bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioremediation of industrial pollutants by insects expressing a fungal laccase
Authors: Clark Michael , Tepper Kate , Petroll Kerstin , Kumar Sheemal , Sunna Anwar , Maselko Maciej 
Published: April 2021

AbstractInadequate management of household and industrial wastes pose major challenges to human and environmental health. Advances in synthetic biology may help address these challenges by engineering biological systems to perform new functions such as biomanufacturing of high-value compounds from low-value waste streams and bioremediation of industrial pollutants. The current emphasis on microbial systems for biomanufacturing, which often require highly pre-processed inputs and sophisticated infrastructure, is not feasible for many waste streams. Concerns about transgene biocontainment have limited the release of engineered microbes or plants for bioremediation. Engineering animals may provide opportunities for utilizing various waste streams that are not suitable for microbial biomanufacturing while effective transgene biocontainment options should enablein situbioremediation. Here, we engineer the model insectDrosophila melanogasterto express a functional laccase from the fungusTrametes trogii. Laccase expressing flies reduced concentrations of the endocrine disruptor bisphenol A by more than 50% when present in their growth media. A lyophilized powder made from engineered adult flies retained substantial enzymatic activity, degrading more than 90% of bisphenol A and the textile dye indigo carmine in aqueous solutions. Our results demonstrate that transgenic animals may be used to bioremediate environmental contaminantsin vivoand serve as novel production platforms for industrial enzymes. These results support further development of insects, and possibly other animals, as bioproduction platforms and their potential use in bioremediation.
Will Current Protected Areas Harbour Refugia for Threatened Arctic Vegetation Types until 2050?
Authors: Chacko Merin Reji , Goerens Ariane K.A. , Oehri Jacqueline , Plekhanova Elena , Schaepman-Strub Gabriela 
Published: April 2021

AbstractArctic vegetation is crucial for fauna and the livelihoods of Northern peoples, and tightly linked to climate, permafrost soils, and water. Yet, a comprehensive understanding of climate change effects on Arctic vegetation is lacking. Protected areas cannot halt climate change, but could reduce future pressure from additional drivers, such as land use change and local industrial pollution. Therefore, it is crucial to understand the contribution of protected areas in safeguarding threatened Arctic vegetation types. We compare the 2003 baseline with existing 2050 predictions of circumpolar Arctic vegetation type distributions and demonstrate an overrepresentation of dominant and underrepresentation of declining vegetation types within protected areas. According to IUCN criteria, five of eight assessed vegetation types were classified as threatened by 2050. Potential climate change refugia, areas with the highest potential for safeguarding threatened vegetation types, were also identified. This study provides an essential first step to assessing vegetation type vulnerability based on predictions covering 46% of Arctic landscapes. The co-development of new protective measures by policymakers and indigenous peoples at a pan-Arctic scale requires more robust and spatially complete vegetation prediction, as increasing pressures from resource exploration and infrastructure development threaten the sustainable development of the rapidly thawing and greening Arctic.
Testing the adaptive walk model of gene evolution
Authors: Moutinho Ana Filipa , Eyre-Walker Adam , Dutheil Julien Y. 
Published: April 2021

AbstractUnderstanding the dynamics of species adaptation to their environments has long been a central focus of the study of evolution. Theories of adaptation propose that populations evolve by “walking” in a fitness landscape. This “adaptive walk” is characterised by a pattern of diminishing returns, where populations further away from their fitness optimum take larger steps than those closer to their optimal conditions. Hence, we expect young genes to evolve faster and experience mutations with stronger fitness effects than older genes because they are further away from their fitness optimum. Testing this hypothesis, however, constitutes an arduous task. Young genes are small, encode proteins with a higher degree of intrinsic disorder, are expressed at lower levels, and are involved in species-specific adaptations. Since all these factors lead to increased protein evolutionary rates, they could be masking the effect of gene age. While controlling for these factors, we used population genomic datasets ofArabidopsisandDrosophilaand estimated the rate of adaptive substitutions across genes from different phylostrata. We found that a gene’s evolutionary age significantly impacts the molecular rate of adaptation. Moreover, we observed that substitutions in young genes tend to have larger physicochemical effects. Our study, therefore, provides strong evidence that molecular evolution follows an adaptive walk model across a large evolutionary timescale.
Five years of GenoTyphi: updates to the globalSalmonellaTyphi genotyping framework
Authors: Dyson Zoe A. , Holt Kathryn E. 
Published: April 2021

