bluuebunny/crossref_metadata_2025_split huggingface dataset:
CBL-INTERACTING PROTEIN KINASE 9 regulates ammonium-dependent root growth downstream of IDD10 in rice (Oryza sativa)
Authors: Xuan Yuan Hu , Kumar Vikranth , Han Xiao , Kim Sung Hoon , Jeong Jin Hee , Kim Chul Min , Gao Yue , Han Chang-deok 
Published: January 2019

AbstractBackground and AimsINDETERMINATE DOMAIN 10 (IDD10) is a key transcription factor gene that activates the expression of a large number of NH4+-responsive genes including AMMONIUM TRANSPORTER 1;2 (AMT1;2). Primary root growth of rice (Oryza sativa) idd10 mutants is hypersensitive to NH4+. The involvement of CALCINEURIN B-LIKE INTERACTING PROTEIN KINASE (CIPK) genes in the action of IDD10 on NH4+-mediated root growth was investigated.MethodsQuantitative reverse transcription–PCR was used to analyse NH4+- and IDD10-dependent expression of CIPK genes. IDD10-regulated CIPK target genes were identified using electrophoretic mobility shift assays, chromatin immunoprecipitation and transient transcription assays. Root growth rate, ammonium content and 15N uptake of cipk mutants were measured to determine their sensitivity to NH4+ and to compare these phenotypes with those of idd10. The genetic relationship between CIPK9 OX and idd10 was investigated by crosses between the CIPK9 and IDD10 lines.Key ResultsAMT1;2 was overexpressed in idd10 to determine whether NH4+-hypersensitive root growth of idd10 resulted from limitations in NH4+ uptake or from low cellular levels of NH4+. High NH4+ levels in idd10/AMT1;2 OX did not rescue the root growth defect. Next, the involvement of CIPK genes in NH4+-dependent root growth and interactions between IDD10 and CIPK genes was investigated. Molecular analysis revealed that IDD10 directly activated transcription of CIPK9 and CIPK14. Expression of CIPK8, 9, 14/15 and 23 was sensitive to exogenous NH4+. Further studies revealed that cipk9 and idd10 had almost identical NH4+-sensitive root phenotypes, including low efficiency of 15NH4+ uptake. Analysis of plants containing both idd10 and CIPK9 OX showed that CIPK9 OX could rescue the NH4+-dependent root growth defects of idd10.ConclusionsCIPK9 was involved in NH4+-dependent root growth and appeared to act downstream of IDD10. This information will be useful in future explorations of NH4+ signalling in plants.
News about non-secretory exocytosis: mechanisms, properties, and functions
Authors: D’Alessandro Rosalba , Meldolesi Jacopo 
Published: January 2019

AbstractThe fusion by exocytosis of many vesicles to the plasma membrane induces the discharge to the extracellular space of their abundant luminal cargoes. Other exocytic vesicles, however, do not contain cargoes, and thus, their fusion is not followed by secretion. Therefore, two distinct processes of exocytosis exist, one secretory and the other non-secretory. The present review deals with the knowledge of non-secretory exocytosis developed during recent years. Among such developments are the dual generation of the exocytic vesicles, initially released either from the trans-Golgi network or by endocytosis; their traffic with activation of receptors, channels, pumps, and transporters; the identification of their tethering and soluble N-ethylmaleimide-sensitive factor attachment protein receptor complexes that govern membrane fusions; the growth of axons and the membrane repair. Examples of potential relevance of these processes for pathology and medicine are also reported. The developments presented here offer interesting chances for future progress in the field.
Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk
Authors: Reeves Katherine W , Díaz Santana Mary , Manson JoAnn E , Hankinson Susan E , Zoeller R Thomas , Bigelow Carol , Sturgeon Susan R , Spiegelman Donna , Tinker Lesley , Luo Juhua , Chen Bertha , Meliker Jaymie , Bonner Matthew R , Cote Michele L , Cheng Ting-Yuan David , Calafat Antonia M 
Published: January 2019

Abstract

Background
Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking.

