bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistence of Anti-Zika Virus Immunoglobulin M Antibodies in Children with Microcephaly up to Four Years after Primary Infection
Authors: Campos Gubio S. , Carvalho Rejane H. , da Glória Teixeira Maria , Britto e Silva Giovanna F. , Rolo Carolina A. , Menezes Aline D. L. , Souza Rafael. R. M. , Sardi Silvia I. 
Published: December 2019

AbstractZika virus (ZIKV) is a member of the flaviviridae family of virus, considered to cause acute self-limited infection in adults, though it may lead to severe complications. It is believed that ZIKV infection elicit a classical viral immune reaction, with primary IgM antibody response and secondary IgG immunity. Persistence of IgM antibodies has been identified for other viruses belonging to the same family as ZIKV. We investigated, therefore, the presence of anti-ZIKV IgM antibodies in children with microcephaly born between January 2015 and November 2018, and their parents. We have detected persistence of IgM in 22% of children with microcephaly up to four years after primary infection. Long term IgM persistence have implications for the diagnosis of acute infection. More investigation is needed in order to correctly construe the significance of anti-ZIKV IgM persistence in the population in general, and in children with microcephaly in particular. The dynamics of IgM antibody responses against ZIKV must be known and understood to avoid misinterpretation of diagnosis for acute infection, re-infection and antibody persistence.
Discoidin domain receptor 2 drives melanoma drug resistance through AXL-dependent phenotype switching
Authors: Sala Margaux , Allain Nathalie , Jabouille Arnaud , Henriet Elodie , Abou-Ammoud Aya , Uguen Arnaud , Di-Tommaso Sylvaine , Dhourte Cyril , Raymond Anne-Aurélie , Dupuy Jean-William , Gerard Emilie , Dugot-Senant Nathalie , Rousseau Benoit , Merlio Jean-Phillipe , Pham-Ledart Anne , Vergier Béatrice , Moreau Violaine , Saltel Frédéric 
Published: December 2019

AbstractAnti-BRAF plus anti-MEK are used as first-line treatment of patients with metastatic melanomas harboringBRAFV600E mutation. The main issue with targeted therapy is acquired cellular resistance. In 70% of acquired resistance, melanoma cells switch their phenotype and become more aggressive and invasive. The molecular signature of this phenotype is MITF low, AXL high associated with actin cytoskeleton reorganization. After this switch, resistant cells present an anarchic cell proliferation due to MAP kinase pathway hyper-activation. We demonstrate that resistant cell lines presenting phenotype switching overexpress DDR1 and DDR2. We show that DDR2 inhibition induces a decrease in AXL and reduces actin stress fiber formation. Once this phenotype switching is acquired, we report that both DDRs promotes tumor cell proliferation, but only DDR2 can over-activate the MAP kinase pathway in resistant invasive cellsin vitroandin vivo. Therefore, DDRs inhibition could be a promising strategy for countering this resistance mechanism.SignificanceOur results show that DDR2 is a relevant target in melanoma resistance. DDR2 is required at the beginning of resistance for melanoma cell phenotype switching to occur. After phenotype switching, DDRs promote tumor cell proliferation of resistant invasive melanoma cells, but only DDR2 is able to over-activate the MAP kinase pathway. We put forward dasatinib (a DDR inhibitor) as a potential second-line treatment after targeted dual therapy for resistant patients overexpressing DDRs.
Corollary Discharge Promotes a Sustained Motor State in a Neural Circuit for Navigation
Authors: Ji Ni , Venkatachalam Vivek , Rodgers Hillary , Hung Wesley , Kawano Taizo , Clark Christopher M. , Lim Maria , Alkema Mark J. , Zhen Mei , Samuel Aravinthan D.T. 
Published: December 2019

AbstractAnimals exhibit behavioral and neural responses that persist on longer time scales than transient or fluctuating stimulus inputs. Here, we report that C. elegans uses feedback from the motor circuit to a sensory processing interneuron to sustain its motor state during thermotactic navigation. By imaging circuit activity in behaving animals, we show that a principal postsynaptic partner of the AFD thermosensory neuron, the AIY interneuron, encodes both temperature and motor state information. By optogenetic and genetic manipulation of this circuit, we demonstrate that the motor state representation in AIY is a corollary discharge signal. RIM, an interneuron that is connected with premotor interneurons, is required for this corollary discharge. Ablation of RIM eliminates the motor representation in AIY, allows thermosensory representations to reach downstream premotor interneurons, and reduces the animal’s ability to sustain forward movements during thermotaxis. We propose that feedback from the motor circuit to the sensory processing circuit underlies a positive feedback mechanism to generate persistent neural activity and sustained behavioral patterns in a sensorimotor transformation.
Regulatory T cell expansion by a highly CD25-dependent IL-2 mutein arrests ongoing autoimmunity
Authors: Khoryati Liliane , Pham Minh Nguyet , Sherve McKenna , Kumari Swarnima , Cook Kevin , Pearson Josh , Bogdani Marika , Campbell Daniel J. , Gavin Marc A. 
Published: December 2019