AbstractIn 2016 a whole genome sequence (WGS) based genotyping framework (GenoTyphi) was developed providing a phylogenetically informative nomenclature for lineages ofSalmonellaTyphi, the aetiological agent of typhoid fever. Subsequent surveillance studies have revealed additional epidemiologically important subpopulations, necessitating the definition of new genotypes and extension of associated software to facilitate the detection of antimicrobial resistance (AMR) mutations. Analysis of 4,632 WGS provide an updated overview of the globalS.Typhi population structure and genotyping framework, revealing the widespread nature of H58 (4.3.1) genotypes and the diverse range of genotypes carrying AMR mutations.
Selective neural coding of object, feature, and geometry spatial cues in humans
Authors: Ramanoël Stephen , Durteste Marion , Bizeul Alice , Ozier-Lafontaine Anthony , Bécu Marcia , Sahel José-Alain , Habas Christophe , Arleo Angelo 
Published: April 2021

SummaryOrienting in space requires the processing and encoding of visual spatial cues. The dominant hypothesis about the brain structures mediating the coding of spatial cues stipulates the existence of a hippocampal-dependent system for the representation of geometry and a striatal-dependent system for the representation of landmarks. However, this dual-system hypothesis is based on paradigms that presented spatial cues conveying either conflicting or ambiguous spatial information and that amalgamated the concept of landmark into both discrete 3D objects and wall features. These confounded designs introduce difficulties in interpreting the spatial learning process. Here, we test the hypothesis of a complex interaction between the hippocampus and the striatum during landmark and geometry visual coding in humans. We also postulate that object-based and feature-based navigation are not equivalent instances of landmark-based navigation as currently considered in human spatial cognition. We examined the neural networks associated with geometry-, object-, and feature-based spatial navigation in an unbiased, two-choice behavioral paradigm using fMRI. We showed evidence of a synergistic interaction between hippocampal and striatal coding underlying flexible navigation behavior. The hippocampus was involved in all three types of cue-based navigation, whereas the striatum was more strongly recruited in the presence of geometric cues than object or feature cues. We also found that unique, specific neural signatures were associated with each spatial cue. Critically, object-based navigation elicited a widespread pattern of activity in temporal and occipital regions relative to feature-based navigation. These findings challenge and extend the current view of a dual, juxtaposed hippocampal-striatal system for visual spatial coding in humans. They also provide novel insights into the neural networks mediating object vs. feature spatial coding, suggesting a need to distinguish these two types of landmarks in the context of human navigation.HighlightsComplex hippocampal-striatal interaction during visual spatial coding for flexible human navigation behavior.Distinct neural signatures associated with object-, feature-, and geometry-based navigation.Object- and feature-based navigation are not equivalent instances of landmark-based navigation.
Met-signaling Controls Dendritic Cell Migration by Regulating Podosome Formation and Function
Authors: Hamouda Ahmed E.I. , Schalla Carmen , Sechi Antonio , Zenke Martin , Hieronymus Thomas 
Published: April 2021