Methods
We conducted a nested case-control study within the Women’s Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up.

Results
Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years.

Conclusions
In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.
Chikungunya and O’nyong-nyong Viruses in Uganda: Implications for Diagnostics
Authors: Clements Tamara L , Rossi Cynthia A , Irish Amanda K , Kibuuka Hannah , Eller Leigh Anne , Robb Merlin L , Kataaha Peter , Michael Nelson L , Hensley Lisa E , Schoepp Randal J 
Published: January 2019

AbstractBackgroundA serosurvey of healthy blood donors provided evidence of hemorrhagic fever and arthropod-borne virus infections in Uganda.MethodsAntibody prevalence to arthropod-borne and hemorrhagic fever viruses in human sera was determined using enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT).ResultsThe greatest antibody prevalence determined by ELISA was to chikungunya virus (CHIKV) followed in descending order by West Nile virus (WNV), Crimean-Congo hemorrhagic fever virus (CCHFV), Ebola virus (EBOV), dengue virus (DEN), yellow fever virus (YFV), Rift Valley fever virus (RVFV), Marburg virus (MARV), and Lassa virus (LASV). Further investigation of CHIKV-positive sera demonstrated that the majority of antibody responses may likely be the result of exposure to the closely related alphavirus o’nyong-nyong virus (ONNV).ConclusionsAs the use of highly specific and sensitive polymerase chain reaction–based assays becomes the diagnostic standard without the corresponding use of the less sensitive but more broadly reactive immunological-based assays, emerging and re-emerging outbreaks will be initially missed, illustrating the need for an orthogonal system for the detection and identification of viruses causing disease.
Effects of partial, combined and total replacement of sodium chloride in beef sausage on microbial load, sensory acceptability and physical properties
Authors: Oshibanjo Olusegun D. , Ikhimiukor Odion O. 
Published: January 2019

AbstractThis study evaluates the effects of partial, combined or total replacement of NaCl on microbial load, sensory evaluation and physical properties of beef sausage. Beef sausage was prepared (g/100g: beef 65.0, corn flour 10.0, oil 10.0, soya bean, wet and dry spice 15.0). Sodium chloride (SC) was replaced with potassium chloride (PC), potassium lactate (PL) or calcium ascorbate (CA) at 25%, 50% and 100%, and then stored for 15 days in a factorial arrangement in complete randomized design. Sausages were subjected to microbial load, sensory evaluation and pH, cooking yield and cooking loss using standard procedure. Data were analysed using descriptive statistic and ANOVA at α0.05. The microbial load was generally lower. The pH increased with storage time. The cooking yield was significantly higher in salt combination of 50% SC and CA each at storage day 5 with least cooking loss at same storage day. The most preferred sausage colour was obtained with a salt combination of 50% SC and CA each with least colour in a salt combination of 50% SC, 25% PL and). In tenderness, a salt combination of 50% of both SC and CA was significantly tender with least tenderness in 100% PL total replacement. The panelists rated salt combination of 50% SC and CA as the most overall accepted salt combination than others salt combination. Sodium chloride replacement with Calcium Ascorbate at 50% enhanced the most preferred sausage for overall acceptability and aerobic bacteria count lower than the international standard limit.Summary statementHigh intake of sodium chloride had been seen as one of the main contributing factors in the development of specific, non-transmittable diseases, such as, high blood pressure and related secondary such as cardiovascular disease. The use of other derivative of salt is therefore needed. This study evaluates the effects of partial, combined or total replacement of NaCl on microbial load, sensory evaluation and physical properties of beef sausage.
Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson’s disease
Authors: Fava Vinicius M. , Xu Yong Zhong , Lettre Guillaume , Van Thuc Nguyen , Orlova Marianna , Thai Vu Hong , Cambri Geison , Tao Shao , Lahiri Ramanuj , Adams Linda , Cobat Aurélie , Alcaïs Alexandre , Abel Laurent , Schurr Erwin 
Published: January 2019

