bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallel signatures of mammalian domestication and human industrialization in the gut microbiota
Authors: Reese Aspen T. , Chadaideh Katia S. , Diggins Caroline E. , Beckel Mark , Callahan Peggy , Ryan Roberta , Thompson Melissa Emery , Carmody Rachel N. 
Published: April 2019

AbstractDomestication may have had convergent effects on the microbiota of domesticates and humans through analogous ecological shifts. Comparing the gut microbiota of domestic and related wild mammals plus humans and chimpanzees, we found consistent shifts in composition in domestic animals and in humans from industrialized but not traditional societies. Reciprocal diet switches in mice and canids demonstrated that diet played a dominant role in shaping the domestic gut microbiota, with stronger responses in the member of the wild-domestic pair with higher dietary and microbial diversity. Laboratory mice recovered wild-like microbial diversity and responsiveness with experimental colonization. We conclude that domestication and industrialization have similarly impacted the gut microbiota, emphasizing the utility of domestic animal models and diets for understanding host-microbial interactions in rapidly changing environments.
A framework for the modular and combinatorial assembly of synthetic gene circuits
Authors: Santos-Moreno Javier , Schaerli Yolanda 
Published: April 2019

ABSTRACTSynthetic gene circuits emerge from iterative design-build-test cycles. Most commonly, the time-limiting step is the circuit construction process. Here, we present a hierarchical cloning scheme based on the widespread Gibson assembly method and make the set of constructed plasmids freely available. Our two-step modular cloning scheme allows for simple, fast, efficient and accurate assembly of gene circuits and combinatorial circuit libraries inEscherichia coli. The first step involves Gibson assembly of transcriptional units from constituent parts into individual intermediate plasmids. In the second step, these plasmids are digested with specific sets of restriction enzymes. The resulting flanking regions have overlaps that drive a second Gibson assembly into a single plasmid to yield the final circuit. This approach substantially reduces time and sequencing costs associated with gene circuit construction and allows for modular and combinatorial assembly of circuits. We demonstrate the usefulness of our framework by assembling a double-inverter circuit and a combinatorial library of 3-node networks.
TheCoxiella burnetiisecreted protein kinase CstK influences vacuole development and interacts with the GTPase-activating protein TBC1D5
Authors: Brelle Solene , Martinez Eric , Huc-Brandt Sylvaine , Allombert Julie , Cantet Franck , Gannoun-Zaki Laila , Letourneur François , Bonazzi Matteo , Molle Virginie 
Published: April 2019

ABSTRACTCoxiella burnetiiis the etiological agent of the emerging zoonosis Q fever. Crucial to the pathogenesis of this intracellular pathogen is the secretion of bacterial effectors into host cells by a Type 4b Secretion System (T4SS), to subvert host cell membrane trafficking, leading to the biogenesis of a parasitophorous vacuole allowing intracellular replication. The characterization of prokaryotic Serine/Threonine Protein Kinases (STPKs) in bacterial pathogens is emerging as an important strategy to better understand host-pathogen interactions. In this study, we investigated CstK (forCoxiellaSer/Thr kinase), a bacterial protein kinase identified inC. burnetiibyin silicoanalysis. Here, we demonstrated that this putative protein kinase undergoes autophosphorylation on Ser, Thr, and Tyr residues, and phosphorylates a classical eukaryotic protein kinase substratein vitro. This dual Ser/Thr and Tyr kinase activity is similarly observed for eukaryotic dual specificity Tyr phosphorylation-regulated kinase class. CstK is translocated during infections and localizes atCoxiella-containing vacuoles (CCVs). Moreover, aC. burnetiimutant strain overexpressing CstK displays a severe CCVs development phenotype, suggesting a finely tuned regulation by the bacterial kinase during infection. Protein-protein interaction studies identified the Rab7-GTPase activating protein (GAP) TBC1D5 as a candidate CstK-specific host target, suggesting a role for this eukaryotic GAP inCoxiellainfections. Indeed, CstK colocalizes with TBC1D5 in non-infected cells, and TBC1D5 is recruited at CCVs during infection. Accordingly, depletion of TBC1D5 from infected cells significantly affects CCVs development. Our results indicate that CstK has a critical role during infection as a bacterial effector protein that interacts with host proteins to facilitate vacuole biogenesis and intracellular replication.
Single-cell analysis of Foxp1-driven mechanisms essential for striatal development
Authors: Anderson Ashley G. , Kulkarni Ashwinikumar , Harper Matthew , Konopka Genevieve 
Published: April 2019