AbstractInterleukin-2 (IL-2) controls the homeostasis and function of regulatory T cells (Tregs) and defects in the IL-2 pathway contribute to multiple autoimmune diseases. Although recombinant IL-2 therapy has been efficacious in certain inflammatory conditions, the capacity for IL-2 to also activate inflammatory effector responses highlights the need for IL-2-based therapeutics with improved Treg-specificity. From a panel of rationally designed IL-2 variants, we identified IL-2 muteins with reduced potency and enhanced Treg-selectivity due to increased dependence on the IL-2-receptor component CD25. As an Fc-fused homodimer, the optimal Fc.IL-2 mutein induced selective Treg enrichment and reduced agonism of effector cells across a wide dose range. Furthermore, despite being a weaker agonist, overall Treg growth was greater and more sustained due to reduced receptor-mediated clearance of the Fc.IL-2 mutein compared to Fc-fused wild-type IL-2. Preferential Treg enrichment was also observed in the presence of activated pathogenic T cells in the autoimmune target organ, despite a loss of Treg-selectivity in an IL-2R-proximal response. These features allowed for extended resolution of spontaneous autoimmunity using infrequent dosing schedules. Thus, IL-2 muteins enable efficient, flexible, and targeted control of the autoimmune response.One Sentence SummaryA CD25-dependent IL-2 mutein selectively expands regulatory T cells and provides potent and targeted control of autoimmunity.
Premature termination codon readthrough inDrosophilavaries in a developmental and tissue-specific manner
Authors: Chen Yanan , Sun Tianhui , Bi Zhuo , Ni Jian-Quan , Pastor-Pareja Jose C. , Javid Babak 
Published: December 2019

AbstractDespite their essential function in terminating translation, readthrough of stop codons occurs more frequently than previously supposed. However, little is known about the regulation of stop codon readthrough by anatomical site and over the life cycle of animals. Here, we developed a set of reporters to measure readthrough inDrosophila melanogaster. A focused RNAi screen in whole animals identifiedupf1as a mediator of readthrough, suggesting that the stop codons in the reporters were recognized as premature termination codons (PTCs). We found readthrough rates of PTCs varied significantly throughout the life cycle of flies, being highest in older adult flies. Furthermore, readthrough rates varied dramatically by tissue and, intriguingly, were highest in fly brains, specifically neurons and not glia. This was not due to differences in reporter abundance or nonsense-mediated mRNA decay (NMD) surveillance between these tissues. Overall, our data reveal temporal and spatial variation of PTC-mediated readthrough in animals, and suggest that readthrough may be a potential rescue mechanism for PTC-harboring transcripts when the NMD surveillance pathway is inhibited.
ExpansionHunter Denovo: A computational method for locating known and novel repeat expansions in short-read sequencing data
Authors: Dolzhenko Egor , Bennett Mark F. , Richmond Phillip A. , Trost Brett , Chen Sai , van Vugt Joke J.F.A. , Nguyen Charlotte , Narzisi Giuseppe , Gainullin Vladimir G. , Gross Andrew , Lajoie Bryan , Taft Ryan J. , Wasserman Wyeth W. , Scherer Stephen W. , Veldink Jan H. , Bentley David R. , Yuen R K.C. , Bahlo Melanie , Eberle Michael A. 
Published: December 2019

AbstractExpansions of short tandem repeats are responsible for over 40 monogenic disorders, and undoubtedly many more pathogenic repeat expansions (REs) remain to be discovered. Existing methods for detecting REs in short-read sequencing data require predefined repeat catalogs. However recent discoveries have emphasized the need for detection methods that do not require candidate repeats to be specified in advance. To address this need, we introduce ExpansionHunter Denovo, an efficient catalog-free method for genome-wide detection of REs. Analysis of real and simulated data shows that our method can identify large expansions of 41 out of 44 pathogenic repeats, including nine recently reported non-reference REs not discoverable via existing methods.ExpansionHunter Denovo is freely available at https://github.com/Illumina/ExpansionHunterDenovo
Bacteriophages inhibit biofilms formed by multi-drug resistant bacteria isolated from septic wounds
Authors: Pallavali Roja Rani , Degati Vijaya Lakshmi , Durbaka Vijaya Raghava Prasad 
Published: December 2019

