bluuebunny/crossref_metadata_2025_split huggingface dataset:
A reference haplotype panel for genome-wide imputation of short tandem repeats
Authors: Saini Shubham , Mitra Ileena , Mousavi Nima , Fotsing Stephanie Feupe , Gymrek Melissa 
Published: October 2018

AbstractShort tandem repeats (STRs) are involved in dozens of Mendelian disorders and have been implicated in complex traits. However, genotyping arrays used in genome-wide association studies focus on single nucleotide polymorphisms (SNPs) and do not readily allow identification of STR associations. We leverage next-generation sequencing (NGS) from 479 families to create a SNP + STR reference haplotype panel. Our panel enables imputing STR genotypes into SNP array data when NGS is not available for directly genotyping STRs. Imputed genotypes achieve mean concordance of 97% with observed genotypes in an external dataset compared to 71% expected under a naive model. Performance varies widely across STRs, with near perfect concordance at bi-allelic STRs vs. 70% at highly polymorphic repeats. Imputation increases power over individual SNPs to detect STR associations with gene expression. Imputing STRs into existing SNP datasets will enable the first large-scale STR association studies across a range of complex traits.
Design of Peptoid-peptide Macrocycles to Inhibit the β-catenin TCF Interaction in Prostate Cancer
Authors: Schneider Jeffrey A. , Craven Timothy W. , Kasper Amanda C. , Yun Chi , Haugbro Michael , Briggs Erica M. , Svetlov Vladimir , Nudler Evgeny , Knaut Holger , Bonneau Richard , Garabedian Michael J. , Kirshenbaum Kent , Logan Susan K. 
Published: October 2018

AbstractNew chemical inhibitors of protein–protein interactions are needed to propel advances in molecular pharmacology. Peptoids are peptidomimetic oligomers with the capability to inhibit protein-protein interactions by mimicking protein secondary structure motifs. Here we report the in silico design of a macrocycle primarily composed of peptoid subunits that targets the β-catenin:TCF interaction. The β-catenin:TCF interaction plays a critical role in the Wnt signaling pathway which is over-activated in multiple cancers, including prostate cancer. Using the Rosetta suite of protein design algorithms, we evaluate how different macrocycle structures can bind a pocket on β-catenin that associates with TCF. The in silico designed macrocycles are screened in vitro using luciferase reporters to identify promising compounds. The most active macrocycle inhibits both Wnt and AR-signaling in prostate cancer cell lines, and markedly diminishes their proliferation. In vivo potential is demonstrated through a zebrafish model, in which Wnt signaling is potently inhibited.
Appreciation of different styles of humor: An fMRI study
Authors: Chan Yu-Chen , Hsu Wei-Chin , Liao Yi-Jun , Chen Hsueh-Chih , Tu Cheng-Hao , Wu Ching-Lin 
Published: October 2018

AbstractHumor styles are important in facilitating social relationships. Following humor styles theory, this functional magnetic resonance imaging (fMRI) study is the first to use “one-liner” humor to investigate the neural correlates involved in appreciating humor styles that differ in terms of target (self or other) and motivation (benign or detrimental). Interestingly, we observed greater activation in response to humor that facilitates relationships with others (self-defeating and affiliative humor) than to humor that enhances the self (self-enhancing and aggressive humor). Self-defeating humor may play an important role in Chinese culture in facilitating social relationships at one’s own expense. Psychophysiological interaction (PPI) analysis revealed temporal pole (TP)-frontal functional connectivity underlying the appreciation of self-directed humor, and temporo-parietal junction (TPJ)-frontal connectivity underlying the appreciation of other-directed humor. Amygdala-frontal coupling was observed during the appreciation of detrimental humor, while nucleus accumbens (NAc)-temporal coupling and midbrain-frontal coupling appear to play a role in the affective experience of amusement in response to benign humor. This study contributes to our understanding of the neural correlates of appreciating different humor styles, including humor that facilitates social relationships.
Genome-wide identification of AP2/ERF superfamily genes and their expression during fruit ripening of Chinese jujube
Authors: Zhang Zhong , Li Xingang 
Published: October 2018

