bluuebunny/crossref_metadata_2025_split huggingface dataset:
A global map of RNA binding protein occupancy guides functional dissection of post-transcriptional regulation of the T cell transcriptome
Authors: Litterman Adam J. , Zhu Wandi S. , Kageyama Robin , Zhao Wenxue , Zaitlen Noah , Erle David J. , Ansel K. Mark 
Published: October 2018

AbstractRNA binding proteins (RBPs) mediate constitutive RNA metabolism and gene specific regulatory interactions. To identify RNA cis-regulatory elements, we developed GCLiPP, a biochemical technique for detecting RBP occupancy transcriptome-wide. GCLiPP sequence tags corresponded with known RBP binding sites, specifically correlating to abundant cytosolic RBPs. To demonstrate the utility of our occupancy profiles, we performed functional dissection of 3′ UTRs with CRISPR/Cas9 genome editing. Two RBP occupied sites in the CD69 3′ UTR destabilized the transcript of this key regulator of lymphocyte tissue egress. Comparing human Jurkat T cells and mouse primary T cells uncovered hundreds of biochemically shared peaks of GCLiPP signal across homologous regions of human and mouse 3′ UTRs, including a cis-regulatory element that governs the stability of the mRNA that encodes the proto-oncogene PIM3 in both species. Our GCLiPP datasets provide a rich resource for investigation of post-transcriptional regulation in the immune system.
sRNA-target Prediction Organizing Tool (SPOT) integrates computational and experimental data to facilitate functional characterization of bacterial small RNAs
Authors: King Alisa M. , Vanderpool Carin K. , Degnan Patrick H. 
Published: October 2018

ABSTRACTSmall RNAs (sRNAs) post-transcriptionally regulate mRNA targets, typically under conditions of environmental stress. Although hundreds of sRNAs have been discovered in diverse bacterial genomes, most sRNAs remain uncharacterized, even in model organisms. Identification of mRNA targets directly regulated by sRNAs is rate-limiting for sRNA functional characterization. To address this, we developed a computational pipeline that we named SPOT for sRNA-targetPredictionOrganizingTool. SPOT incorporates existing computational tools to search for sRNA binding sites, allows filtering based on experimental data, and organizes the results into a standardized report. SPOT sensitivity (Correctly Predicted Targets/Total Known Targets) was equal to or exceeded any individual method when used on 12 characterized sRNAs. Using SPOT, we generated a set of target predictions for the sRNA RydC, which was previously shown to positively regulatecfamRNA, encoding cyclopropane fatty acid synthase. SPOT identifiedcfaalong with additional putative mRNA targets, which we then tested experimentally. Our results demonstrated that in addition tocfamRNA, RydC also regulatestrpEandpheAmRNAs, which encode aromatic amino acid biosynthesis enzymes. Our results suggest that SPOT can facilitate elucidation of sRNA target regulons to expand our understanding of the many regulatory roles played by bacterial sRNAs.IMPORTANCESmall RNAs (sRNAs) regulate gene expression in diverse bacteria by interacting with mRNAs to change their structure, stability or translation. Hundreds of sRNAs have been identified in bacteria, but characterization of their regulatory functions is limited by difficulty with sensitive and accurate identification of mRNA targets. Thus, new robust methods of bacterial sRNA target identification are in demand. Here, we describe ourSmall RNA-targetPredictionOrganizingTool, which streamlines the process of sRNA target prediction by providing a single pipeline that combines available computational prediction tools with customizable results filtering based on experimental data. SPOT allows the user to rapidly produce a prioritized list of predicted sRNA-target mRNA interactions that serves as a basis for further experimental characterization. This tool will facilitate elucidation of sRNA regulons in bacteria, allowing new discoveries regarding the roles of sRNAs in bacterial stress responses and metabolic regulation.
Sex differences in IL-17 determine chronicity in male versus female urinary tract infection
Authors: Scharff Anna Zychlinsky , Rousseau Matthieu , Mariano Livia Lacerda , Canton Tracy , Albert Matthew L , Fontes Magnus , Duffy Darragh , Ingersoll Molly A 
Published: October 2018