ABSTRACTGlobally, indiscriminate use of antibiotics contributed to the development of antibiotic resistance by the majority of microbial pathogens. As an alternative to antibiotics, using bacteriophages as antibiofilm agents to tackle multi-drug resistant bacteria has gained importance in recent years. In the present study, we explored the ability of bacteriophages to inhibit biofilm formation under various conditions. Under dynamic condition (DR), wherein the medium is a renewal for every 12 h amount of biomass produced (0.74 ± 0.039), log10CFU count (6.3 ± 0.55) was highest when compared to other physical conditions tested. Biomass of biofilms produced byStaphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, andEscherichia colidrastically reduced when incubated for 2 or 4 h with bacteriophages vB_SAnS_SADP1, vB_PAnP_PADP4, vB_KPnM_KPDP1, and vB_ECnM_ECDP3 respectively at the time points tested (24, 48 and 72 h). Among the phages, vB_ECnM_ECDP3 effectively inhibited the biomass of biofilm when incubated for 2 h (0.35 ± 0.04, (44 %) (p < 0.0001) or 4 h (0.17 ± 0.015, (21.5%) (p<0.0001). Bacteriophages ofE. coli(vB_ECnM_ECDP3)P. aeruginosa(vB_PAnP_PADP4),K. pneumoniae(vB_KPnM_KPDP1) andS. aureus(vB_SAnS_SADP1) also significantly inhibited the biomass of biofilm formation as evidenced by Scanning Electron Microscopy and Confocal laser scanning microscopy.
The Use of GC-, Codon-, and Amino Acid-frequencies to Understand the Evolutionary Forces at a Genomic Scale
Authors: Elofsson Arne 
Published: December 2019

1AbstractIt is well known that the GC content varies enormously between organisms; this is believed to be caused by a combination of mutational preferences and selective pressure. Within coding regions, the variation of GC is more substantial in position three and smaller in position one and two. Less well known is that this variation also has an enormous impact on the frequency of amino acids as their codons vary in GC content. For instance, the fraction of alanines in different proteomes varies from 1.1% to 16.5%. In general, the frequency of different amino acids correlates strongly with the number of codons, the GC content of these codons and the genomic GC contents. However, there are clear and systematic deviations from the expected frequencies. Some amino acids are more frequent than expected by chance, while others are less frequent. A plausible model to explain this is that there exist two different selective forces acting on the genes; First, there exists a force acting to maintain the overall GC level and secondly there exists a selective force acting on the amino acid level. Here, we use the divergence in amino acid frequency from what is expected by the GC content to analyze the selective pressure acting on codon frequencies in the three kingdoms of life. We find four major selective forces; First, the frequency of serine is lower than expected in all genomes, but most in prokaryotes. Secondly, there exist a selective pressure acting to balance positively and negatively charged amino acids, which results in a reduction of arginine and negatively charged amino acids. This results in a reduction of arginine and all the negatively charged amino acids. Thirdly, the frequency of the hydrophobic residues encoded by a T in the second codon position does not change with GC. Their frequency is lower in eukaryotes than in prokaryotes. Finally, some amino acids with unique properties, such as proline glycine and proline, are limited in their frequency variation.
Improving Bacterial Ribosome Profiling Data Quality
Authors: Glaub Alina , Huptas Christopher , Neuhaus Klaus , Ardern Zachary 
Published: December 2019