AbstractThe Ethylene response factor (ERF) belongs to the APETALA2/ethylene response factor (AP2/ERF) superfamily, located at the end of the ethylene signalling pathway, and has important roles in regulating the ethylene-related response genes. Thus, identifying and charactering this transcription factor would be helpful to elucidate ethylene related fruit ripening regulation in Chinese jujube (Ziziphus jujuba Mill.). In the present study, 119 AP2/ERF genes, including 5 Related to ABI3/VPs (RAV), 17 AP2s, 57 ERFs, 39 dehydration-responsive element-binding (DREB) factors and 1 soloist gene, were identified from the jujube genome sequences. Genome localization, gene duplication, phylogenetic relationships and conserved motifs were simultaneously analysed. Using available transcriptomic data, 85 genes with differential transcripts in the flower, leaf and fruit were detected, suggesting a broad regulation of AP2/ERF genes in the growth and development of jujube. Among them, 44 genes were expressed in the fruit. As assessed by quantitative PCR, 15 up- and 23 downregulated genes corresponding to fruit full maturity were found, while in response to 100 μl l−1 ethylene, 6 up- and 16 downregulated genes were generated. By comparing the output, ZjERF54 and DREB39 were found to be the best candidate genes that positively participated in jujube fruit ripening, while ZjERF25 and ZjERF36, which had an ERF-associated amphiphilic repression (EAR) motif, were ripening repressors. These findings help to gain insights into AP2/ERF gene evolution and provide a useful resource to further understand the ethylene regulatory mechanisms underlying Chinese jujube fruit ripening.
Characterization of the miRNA regulators of the human ovulatory cascade
Authors: Yerushalmi G. M. , Salmon-Divon M. , Ophir L. , Yung Y. , Baum M. , Coticchio G. , Fadini R. , Mignini-Renzini M. , Dal Canto M. , Machtinger R. , Maman E. , Hourvitz A. 
Published: October 2018

AbstractOvarian follicular development and ovulation are complex and tightly regulated processes that involve regulation by microRNAs (miRNAs). We previously identified differentially expressed mRNAs between human cumulus granulosa cells (CGCs) from immature early antral follicles (germinal vesicle - GV) and mature preovulatory follicles (metaphase II - M2). In this study, we performed an integrated analysis of the transcriptome and miRNome in CGCs obtained from the GV cumulus-oocyte complex (COC) obtained from IVM and M2 COC obtained from IVF. A total of 43 differentially expressed miRNAs were identified. Using Ingenuity IPA analysis, we identified 7288 potential miRNA-regulated target genes. Two hundred thirty-four of these target genes were also found in our previously generated ovulatory gene library while exhibiting anti-correlated expression to the identified miRNAs. IPA pathway analysis suggested that miR-21 and FOXM1 cooperatively inhibit CDC25A, TOP2A and PRC1. We identified a mechanism for the temporary inhibition of VEGF during ovulation by TGFB1, miR-16-5p and miR-34a-5p. The linkage bioinformatics analysis between the libraries of the coding genes from our preliminary study with the newly generated library of regulatory miRNAs provides us a comprehensive, integrated overview of the miRNA-mRNA co-regulatory networks that may play a key role in controlling post-transcriptomic regulation of the ovulatory process.
Task-irrelevant spatial dividers facilitate counting and numerosity estimation
Authors: Li Qi , Nakashima Ryoichi , Yokosawa Kazuhiko 
Published: October 2018

AbstractCounting is characterized as a slow and error-prone action relying heavily on serial allocation of focused attention. However, quick and accurate counting is required for many real-world tasks (e.g., counting heads to ensure everyone is evacuated to a safe place in an emergency). Previous research suggests that task-irrelevant spatial dividers, which segment visual displays into small areas, facilitate focused attention and improve serial search. The present study investigated whether counting, which is also closely related to focused attention, can be facilitated by spatial dividers. Furthermore, the effect of spatial dividers on numerosity estimation, putatively dependent upon distributed attention, was also examined to provide insights into different types of number systems and different modes of visual attention. The results showed profound performance improvement by task-irrelevant spatial dividers in both counting and numerosity estimation tasks, indicating that spatial dividers may activate interaction between number and visual attention systems. Our findings provide the first evidence that task-irrelevant spatial dividers can be used to facilitate various types of numerical cognition.
Identification of Differentially Expressed Non-coding RNA in Porcine Alveolar Macrophages from Tongcheng and Large White Pigs Responded to PRRSV
Authors: Zhen Yueran , Wang Fengqing , Liang Wan , Liu Jianjian , Gao Guoli , Wang Yan , Xu Xuewen , Su Qiuju , Zhang Qingde , Liu Bang 
Published: October 2018