AbstractSex-based differences influence incidence and outcome of infectious disease. Women have a significantly greater incidence of urinary tract infection (UTI) than men, yet, conversely, male UTI is more persistent with greater associated morbidity. Mechanisms underlying these sex-based differences are unknown, in part due to a lack of experimental models. We optimized a model to transurethrally infect male mice and directly compared UTI in both sexes. Although both sexes were initially equally colonized by uropathogenicE. coli, only male and testosterone-treated female mice remained chronically infected for up to 4 weeks. Female mice had more robust innate responses, including higher IL-17 expression, and increased γδ T and LTi-like cells in the bladder following infection. Accordingly, neutralizing IL-17 abolished resolution in female mice, identifying the cytokine pathway necessary for bacterial clearance. Our findings support the concept that sex-based responses to UTI contribute to impaired innate immunity in males and provide a rationale for non-antibiotic-based immune targeting to improve the response to UTI.One Sentence SummaryWe investigated mechanisms underlying the clinical observation that while urinary tract infection is more prevalent in women, it is more severe in men, observing that in contrast to robust immune responses characterized by IL-17 in female animals, male mice develop chronic infection, following a failure to initiate innate immunity.
Novel diversity within marine Mamiellophyceae (Chlorophyta) unveiled by metabarcoding
Authors: Tragin Margot , Vaulot Daniel 
Published: October 2018

ABSTRACTThe Ocean Sampling Day (OSD) project provided metabarcoding data for the V4 hyper-variable regions of the 18S rRNA gene from 157 samples collected at 143 mostly coastal stations. In this paper we focus on the class Mamiellophyceae, which was found at nearly all OSD stations and represented 55 % of the green microalgae (Chlorophyta) reads in the 2014 OSD dataset. We performed phylogenetic analyses of unique OSD metabarcodes (ASV, amplicon single variants) and reference GenBank sequences from cultures and from the environment, focusing on the four most represented genera: Ostreococcus (45 % of the Mamiellophyceae reads), Micromonas (34 %), Bathycoccus (10 %) and Mantoniella (8.7 %). These analyses uncovered novel diversity within each genus except Bathycoccus. In Ostreococcus, a new clade (E) with 2 very clear base pair differences compared to the oceanic clade B in the V4 region was the second most represented clade after the coastal Ostreococcus “lucimarinus”. Within Micromonas, ten clades were found exceeding the 4 species and 2 candidate species already described. Finally, we found 2 new environmental clades of Mantoniella. Each Mamiellophyceae clade had a specific distribution in the OSD dataset suggesting that they are adapted to different ecological niches.
Epiblast formation by Tead-Yap-dependent expression of pluripotency factors and competitive elimination of unspecified cells
Authors: Hashimoto Masakazu , Sasaki Hiroshi 
Published: October 2018

AbstractThe epiblast is a pluripotent cell population first formed in preimplantation embryos and its quality is important for proper development. Here, we examined the mechanisms of epiblast formation and found that the Hippo pathway transcription factor Tead and its coactivator Yap regulate expression of pluripotency factors. After specification of the inner cell mass, Yap accumulates in the nuclei and activates Tead. Tead activity is required for strong expression of pluripotency factors and is variable in the forming epiblast. Cells showing low Tead activity are eliminated from the epiblast through cell competition. Pluripotency factor expression and Myc control cell competition downstream of Tead activity. Cell competition eliminates unspecified cells and is required for proper organization of the epiblast. These results suggest that induction of pluripotency factors by Tead activity and elimination of unspecified cells via cell competition ensure the production of an epiblast with naïve pluripotency.
Single-cell RNA-seq reveals that glioblastoma recapitulates normal brain development
Authors: Couturier Charles P. , Ayyadhury Shamini , Le Phuong U. , Monlong Jean , Riva Gabriele , Allache Redouane , Baig Salma , Yan Xiaohua , Bourgey Mathieu , Lee Changseok , Wang Yu Chang David , Yong V. Wee , Guiot Marie-Christine , Misic Bratislav , Antel Jack , Bourque Guillaume , Ragoussis Jiannis , Petrecca Kevin 
Published: October 2018

SummaryCancer stem cells are critical for cancer initiation, development, and resistance to treatments. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA-sequencing on 38 296 glioblastoma cells and 22 637 normal human fetal brain cells. Using an unbiased approach, we mapped the lineage hierarchy of the developing human brain and compared the transcriptome of each cancer cell to this roadmap. We discovered a conserved neural trilineage cancer hierarchy with glial progenitor-like cells at the apex. We also found that this progenitor population contains the majority of cancer’s cycling cells and is the origin of heterogeneity. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, unravels the origin of glioblastoma heterogeneity, and helps to identify cancer stem cell-specific targets.
Scaling principles of distributed circuits
Authors: Srinivasan Shyam , Stevens Charles F 
Published: October 2018

