bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in GluN2B-containing NMDA receptors result in opposite long-term plasticity and dopaminergic modulation at ipsilateralvs. contralateral cortico-striatal synapses
Authors: Li Wei , Pozzo-Miller Lucas 
Published: April 2019

AbstractExcitatory neurons in the primary motor cortex project bilaterally to the striatum. However, whether synaptic structure and function in ipsilateral and contralateral cortico-striatal pathways is identical or different remains largely unknown. Here, we describe that excitatory synapses in the contralateral pathway have higher levels of NMDA-type of glutamate receptors (NMDARs) than those in the ipsilateral pathway, although both synapses utilize the same presynaptic vesicular glutamate transporter. We also show that NMDARs containing the GluN2B subunit, but not GluN2A, contribute to this difference. The altered NMDAR subunit composition in these two pathways results in opposite synaptic plasticity: long-term depression in the ipsilateral pathway and long-term potentiation in the contralateral pathway. Furthermore, we demonstrate that activation of D1 and D2 dopamine (DA) receptors by either selective pharmacological agonists or light-induced release of endogenous DA have no effect on NMDAR-mediated neurotransmission in either pathway. However, blocking basal DAergic tone with either D1 or D2 with selective antagonists revealed that GluN2B-containing NMDARs are modulated by D1 receptors in the contralateral pathway and by D2 receptors in the ipsilateral pathway. Such distinct modulatory actions seem to be permissive rather than sufficient for the induction of long-term synaptic plasticity. Altogether, our results provide novel and unexpected evidence for the lack of bilaterality of NMDAR-mediated synaptic transmission at cortico-striatal pathways due to differences in the expression of GluN2B subunits, which results in differences in bidirectional synaptic plasticity and modulation by dopaminergic inputs.
Perturbation of the human gut microbiome by a non-antibiotic drug contributes to the resolution of autoimmune disease
Authors: Nayak Renuka R. , Alexander Margaret , Stapleton-Grey Kye , Ubeda Carles , Scher Jose U. , Turnbaugh Peter J. 
Published: April 2019

AbstractThe trillions of microorganisms (microbiota) found within the human gut play a critical role in shaping the immune system, yet these complex microbial communities are also highly sensitive to numerous environmental factors. While much of the focus to date has been on dietary intake, emerging data has begun to suggest that the use of pharmaceutical drugs, even those that are not considered to be antibiotics, can alter the human gut microbiota with unknown consequences for treatment outcomes. Here, we use a combination ofin vitro, in vivo, andex vivomethods to demonstrate that the first-line therapy for rheumatoid arthritis (RA), methotrexate (MTX), has off-target effects on the human gut microbiota, resulting in a significant growth advantage for drug-resistant Firmicutes over the Bacteroidetes, which tend to be more sensitive. Longitudinal analyses of the gut microbiotas of RA patients revealed that MTX-induced shifts in bacterial relative abundance are associated with improved drug response and transplant experiments in gnotobiotic mice show that these shifts lead to reduced inflammation. Together, these results suggest that the mechanism-of-action of non-antibiotic drugs may be due in part to off-target effects on the gut microbiota, while providing a critical first step towards explaining long-standing differences in drug response between patients.
Diurnal profiles of physical activity and postures derived from wrist-worn accelerometry in UK adults
Authors: Perez-Pozuelo Ignacio , White Thomas , Westgate Kate , Wijndaele Katrien , Wareham Nicholas J. , Brage Soren 
Published: April 2019