AbstractRibosome profiling (RIBO-seq) in prokaryotes has the potential to facilitate accurate detection of translation initiation sites, to increase understanding of translational dynamics, and has already allowed detection of many unannotated genes. However, protocols for ribosome profiling and corresponding data analysis are not yet standardized. To better understand the influencing factors, we analysed 48 ribosome profiling samples from 9 studies on E. coli K12 grown in LB medium. We particularly investigated the size selection step in each experiment since the selection for ribosome-protected footprints (RPFs) has been performed at various read lengths. We suggest choosing a size range between 22-30 nucleotides in order to obtain protein-coding fragments. In order to use RIBO-seq data for improving gene annotation of weakly expressed genes, the total amount of reads mapping to protein-coding sequences and not rRNA or tRNA is important, but no consensus about the appropriate sequencing depth has been reached. Again, this causes significant variation between studies. Our analysis suggests that 20 million non rRNA/tRNA mapping reads are required for global detection of translated annotated genes. Further, we highlight the influence of drug induced ribosome stalling, causing bias at translation start sites. Drug induced stalling may be especially useful for detecting weakly expressed genes. These suggestions should improve both gene detection and the comparability of resulting ribosome profiling datasets.
Multiscale criticality measures as general-purpose gauges of proper brain function
Authors: Fekete Tomer , Hinrichs Hermann , Sitt Jacobo Diego , Heinze Hans-Jochen , Shriki Oren 
Published: December 2019

ABSTRACTThe brain is universally regarded as a system for processing information. If so, any behavioral or cognitive dysfunction should lend itself to depiction in terms of information processing deficiencies. Information is characterized by recursive, hierarchical complexity. The brain accommodates this complexity by a hierarchy of large/slow and small/fast spatiotemporal loops of activity. Thus, successful information processing hinges upon tightly regulating the spatiotemporal makeup of activity, to optimally match the underlying multiscale delay structure of such hierarchical networks. Reduced capacity for information processing will then be expressed as deviance from this requisite multiscale character of spatiotemporal activity. This deviance is captured by a general family of multiscale criticality measures (MsCr). We applied MsCr to MEG and EEG data in four telling degraded information processing scenarios: disorders of consciousness, mild cognitive impairment, schizophrenia and preictal activity. Consistently with our previous modeling work, MsCr measures systematically varied with information processing capacity. MsCr measures might thus be able to serve as general gauges of information processing capacity and, therefore, as normative measures of brain health.
Genetic dominance governs the evolution and spread of mobile genetic elements in bacteria
Authors: Rodríguez-Beltrán Jerónimo , Sørum Vidar , Toll-Riera Macarena , de la Vega Carmen , Peña-Miller Rafael , San Millán Alvaro 
Published: December 2019

AbstractMobile genetic elements (MGEs), such as plasmids, promote bacterial evolution through horizontal gene transfer (HGT). However, the rules governing the repertoire of traits encoded on MGEs remain unclear. In this study, we uncovered the central role of genetic dominance shaping genetic cargo in MGEs, using antibiotic resistance as a model system. MGEs are typically present in more than one copy per host bacterium and, as a consequence, genetic dominance favors the fixation of dominant mutations over recessive ones. Moreover, genetic dominance also determines the phenotypic effects of horizontally acquired MGE-encoded genes, silencing recessive alleles if the recipient bacterium already carries a wild-type copy of the gene. The combination of these two effects governs the catalogue of genes encoded on MGEs, dictating bacterial evolution through HGT.
Klf9 is a key feedforward regulator of the transcriptomic response to glucocorticoid receptor activity
Authors: Gans Ian , Hartig Ellen I. , Zhu Shusen , Tilden Andrea R. , Hutchins Lucie N. , Maki Nathaniel J. , Graber Joel H. , Coffman James A. 
Published: December 2019

AbstractThe zebrafish has recently emerged as a model system for investigating the developmental roles of glucocorticoid signaling and the mechanisms underlying glucocorticoid-induced developmental programming. To assess the role of the Glucocorticoid Receptor (GR) in such programming, we used CRISPR-Cas9 to produce a new frameshift mutation, GR369-, which eliminates all potential in-frame initiation codons upstream of the DNA binding domain. Using RNA-seq to ask how this mutation affects the larval transcriptome under both normal conditions and with chronic cortisol treatment, we find that GR mediates most of the effects of the treatment, and paradoxically, that the transcriptome of cortisol-treated larvae is more like that of larvae lacking a GR than that of larvae with a GR, suggesting that the cortisol-treated larvae develop GR resistance. The one transcriptional regulator that was both underexpressed in GR369- larvae and consistently overexpressed in cortisol-treated larvae was klf9. We therefore used CRISPR-Cas9-mediated mutation of klf9 and RNA-seq to assess Klf9-dependent gene expression in both normal and cortisol-treated larvae. Our results indicate that Klf9 contributes significantly to the transcriptomic response to chronic cortisol exposure, mediating the upregulation of proinflammatory genes that we reported previously.
Hypoxia on vhl-deficient cells to obtain hif related genes through bioinformatics analysis
Authors: Lin Hua , Liu Hongwei 
Published: December 2019