AbstractDistributed circuits like the olfactory cortex, hippocampus, and cerebellum contain sub-circuits whose inputs distribute their axons over the entire circuit creating a puzzle of how information is encoded. One method for approaching the puzzle is to view them as scalable systems. In scalable systems the quantitative relationship between circuit components is conserved across brain sizes, and by mapping circuit size to functional abilities - e.g. visual acuity in the visual circuit - scientists have explained information encoding. This approach has not been applied to anti-map circuits as their scalability is unknown. To address this gap in knowledge, we obtained quantitative descriptions of the olfactory bulb and piriform cortex in six mammals using stereology techniques and light microscopy. We found that the olfactory circuit is scalable as it satisfies three requirements of scalable systems. First, quantitative relationships between circuit components are conserved: the number piriform neuronsnscales with bulb glomeruligasn∼g3/2. Second, the olfactory circuit has an invariant property: the average number of synapses between a bulb glomerulus and piriform neuron is one. Third, the olfactory circuit is symmorphic, i.e. olfactory ability improves with circuit size. Other distributed circuits with similar properties might also be scalable.
Impaired chromosome segregation results in sperms with excess centrosomes inemb-27APC6mutantC. elegans
Authors: Kondo Tomo , Kimura Akatsuki 
Published: October 2018

AbstractThe anaphase-promoting complex (APC) is a major regulator of chromosome segregation and is implicated in centriole engagement, whose de-regulation causes abnormal number of centrosomes. Theemb-27gene inC. elegansencodes a subunit of APC. The paternalemb-27mutant was reported to show cell division with multiple furrows, suggesting the presence of excess centrosomes. In this study, we examined the number of centrosomes and the mechanism underlying de-regulation of centrosome number inemb-27mutants. Our observations indicated excess centrosomes inemb-27sperms, which resulted in zygotes with excess centrosomes. Further, the secondary spermatocyte ofemb-27produced reduced number of spermatids, which is likely the direct cause of the excess number of centrosomes per sperm. We propose that a chromosome segregation defect inemb-27induced centrosome separation defect, resulting in reduced number of buds. Additionally, treatment with cytoskeletal inhibiting drugs indicated presence of three kinds of forces working in combination to move the centrosomes into the spermatids. The present study suggested a novel role of microtubule in the budding cytokinesis of spermatocytes.
Macrophage migration inhibitory factor of Syrian golden hamster has similar structure and function as human MIF and promotes pancreatic tumor growth
Authors: Dash Pujarini , Sundaram Rajivgandhi , Suresh Voddu , Sabat Surendra Chandra , Mohapatra Debasish , Mohanty Sneha , Vasudevan Dileep , Senapati Shantibhusan 
Published: October 2018

AbstractMacrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases. Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from these models is biased towards a specific species. In experimental science, results obtained from multiple clinically relevant animal models always provide convincing data that might recapitulate in humans. Syrian golden hamster (Mesocricetus auratus), is a clinically relevant animal model for multiple human diseases. Hence, the major objectives of this study were to characterize structure and function of hamster MIF, and finally evaluate its effect on pancreatic tumor growthin vivo. Initially, the recombinant hamster MIF (rha-MIF) was cloned, expressed and purified in bacterial expression system. The rha-MIF primary sequence, biochemical properties and crystal structure analysis showed a greater similarity with human MIF. The crystal structure of hamster MIF illustrates that it forms a homotrimer as known in human and mouse. However, hamster MIF exhibits some minor structural variations when compared to human and mouse MIF. Thein vitrofunctional studies show that rha-MIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs). Interestingly, injection of rha-MIF into HapT1 pancreatic tumor bearing hamsters significantly enhanced the tumor growth and tumor associated angiogenesis. Together, the current study shows a structural and functional similarity between hamster and human MIF. Moreover, it has demonstrated that a high-level of circulating MIF originating from non-tumor cells might also promote pancreatic tumor growthin vivo.
Wakeful rest benefits memory when materials can be rehearsed
Authors: Millar Peter R. , Balota David A. 
Published: October 2018

