bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippocampal spike-time correlations and place-field overlaps during open field foraging
Authors: Monsalve-Mercado Mauro M. , Roudi Yasser 
Published: October 2019

AbstractPhase precessing place cells encode spatial information on fine timescales via the timing of their spikes. This phase code has been extensively studied on linear tracks and for short runs in the open field. However, less is known about the phase code on unconstrained trajectories lasting tens of minutes, typical of open field foraging. In previous work (Monsalve-Mercado and Leibold, 2017), an analytic expression was derived for the spike-time cross-correlation between phase precessing place cells during natural foraging in the open field. This expression makes two predictions on how this phase code differs from the linear track case: cross-correlations are symmetric with respect to time, and they represent the distance between pairs of place fields in that the theta-filtered cross-correlations around zero time-lag are positive for cells with nearby fields while they are negative for those with fields further apart. Here we analyze several available open field recordings and show that these predictions hold for pairs of CA1 place cells. We also show that the relationship remains during remapping in CA1, and it is also present in place cells in area CA3. For CA1 place cells of Fmr1-null mice, which exhibit normal place fields but somewhat weaker temporal coordination with respect to theta compared to wild type, the cross-correlations still remain symmetric but the relationship to place field overlap is largely lost. The relationship discussed here describes how spatial information is communicated by place cells to downstream areas in a finer theta-timescale, relevant for learning and memory formation in behavioural tasks lasting tens of minutes in the open field.
Switchgrass Rhizosphere Metabolite Chemistry Driven by Nitrogen Availability
Authors: Smercina Darian N. , Bowsher Alan W. , Evans Sarah E. , Friesen Maren L. , Eder Elizabeth K. , Hoyt David W. , Tiemann Lisa K. 
Published: October 2019

AbstractPlants and soil microorganisms interact closely in the rhizosphere where plants may exchange carbon (C) for functional benefits from the microbial community. For example, the bioenergy crop, switchgrass (Panicum virgatum) is thought to exchange root-exuded C for nitrogen (N) fixed by diazotrophs (free-living N-fixers). However, this interaction is not well characterized and it is not known how or if switchgrass responds to diazotrophs or their activity. To explore this question, we assessed rhizosphere metabolite chemistry of switchgrass grown in a hydroponic system under two N levels and under inoculated or uninoculated conditions. We found switchgrass root exudate chemistry to be more responsive to N availability than to diazotroph presence. Total metabolite concentrations were generally greater under high N versus low N and unaffected by inoculation. Examination of rhizosphere chemical fingerprints indicates metabolite chemistry was also driven strongly by N availability with a greater relative abundance of carbohydrates under high N and greater relative abundance of organic acids under low N. We also found evidence of changes in rhizosphere chemical fingerprints by inoculation treatment suggesting a potential for switchgrass to respond or even recruit diazotrophs. However, we found little evidence of N treatment and inoculation interaction effects which suggests switchgrass response to diazotroph presence is not mediated by N availability.
In situ protein identification and mapping using secondary ion mass spectrometry
Authors: Kotowska Anna M. , Williams Philip M. , Aylott Jonathan W. , Shard Alexander G. , Alexander Morgan R. , Scurr David J. 
Published: October 2019

AbstractProtein characterisation at surfaces currently requires digestion prior to either liquid extraction of the protein for mass spectrometry analysis or in situ matrix-assisted desorption/ionisation. Here, we show that direct assignment of individual proteins and mixtures at surfaces can be achieved by employing secondary ion mass spectrometry (SIMS) with gas cluster ion beam (GCIB) bombardment and an Orbitrap™ analyser. Potential applications of the method are illustrated by demonstrating imaging of a protein film masked by a gold grid and the analysis of a protein monolayer biochip.
An Enzymatic Active Site Embedded in a DNA Nanostructure
Authors: Kekic Tadija , Ahmadi Yasaman , Barisic Ivan 
Published: October 2019

