced motor tasks. This study contributes experimental evidence for a regulatory role of the subthalamic nucleus in motor control.HighlightsBilateral optogenetic excitation of the subthalamic nucleus in freely-moving mice reduces forward locomotion while optogenetic inhibition leads to its increase.Unilateral optogenetic excitation and inhibition of the subthalamic nucleus cause opposite rotational behavior.Bilateral optogenetic excitation, but not inhibition, of the subthalamic nucleus induces jumping and self-grooming behavior.Engaged in advanced motor tasks, bilateral optogenetic excitation causes mice to lose motor coordination.The results provide experimental support for predictions by the basal ganglia motor model on the role of the subthalamic nucleus in locomotion, and identifies a causal role for the subthalamic nucleus in self-grooming.
Identification of the unwinding region in theClostridioides difficilechromosomal origin of replication
Authors: Oliveira Paiva Ana M. , van Eijk Erika , Friggen Annemieke H. , Weigel Christoph , Smits Wiep Klaas 
Published: July 2020

AbstractFaithful DNA replication is crucial for viability of cells across all kingdoms of life. Targeting DNA replication is a viable strategy for inhibition of bacterial pathogens.Clostridioides difficileis an important enteropathogen that causes potentially fatal intestinal inflammation. Knowledge about DNA replication in this organism is limited and no data is available on the very first steps of DNA replication. Here, we use a combination ofin silicopredictions andin vitroexperiments to demonstrate thatC. difficileemploys a bipartite origin of replication that shows DnaA-dependent melting atoriC2,located in thednaA-dnaNintergenic region. Analysis of putative origins of replication in different clostridia suggests that the main features of the origin architecture are conserved. This study is the first to characterize aspects of the origin region ofC. difficileand contributes to our understanding of the initiation of DNA replication in clostridia.
Extracellular vesicles containing ACE2 efficiently prevent infection by SARS-CoV-2 Spike protein-containing virus
Authors: Cocozza Federico , Piovesana Ester , Névo Nathalie , Lahaye Xavier , Buchrieser Julian , Schwartz Olivier , Manel Nicolas , Tkach Mercedes , Théry Clotilde , Martin-Jaular Lorena 
Published: July 2020

ABSTRACTSARS-CoV-2 entry is mediated by binding of the spike protein (S) to the surface receptor ACE2 and subsequent priming by TMPRRS2 allowing membrane fusion. Here, we produced extracellular vesicles (EVs) exposing ACE2 and demonstrate that ACE2-EVs are efficient decoys for SARS-CoV-2 S protein-containing lentivirus. Reduction of infectivity positively correlates with the level of ACE2, is 500 to 1500 times more efficient than with soluble ACE2 and further enhanced by the inclusion of TMPRSS2.
Examining gender imbalance in chemistry authorship
Authors: Cotton Adam D. , Seiple Ian B. 
Published: July 2020

AbstractThe gender gap in chemistry has been the topic of much debate, with many perspectives stating that the field has improved, and outdated sexist views are behind us. While these views are common, we wanted to assess the accuracy of these comments from a data-driven perspective. In this study, we use PubMed to obtain the names of first and last authors for every paper published since 2005 across 15 journals. Each name was cross-referenced with a name-based gender API to give a predicted binary gender and a confidence score based on population data. We show that historically there has been an extensive overrepresentation of men in both first and corresponding authorship, and that there is no strong trend towards parity since 2005. We demonstrate that papers with female corresponding authors have more equitable gender representation of first authors. Finally, we find that there is significant variability among journals in the gender make-up of their editorial boards. We hope this analysis spurs creative discussions on how we can improve equitable gender representation in chemistry publications.
Robust bidirectional communication between electronics and an engineered multi-functional microbial community
Authors: Terrell Jessica L. , Tschirhart Tanya , Jahnke Justin P. , Stephens Kristina , Liu Yi , Dong Hong , Hurley Margaret M. , Pozo Maria , McKay Ryan , Tsao Chen Yu , Wu Hsuan-Chen , Vora Gary , Payne Gregory F. , Stratis-Cullum Dimitra N. , Bentley William E. 
Published: July 2020

AbstractWe developed a bidirectional bioelectronic communication system that is enabled by a redox signal transduction modality to exchange information between a living cell-embedded bioelectronics interface and an engineered microbial network. A naturally communicating three-member microbial network is “plugged into” an external electronic system that interrogates and controls biological function in real time. First, electrode-generated redox molecules are programmed to activate gene expression in an engineered population of electrode-attached bacterial cells. These cells interpret and translate electronic signals and then transmit this information biologically by producing quorum sensing molecules that are, in turn, interpreted by a planktonic co-culture. The propagated molecular communication drives expression and secretion of a therapeutic peptide from one strain and, simultaneously, enables direct electronic feedback from the second strain thus enabling real time electronic verification of biological signal propagation. Overall, we show how this multi-functional bioelectronic platform, termed BioLAN, reliably facilitates on-demand bioelectronic communication and concurrently performs programmed tasks.
Complete Genome Sequence of the Polysaccharide-Degrading Rumen BacteriumPseudobutyrivibrio xylanivoransMA3014
Authors: Palevich Nikola , Maclean Paul H. , Kelly William J. , Leahy Sinead C. , Rakonjac Jasna , Attwood Graeme T. 
Published: July 2020