AbstractSignaling by the HGF receptor/Met in skin-resident Langerhans cells (LC) and dermal dendritic cells (dDC) is essential for their emigration toward draining lymph nodes upon inflammation-induced activation. Here we addressed the role of Met-signaling in distinct steps of LC/dDC emigration from skin by employing a conditional Met-deficient mouse model (Metflox/flox). We found that Met deficiency severely impaired podosome formation in DC and concomitantly decreased proteolytic degradation of gelatin. Accordingly, Met-deficient LC failed to efficiently cross the extracellular matrix (ECM) rich basement membrane between epidermis and dermis. We further observed that Met-signaling by HGF reduced adhesion of bone marrow-derived LC to various ECM factors and enhanced the motility of Met-signaling competent DC in a 3D collagen matrix, which was not the case for Met-deficient LC/DC. We found no impact of Met-signaling on the integrin-independent amoeboid migration of DC in response to the CCR7 chemokine CCL19. Collectively, our data show that the Met-signaling pathway regulates the migratory properties of DC in HGF-dependent and HGF-independent manners.
Structural basis of the P4B ATPase lipid flippase activity
Authors: Bai Lin , Jain Bhawik K. , You Qinglong , Duan H. Diessel , Graham Todd R. , Li Huilin 
Published: April 2021

ABSTRACTP4 ATPases are lipid flippases that are phylogenetically grouped into P4A, P4B and P4C clades. The P4A ATPases are heterodimers composed of a catalytic α-subunit and accessory β-subunit, and the structures of several heterodimeric flippases have been reported. TheS. cerevisiaeNeo1 and its orthologs represent the P4B ATPases, which function as monomeric flippases without a β-subunit. It has been unclear whether monomeric flippases retain the architecture and transport mechanism of the dimeric flippases. Here we report the first structure of a P4B ATPase, Neo1, in its E1-ATP, E2P-transition, and E2P states. The structure reveals a conserved architecture as well as highly similar functional intermediate states relative to dimeric flippases. Consistently, structure-guided mutagenesis of residues in the proposed substrate translocation path disrupted Neo1’s ability to establish membrane asymmetry. These observations indicate that evolutionarily distant P4 ATPases use a structurally conserved mechanism for substrate transport.
Validation of predicted anonymous proteins simply using Fisher’s exact test
Authors: Claverie Jean-Michel , Santini Sébastien 
Published: April 2021

AbstractMotivationGenomes sequencing has become the primary (and often the sole) experimental method to characterize newly discovered organisms, in particular from the microbial world (bacteria, archaea, viruses). This generates an ever increasing number of predicted proteins the existence of which is unwarranted, in particular among those without homolog in model organisms. As a last resort, the computation of the selection pressure from pairwise alignments of the corresponding “Open Reading Frames” (ORFs) can be used to validate their existences. However, this approach is error-prone, as not usually associated with a significance test.ResultsWe introduce the use of the straightforward Fisher’s exact test as a post processing of the results provided by the popular CODEML sequence comparison software. The respective rates of nucleotide changes at the non-synonymous vs. synonymous position (as determined by CODEML), are turned into entries into a 2×2 contingency table, the probability of which is computed under the Null hypothesis that they should not behave differently if the ORFs do not encode actual proteins. Using the genome sequences of two recently isolated giant viruses, we show that strong negative selection pressures do not always provide a solid argument in favor of the existence of proteins.ContactJean-Michel.Claverie@univ-amu.fr
Modeling intracranial electrodes
Authors: Blenkmann Alejandro , Solbakk Anne-Kristin , Ivanovic Jugoslav , Larsson Pål Gunnar , Knight Robert T. , Endestad Tor 
Published: April 2021