ABSTRACTArtificial enzymes hold a great potential in the field of biotechnology. The currently available design strategies are limited to recruit and organise secondary and tertiary structural elements, and functional motifs of native enzymes. Here, we demonstrate an approach towards the bottom-up development of an artificial enzyme based on DNA nanotechnology. Structural analyses of the FlaI ATPase were used to identify a set of amino acids essential for the catalytic reaction. The selected amino acids were used to design four peptide-oligonucleotide conjugates (POCs). The POCs were integrated into a DNA nanostructure and reconstituted the catalytic site of FlaI. DNA origami technology was employed to maintain the relative orientations of the amino acids and their positions analogous to those in the protein catalytic site. The substrate turnover rates were found to be comparable in our artificial nanozyme (kcat = 0.3622 s-1) and the native enzyme (kcat ≈ 0.016 s-1). The nanozymes could be recycled using an ultrafiltration protocol and reused in multiple experiments allowing a reliable reproduction of the measurements. The emulation of enzymatic activity, by this novel and computable technological framework, can be of high relevance in many different areas.
The SMYD3 methyltransferase promotes myogenesis by activating the myogenin regulatory network
Authors: Codato Roberta , Perichon Martine , Divol Arnaud , Fung Ella , Sotiropoulos Athanassia , Bigot Anne , Weitzman Jonathan B. , Medjkane Souhila 
Published: October 2019

ABSTRACTThe coordinated expression of myogenic regulatory factors, including MyoD and myogenin, orchestrates the steps of skeletal muscle development, from myoblast proliferation and cell-cycle exit, to myoblast fusion and myotubes maturation. Yet, it remains unclear how key transcription factors and epigenetic enzymes cooperate to guide myogenic differentiation. Proteins of the SMYD (SET and MYND domain-containing) methyltransferase family participate in cardiac and skeletal myogenesis during development in zebrafish, Drosophila and mice. Here, we show that the mammalian SMYD3 methyltransferase coordinates skeletal muscle differentiation in vitro. Overexpression of SMYD3 in myoblasts promoted muscle differentiation and myoblasts fusion. Conversely, silencing of endogenous SMYD3 or its pharmacological inhibition impaired muscle differentiation. Genome-wide transcriptomic analysis of murine myoblasts, with silenced or overexpressed SMYD3, revealed that SMYD3 impacts skeletal muscle differentiation by targeting the key muscle regulatory factor myogenin. The role of SMYD3 in the regulation of skeletal muscle differentiation and myotube formation, partially via the myogenin transcriptional network, highlights the importance of methyltransferases in mammalian myogenesis.
Prophage induction mediated by quorum sensing signals alters soil bacterial community structure
Authors: Liang Xiaolong , Wagner Regan E. , Li Bingxue , Zhang Ning , Radosevich Mark 
Published: October 2019

AbstractRecent findings have revealed a role for bacterial quorum sensing communication in bacteriophage (phage) reproduction decisions. However quorum sensing based phage-host interactions remain largely unknown, with the mechanistic details revealed for only a few phage-host pairs and a dearth of information available at the microbial community level. Here we report on the specific action of individual quorum-sensing signals (acyl-homoserine lactones; AHLs varying in acyl-chain length from four to 14 carbon atoms) on prophage induction in soil microbial communities. AHL treatment significantly decreased the bacterial diversity (Shannon Index) but did not significantly impact species richness. Exposure to short chain-length AHLs resulted in a decrease in the abundance of different taxa than exposure to higher molecular weight AHLs. Each AHL targeted a different subset of bacterial taxa. Our observations demonstrate that individual AHLs trigger prophage induction in different bacterial taxa leading to changes in microbial community structure.
Microtubule polymerization state and clathrin-dependent internalization regulate dynamics of cardiac potassium channel
Authors: Melgari Dario , Barbier Camille , Dilanian Gilles , Rücker-Martin Catherine , Doisne Nicolas , Coulombe Alain , Hatem Stéphane N. , Balse Elise 
Published: October 2019