ABSTRACTBackgroundWrist-worn accelerometry is the commonest objective method for measuring physical activity in large-scale epidemiological studies. Research-grade devices capture raw triaxial acceleration which, in addition to quantifying movement, facilitates assessment of orientation relative to gravity. No population-based study has yet described the interrelationship and variation of these features by time and personal characteristics.Methods2043 UK adults (35-65years) wore an accelerometer on the non-dominant wrist and a chest-mounted combined heart-rate-and-movement sensor for 7days free-living. From raw (60Hz) wrist acceleration, we derived movement (non-gravity acceleration) and pitch and roll (arm) angles relative to gravity. We inferred physical activity energy expenditure (PAEE) from combined sensing and sedentary time from approximate horizontal arm-angle coupled with low movement.ResultsMovement differences by time-of-day and day-of-week were associated with arm-angles; more movement in downward arm-positions. Mean(SD) movement was similar between sexes ∼31(42)mg, despite higher PAEE in men, 53(22) vs 48(19)J·min-1·kg-1. Women spent longer with the arm pitched >0° (53% vs 36%) and less time at <0° (37% vs 53%). Diurnal pitch was 2.5-5° above and 0-7.5° below horizontal during night and daytime, respectively; corresponding roll angles were ∼0° and ∼20° (thumb-up). Differences were more pronounced in younger participants. All diurnal profiles indicated later wake-times on weekends. Daytime pitch was closer to horizontal on weekdays; roll was similar. Sedentary time was higher (17 vs 15hours/day) in obese vs normal-weight individuals.ConclusionsMore movement occurred in arm positions below horizontal, commensurate with activities including walking. Findings suggest time-specific population differences in behaviours by age, sex, and BMI.
Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development
Authors: Liu Dong , Kousa Anastasia I. , O’Neill Kathy E. , Guillemot Francois , Popis Martyna , Farley Alison M. , Tomlinson Simon R. , Ulyanchenko Svetlana , Seymour Philip A. , Serup Palle , Koch Ute , Radtke Freddy , Blackburn C. Clare 
Published: April 2019

AbstractThymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH-independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPC at the expense of cTEC differentiation. Finally, we uncover a direct interaction between NOTCH and FOXN1, the master regulator of TEC differentiation. These data establish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development and are thus of high relevance to strategies aimed at generating/regenerating functional thymic tissue in vitro and in vivo.
A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle
Authors: Comai Glenda , Heude Églantine , Mella Sebastien , Paisant Sylvain , Pala Francesca , Gallardo Mirialys , Kardon Gabrielle , Gopalakrishnan Swetha , Tajbakhsh Shahragim 
Published: April 2019

SUMMARYIn most vertebrates, the upper digestive tract is composed of muscularised jaws linked to the esophagus that permit food uptake and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factorsTbx1andIsl1are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to Met/HGF signalling for antero-posterior migration of esophagus muscle progenitors, where HGF ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish aTbx1-Isl1-Metgenetic hierarchy that uniquely regulate esophagus myogenesis and identify distinct genetic signatures that can be used as a framework to interpret pathologies arising within CPM derivatives.
Precise Memory is Predicted by Learning-Induced Sensory System Neurophysiological Plasticity
Authors: Rotondo Elena K. , Bieszczad Kasia. M. 
Published: April 2019

AbstractDespite identical learning experiences, individuals differ in the memory formed of those experiences. Memory formed with sensory specificity determines its utility for selectively cueing subsequent behavior, even in novel situations. If an individual forms generalized memory, then there is potential for novel sensory cues to interfere with accurate behavioral performance. Here, a rodent model of auditory learning capitalized on individual differences in learning-induced auditory neuroplasticity to identify and characterize neural substrates for sound-specific (vs. general) memory of the training signal’s acoustic frequency. Animals with naturally or pharmacologically induced signal-“specific” memory revealed behaviorally, exhibited long-lasting signal-specific neurophysiological plasticity in auditory cortical and subcortical evoked responses, while learning-induced changes were not detected in animals with “general” memories. Individual differences validated this brain-behavior relationship, such that the degree of change in neurophysiological responses could be used to determine the precision of memory formation.
Icosahedral viruses defined by their positively charged domains: a signature for viral identity and capsid assembly strategy
Authors: Requião Rodrigo D. , Carneiro Rodolfo L. , Moreira Mariana Hoyer , Ribeiro-Alves Marcelo , Rossetto Silvana , Palhano Fernando L. , Domitrovic Tatiana 
Published: April 2019