AbstractPorcine reproductive and respiratory syndrome (PRRS) is one of the most ruinous diseases in pig production. Our previous work showed that Tongcheng pigs (TC) were less susceptible to PRRS virus (PRRSV) than Large White (LW) pigs. To elucidate the difference in PRRSV resistance between the two breeds, small RNA-seq and ribo-zero RNA-seq were used to identify differentially expressed non-coding RNAs (including miRNAs and lincRNAs) responded to PRRSV in porcine alveolar macrophages (PAMs) from TC and LW pigs. Totally, 250 known mature miRNAs were detected. For LW pigs, there were 44 down-regulated and 67 up-regulated miRNAs in infection group; while for TC pigs, 12 down-regulated and 23 up-regulated miRNAs in TC infection group were identified. The target genes of the common differentially expressed miRNAs (DEmiRNAs) in these two breeds were enriched in immune-related processes, including apoptosis process, inflammatory response, T cell receptor signaling pathway and so on. In addition, 5 shared DEmiRNAs (miR-181, miR-1343, miR-296-3p, miR-199a-3p and miR-34c) were predicted to target PRRSV receptors, of which miR-199a-3p was validated to inhibit the expression of CD151. Interestingly, miR-378 and miR-10a-5p, which could inhibit PRRSV replication, displayed higher expression level in TC control group than that in LW control group. Contrarily, miR-145-5p and miR-328, which were specifically down-regulated in LW pigs, could target inhibitory immunoreceptors and may involve in immunosuppression caused by PRRSV. This indicates that DEmiRNAs are involved in the regulation of the immunosuppression and immune escape of the two breeds. Furthermore, we identified 616 lincRNA transcripts, of which 48 and 30 lincRNAs were differentially expressed in LW and TC pigs, respectively. LincRNATCONS_00125566may play an important role in the entire regulatory network, and was predicted to regulate the expression of immune-related genes through binding with miR-1343 competitively. In conclusion, this study provides an important resource for further revealing the interaction between host and virus, which will specify a new direction for anti-PRRSV research.
Vision facilitates tactile perception when grasping an object
Authors: Juravle Georgiana , Colino Francisco L. , Meleqi Xhino , Binsted Gordon , Farnè Alessandro 
Published: October 2018

AbstractTactile sensitivity measured on the hand is significantly decreased for a moving (MH), as opposed to a resting hand (RH). This process (i.e., tactile suppression) is affected by the availability of visual information during goal-directed action. However, the timing of the contribution of visual information is currently unclear for reach-to-grasp movements, especially in the period before the digits land on the object to grasp it. Here participants reached for, grasped, and lifted an object placed in front of them in conditions of full/limited vision. Tactile perception was assessed by measures of signal detection theory (d’ & c’). Electro-cutaneous stimulation could be delivered/not at the MH/RH, either during movement preparation, execution, before grasping, or while lifting the object. Results confirm tactile gating at the MH. This result is accompanied by a significant conservative criterion shift at the MH for the latter movement stages. Importantly, visual information enhances MH sensitivity just before grasping the object, but also improves RH sensitivity, during object lift. These findings reveal that tactile suppression is shaped by visual inputs at critical action stages. Further, they indicate that such a time-dependent modulation from vision to touch extends beyond the MH, suggesting a dynamic monitoring of the grasp space.
Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II–III colorectal cancer
Authors: Huang Chih-Yang , Chiang Shu-Fen , Ke Tao-Wei , Chen Tsung-Wei , You Ying-Shu , Chen William Tzu-Liang , Chao K. S. Clifford 
Published: October 2018