ABSTRACTIon channel trafficking powerfully influences cardiac electrical activity as it regulates the number of available channels at the plasma membrane. Studies have largely focused on identifying the molecular determinants of the trafficking of the atria-specific KV1.5 channel, the molecular basis of the ultra-rapid delayed rectifier current IKur. Besides, regulated KV1.5 channel recycling upon changes in homeostatic state and mechanical constraints in native cardiomyocytes has been well documented. Here, using cutting-edge imaging in live myocytes, we investigated the dynamics of this channel in the plasma membrane. We demonstrate that the clathrin pathway is a major regulator of the functional expression of KV1.5 channels in atrial myocytes, with the microtubule network as the prominent organizer of KV1.5 transport within the membrane. Both clathrin blockade and microtubule disruption result in channel clusturization with reduced membrane mobility and internalization, whereas disassembly of the actin cytoskeleton does not. Mobile KV1.5 channels are associated with the microtubule plus-end tracking protein EB1 whereas static KV1.5 clusters are associated with stable acetylated microtubules. In human biopsies from patients in atrial fibrillation associated with atrial remodeling, drastic modifications in the trafficking balance occurs together with alteration in microtubule polymerization state resulting in modest reduced endocytosis and increased recycling. Consequently, hallmark of atrial KV1.5 dynamics within the membrane is clathrin- and microtubule-dependent. During atrial remodeling, predominance of anterograde trafficking activity over retrograde trafficking could result in accumulation ok KV1.5 channels in the plasma membrane.
Modulated efficacy CRISPRi reveals evolutionary conservation of essential gene expression-fitness relationships in bacteria
Authors: Hawkins John S. , Silvis Melanie R. , Koo Byoung-Mo , Peters Jason M. , Jost Marco , Hearne Cameron C. , Weissman Jonathan S. , Todor Horia , Gross Carol A. 
Published: October 2019

AbstractEssential genes are the central hubs of cellular networks. Despite their importance, the lack of high-throughput methods for titrating their expression has limited our understanding of the fitness landscapes against which essential gene expression levels are optimized. We developed a modified CRISPRi system leveraging the predictable reduction in efficacy of imperfectly matched sgRNAs to generate specific levels of CRISPRi activity and demonstrate its broad applicability in bacteria. Using libraries of mismatched sgRNAs, we characterized the expression-fitness relationships of essential genes inEscherichia coliandBacillus subtilis. Remarkably, these relationships co-vary by pathway and are predominantly conserved betweenE. coliandB. subtilisdespite ~ 2 billion years of evolutionary separation, suggesting that deeply conserved tradeoffs underlie bacterial homeostasis.One Sentence SummaryBacterial essential genes have varying responses to CRISPRi knockdown that are largely conserved across ~2 billion years of evolution.
A weak link with actin organizes tight junctions to control epithelial permeability
Authors: Belardi Brian , Hamkins-Indik Tiama , Harris Andrew R. , Fletcher Daniel A. 
Published: October 2019

SUMMARYIn vertebrates, epithelial permeability is regulated by the tight junction (TJ) formed by specialized adhesive membrane proteins, adaptor proteins, and the actin cytoskeleton. Despite the TJ’s critical physiological role, a molecular-level understanding of how TJ assembly sets the permeability of epithelial tissue is lacking. Here, we identify a 28-amino acid sequence in the TJ adaptor protein ZO-1 that is responsible for actin binding and show that this interaction is essential for TJ permeability. In contrast to the strong interactions at the adherens junction, we find that the affinity between ZO-1 and actin is surprisingly weak, and we propose a model based on kinetic trapping to explain how affinity could affect TJ assembly. Finally, by tuning the affinity of ZO-1 to actin, we demonstrate that epithelial monolayers can be engineered with a spectrum of permeabilities, which points to a new target for treating transport disorders and improving drug delivery.
AKT2 deficiency causes sarcopenia and metabolic disorder of skeletal muscle
Authors: Chen Miao , Ji Caoyu , Xiao Fei , Chen Dandan , Gao Shuya , Yang Qingchen , Peng Yue , Sanchis Daniel , Yan Fangrong , Ye Junmei 
Published: October 2019