AbstractBackgroundIntracranial electrodes are implanted in patients with drug-resistant epilepsy as part of their pre-surgical evaluation. This allows investigation of normal and pathological brain functions with excellent spatial and temporal resolution. The spatial resolution relies on methods that precisely localize the implanted electrodes in the cerebral cortex, which is critical for drawing valid anatomical inferences about brain function.Multiple methods have been developed to localize implanted electrodes, mainly relying on pre-implantation MRI and post-implantation CT images. However, there is no standard approach to quantify the performance of these methods systematically.The purpose of our work is to model intracranial electrodes to simulate realistic implantation scenarios, thereby providing methods to optimize localization algorithm performance.ResultsWe implemented novel methods to model the coordinates of implanted grids, strips, and depth electrodes, as well as the CT artifacts produced by these.We successfully modeled a large number of realistic implantation“scenarios”, including different sizes, inter-electrode distances, and brain areas. In total, more than 3300 grids and strips were fitted over the brain surface, and more than 850 depth electrode arrays penetrating the cortical tissue were modeled. More than 37000 simulations of electrode array CT artifacts were performed in these“scenarios”, mimicking the intensity profile and orientation of real artifactual voxels. Realistic artifacts were simulated by introducing different noise levels, as well as overlapping electrodes.ConclusionsWe successfully developed the first platform to model implanted intracranial grids, strips, and depth electrodes and realistically simulate CT artifacts and noise.These methods set the basis for developing more complex models, while simulations allow the performance evaluation of electrode localization techniques systematically.The methods described in this article, and the results obtained from the simulations, are freely available via open repositories. A graphical user interface implementation is also accessible via the open-source iElectrodes toolbox.
Regulation of Lysosome-Associated Membrane Protein 3 (LAMP3) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling
Authors: Ramana Chilakamarti V. 
Published: April 2021

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major risk factor for mortality and morbidity in critical care hospitals around the world. Lung epithelial type II cells play a major role in several physiological processes, including recognition and clearance of respiratory viruses as well as repair of lung injury in response to environmental toxicants. Gene expression profiling of lung epithelial type II-specific genes led to the identification of lysosomal-associated membrane protein 3 (LAMP3). Intracellular locations of LAMP3 include plasma membrane, endosomes, and lysosomes. These intracellular organelles are involved in vesicular transport and facilitate viral entry and release of the viral RNA into the host cell cytoplasm. In this study, regulation of LAMP3 expression in human lung epithelial cells by several respiratory viruses and type I interferon signaling was investigated. Coronaviruses including SARS-CoV-1 and SARS-CoV-2 significantly induced LAMP3 expression in lung epithelial cells within 24 hours after infection that required the presence of ACE2 viral entry receptor. Time-course experiments revealed that the induced expression of LAMP3 by SARS-CoV-2 was correlated with the induced expression of interferon-beta1 (IFNB1) and signal transducers and activator of transcription 1 (STAT1) mRNA levels. LAMP3 was also induced by direct IFN-beta treatment or by infection with influenza virus lacking the non-structural protein1(NS1) in NHBE bronchial epithelial cells. LAMP3 expression was induced in human lung epithelial cells by several respiratory viruses, including respiratory syncytial virus (RSV) and the human parainfluenza virus 3 (HPIV3). Location in lysosomes and endosomes as well as induction by respiratory viruses and type I Interferon suggests that LAMP3 may have an important role in inter-organellar regulation of innate immunity and a potential target for therapeutic modulation in health and disease. Furthermore, bioinformatics revealed that a subset of lung type II cell genes were differentially regulated in the lungs of COVID-19 patients.
Efficacy of oseltamivir treatment in influenza virus infected obese mice
Authors: Honce Rebekah , Jones Jeremy , Livingston Brandi , Estrada Leonardo D. , Wang Lindsey , Caulfield William , Freeman Burgess , Govorkova Elena , Schultz-Cherry Stacey 
Published: April 2021