AbstractType-1 reactions (T1Rs) are pathological inflammatory episodes and main contributors to nerve damage in leprosy. Here, we evaluate the gene-wise enrichment of rare protein altering variants in seven genes where common variants were previously associated with T1R. We selected 474 Vietnamese leprosy-patients of which 237 were T1R-affected and 237 were T1R-free matched controls. Gene-wise enrichment of nonsynonymous variants was tested with both kernel based (SKAT) and burden methods. Of the seven genes tested two showed statistical evidence of association with T1R. For theLRRK2gene an enrichment of nonsynonymous variants was observed in T1R-free controls (pSKAT-O= 1.6×10−4). This gene-wise association was driven almost entirely by the gain of function variant R1628P (p= 0.004; OR = 0.29). The second gene-wise association was found for the Parkin coding genePRKN(formerlyPARK2) where seven rare variants were enriched in T1R-affected cases (pSKAT-O= 7.4×10−5). Mutations in bothPRKNandLRRK2are known causes of Parkinson’s Disease (PD). Hence, we evaluated to what extent such rare amino acid changes observed in T1R are shared with PD. We observed that nonsynonymous T1R-risk mutations in Parkin were enriched for amino acid mutations implicated in PD (p= 1.5×10−4). Hence, neuro-inflammation in PD and peripheral nerve damage due to inflammation in T1R share overlapping mechanisms of pathogenicity.
Effect of Adhesion and Substrate Elasticity on Neutrophil Extracellular Trap Formation
Authors: Erpenbeck Luise , Gruhn Antonia Luise , Kudryasheva Galina , Günay Gökhan , Meyer Daniel , Neubert Elsa , Grandke Julia , Schön Michael P. , Rehfeldt Florian , Kruss Sebastian 
Published: January 2019

AbstractNeutrophils are the most abundant type of white blood cells. Upon stimulation, they are able to decondense and release their chromatin as neutrophil extracellular traps (NETs). This process (NETosis) is part of immune defense mechanisms but also plays an important role in many chronic and inflammatory diseases such as atherosclerosis, rheumatoid arthritis, diabetes and cancer. For this reason, much effort has been invested into understanding biochemical signaling pathways in NETosis. However, the impact of the mechanical micro-environment and adhesion on NETosis is not well understood.Here, we studied how adhesion and especially substrate elasticity affect NETosis. We employed polyacrylamide (PAA) gels with distinctly defined elasticities (Young’s modulus E) within the physiologically relevant range from 1 kPa to 128 kPa and coated the gels with integrin ligands (collagen I, fibrinogen). Neutrophils were cultured on these substrates and stimulated with potent inducers of NETosis: phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS). Interestingly, PMA-induced NETosis was neither affected by substrate elasticity nor by different integrin ligands. In contrast, for LPS stimulation, NETosis rates increased with increasing substrate elasticity (E > 20 kPa). LPS-induced NETosis increased with increasing cell contact area, while PMA-induced NETosis did not require adhesion at all. Furthermore, inhibition of phosphatidylinositide 3 kinase (PI3K), which is involved in adhesion signaling, completely abolished LPS-induced NETosis but only slightly decreased PMA-induced NETosis.In summary, we show that LPS-induced NETosis depends on adhesion and substrate elasticity while PMA-induced NETosis is completely independent of adhesion.
Removal of a subset of non-essential genes fully attenuates a highly virulentMycoplasmastrain
Authors: Jores Joerg , Ma Li , Ssajjakambwe Paul , Schieck Elise , Liljander Anne , Chandran Suchismita , Stoffel Michael , Cippa Valentina , Arfi Yonathan , Asad-Garcia Nacyra , Falquet Laurent , Sirand-Pugnet Pascal , Blanchard Alain , Lartigue Carole , Posthaus Horst , Labroussaa Fabien , Vashee Sanjay 
Published: January 2019