AbstractSkeletal muscle is responsible for the majority of glucose disposal in the body. Insulin resistance in the skeletal muscle accounts for 85-90% of the impairment of total body glucose disposal in patients with tye 2 diabetes (T2D). However, the mechanism remains controversial. AKT2 is a protein kinase performing important functions in the regulation of glucose metabolism. We observed that mice deficient for AKT2 (AKT2 KO) exhibited decreased body weight and lean mass and showed impaired glucose tolerance, compared to their age- and gender-matched wild type mice (WT). Therefore, to test whether AKT2 deficiency causes deficits in skeletal muscle development and metabolism, we analyzed the expression of molecules related to skeletal muscle development, glucose uptake and metabolism in young (3 months) and old (8 months) mice. We found that AMPK phosphorylation and MEF2A expression were downregulated in young AKT2 KO mice, and this downregulation was inverted by AMPK activation. We also observed reduced mtDNA abundance and reduced expression of genes involved in mitochondrial biogenesis in the skeletal muscle of adult AKT2 KO mice, which was prevented by AMPK activation. However, GLUT4 expression was regulated by AKT2 in an AMPK-independent manner in skeletal muscle. During high-fat-diet (HFD)-induced obesity, AKT2 KO mice exhibited increased insulin resistance compared to WT mice. Our study establishes a new and important function of AKT2 in regulating glucose uptake and AMPK-dependent development and mitochondrial biogenesis in skeletal muscle.
Dis3L2 regulates cellular proliferation through a PI3-Kinase dependent signalling pathway
Authors: Towler Benjamin P. , Pashler Amy L. , Haime Hope J. , Przybyl Katarzyna M. , Viegas Sandra C. , Matos Rute G. , Morley Simon J. , Arraiano Cecilia M. , Newbury Sarah F. 
Published: October 2019

AbstractDis3L2 is a highly conserved 3’-5’ exoribonuclease which is mutated in the human overgrowth disorders Perlman syndrome and Wilms’ tumour. Here, we have generated a newdis3L2 null mutant and a UAS-nuclease-dead line inDrosophilato demonstrate that the catalytic activity of Dis3L2 is required to control proliferation in imaginal discs. Using RNA-seq ondis3L2mutant wing discs, we show that the imaginal disc growth factor Idgf2 is responsible for driving the wing overgrowth observed indis3L2null mutants. IDGFs are conserved proteins homologous to human chitinase-like proteins such as CHI3L1/YKL-40 which are implicated in tissue regeneration as well as cancers including colon cancer and non-small cell lung cancer. We also show that loss of DIS3L2 in human HEK-293T cells results in cell proliferation, illustrating the conservation of this important cell proliferation pathway. Using these human cells we show that loss of DIS3L2 results in an increase in the activity of the PI3-Kinase/AKT signalling pathway, which we subsequently show to also have a role in driving the proliferation phenotype inDrosophila. Our work therefore provides the first mechanistic explanation for DIS3L2-induced overgrowth in humans and flies and identifies an ancient proliferation pathway controlled by Dis3L2 to regulate cell proliferation and tissue growth.
Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals
Authors: Vaga Stefania , Lee Sunjae , Ji Boyang , Andreasson Anna , Talley Nicholas J , Agréus Lars , Bidkhori Gholamreza , Kovatcheva-Datchary Petia , Park Junseok , Lee Doheon , Proctor Gordon , Ehrlich Dusko , Nielsen Jens , Engstrand Lars , Shoaie Saeed 
Published: October 2019

ABSTRACTGut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
Neev, a novel long non-coding RNA, is expressed in chaetoblasts during regeneration of Eisenia fetida
Authors: Patel Surendra Singh , Zunjarrao Sanyami , Pillai Beena 
Published: October 2019