AbstractProgrammed cell death-1 (PDCD1/PD-1) and its ligand programmed cell death 1 ligand 1 (CD274/PD-L1) have been reported to suppress anti-tumor T cell-mediated immune responses. However, the clinical significance of CD274 in colorectal cancer were still elusive. We aim to clarify the relationships between CD8+ intratumor-infiltrating lymphocytes (TILs) and CD274 as well as their prognostic values in stage II-III colon carcinoma. Tumor differentiation, perineural invasion (PNI), pN stage and DNA mismatch repair (MMR)-deficient were clearly correlated with CD8+ TILs counts within the tumor microenvironment (p < 0.0001). Furthermore, tumor differentiation and PNI were suggestively correlated with tumor CD274 expression (p = 0.02 and p = 0.0195). Tumor CD274 level was significantly correlated with higher CD8+ TILs (p < 0.0001) but was not associated with MMR-deficient status (p = 0.14). High tumor CD274 expression [hazard ratio (HR) = 2.16, 95% CI = 1.63–2.86, p < 0.0001] and CD8+ TILs [HR = 1.51, 95% CI = 1.19–1.91, p = 0.0007] were associated with improved disease-free survival and overall survival. Additionally, the subgroup of patients who had a high CD8+ TILs/tumor CD274 have better survival outcomes compared with other subgroups (71% vs 53%; p < 0.0001). Therefore, the CD8+ TILs counts and tumor CD274 may be prognostic factors to predict survival and therapeutic responses in stage II–III colon carcinoma patients.
A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area
Authors: Jenkins Timothy P. , Formenti Fabio , Castro Cecilia , Piubelli Chiara , Perandin Francesca , Buonfrate Dora , Otranto Domenico , Griffin Julian L. , Krause Lutz , Bisoffi Zeno , Cantacessi Cinzia 
Published: October 2018

AbstractData from recent studies support the hypothesis that infections by human gastrointestinal (GI) helminths impact, directly and/or indirectly, on the composition of the host gut microbial flora. However, to the best of our knowledge, these studies have been conducted in helminth-endemic areas with multi-helminth infections and/or in volunteers with underlying gut disorders. Therefore, in this study, we explore the impact of natural mono-infections by the human parasite Strongyloides stercoralis on the faecal microbiota and metabolic profiles of a cohort of human volunteers from a non-endemic area of northern Italy (S+), pre- and post-anthelmintic treatment, and compare the findings with data obtained from a cohort of uninfected controls from the same geographical area (S−). Analyses of bacterial 16S rRNA high-throughput sequencing data revealed increased microbial alpha diversity and decreased beta diversity in the faecal microbial profiles of S+ subjects compared to S−. Furthermore, significant differences in the abundance of several bacterial taxa were observed between samples from S+ and S− subjects, and between S+ samples collected pre- and post-anthelmintic treatment. Faecal metabolite analysis detected marked increases in the abundance of selected amino acids in S+ subjects, and of short chain fatty acids in S− subjects. Overall, our work adds valuable knowledge to current understanding of parasite-microbiota associations and will assist future mechanistic studies aimed to unravel the causality of these relationships.
Using insects to detect, monitor and predict the distribution of Xylella fastidiosa: a case study in Corsica
Authors: Cruaud Astrid , Gonzalez Anne-Alicia , Godefroid Martin , Nidelet Sabine , Streito Jean-Claude , Thuillier Jean-Marc , Rossi Jean-Pierre , Santoni Sylvain , Rasplus Jean-Yves 
Published: October 2018