AbstractCapsid proteins often present a positively charged arginine-rich region at the N and/or C-termini that for some icosahedral viruses has a fundamental role in genome packaging and particle stability. These sequences show little to no conservation at the amino-acid level and are structurally dynamic so that they cannot be easily detected by common sequence or structure comparison. As a result, the occurrence and distribution of positively charged protein domain across the viral and the overall protein universe are unknown. We developed a methodology based on the net charge calculation of discrete segments of the protein sequence that allows us to identify proteins containing amino-acid stretches with an extremely high net charge. We observed that among all organisms, icosahedral viruses are especially enriched in extremely positively charged segments (Q ≥ +17), with a distinctive bias towards arginine instead of lysine. We used viral particle structural data to calculate the total electrostatic charge derived from the most positively charged protein segment of capsid proteins and correlated these values with genome charge arising from the phosphates of each nucleotide. We obtained a positive correlation (r = 0.91, p-value < 0001) for a group of 17 viral families, corresponding to 40% of all families with icosahedral structures described so far. These data indicated that unrelated viruses with diverse genome types adopt a common underlying mechanism for capsid assembly and genome stabilization based on R-arms. Outliers from a linear fit pointed to families with alternative strategies of capsid assembly and genome packaging.Significance StatementViruses can be characterized by the existence of a capsid, an intricate proteinaceous container that encases the viral genome. Therefore, capsid assembly and function are essential to viral replication. Here we specify virus families with diverse capsid structure and sequence, for each capsid packing capacity depends on a distinctive structural feature: a highly positively charged segment of amino acids residues, preferentially made of arginine. We also show that proteins with the same characteristics are rarely found in cellular proteins. Therefore, we identified a conserved viral functional element that can be used to infer capsid assembly mechanisms and inspire the design of protein nanoparticles and broad-spectrum antiviral treatments.
Inhibition of Stearoyl-CoA desaturase suppresses follicular help T and germinal center B cell responses
Authors: Min Son Young , Cheon In Su , Goplen Nick P. , Dent Alexander L. , Sun Jie 
Published: April 2019

AbstractStearoyl-CoA desaturases (SCD) are endoplasmic reticulum (ER) associated enzymes that catalyze the synthesis of the monounsaturated fatty acids (MUFAs). As such, SCD play important roles in maintaining the intracellular balance between saturated fatty acid (SFAs) and MUFAs. The roles of SCD in CD4+ T helper cell responses are currently unexplored. Here, we have found that murine and human follicular helper T (TFH) cells express higher levels of SCD1 compared to non-TFH cells. Further, the expression of SCD1 in TFH cells is dependent on the TFH lineage-specification transcription factor BCL6. We found that the inhibition of SCD1 impaired TFH cell maintenance and shifted the balance between TFH and follicular regulatory T (TFR) cells in the spleen. Consequently, SCD1 inhibition dampened germinal center B cell responses following influenza immunization. Mechanistically, we found that SCD inhibition led to increased ER stress and enhanced TFH cell apoptosis in vitro and in vivo. These results reveal a possible link between fatty acid metabolism and cellular and humoral responses induced by immunization or potentially, autoimmunity.
In silicoanalysis of coding SNPs and 3′-UTR associated miRNAs inDCAF17gene that may affect the regulation and pathogenesis of Woodhouse-Sakati Syndrome
Authors: Abdelmoneim Abdelrahman H. , Elrashied Asia M. , Mohammed Alaa I. , Mirghani Sara A. , Osman Rania E. , Gadim Esraa O. , Hassan Mohamed A. 
Published: April 2019