AbstractThe striatum is a critical forebrain structure for integrating cognitive, sensory, and motor information from diverse brain regions into meaningful behavioral output. However, the transcriptional mechanisms that underlie striatal development and organization at single-cell resolution remain unknown. Here, we show that Foxp1, a transcription factor strongly linked to autism and intellectual disability, regulates organizational features of striatal circuitry in a cell-type-dependent fashion. Using single-cell RNA-sequencing, we examine the cellular diversity of the early postnatal striatum and find that cell-type-specific deletion ofFoxp1in striatal projection neurons alters the cellular composition and neurochemical architecture of the striatum. Importantly, using this approach, we identify the non-cell autonomous effects produced by disruptingFoxp1in one cell-type and the molecular compensation that occurs in other populations. Finally, we identify Foxp1-regulated target genes within distinct cell-types and connect these molecular changes to functional and behavioral deficits relevant to phenotypes described in patients withFOXP1loss-of-function mutations. These data reveal cell-type-specific transcriptional mechanisms underlying distinct features of striatal circuitry and identify Foxp1 as a key regulator of striatal development.
Niche differentiation is spatially and temporally regulated in the rhizosphere
Authors: Nuccio Erin E. , Starr Evan , Karaoz Ulas , Brodie Eoin L. , Zhou Jizhong , Tringe Susannah , Malmstrom Rex R. , Woyke Tanja , Banfield Jillian F. , Firestone Mary K. , Pett-Ridge Jennifer 
Published: April 2019

AbstractThe rhizosphere is a hotspot for microbial C transformations, and the origin of root polysaccharides and polymeric carbohydrates that are important precursors to soil organic matter. However, the ecological mechanisms that underpin rhizosphere carbohydrate depolymerization are poorly understood. UsingAvena fatua, a common annual grass, we analyzed time-resolved metatranscriptomes to compare microbial function in rhizosphere, detritusphere, and combined rhizosphere-detritusphere habitats. Population transcripts were binned with a unique reference database generated from soil isolate and single amplified genomes, metagenomes, and stable isotope probing metagenomes. While soil habitat significantly affected both community composition and overall gene expression, succession of microbial functions occurred at a faster time scale than compositional changes. Using hierarchical clustering of upregulated decomposition gene expression, we identified four distinct microbial guilds populated by taxa whose functional succession patterns suggest specialization for substrates provided by fresh growing roots, decaying root detritus, the combination of live and decaying root biomass, or aging root material. Carbohydrate depolymerization genes were consistently upregulated in the rhizosphere, and both taxonomic and functional diversity were high in the combined rhizosphere-detritusphere—suggesting coexistence of rhizosphere guilds is facilitated by niche differentiation. Metatranscriptome-defined guilds provide a framework to model rhizosphere succession and its consequences for soil carbon cycling.
On the efficacy of restoration in stream networks: comments, critiques, and prospective recommendations
Authors: Murray-Stoker David 
Published: April 2019

AbstractSwan and Brown (2017) recently addressed the effects of restoration on stream communities under the meta-community framework. Using a combination of headwater and mainstem streams, Swan and Brown (2017) evaluated how position within a stream network affected the outcome of restoration on invertebrate communities. Ostensibly, their hypotheses were partially supported as restoration had stronger effects in headwater streams: invertebrate taxonomic richness was increased and temporal variability decreased in restored reaches; however, these results were not consistent upon closer scrutiny for both the original paper (Swan and Brown 2017) and the later erratum (Swan and Brown 2018). Here, I provide a secondary analysis of the data, with hypotheses and interpretations in the context of stream, meta-community, and restoration ecology. Swan and Brown (2017, 2018) evaluated the effect of restoration on sites receiving various combinations of in-channel manipulation and riparian reforestation treatments. Given the difference in the relative importance of environmental filtering and dispersal between headwaters and mainstems and the structure of river networks, I contend that different restoration treatments have differential effects between headwaters and mainstems. I hypothesized in-channel manipulations would have more consistent effects between headwaters and mainstems compared to riparian reforestation, and I used this hypothesis to guide site selection in the re-analysis. I then compared results from the re-analysis to those presented by Swan and Brown (2017, 2018). I did not find any effects of restoration on local diversity, spatial dissimilarity, or temporal variability, let alone differential effects of restoration between headwaters and mainstems; these results are contrary Swan and Brown (2017, 2018), who reported that restoration increased taxonomic richness, increased spatial dissimilarity, and decreased temporal variability in restored headwater streams. I demonstrate further that the statistical tests conducted by Swan and Brown (2017, 2018) were invalid and, therefore, recommend the use of the results presented here. More broadly, I suggest, in agreement with Swan and Brown (2017, 2018) and a growing body of research, that river and stream restoration will likely have greater success if a regional approach is taken to designing and implementing restoration projects.
The Role offosAin Challenges with Fosfomycin Susceptibility Testing of MultispeciesKlebsiella pneumoniaeCarbapenemase-Producing Clinical Isolates
Authors: Elliott Zachary S. , Barry Katie E. , Cox Heather L. , Stoesser Nicole , Carroll Joanne , Vegesana Kasi , Kotay Shireen , Sheppard Anna E. , Wailan Alex , Crook Derrick W. , Parikh Hardik , Mathers Amy J. 
Published: April 2019