AbstractWakeful rest is a brief (e.g., 10 minutes), quiet period of minimal stimulation, which has been shown to facilitate memory performance, compared to a distractor task. Researchers have argued that this benefit is driven by automatic consolidation during the wakeful rest period. However, prior studies have not fully ruled out a controlled rehearsal mechanism, which might also occur during wakeful rest. In the current study, we attempted to replicate the wakeful rest effect under conditions that more strictly limit the possibility of rehearsal. Across six experiments, we manipulated parameters of a standard wakeful rest paradigm, including the type of target materials (word lists or abstract shapes), intentionality of encoding (incidental or intentional), and final retrieval delay (immediate or delayed). Additionally, we tested both younger and older adults to test whether these effects are consistent across the adult lifespan. Importantly, we observed the expected wakeful rest memory benefit in recall for verbal targets, which are easily rehearseable, but not for abstract shapes, which cannot be readily rehearsed. This pattern occurred in both younger and older adults. These results place constraints on the generalizability of wakeful rest memory benefits and suggest that the effect may be at least partly driven by rehearsal processes, rather than an automatic consolidation process.
Inactivation of the core cheVAWY chemotaxis genes disrupts chemotactic motility and organised biofilm formation in Campylobacter jejuni
Authors: Reuter Mark , Ultee Eveline , Toseafa Yasmin , Tan Andrew , van Vliet Arnoud H.M. 
Published: October 2018

ABSTRACTFlagellar motility plays a central role in the bacterial foodborne pathogen Campylobacter jejuni, as flagellar motility is required for reaching the intestinal epithelium and subsequent colonisation or disease. Flagellar proteins also contribute strongly to biofilm formation during transmission. Chemotaxis is the process directing flagellar motility in response to attractant and repellent stimuli, but its role in biofilm formation of C. jejuni is not well understood. Here we show that inactivation of the core chemotaxis genes cheVAWY in C. jejuni strain NCTC 11168 affects both chemotactic motility and biofilm formation. Inactivation of any of the core chemotaxis genes (cheA, cheY, cheV or cheW) impaired chemotactic motility but did not affect flagellar assembly or growth. The ΔcheY mutant swam in clockwise loops, while complementation restored normal motility. Inactivation of the core chemotaxis genes interfered with the ability to form a discrete biofilm at the air-media interface, and the ΔcheY mutant displayed reduced dispersal/shedding of bacteria into the planktonic fraction. This suggests that while the chemotaxis system is not required for biofilm formation per se, it is necessary for organized biofilm formation. Hence interference with the Campylobacter chemotaxis system at any level disrupts optimal chemotactic motility and transmission modes such as biofilm formation.
Molecular epidemiology of ColombianHistoplasma capsulatumisolates shows their polyphyletic behavior and point out raw chicken manure as one of the infections sources
Authors: Gómez Luisa F. , Arango Myrtha , McEwen Juan G. , Gómez Oscar M. , Zuluaga Alejandra , Peláeze Carlos A. , Acevedo Jose M. , Taylor María L. , Jiménez María del P. 
Published: October 2018

AbstractThe thermally dimorphic fungusHistoplasma capsulatumis the causative agent of histoplasmosis, which is the most prevalent endemic mycosis in America. The replacement of organic matter in agro-ecosystems is necessary in the tropics, and the use of organic fertilizers has increased. Cases and outbreaks due to the presence of the fungus in these components have been reported. In Colombia, chicken manure is the most common raw material in the organic fertilizers production. In this work, we reached the isolation of the fungus from a chicken manure. Then, we were able to compare genetically 3 environmental isolates with 42 Colombian human clinical isolates. The genetic comparison showed the environmental isolates grouping together with the clinical isolates. This result suggests chicken manure as one of the infection source withH. capsulatum. Also, the phylogenetic analysis using anotherH. capsulatumisolates from databases showed that the Colombian isolates widely distributed in the relation tree. This result pointed out the great genetic diversity amongH. capsulatumColombian population.
Cytologic, Genetic, and Proteomic Analysis of a Yellow Leaf Mutant of Sesame (Sesamum indicumL.),Siyl-1
Authors: Gao Tongmei , Wei Shuangling , Chen Jing , Wu Yin , Li Feng , Wei Libin , Li Chun , Zeng Yanjuan , Tian Yuan , Wang Dongyong , Zhang Haiyang 
Published: October 2018