AbstractBackgroundWoodhouse-Sakati Syndrome refers to a group of inherited disorders characterized by alopecia, hypogonadism, diabetes mellitus, hypothyroidism and progressive extrapyramidal signs. The aim of this study is to identify the pathogenic SNPs in theDCAF17gene with their related mciroRNAs and their effect on the structure and function of the protein.Material and MethodsWe used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein. After that we defined the miRNAs founded in the 3′-UTR region on theDCAF17gene and studied the annotations relative to it.ResultsTen deleterious SNPs out of 339 were found to have a damaging effect on the protein structure and function, with one significant micoRNA in the 3′-UTR region.ConclusionThis was the first in silico analysis ofDCAF17gene, in which 10 novel mutations were found using different bioinformatics tools that could be used as a diagnostic markers for Woodhouse-Sakati syndrome, with one relevant microRNA that can regulate the function of the protein.
Seed treatment with chitosan synergizes plant growth promoting ability ofPseudomonas aeruginosa-P17 in sorghum (Sorhum bicolorL.)
Authors: Praveen Kumar G. , Desai Suseelendra , Moerschbacher Bruno M. , Gueddari Nour Eddine-El 
Published: April 2019

AbstractInoculation of crop plants with PGPR has in a large number of investigations resulted in increased plant growth and yield both in the greenhouse and in the field. This plant growth promoting effect of bacteria could be due to net result of synergistic effect of various pgpr traits that they exert in the rhizosphere region of the plant. Four (04) bacterial strain of fluorescent Pseudomonas spp. viz. P1, P17, P22 and P28 were identified previously for their plant growth promoting nature and abiotic stress tolerance and selected further to assess their chitinolytic activity and growth promotion on sorghum in combination with chitosans of low and high degree of acetylation. It was found that P1 has no chitin degrading nature and rest of the three strains have this property. When studied for their ability to grow in presence of chitosans of DA 1.6, 11, 35 and 56% all the strains showed growth in presence of chitosans. Seed bacterization of sorghum seeds with 04 bacterial strains in the presence and absence of chitosans (both low and high DA) and assessment of plant growth promotion after 15 days of sowing showed that P17+DA 56% chitosan combination showed higher growth of seedlings in plant growth chamber with highest root length of 25.9 cm, highest shoot length of 32.1 cm and dry mass of 132.7 mg/ plant. In P17+DA 56% chitosan treated seedlings various defence enzymes and PR-proteins were found to be present in highest quantities as compared to P1 and un-inoculated controls. Since this strain showed highest growth promotion of sorghum seedlings chitin-chitosan modifying enzyme (CCME) of this strain was partially characterized using different proteomic tools and techniques. CCME of P17 had one active polypeptide with a Pi in the range of 3.0-4.0. The digestion pattern of acetylated and deacetylated chitosans showed that P17 enzyme has endochitinase activity. Substrate specificity assay showed that the enzyme had more specificity towards highly acetylated chitosans. Two dimensional PAGE and MS analysis of the protein revealed similarities of this enzyme with protein of Pseudomonas aeruginosa chitinase PA01 strain of GenBank. In conclusion, the study established the option of opening new possibilities for developing bacterial-chitosan (P17+DA 56% chitosan) product for plant growth promotion and induced systemic resistance in sorghum.
Bacillus subtilis ALBA01 can mitigate onion pink root symptoms caused by Setophoma terrestris
Authors: Sayago P , Juncosa F , Albarracín Orio A , Luna D.F. , Molina G , Lafi J , Ducasse D.A 
Published: April 2019

AbstractSoil-borne pathogen Setophoma terrestris is the causal agent of pink root of onion, one of the most challenging diseases in onion production. Conventional approaches for managing the disease like solarization, soil fumigation and crop rotation have not been proven effective enough. In this work, we evaluated the biocontrol capacity of Bacillus subtilis ALBA01 (BsA01) against S. terrestris, in a highly susceptible onion cultivar, both under greenhouse and field conditions. Disease incidence and severity were evaluated together with growth, photosynthesis among other physiological variables and yield parameters. When compared with plants infected with the pathogen, those plants co-inoculated with BsA01 showed significantly less damage and levels of biocontrol above 50%. With regard to physiological parameters, plants challenged with S terrestris and inoculated with BsA01 performed as well as the control non-infected plants revealing a growth promotion effect of BsA01 on onion plants.
Role of sortase-assembled Ebp pili inEnterococcus faecalisadhesion to iron oxides and its impact on extracellular electron transfer
Authors: Ho Foo Kiong , Lam Ling Ning , Matysik Artur , Watts Thomas Dean , Wong Jun Jie , Chong Kelvin Kian Long , Choo Pei Yi , Tolar Joe , Low Pui Man , Chua Zhi Sheng , Paxman Jason J. , Heras Begoña , Marsili Enrico , Ajo-Franklin Caroline M. , Kline Kimberly A. 
Published: April 2019