ABSTRACTObesity has been epidemiologically and empirically linked with more severe disease upon influenza infection. To ameliorate severe disease, treatment with antivirals, such as the neuraminidase inhibitor oseltamivir, are suggested to begin within days of infection, especially in hosts at higher risk for poor outcomes. However, this treatment is often poorly effective and can generate resistance variants within the treated host. Here, we hypothesized that oseltamivir treatment would not be effective in genetically obese mice and would generate a more diverse and drug resistant viral population. We demonstrated that oseltamivir treatment does not improve viral clearance in obese mice. While no traditional variants associated with oseltamivir resistance emerged, we did note that drug treatment failed to quench the viral population and did lead to phenotypic drug resistancein vitro.Mechanistically, we demonstrate the blunted interferon response in obese hosts may be contributing to treatment failure, as type I interferon receptor deficient mice also fail to clear influenza virus infection upon oseltamivir administration. Together, these studies suggest that the unique pathogenesis and immune responses in obese mice could have implications for pharmaceutical interventions and the within-host dynamics of the influenza virus population.IMPORTANCEInfluenza virus infections, while typically resolving within days to weeks, can turn critical especially in high-risk populations. Prompt antiviral administration is crucial to mitigating these severe sequalae, yet concerns remain if antiviral treatment is effective in hosts with obesity. Here, we show that oseltamivir does not improve viral clearance in genetically obese or type I IFN receptor-deficient mice and increases the genetic entropy of the within-host viral population. This suggests a blunted immune response may impair oseltamivir efficacy and render a host more susceptible to severe disease. This study furthers our understanding of oseltamivir treatment dynamics both systemically and in the lungs of obese mice, as well as the consequences of oseltamivir treatment for the within-host emergence of drug-resistant variants.
Regulation of layered T cell tolerance mechanisms by the NR4A family is essential to preserve immune homeostasis and suppress autoimmunity
Authors: Hiwa Ryosuke , Nielsen Hailyn V. , Mueller James L. , Zikherman Julie 
Published: April 2021

ABSTRACTThe NR4A family of orphan nuclear receptors (Nr4a1-3) plays redundant roles upstream ofFoxp3to establish and maintain Treg identity; deletion of multiple family members in the thymus results in Treg deficiency and a severe inflammatory disease. Consequently, it has been challenging to isolate the functions of this family in other immune cells. Here we take advantage of a competitive bone marrow chimera strategy, coupled with conditional genetic tools, to rescue Treg homeostasis and unmask such functions. Unexpectedly, chimeras harboringNr4a1−/−Nr4a3−/−(DKO) bone marrow develop autoantibodies and a systemic inflammatory disease despite a replete Treg compartment of largely wild-type origin. This disease differs qualitatively from that seen with Treg-deficiency and is B cell-extrinsic. Negative selection of DKO thymocytes is profoundly impaired in a cell-intrinsic manner. Consistent with escape of self-reactive T cells into the periphery, DKO T cells with functional and phenotypic features of anergy accumulate in chimeric mice. Despite this, DKO T cells exhibit enhanced IL-2 production, implying a cell-intrinsic role for the NR4A family in peripheral T cell tolerance. These studies reveal roles for the NR4A family in multiple layered T cell tolerance mechanisms and demonstrate that each is essential to preserve immune homeostasis.
Key motivations for leading Facebook communities: a uses and gratifications approach
Authors: Gazit Tali 
Published: April 2021

PurposeFacebook community leaders, often nonprofessionals who make a personal decision to create and manage online spaces, are becoming key players on social media sites. Using the theoretical framework of the uses and gratifications theory, this paper reveals the motivations of these individuals who are responsible for the community's information flow, limits and members' well-being. While some studies have begun acknowledging community leaders' important role in the social media, very little is known about their motivations for creating and leading the communities, often voluntarily.Design/methodology/approachUsing both quantitative and qualitative analyses, data were collected through a survey of 94 Facebook community leaders about their motivations for creating and leading their communities.FindingsThe content analysis of the open-ended question reveals that leaders are motivated to create communities to satisfy informational needs, social needs and individual interests. A factor analysis shows five distinct motivations for leading: social, personal, influence, efficacy and community goals. Finally, a hierarchical regression indicates that extroversion, neuroticism, agreeableness, time spent per day and being the creator of the community can predict the level of motivation to lead the Facebook community.Originality/valueAs more and more organizations use online communities, the findings of this study may provide insights into leaders' motivations that can help organizations select their community leaders. This study expands on current research about a popular communication tool, Facebook communities, by examining it within the context of the unique role of online leadership in the social media environment.