AbstractVhl is responsible for degrading the transcription factor hif-1. Hif-1 transcription factors drive changes in hypoxic gene expression to adapt cells to exposure to hypoxic environments. This study hopes to analyze the effect of hypoxia on the vhl-deficient cells to obtain hif regulated genes through bioinformatics analysis. The top ten genes evaluated by connectivity degree in the PPI network were identified. CDK1, CTNNB1, NHP2, CCNA2, CTNNB1, MRPL16, CCND1 were down-regulated. CDK1, RPL12, RPL17, RPL27, RPS10 were up-regulated.
Acute inflammatory events attenuate high-sucrose diet-induced neurodegenerative processes in reproductively normal female wild-type mice
Authors: Pacholko Anthony G. , Bekar Lane K. 
Published: December 2019

AbstractIt is known that diabetic and chronic inflammatory conditions can increase the risk of Alzheimer’s disease (AD)-like neurodegeneration in isolation. As certain elements of the diabetic/pre-diabetic state may sensitize the brain to inflammatory insult (i.e. excess glucocorticoid activity), there is reason to believe that obesogenic and inflammatory factors may accelerate neurodegeneration in a synergistic manner. Also, given that most AD research utilizes male animal models despite increased prevalence of AD among women, we sought to characterize elements of the established (in males) high-sucrose model of neurodegeneration, for the first time, in reproductively normal (pre-menopausal) female mice. A high-sucrose diet (20% of the drinking water) was combined with systemic intraperitoneal lipopolysaccharide (LPS) injections (0.1 mg/kg; 1x/month over 3 months) over seven months in reproductively normal female wild-type mice (C57Bl/6; n=10/group). Although a deleterious effect was hypothesized, low-dose LPS proved to protect against high sucrose diet-induced pathologies in female wild-type mice. Results from our high-sucrose group confirmed that a high-sucrose diet is a mild model of neurodegeneration in wild-type females, as evidenced by exaggerated glucocorticoid expression, spatial learning deficits, irregularities within the insulin pathway, and increased β-amyloid production and Tau phosphorylation. While LPS had little to no effect in isolation, it exerted a protective influence when added to animals sustained on a high-sucrose diet. Corticosterone homeostasis, and levels of amyloid-β (Aβ) and pTau were rescued following addition of LPS. The work presented supports a high-sucrose diet as a model of mild neurodegeneration in female mice and highlights a protective role for transient inflammation against dietary-insult that may be sex dependent.
Genome-wide analysis of chalcone synthase (CHS) family from eggplant (Solanum melongena L.) in flavonoid biosynthetic pathway and expression pattern in response to heat stress
Authors: Wu Xuexia , Zhang Shengmei , Liu Xiaohui , Shang Jing , Zhang Aidong , Zhu Zongwen , Zha Dingshi 
Published: December 2019

AbstractEnzymes of chalcone synthase (CHS) family participate in the synthesis of a series of secondary metabolites in plants, fungi and bacteria. CHS showed significant correlation to the accumulation patterns of anthocyanin. The peel color mainly determined by the content of anthocyanin, is a majority economic trait for eggplant affected by heat stress. A total of 7 CHS(SmCHS1-7) putative genes were identified in genome-wide of eggplant (S. melongena L.). The SmCHS genes distribute on 7 scaffolds and were classified into 3 clusters. Phylogenetic relationships analysis showed that 73 CHS genes from 7 Solanaceae species were classified into 10 groups. SmCHS5, SmCHS6 and SmCHS7 were continuously down-regulated under 38°C and 45°C treatment, while SmCHS4 was up-regulated under 38°C but little change at 45°C in peel. Expression profiles of anthocyanin biosynthesis key genes families showed that the PAL, 4CL and AN11 genes were mainly expressed in all five tissues. CHI, F3H, F3’5’H, DFR, 3GT and bHLH1 genes were expressed in flower and peel. Under heat stress, 52 key genes expression level were reduced under heat stress. By contrast, expression patterns of eight key genes similar to SmCHS4 up-regulated at the 38°C-3h. Comparative analysis of putative CHS protein biochemical characteristics, cis-regulatory elements, regulatory network revealed that SmCHS genes family have conservation gene structure and functional diversification. SmCHS showed two or more expression patterns and execute multiple functions to regulate anthocyanin content. Combined with regulatory networks, it is possible to further understand the regulation mechanism of peel color in eggplant.