AbstractWith multidrug resistant (MDR) Enterobacteriales on the rise, a non-toxic agent with a unique mechanism of action such as fosfomycin seems attractive. However, establishing accurate fosfomycin susceptibility testing for non-E. coliin a clinical microbiology laboratory remains problematic. We evaluated fosfomycin susceptibility by multiple methods with multiple strains and species of KPC-producing clinical isolates collected at a single center between 2008 and 2016. In addition, we assessed the presence of fosfomycin resistance genes from whole genome sequencing (WGS) data using NCBI’s AMRFinder and custom HMM search. Susceptibility testing was performed using glucose-6-phosphate supplemented fosfomycin E-Test and Kirby-Bauer disk diffusion (DD) assays, and compared to agar dilution. Clinical Laboratory and Standards Institute (CLSI) breakpoints forE. coliwere applied for interpretation. Overall, 63% (60/96) of isolates were susceptible by E-Test, 70% (67/96) by DD, and 88% (84/96) by agar dilution.FosAwas detected in 80% (70/88) of previously sequenced isolates, with species-specific associations and alleles, andfosA-positive isolates were associated with higher MIC distributions. Disk potentiation testing was performed using sodium phosphonoformate to inhibitfosAand showed significant increases in the zone diameter of DD testing for isolates that werefosA-positive compared tofosA-negative. The addition of sodium phosphonoformate (PPF) corrected 10/14 (71%) major errors in categorical agreement with agar dilution. Our results indicate thatfosAinfluences the inaccuracy of susceptibility testing by methods readily available in a clinical laboratory when compared to agar dilution. Further research is needed to determine the impact offosAon clinical outcomes.
Modelling spatial variation in agricultural field trials with INLA
Authors: Selle Maria Lie , Steinsland Ingelin , Hickey John M. , Gorjanc Gregor 
Published: April 2019

AbstractThe objective of this paper was to fit different established spatial models for analysing agricultural field trials using the open-source R package INLA. Spatial variation is common in field trials and accounting for it increases the accuracy of estimated genetic effects. However, this is still hindered by the lack of available software implementations. Here we compare some established spatial models and show possibilities for flexible modelling with respect to field trial design and joint modelling over multiple years and locations. We use a Bayesian framework and for statistical inference the Integrated Nested Laplace Approximations (INLA) implemented in the R package INLA. The spatial models we use are the well-known independent row and column effects, separable first-order autoregressive (AR1⊗AR1) models and a geostatistical model using the stochastic partial differential equation (SPDE) approach. The SPDE approach models a Gaussian random field, which can accommodate flexible field trial designs and yields interpretable parameters. We test the models in a simulation study imitating a wheat breeding program with different levels of spatial variation, with and without genome-wide markers, and with combining data over two locations, modelling spatial and genetic effects jointly. We evaluate predictive performance by correlation between true and estimated breeding values, the continuous rank probability score and how often the best individuals rank at the top. The results show best predictive performance with the AR1⊗AR1 and the SPDE. We also present an example of fitting the models to real wheat breeding data and simulated tree breeding data with the Nelder wheel design.Key messageEstablished spatial models improve the analysis of agricultural field trials with or without genomic data and can be fitted with the open-source R package INLA.
Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness
Authors: Hermann Bertrand , Raimondo Federico , Hirsch Lukas , Huang Yu , Denis-Valente Mélanie , Pérez Pauline , Engemann Denis , Faugeras Frédéric , Weiss Nicolas , Demeret Sophie , Rohaut Benjamin , Parra Lucas C. , Sitt Jacobo D. , Naccache Lionel 
Published: April 2019

ABSTRACTSevere brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.
The self-organized learning of noisy environmental stimuli requires distinct phases of plasticity
Authors: Krüppel Steffen , Tetzlaff Christian 
Published: April 2019