AbstractEnterococcus faecalissortase-assembled endocarditis and biofilm-associated pili (Ebp) are a virulence factor implicated in enterococcal biofilm-associated infections and gastrointestinal colonization. We previously showed thatE. faecalisbiofilm metabolism is influenced by extracellular electron transfer (EET) under iron-rich conditions, raising the question of whether Ebp pili also play a role in EET. Here, we report a novel role of Ebp pili inE. faecalisadhesion to the iron oxides magnetite, goethite and hematite, where the EbpA tip adhesin contributes to this interaction. Adhesion by Ebp pili is conditionally important for EET to iron oxides, as pilus mutants are attenuated in EET under non-static growth conditions. In alignment with the established role of EET in redox homeostasis, we find that EET to ferricyanide supportsE. faecalisanaerobic growth on glycerol. Further, in an antibiotic-treated mouse gastrointestinal colonization model, we show thatE. faecalismutants deficient in EET poorly colonize the intestinal niche. Taken together, our findings suggest that Ebp pili can influenceE. faecalismetabolic fitness by promoting EET to iron oxides, raising new questions of how Ebp pili shapeE. faecalisinteractions with environmental ecosystems. Furthermore, the important role of EET inE. faecaliscolonization of the dysbiotic gastrointestinal environment highlights the need for further inquiry into how EET contributes toE. faecalismicrobial pathogenesis.ImportanceIn this study, we explored the interplay between extracellular electron transfer (EET) and anEnterococcus faecalisbiofilm factor, the endocarditis and biofilm-associated pili (Ebp). We demonstrate that Ebp pili have a novel role in adhesion to iron oxides, which consequently promotes EET to iron oxides under non-static conditions. Along with our findings thatE. faecalisEET can be coupled to anaerobic cell growth, our results point to a potential ecological role of Ebp pili in natural environments, outside of its established function in adhesion to host ligands. We provide the first evidence of the contribution of EET toE. faecaliscolonization of the antibiotic-treated murine intestinal niche, which adds to the limited experimental evidence linking EET and microbial pathogenesis, as well as highlights the need for further studies of EET in bacterial pathogens.
Imaging chromatin interactions at sub-kilobase resolution Via Tn5-FISH
Authors: Zhang Xu , Niu Jing , Li Guipeng , Dai Qionghai , Jin Dayong , Gao Juntao , Zhang Michael Q. 
Published: April 2019

ABSTRACTThere is increasing interest in understanding how the three-dimensional organization of the genome is regulated. Different strategies have been employed to identify chromatin interactions genome wide. However, due to the current limitations in resolving genomic contacts, visualization and validation of these genomic loci with sub-kilobase resolution remain the bottleneck for many years. Here, we describe Tn5 transposase-based Fluorescence in situ Hybridization (Tn5-FISH), a Polymerase Chain Reaction (PCR)-based, cost-effective imaging method, which achieved the co-localization of genomic loci with sub-kilobase resolution, to fine dissect genome architecture at sub-kilobase resolution and to verify chromatin interactions detected by Chromatin Configuration Capture (3C)-derivative methods. Especially, Tn5-FISH is very useful to verify short-range chromatin interactions inside of contact domain and Topologically Associated Domain (TAD). It also offers one powerful molecular diagnosis tool for clinical detection of cytogenetic changes in cancers.