AbstractWe sampledca2500 specimens ofPhilaenus spumarius(Hemiptera: Aphrophoridae) throughout Corsica withouta prioriknowledge on the presence of symptoms on plants. We screened 448 specimens for the presence ofXylella fastidiosa (Xf)using qPCR and a custom nested PCR. qPCR appeared versatile and under-estimated the prevalence ofXf. Nested PCR showed thatXfwas present in all populations. Molecular results were validated by prediction on the distribution ofXfmade from tests conducted on plants, which shows the pertinence of using vectors in risk assessment studies.Xfwas detected in tenerals and adults. Thus,P.spumariuscould acquireXffrom its host plant, mostlyCistus monspeliensisin Corsica, which may act as reservoir for the next season. This contrasts with other observations and suggests that management strategies may have to be adapted on a case-by-case basis. At least two genetic entities and several variants ofXfnot yet identified on plants were present in the insects, which suggests ancient introductions ofXfand a probable underestimation of the current diversity of the strains present in Corsica. Interestingly 6% of the specimens carried two subspecies ofXf. Studies are required to better characterize the strains present in Corsica and to determine how the disease was introduced, spread and why no sign of a potential epidemic was detected earlier. This study shows that, when sensitive enough methods are implemented, spittlebugs (and more specificallyP.spumariusfor which species distribution modelling shows it could be a good sentinel for Europe) can be used to predict and better assess the exact distribution ofXf. Furthermore,Xfmultiply only in their foregut and does not become circulative, which facilitates its detection.
Differences in the fecal microbiota of neonates born at home or in the hospital
Authors: Combellick Joan L. , Shin Hakdong , Shin Dongjae , Cai Yi , Hagan Holly , Lacher Corey , Lin Din L. , McCauley Kathryn , Lynch Susan V. , Dominguez-Bello Maria Gloria 
Published: October 2018

AbstractResearch on the neonatal microbiome has been performed mostly on hospital-born infants, who often undergo multiple birth-related interventions. Both the hospital environment and interventions around the time of birth may affect the neonate microbiome. In this study, we determine the structure of the microbiota in feces from babies born in the hospital or at home, and from vaginal samples of their mothers. We included 35 vaginally-born, breast-fed neonates, 14 of whom delivered at home (4 in water), and 21 who delivered in the hospital. Feces from babies and mothers and maternal vaginal swab samples were collected at enrollment, the day of birth, followed by days 1, 2, 7, 14, 21, and 28. At the time of birth, the diversity of the vaginal microbiota of mothers delivering in the hospital was lower than in mothers delivering at home, and showed higher proportion of Lactobacillus. Among 20 infants not exposed to perinatal maternal antibiotics or water birth, fecal beta diversity differed significantly by birth site, with hospital-born infants having lower Bacteroides, Bifidobacterium, Streptococcus, and Lactobacillus, and higher Clostridium and Enterobacteriaceae family (LDA > 3.0), than babies born at home. At 1 month of age, feces from infants born in the hospital also induced greater pro-inflammatory gene expression (TLR4, IL-8, occludin and TGFβ) in human colon epithelial HT-29 cells. The results of this work suggest that hospitalization (perinatal interventions or the hospital environment) may affect the microbiota of the vaginal source and the initial colonization during labor and birth, with effects that could persist in the intestinal microbiota of infants 1 month after birth. More research is needed to determine specific factors that alter bacterial transmission between mother and baby and the long-term health implications of these differences for the developing infant.
Inhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases
Authors: Hammitzsch Ariane , Chen Liye , de Wit Jelle , Al-Mossawi M. Hussein , Ridley Anna , Sekine Takuya , Simone Davide , Doig Karen , Skapenko Alla , Bowness Paul 
Published: October 2018

AbstractTreatment options for Ankylosing Spondylitis (AS) are still limited. The T helper cell 17 (Th17) pathway has emerged as a major driver of disease pathogenesis and a good treatment target. Janus kinases (JAK) are key transducers of cytokine signals in Th17 cells and therefore promising targets for the treatment of AS. Here we investigate the therapeutic potential of four different JAK inhibitors on cells derived from AS patients and healthy controls, culturedin-vitrounder Th17-promoting conditions. Levels of IL-17A, IL-17F, IL-22, GM-CSF and IFNγ were assessed by ELISA and inhibitory effects were investigated with Phosphoflow. JAK1/2/3 and TYK2 were silenced in CD4+ T cells with siRNA and effects analyzed by ELISA (IL-17A, IL-17F and IL-22), Western Blot, qPCR and Phosphoflow.In-vitroinhibition of CD4+ T lymphocyte production of multiple Th17 cytokines (IL-17A, IL-17F and IL-22) was achieved with JAK inhibitors of differing specificity, as well as by silencing ofJAK1-3andTyk2, without impacting on cell viability or proliferation. Our preclinical data suggest JAK inhibitors as promising candidates for therapeutic trials in AS, since they can inhibit multiple Th17 cytokines simultaneously. Improved targeting of TYK2 or other JAK isoforms may confer tailored effects on Th17 responses in AS.