AbstractRuminants are essential for maintaining the global population and managing greenhouse gas emissions. In the rumen, bacterial species belonging to the genera rumenButyrivibrioandPseudobutyrivibrioconstitute the core bacterial rumen microbiome and are important degraders of plant-derived complex polysaccharides.Pseudobutyrivibrio xylanivoransMA3014 was selected for genome sequencing in order to examine its ability to breakdown and utilize plant polysaccharides. The complete genome sequence of MA3014 is 3.58 Mb, consists of three replicons (a chromosome, chromid and plasmid), has an overall G+C content of 39.6% and encodes 3,265 putative protein-coding genes (PCGs). Comparative pan-genomics of all cultivated and currently availableP. xylanivoransgenomes has revealed highly open genomes and a strong correlation of orthologous genes within this species of rumen bacteria. MA3014 is metabolically versatile and capable of utilizing a range of simple mono-or oligosaccharides to complex plant polysaccharides such as pectins, mannans, starch and hemicelluloses for growth, with lactate, butyrate and formate as the principal fermentation end-products. The genes encoding these metabolic pathways have been identified and MA3014 is predicted to encode an extensive repertoire of Carbohydrate-Active enZYmes (CAZymes) with 80 Glycoside Hydrolases (GHs), 28 Carbohydrate Esterases (CEs) and 51 Glycosyl Transferases (GTs), that suggest its role as an initiator of primary solubilization of plant matter in the rumen.
High levels of SARS-CoV-2 specific T-cells with restricted functionality in patients with severe course of COVID-19
Authors: Schub David , Klemis Verena , Schneitler Sophie , Mihm Janine , Lepper Philipp M. , Wilkens Heinrike , Bals Robert , Eichler Hermann , Gärtner Barbara C. , Becker Sören L. , Sester Urban , Sester Martina , Schmidt Tina 
Published: July 2020

AbstractPatients infected with SARS-CoV-2 differ in the severity of disease. In this study, SARS-CoV-2 specific T-cells and antibodies were characterized in patients with different COVID-19 related disease severity. Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2 specific T-cells as compared to convalescent individuals. SARS-CoV-2 specific CD4 T-cells dominated over CD8 T-cells and closely correlated with the number of plasmablasts and SARS-CoV-2 specific IgA- and IgG-levels. Unlike in convalescents, SARS-CoV-2 specific T-cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 and CD8 T-cells in general. Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered phenotype may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.
Regulative distance, international connectivity and innovation systems: Turkey’s links to the EU
Authors: Onuklu Atilla , Darendeli Izzet , Mudambi Ram 
Published: July 2020

PurposeThe purpose of this study is to assess the effect of institutional distance on national innovation systems.Design/methodology/approachThis study uses social network analysis to analyze the connectivity between national systems of innovation. A regulative distance index is constructed by coding the European Commission progress reports and using weights to account for relevance to research and innovation.FindingsReductions in institutional distance (proxied by regulative distance) increase international innovation connectivity between national systems of innovation. More importantly, it leads to increase in both the complexity and resilience of innovation connectivity between countries.Originality/valueThis study provides fresh evidence on the pathways through which institutions affect international business systems. Policy harmonization has strong effects on firm-level corporate strategy.
Determinants of adaptation strategies to climate change among the smallholder farmers in Adama District, Ethiopia
Authors: Hirpha Hurgesa Hundera , Mpandeli Sylvester , Bantider Amare 
Published: July 2020

Purpose
The Ethiopian economy is mainly based on the rain-fed agriculture practiced by smallholder farmers. The sector is highly vulnerable to climate change impacts. This study aims to examine the determinants of adaptation strategies to climate change among the smallholder farmers in Adama District, Ethiopia.

Design/methodology/approach
A cross-sectional survey design was used to collect quantitative data using questionnaire with 351 randomly selected smallholder farmers. To collect qualitative data focus group discussions, key informant interviews and field observations were also used. Triangulated with thematic analysis, descriptive statistics and binary logistic regression model were used for the analysis.

Findings
The result indicated that the majority of the smallholder farmers use at least one climate change adaptation strategy in their local areas though the strategy is generally weak. In this regard, some of the dominant climate change adaptation activities identified in the study area are using improved crop varieties, planting trees, watershed management, adjusting planting date and terracing. The result from binary logistic regression model showed that age and sex of household head, as well as their education, family size, access to agricultural extension services and training on climate change significantly influence the practices of adaptation measures.

Originality/value
This study would help the practitioners to modify the existing weak adaptation activities by introducing advanced and technological-based adaptation strategies to the rural farming communities.
Knowledge-oriented leadership, knowledge management behaviour and innovation performance in project-based SMEs. The moderating role of goal orientations
Authors: Zia Najam Ul 
Published: July 2020

Purpose
This study aims to examine the association of knowledge-oriented leadership (KOL), knowledge management (KM) behaviour and innovation performance in project-based small and medium-sized enterprises. It investigates the moderation of goal-orientation in the relationship of KOL with knowledge-acquisition, transfer, documentation and application.

Design/methodology/approach
Data are collected from 215 employees in 32 small project-based software firms in Pakistan. Partial least square is used to test the hypotheses.

Findings
KOL is positively associated with KM behaviour and innovation performance. KM mediates the relationship of KOL and innovation performance. Furthermore, goal orientations play a moderating role in the relationship of KOL with knowledge acquisition, transfer and application activities.

Originality/value
This study extends the literature on knowledge-based dynamic capabilities, by examining the relationship of KOL, KM behaviour and project-based innovation performance. Investigating the moderation of goal-orientation in the relationship of KOL with KM behaviour is also an original contribution.