AbstractLeaf color mutation in sesame always affects the growth and development of plantlets, and their yield. To clarify the mechanisms underlying leaf color regulation in sesame, we analyzed a yellow-green leaf mutant. Genetic analysis of the mutant selfing revealed 3 phenotypes—YY, light-yellow (lethal);Yy, yellow-green; andyy, normal green—controlled by an incompletely dominant nuclear gene,Siyl-1. InYYandYy, the number and morphological structure of the chloroplast changed evidently, with disordered inner matter, and significantly decreased chlorophyll content. To explore the regulation mechanism of leaf color mutation, the proteins expressed amongYY,Yy, andyywere analyzed. All 98 differentially expressed proteins (DEPs) were classified into 5 functional groups, in which photosynthesis and energy metabolism (82.7%) occupied a dominant position. Our findings provide the basis for further molecular mechanism and biochemical effect analysis of yellow leaf mutants in plants.
Designer Sinorhizobium meliloti strains and multi-functional vectors for direct inter-kingdom transfer of high G+C content DNA
Authors: Brumwell Stephanie L. , MacLeod Michael R. , Huang Tony , Cochrane Ryan , Meaney Rebecca S. , Zamani Maryam , Matysiakiewicz Ola , Janakirama Preetam , Edgell David R. , Charles Trevor C. , Finan Turlough M. , Karas Bogumil J. 
Published: October 2018

AbstractStorage and manipulation of large DNA fragments is crucial for synthetic biology applications, yet DNA with high G+C content can be unstable in many host organisms. Here, we report the development of Sinorhizobium meliloti as a new universal host that can store DNA, including high G+C content, and mobilize DNA to Escherichia coli, Saccharomyces cerevisiae, and the eukaryotic microalgae Phaeodactylum tricornutum. We deleted the S. meliloti hsdR restriction-system to enable DNA transformation with up to 1.4 x 105 efficiency. Multi-host and multi-functional shuttle vectors (MHS) were constructed and shown to stably replicate in S. meliloti, E. coli, S. cerevisiae, and P. tricornutum, with a copy-number inducible E. coli origin for isolating plasmid DNA. Crucially, we demonstrated that S. meliloti can act as a universal conjugative donor for MHS plasmids with a cargo of at least 62 kb of G+C rich DNA derived from Deinococcus radiodurans.
Assessment of menstrual hygiene management and its determinants among adolescent girls: A cross-sectional study in school adolescent girls in Addis Ababa, Ethiopia
Authors: Biruk Ephrem , Tefera Worku , Tadesse Nardos , Sisay Ashagre 
Published: October 2018

AbstractIntroductionManaging menstruation is essentially dealing with menstrual flow and also in continuing regular activities like going to school, working etc. However, menstruation can place significant obstacles in girls’ access to health, education and future prospects if they are not equipped for effective menstrual hygiene management.ObjectiveTo assess the menstrual hygiene management and its determinant among school girls in Addis Ababa, Ethiopia.MethodsCross-sectional study design with quantitative method was carried out among 770 systematically selected adolescent school girls of Addis Ababa from April 1 to May 5, 2017. A self-administered pre-test close ended Amharic questionnaire at school setting was used for data collection. The coding was done using the original English version and entered to EPI-7 software. The quantitative file exported to statistical package for social science (SPSS) version 25.0 software for analysis. Total mean score was used to categorize individuals as good and poor while AOR; 95% CI with p < 0.05 was used to determine factors of menstrual hygiene management practice.ResultThis study had 98% response rate. 530 (70.1%) and 388(51.3%) respondents had good knowledge and practice of menstrual hygiene respectively. The findings also showed a significant positive association between good knowledge of menstruation and girls from mother’s whose education were secondary (AOR = 10.012, 95 % CI = 3.628-27.629). Wealth index quantile five (AOR = 9.038, 95 % CI = 3.728-21.909) revealed significant positive association with good practice of menstrual hygiene.Conclusion and recommendationMajority of participants had good knowledge and practice of menstrual hygiene and majority of them were from private school. Although knowledge was better than practice, girls should be educated about the process, use of proper pads or absorbents and its proper disposal.