AbstractEisenia fetida, the common vermicomposting earthworm, shows robust regeneration of posterior segments removed by amputation. During the period of regeneration, the newly formed tissue initially contains only undifferentiated cells but subsequently differentiates into a variety of cell types including muscle, nerve and vasculature. Transcriptomics analysis, reported previously, provided a number of candidate non-coding RNAs that were induced during regeneration. We found that one such long non-coding RNA (lncRNA) is expressed in the skin, only at the base of newly formed chaetae. The spatial organization and precise arrangement of the regenerating chaetae and the cells expressing the lncRNA on the ventral side clearly support a model wherein the regenerating tissue contains a zone of growth and cell division at the tip and a zone of differentiation at the site of amputation. The temporal expression pattern of the lncRNA, christened Neev, closely resembled the pattern of chitin synthase genes, implicated in chaetae formation. We found that the lncRNA harbours 49 sites for binding a set of four miRNAs while the Chitin Synthase 8 mRNA comprises 478 sites. The over-representation of shared miRNA sites suggests that lncRNA Neev may act as a miRNA sponge to transiently de-repress chitin synthase 8 during formation of new chaetae in the regenerating segments of Eisenia fetida.Summary statementThe earthworm, Eisenia fetida, regenerates posterior segments following amputation. The transcriptome of the regenerating worm revealed a novel lncRNA, expressed only at the base of regenerating chaetae. We propose that this lncRNA is a miRNA sponge that modulates chitin synthesis.
Essentiality of local topology and regulation in kinetic metabolic modeling
Authors: Li Gaoyang , Du Wei , Cao Huansheng 
Published: October 2019

AbstractGenome-scale metabolic networks (GSMs) are mathematic representation of a set of stoichiometrically balanced reactions. However, such static GSMs do not reflect or incorporate functional organization of genes and their dynamic regulation (e.g., operons and regulons). Specifically, there are numerous topologically coupled local reactions through which fluxes are coordinated; and downstream metabolites often dynamically regulate the gene expression of their reactions via feedback. Here, we present a method which reconstructs GSMs with locally coupled reactions and transcriptional regulation of metabolism by key metabolites. The proposed method has outstanding performance in phenotype prediction of wild-type and mutants inEscherichia coli(E. coli),Saccharomyces cerevisiae(S. cerevisiae) andBacillus subtilis(B. subtilis) growing in various conditions, outperforming existing methods. The predicted growth rate and metabolic fluxes are highly correlated with those experimentally measured. More importantly, our method can also explain the observed growth rates by capturing the ‘real’ (experimentally measured) changes in flux between the wild-types and mutants. Overall, by identifying and incorporating locally organized and regulated functional modules into GSMs, Decrem achieves accurate predictions of phenotypes and has broad applications in bioengineering, synthetic biology and microbial pathology.
Differential contribution of p300 and CBP to regulatory elements in mESCs
Authors: Martire Sara , Sundaresan Aishwarya , Banaszynski Laura A. 
Published: October 2019

AbstractThe transcription coactivators CREB binding protein (CBP) and p300 are highly homologous acetyltransferases that mediate histone 3 lysine 27 acetylation (H3K27ac) at regulatory elements such as enhancers and promoters. Although in most cases, CBP and p300 are considered to be functionally identical, both proteins are indispensable for development and there is evidence of tissue-specific nonredundancy. However, characterization of chromatin and transcription states regulated by each protein is lacking. In this study we analyze the individual contribution of p300 and CBP to the H3K27ac landscape, chromatin accessibility, and transcription in mouse embryonic stem cells (mESC). We demonstrate that p300 is responsible for the majority of H3K27ac in mESCs and that loss of acetylation in p300-depleted mESCs is more pronounced at enhancers compared to promoters. While loss of either CBP or p300 has little effect on the open state of chromatin, we observe that distinct gene sets are transcriptionally dysregulated upon depletion of p300 or CBP. Transcriptional dysregulation is generally correlated with dysregulation of promoter acetylation upon depletion of p300 (but not CBP) and appears to be relatively independent of dysregulated enhancer acetylation. Interestingly, both our transcriptional and genomic analyses demonstrate that targets of the p53 pathway are stabilized upon deletion of p300, suggesting that this pathway is highly prioritized when p300 levels are limited.