AbstractAlong sensory pathways, representations of environmental stimuli become increasingly sparse and expanded. If additionally the feed-forward synaptic weights are structured according to the inherent organization of stimuli, the increase in sparseness and expansion leads to a reduction of sensory noise. However, it is unknown how the synapses in the brain form the required structure, especially given the omnipresent noise of environmental stimuli. Here, we employ a combination of synaptic plasticity and intrinsic plasticity - adapting the excitability of each neuron individually - and present stimuli with an inherent organization to a feed-forward network. We observe that intrinsic plasticity maintains the sparseness of the neural code and thereby enables synaptic plasticity to learn the organization of stimuli in low-noise environments. Nevertheless, even high levels of noise can be handled after a subsequent phase of readaptation of the neuronal excitabilities by intrinsic plasticity. Interestingly, during this phase the synaptic structure has to be maintained. These results demonstrate that learning in the presence of noise requires adaptation of the synaptic structure but also of the neuronal properties in two distinct phases of learning: an encoding phase, during which the inherent organization of the environmental stimuli is learned, followed by a readaptation phase to readapt the neuronal system according to the current level of noise. The necessity of these distinct phases of learning suggests a new role for synaptic consolidation.
Predictors of colony extinction vary by habitat type in social spiders
Authors: McEwen Brendan L. , Lichtenstein James L. L. , Fisher David N. , Wright Colin M. , Chism Greg T. , Pinter-Wollman Noa , Pruitt Jonathan N. 
Published: April 2019

ABSTRACTMany animal societies are susceptible to mass mortality events and collapse. Elucidating how environmental pressures determine patterns of collapse is key for our understanding of social evolution. Using the social spiderStegodyphus dumicolawe investigated the environmental drivers of colony extinction along two precipitation gradients across southern Africa, using the Namib and Kalahari deserts versus wetter savanna habitats to the north and east. We deployed experimental colonies (n = 242) along two 800km transects and returned to assess colony success in the field after two months. Specifically, we noted colony extinction events after the two-month duration and collected environmental data on the correlates of those extinction events (e.g., evidence of ant attacks, # prey captured). We found that colony extinction events at desert sites were more frequently associated with attacks by predatory ants as compared to savanna sites, while colony extinctions in wetter savannas sites were more tightly associated with fungal outbreaks. Our findings support the hypothesis that environments vary in the selection pressures that they impose on social organisms, which may explain why different social phenotypes are often favored in each habitat.
Comparative analysis of gene expression in virulent and attenuated strains of infectious bronchitis virus at sub-codon resolution
Authors: Dinan Adam M. , Keep Sarah , Bickerton Erica , Britton Paul , Firth Andrew E. , Brierley Ian 
Published: April 2019

ABSTRACTInfectious bronchitis virus (IBV) is a member of the genusGammacoronavirusand the causative agent of avian infectious bronchitis. IBV has a single-stranded, positive-sense RNA genome ~27 kb in length and, like all coronaviruses, produces a set of sub-genomic messenger RNAs (sgmRNAs) synthesised via the viral polymerase. Here, we used RNA sequencing (RNASeq) and ribosome profiling (RiboSeq) to delineate gene expression in the IBV M41-CK and Beau-CK strains at sub-codon resolution. Quantification of reads flanking the programmed ribosomal frameshifting (PRF) signal at the genomic RNA ORF1a/ORF1b junction revealed that PRF in IBV is highly efficient (33–40%), consistent within vitromeasurements. Triplet phasing of the profiling data allowed precise determination of reading frames and revealed the translation of two intergenic genes (4b and 4c on sgmRNA4), which are widely conserved across IBV isolates. RNASeq revealed two novel transcription junction sites in the attenuated Beau-CK strain, one of which would generate a sgmRNA encoding a ribosomally occupied ORF in the viral 3’ untranslated region (dORF). Within IBV transcripts, the nucleocapsid (N) protein was unexpectedly found to be inefficiently translated, despite being an abundant structural component of mature IBV virions. Finally, we demonstrate that the host cell response to IBV occurs primarily at the level of transcription, with a global up-regulation of immune-related mRNA transcripts following infection, and comparatively modest changes in the translation efficiencies of host genes.IMPORTANCEIBV is a major avian pathogen and presents a substantial economic burden to the poultry industry. Improved vaccination strategies are urgently needed to curb the global spread of this pathogen, and the development of suitable vaccine candidates will be aided by an improved understanding of IBV molecular biology. Our high-resolution data have enabled a precise study of transcription and translation in both pathogenic and attenuated forms of IBV, and expand our understanding of gammacoronaviral gene expression. We demonstrate that gene expression shows considerable intra-species variation, with single nucleotide polymorphisms associated with altered production of sgmRNA transcripts, and our RiboSeq data sets enabled us to uncover novel ribosomally occupied ORFs in both strains. We also identify numerous cellular genes and gene networks that are differentially expressed during virus infection, giving insights into the host cell reponse to IBV infection.