ABSTRACTMycoplasmas are the smallest free-living organisms and cause a number of economically important diseases affecting humans, animals, insects and plants. Here, we demonstrate that highly virulentMycoplasma mycoidessubspeciescapri(Mmc) can be fully attenuatedviatargeted deletion of non-essential genes encoding, among others, potential virulence traits. Five genomic regions, representing approximately ten percent of the originalMmcgenome, were successively deleted usingSaccharomyces cerevisiaeas an engineering platform. Specifically, a total of 68 genes out of the 432 genes verified to be individually nonessential in the JCVI-Syn3.0 minimal cell, were excised from the genome.In vitrocharacterization showed that this mutant was similar to its parental strain in terms of its doubling time, even though ten percent of the genome content were removed. A novelin vivochallenge model in goats revealed that the wild-type parental strain caused marked necrotizing inflammation at the site of inoculation, septicemia and all animals reaching endpoint criteria within seven days after experimental infection. This is in contrast to the mutant strain, which caused no clinical signs nor pathomorphological lesions. These results highlight, for the first time, the rational design, construction and complete attenuation of aMycoplasmastrain via synthetic genomics tools. Trait addition using the yeast-based genome engineering platform and subsequentin vitroorin vivotrials employing theMycoplasmachassis will allow us to dissect the role of individual candidateMycoplasmavirulence factors and lead the way for the development of an attenuated designer vaccine.IMPORTANCEMembers of theMycoplasma mycoidescluster cause important animal plaques in Africa and Asia, which impact animal welfare, provision of food and the life of thousands of small-scale farmers. We applied synthetic biology tools toMycoplasma mycoidesin order to design and create a fully attenuatedMycoplasmastrain that was subsequently confirmedin vivousing a novel caprine infection model. This is the first time that aMycoplasmamutant developed by applying synthetic biology tools has been testedin vivoto pin point candidate virulence traits. The mutant strain is similar to “apathogenicE. coliK12” strains that boosted the research on host-pathogen interactions for the genusEscherichiaand other bacterial genera.
Spatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma
Authors: Carow Berit , Hauling Thomas , Qian Xiaoyan , Kramnik Igor , Nilsson Mats , Rottenberg Martin E 
Published: January 2019

AbstractGranulomas are the pathological hallmark of Tuberculosis (TB), and the niche in which bacilli can either grow and disseminate or the immunological microenvironment in which host cells interact to prevent bacterial dissemination. Here, after in situ sequencing, thirty-four immune transcripts in lung sections fromMycobacterium tuberculosis-infected mice were aligned to the tissue morphology at cellular resolution, allowing the analysis of local immune interactions in the granuloma.Co-localizing transcript networks at <10 μm in C57BL/6 mouse granulomas increased in complexity with time after infection. B-cell clusters developed late after infection. Transcripts from activated macrophages were enriched at subcellular distances fromM. tuberculosis. Encapsulated C3HeB/FeJ granulomas showed necrotic centers with transcripts associated with immunosuppression (foxp3, il10), while those in the granuloma rims associated with activated T cells and macrophages. Highly diverse networks with common interactors were observed in similar lesions.Thus, different immune landscapes ofM. tuberculosisgranulomas depending on the time after infection, the histopathological features of the lesion and the proximity to bacteria were here defined.
Identification of multiple kinetic populations of DNA-binding proteins in live cells
Authors: Ho Han N. , Zalami Daniel , Köhler Jürgen , van Oijen Antoine M. , Ghodke Harshad 
Published: January 2019

ABSTRACTUnderstanding how multi-protein complexes function in cells requires detailed quantitative understanding of their association and dissociation kinetics. Analysis of the heterogeneity of binding lifetimes enables interrogation of the various intermediate states formed during the reaction. Single-molecule fluorescence imaging permits the measurement of reaction kinetics inside living organisms with minimal perturbation. However, poor photo-physical properties of fluorescent probes limit the dynamic range and accuracy of measurements of off rates in live cells. Time-lapse single-molecule fluorescence imaging can partially overcome the limits of photobleaching, however, limitations of this technique remain uncharacterized. Here, we present a structured analysis of which timescales are most accessible using the time-lapse imaging approach and explore uncertainties in determining kinetic sub-populations. We demonstrate the effect of shot noise on the precision of the measurements, as well as the resolution and dynamic range limits that are inherent to the method. Our work provides a convenient implementation to determine theoretical errors from measurements and to support interpretation of experimental data.STATEMENT OF SIGNIFICANCEMeasuring lifetimes of interactions between DNA-binding proteins and their substrates is important for understanding how they function in cells. In principle, time-lapse imaging of fluorescently-tagged proteins using single-molecule methods can be used to identify multiple sub-populations of DNA-binding proteins and determine binding lifetimes lasting for several tens of minutes. Despite this potential, currently available guidelines for the selection of binding models are unreliable, and the practical implementation of this approach is limited. Here, using experimental and simulated data we identify the minimum size of the dataset required to resolve multiple populations reliably and measure binding lifetimes with desired accuracy. This work serves to provide a guide to data collection, and measurement of DNA-binding lifetimes from single-molecule time-lapse imaging data.
SpliceV: Analysis and publication quality printing of linear and circular RNA splicing, expression and regulation
Authors: Ungerleider Nathan , Flemington Erik 
Published: January 2019

AbstractIn eukaryotes, most genes code for multiple transcript isoforms that are generated through the complex and tightly regulated process of RNA splicing. Despite arising from identical precursor transcripts, alternatively spliced RNAs can have dramatically different functions. Transcriptome complexity is elevated further by the production of circular RNAs (circRNAs), another class of mature RNA that results from the splicing of a downstream splice donor to an upstream splice acceptor. While there has been a rapid expansion of circRNA catalogs in the last few years through the utilization of next generation sequencing approaches, our understanding of the mechanisms and regulation of circular RNA biogenesis, the impact that circRNA generation has on parental transcript processing, and the functions carried out by circular RNAs remains limited. Here, we present a visualization and analysis tool, SpliceV, that rapidly plots all relevant forward-and back-splice data, with exon and single nucleotide level coverage information from RNA-seq experiments in a publication quality format. SpliceV also integrates analysis features that assist investigations into splicing regulation and transcript functions through the display of predicted RNA binding protein sites and the configuration of repetitive elements along the primary transcript. SpliceV is compatible with both Python 2.7 and 3+, and is distributed under the GNU Public License. The source code is freely available for download at https://github.com/flemingtonlab/SpliceV and can be installed from PyPI using pip.
Integration of gut microbiome, host biomarkers, and urine metabolome data reveals networks of interactions associated with distinct clinical phenotypes
Authors: Li Rui-Jun , Jie Zhu-Ye , Feng Qiang , Fang Rui-Ling , Li Fei , Gao Yuan , Xia Hui-Hua , Zhong Huan-Zi , Tong Bin , Xu Jia-Yu , Madsen Lise , Liu Chun-Lei , Xu Zhen-Guo , Wang Jian , Yang Huan-Ming , Xu Xun , Hou Yong , Brix Susanne , Kristiansen Karsten , Yu RXin-Lei , Jia Hui-Jue , He Kun-Lun 
Published: January 2019

AbstractBackgroundComprehensive analyses of multi-omics data may provide insights into interactions between different biological layers in relation to distinct clinical features. Here we integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations.ResultsTrans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite features covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. Of specific note in relation to clinical parameters of liver function, we identified Eubacterium eligens, Faecalibacterium prausnitzii and Ruminococcus lactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerella nexills, Ruminococcus gnavus, Blautia hansenii, and Atopobium parvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome.ConclusionsDistinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases.