bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pan-genome guided metabolic network reconstruction of five Propionibacterium species reveals extensive metabolic diversity
Authors: McCubbin Tim , Gonzalez-Garcia R. Axayacatl , Palfreyman Robin W. , Stowers Chris , Nielsen Lars K. , Marcellin Esteban 
Published: March 2020

Abstract
Background: Propionibacteria have been studied extensively since the early 1930’s due to their relevance to industry and importance as human pathogens. Still, their unique metabolism is far from fully understood. This is partly due to their signature high GC content which has hampered the acquisition of quality sequence data, the accurate annotation of the few available genomes and the functional characterization of genes. The recent completion of the genome sequences for several species enable a comparative genomic approach to annotation and provides a new opportunity to revisit our understanding of their metabolism. Results: Using pan-genome analysis combined with the reconstruction of the first high-quality Propionibacterium genome-scale metabolic model and a pan-Propionibacterium metabolic model we demonstrate that Propionibacterium have an unexpected diversity in central carbon metabolism and a hidden layer of metabolic complexity. This combined approach gave us new insights into the evolution of Propionibacterium metabolism and led us to propose a novel, putative ferredoxin-linked energy conservation strategy. The pan-genomic approach highlighted key differences in Propionibacterium metabolism that reflect adaptation to their environment. Results were mathematically captured in genome-scale metabolic reconstructions which can be used to further explore metabolism using metabolic modelling techniques. Conclusions: Overall, the data provides a platform to explore Propionibacterium metabolism and provides a tool for the rational design of strains.
Measuring Early Childhood Development with the Early Human Capability Index (eHCI): A Reliability and Validity Study in China
Authors: Zhao Jin , Brinkman Sally Anne , Song Yingquan , Lu Chunling , Young Mary Eming , Zhang Yue , IP Patrick , Shan Wenjie , Zhang Yunting , Fan Jiang 
Published: March 2020

Abstract
Background: With the importance of early childhood development more recognized by the international society, low-cost and cross-culturally comparable measures of early childhood development is in great demand, both in China and worldwide. In this study, we aim to test the psychometrics of the Chinese version of The Early Human Capability Index (eHCI), which is designed as a measurement for school readiness in large population. Methods: We evaluated the internal consistency, test-retest reliability, inter-rater reliability, factor structure, criterion-related validity, and discriminant validity of the eHCI in 20,324 preschool children in Shanghai. We also compared eHCI scores with test result of ASQ in 815 children in Yexian and EAP-ECDS in 6,947 children in Daming. Results: The ICC between parents and teachers were 0.83 and 0.63 for Literacy Numeracy and Overall Development. The confirmatory factor analyses showed good model fit (2 = 509323, p<0.001; CFI=0.901; RMSEA=0.038). The correlations between the scores of eHCI and other ECD metrics ranged between r =-0.42 and r =0.53. The scale discriminated between children’s developmental level based on gender, parental education, family income and family assets.Conclusions: Results from Chinese population suggested that eHCI is valid and reliable for measuring early childhood development in children aged 3-6 years. The eHCI can be applied to map the global distribution of early childhood development for allocating scarce resources to help those in greatest demand. Longitudinal studies are warranted to test its predictive validity for later outcomes.
The role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in Hirschsprung associated enterocolitis
Authors: Chen Feng , Wei Xiaoyu , Chen Xiaohua , Xiang Lei , Meng Xinyao , Feng Jiexiong 
Published: March 2020

Abstract
Background To investigate the role and the underlying mechanism of the α7nAChR-mediated cholinergic anti-inflammatory pathway in the pathogenesis of Hirschsprung(HSCR) associated enterocolitis（HAEC）. Methods Experimental group:twenty-one-day-old Ednrb-/- mice were selected (n=10), with comparable-age wild type(Ednrb+/+) mice controls (n=10). Intestinal samples were collected. The experimental colons were divided into narrow and dilated segments according to morphology changes. The control colons were divided into distal and proximal segments.Colon HE staining was used to judge HAEC.Acetylcholine levels in colon was measured using enzyme-linked immunosorbent assays. Detected phosphorylated Jak2 (p-Jak2), Jak2, phosphorylated Stat3 (p-Stat3), Stat3, phosphorylated IκBα (p-IκBα) and IκBα were studied by Western blotting; mRNA levels of Jak2, Stat3, and IκBα were detected by RT-qPCR. Results Colon HE staining indicated that HAEC mainly occured in the dilated segments of HSCR mice (Ednrb-/- mice) (EDNRB-P).Acetylcholine content in EDNRB-P was significantly lower than that in the narrow segments (EDNRB-D) (P<0.05). Western blotting showed that the Jak2, p-Jak2, Stat3 and p-Stat3 levels in EDNRB-D were significantly higher than those in EDNRB-P (P<0.05). The p-IκBα and IκBα levels in EDNRB-P were significantly higher than those in EDNRB-D(P<0.05). The mRNA levels of Jak2 and Stat3 in EDNRB-D were higher than those in EDNRB-P, but the IκBα mRNA level was significantly lower than that in EDNRB-P (P<0.05). Conclusions During HAEC, the inflammation in the dilated segment was more severe ,while in the narrow segment there was no obvious inflammatory reaction and the content of acetylcholine was higher, which was associated with the α7nAChR-mediated cholinergic anti-inflammatory pathway.
Proximal and distal predictors of self-regulatory growth in children aged 4 to 7 years
Authors: Williams Kate E. , Howard Steven J. 
Published: March 2020

Abstract
Background Growth in early self-regulation skills has been linked to positive health, wellbeing, and achievement trajectories across the lifespan. While individual studies have documented specific influences on self-regulation competencies in early childhood, few have modelled a comprehensive range of predictors of self-regulation growth across health, development, and environment simultaneously. This study aimed to examine the concurrent associations among a range of proximal and distal influences on growth in children’s self-regulation skills over 2 years from age 4-5 years.Methods Data from the Longitudinal Study of Australian Children (N= 4983) were used in a structural equation model, predicting a multi-source composite measure of self-regulation at each of 4-5 years and 6-7 years. By controlling for earlier self-regulation and covariates, the model examined the relative contributions of a comprehensive range of variables to self-regulation growth including health, development, educational, home environment, time-use, and neighbourhood characteristics. Results The significant predictors of children’s self-regulation growth across 4 to 7 years were fewer behavioural sleep problems, higher gross motor and pre-academic skills, lower levels of maternal and paternal angry parenting, and lower levels of financial hardship. There were also marginal effects for high-quality home learning environments and child-educator relationships.Conclusion Findings suggest that if we are to successfully grow children’s self-regulation skills, interventionists would do well to operate not only on children’s current capacities but also key aspects of their surrounding context.
Genome-wide identification and characterization of SnRK family genes in Brassica napus
Authors: Zhu Weizhuo , Wu Dezhi , Jiang Lixi , Ye Lingzhen 
Published: March 2020

Abstract
Background: Sucrose non-fermenting 1 related protein kinases (SnRK) play crucial roles in responding to biotic and abiotic stresses through activating protein phosphorylation pathways. However, little information of SnRK genes was available in Brassica napus, one of important oil crops. Recently, the released sequences of the reference genome of B.napus provide a good chance to perform genome-wide identification and characterization of BnSnRK gene family in the rapeseed.Results: Totally 114 SnRK genes distributed on 19 chromosomes were identified in the genome of B.napus and classified into three subfamilies on the basis of phylogenetic analysis and the domain types. According to gene structure and motif composition analysis, the BnSnRK sequences showed obvious divergence among three subfamilies. Gene duplication and synteny between the genomes of the rapeseed and Arabidopsis were also analyzed to provide insights into the evolutionary characteristics of BnSnRK family genes. Cis-element analysis revealed that BnSnRKs may response to diverse environmental stresses. Moreover, the expression patterns of BnSnRKs in various tissues and under diverse abiotic stresses were distinct difference. Besides, Single Nucleotide Polymorphisms (SNP) distribution analysis suggests the function disparity of BnSnRK family genes in different genotypes of the rapeseed.Conclusion: We examined genomic structures, evolution features, expression patterns and SNP distribution of 114 BnSnRKs. The results provide valuable information for functional characterization of BnSnRK genes in future studies.
In Vitro Hypoxia Responsiveness Of Fdg And Faza Retention: Influence Of Shaking Versus Stagnant Conditions, Glass Versus Polystyrene Substrata And Cell Number Down-Scaling
Authors: Busk Morten , Horsman Michael R , Overgaard Jens , Jakobsen Steen 
Published: March 2020

Abstract
Background. In vitro experiments using radiolabeled molecules is fundamental for Positron emission tomography (PET) or single photon emission computed tomography (SPECT) tracer development and various metabolic assays, but no consensus on appropriate incubation conditions exists. Specifically, the use of shaking versus non-shaking conditions, cell number to medium volume and the choice of cell plating material may unintentionally influence cellular oxygenation and medium composition. This is problematic when testing the oxygen-dependence of tracers including 18F-fluoro-2-deoxyglucose (FDG) and hypoxia-selective 2-nitroimidazoles (e.g., 18F-fluoroazomycin-arabinoside, FAZA) or when doing prolonged experiments. The purpose of this study was to assess the influence of various experimental conditions on tracer retention. Methods. Tumor cells were seeded in a) Glass or standard Polystyrene Petri dishes or as b) discrete droplets in polystyrene Petri dishes or on 9 mm glass coverslips positioned in glass Petri dishes. When confluent, cells were pre-equilibrated for 2h to 21%, 0.5% or 0% O2 and FDG or FAZA was added, followed by cell harvest and analysis of radioactivity 1h (FDG) or 3h (FAZA) after. Experiments were conducted with/without orbital shaking. Results. The influence of hypoxia on tracer retention varied widely among cell lines, but shaking-induced convection did not influence uptake. In contrast, hypoxia-driven FAZA, and to some extent FDG, retention was much lower in cells grown on polyethylene than glass. Scaling-down the number of cells did not compromise accuracy. Conclusions. Most experiments can be performed appropriately in the absence of shaking and with downscaling of cell number but the use of conventional plasticware is highly problematic for studies on tracers and drugs that are metabolized and retained or activated at low O2 levels.
Genome-wide identification of candidate genes associated with β-glucan trait in a hulled and hulless barley (Hordeum vulgare L.) population
Authors: Zhou Longhua , He Ting , Guo Guimei , Li Jing , Lu Ruiju , Huang Jianhua , Li Yingbo , Liu Chenghong 
Published: March 2020

Abstract
Background: To date, excavating the genomic sites based on the whole barley assembled genome sequences associated with β-glucan trait remains blank, resulting in omission of several genetic loci or existence of false positive. Results: Here, of 87 barley resources (39 hulled and 48 hulless) collected from China, the β-glucan content ranged from 2.07% to 6.56%. GWAS (genome-wide association study) was carried out using 191,098 SNP markers by RRGS (Reduced-Representation Genome Sequencing) platform in FarmCPU model excuted in rMVP R package. Four subpopulations (POP1～POP4) were identified. GWAS showed one SNP, in chromosome 7 (chr7), negatively mapped and for two genes HORVU7Hr1G000320, HORVU7Hr1G000040, which are from nucleotide triphosphates hydrolases superfamily; previous study had proved the superfamily could inhibit β-glucan synthase activities. GWAS also showed that five SNPs for β-glucan trait were separately mapped in chr2, chr3, chr4, chr5 and chr6 non-coding regions and one SNP mapped for HORVU1Hr1G000010 in chr1, which is for plant sugar response. Conclusions: Through the highest density of SNP markers to date, this study identifys several SNP genetic loci with high degree of confidence for β-glucan trait, and has a certain value for β-glucan regulatory mechanism research in furture.
Dissection of the genetic basis of oil content in Chinese peanut cultivars by association mapping
Authors: Liu Nian , Huang Li , Chen Weigang , Wu Bei , Pandey Manish K. , Luo Huaiyong , Zhou Xiaojing , Guo Jianbin , Chen Haiwen , Huai Dongxin , Chen Yuning , Lei Yong , Liao Boshou , Ren Xiaoping , Varshney Rajeev K. , Jiang Huifang 
Published: March 2020

Abstract
Background Peanut is one of the primary sources for vegetable oil worldwide, and enhancing oil content is the main objective in these peanut breeding programs. Linked markers for oil content is required for use in genomics-assisted breeding (GAB), and association mapping is one of the promising approaches for discovery of associated markers. Results An association mapping panel consisting of 292 peanut varieties extensively distributed in China were phenotyped for oil content and genotyped with 583 polymorphic SSR markers. These markers amplified 3663 alleles with an average of 6.28 alleles per locus. The results of structure, phylogenetic relationship, and PCA analyses indicated two subgroups majorly differentiating based on geographic regions. Genome-wide association analysis using genetic and phenotypic data identified 12 associated markers including one (AGGS1014_2) highly stable association controlling up to 9.94% phenotypic variance explained (PVE) across multiple environments. Interestingly, the frequency of the favorable alleles for 12 associated markers showed a geographic difference. Two associated markers AGGS1014_2 and AHGS0798 with 6.90-9.94% PVE were verified to enhance oil content in an independent RIL population. The combined genotypes of AGGS1014_2 and AHGS0798 appeared to experience selection during the breeding program. Conclusion This study provided insights into the genetic basis of oil content in peanut and verified that two SSR markers were highly associated with oil content. Our results could facilitate marker-assisted selection for high-oil content breeding.
Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody.
Authors: Matsuoka Hiroshi , Hayashi Takahiro , Takigami Karen , Imaizumi Kazuyoshi , Shiroki Ryoichi , Ohmiya Naoki , Sugiura Kazumitsu , Kawada Kenji , Sawaki Akira , Maeda Koutaro , Ando Yousuke , Uyama Ichiro 
Published: March 2020

Abstract
Background Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) are used for the treatment of various cancer types. However, immune-related adverse events (irAEs) occur in patients treated with ICIs. Several small-scale studies have reported the onset of irAEs and therapeutic effects of ICIs. Here we report a large-scale retrospective study covering a wide range of cancers. We evaluated irAEs and the therapeutic effects of ICIs and determined whether irAEs could be predicted. Methods This study included patients treated with the anti-PD-1 antibodies nivolumab or pembrolizumab at Fujita Health University Hospital between December 2015 and March 2019. We retrospectively reviewed the electronic medical records for age, cancer type, pre-treatment blood test data, presence or absence of irAE onset, type and severity of irAEs, outcome of irAE treatment, response rate, progression-free survival and overall survival. Results The subjects were 280 patients including. The overall incidence of irAEs was 41.1% (115 patients), and the incidence of severe irAEs of grade 3 and higher was 2.8% (eight patients). The most common irAEs were skin disorders, thyroid disorders and interstitial pneumonia. Patients with irAEs were significantly older than those without irAEs (69.7 versus 66.0 years, P=0.02). The objective response rate (ORR) in patients with irAEs was 30.4%, which was significantly higher than in patients without irAEs (12.7%; P<0.01). Both the median overall and progression-free survival were significantly longer in patients with irAEs. Based on the blood test data obtained before ICI therapy, hypothyroidism, thyroid-stimulating hormone levels and thyroglobulin antibody levels were associated with the onset of irAEs. In many patients with irAEs of Common Terminology Criteria for Adverse Events Grade 3 or higher, re-administration of ICIs was difficult, and their outcomes were poor. In contrast, many patients with irAEs of a lower grade were able to resume ICI therapy. Conclusion Although the onset of irAEs was difficult to predict based on pre-treatment tests. Because ICIs were more effective in improving outcomes in patients with irAEs, the continuation of ICI therapy might be beneficial with the control of symptoms after the onset of irAEs.
Exercise training improves the adipocyte accumulation and muscle fibrosis of the muscle by TGF-β1 and α-SMA reduction after botulinum toxin type A administration in mice
Authors: Lee Esther , Im Song I , Kim Yu-jin , Kim Su Young , Na Jungtae , Kim Beom Joon 
Published: March 2020

Abstract
Background: We aimed to investigate the effect of treadmill exercise on functional recovery of the mouse gastrocnemius muscle and nerve after botulinum toxin type A (BoNT-A) administration. Methods: After injecting 0.5 units of BoNT-A into the gastrocnemius muscle of ICR mice, treadmill exercise was carried out for a six-week period, after which the muscle volume, weight, and sciatic functional index (SFI) were obtained and nerve conduction study (NCS) and histological evaluation were performed. Results: There was no change in the gastrocnemius weight and volume, but NCS and SFI increased after exercise. Exercise prevented induced adipocyte accumulation and muscle fibrosis. Moreover, TGF-β1 and α-SMA expression decreased and CD34, BDNF, and SNAP-25 expression increased when treadmill exercise was performed after BoNT-A injection. Conclusions: The exercise was effective in the recovery of nerve function and would help in the recovery of muscle function by preventing accumulation of fat cells and muscle fibrosis after BoNT-A administration.
Genome-wide Identification of ATP Binding Cassette (ABC) Transporter and Heavy Metal Associated (HMA) Gene Families in Flax (Linum usitatissimum L.)
Authors: Khan Nadeem , You Frank , Datla Raju , Ravichandhran Sridhar , Jia Bosen , Cloutier Sylvie 
Published: March 2020

Abstract
Background Flax (Linum usitatissimum L.) is a self-pollinated crop and diversified into two morphotypes for its stem fibre and seed oil. The availability of the flax reference genome sequence, previously assembled into 15 pseudomolecules, enables the characterization of important gene families. The ABC transporter and HMA gene families are considered important gene families in the control of cadmium (Cd) accumulation in crops. To date, the genome-wide analysis of these two gene families has been successfully conducted in several plant species but no systematic study is available for the flax genome. Results Here we described both gene families in flax to provide a comprehensive overview of its evolution and some support towards the functional annotation of its members. The 198 ABC transporter and 12 HMA genes identified in the flax genome were classified into eight ABC transporter and four HMA subfamilies based on their phylogenetic analysis and domain compositions. Nine of these genes, i.e., LuABCC9, LuABCC10, LuABCG58, LuABCG59, LuABCG71, LuABCG72, LuABCG73, LuHMA3, and LuHMA4, were orthologous with the Cd associated genes in Arabidopsis, rice and maize. Ten motifs were identified from all ABC transporter and HMA genes and several motifs were conserved for all genes with similar gene length, but different subfamilies had their different motif structures. Both the ABC transporter and HMA families were highly conserved among subfamilies of flax and with Arabidopsis. While four types of gene duplication were observed at different frequencies, whole-genome or segmental duplications were the most frequent with 162 genes, followed by 29 dispersed, 14 tandem and 4 proximal, suggesting that segmental duplications contributed substantially to the expansion of both gene families in flax. The rates of non-synonymous to synonymous (Ka/Ks) mutations of paired duplicated genes were mostly less than one, indicative of a predominant purifying selection. Only five pairs of genes clearly exhibited positive selection with a Ka/Ks ratio greater than one. Gene ontology analyses suggested that most flax ABC transporter and HMA genes functioned in ATP binding, transporter, catalytic, ATPase activity, and metal ion binding. The RNA-Seq analysis of eight different organs demonstrated diverse expression profiling patterns of the genes and revealed their functional or subfunctional conservation and neo-functionalization. Conclusion Characterization of the ABC transporter and HMA genes will help in the functional analysis of candidate genes in flax and other crop species.
Elevated levels of miR-483-5p in oocytes aggravates premature ovarian insufficiency induced by CDDP by targeting the FKBP4
Authors: zhao huihui , Gu Wenqing , Ouyang Huogui , Pan Wenbin , Zhang Hanbin , Shuai Ling , Diao Ruiying , Wang Liping 
Published: March 2020

Abstract
Background Premature ovarian insufficiency (POI) is characterized by a loss of ovarian function before 40 years-of-age and represents a major cause of female infertility. POI is one of the dominant causes of cis-diaminedichloroplatinum (cisplatin, CDDP)-induced reproductive impairment. However, the detailed mechanisms underlying POI induced by CDDP remain unclear. Methods The POI C57B6/J mouse model was created by administering CDDP. The effects of FKBP4 were investigated using isobaric tags for relative and absolute quantification analysis (iTRAQ), real-time quantitative PCR (qRT-PCR) and western blotting. Target prediction was predicted using TargetScan software. Levels of sex hormones were tested using Enzyme-linked immunosorbent assays (ELISA). Results We found that the FKBP4 protein was down-regulated in the ovaries of CDDP model. Target prediction identified FKBP4 as a potential target for miR-483-5p , which was expressed at high levels in both the ovaries and serum of CDDP-POI mice, and in the serum from POI patients. In vitro experiments further confirmed that FKBP4 was the target for miR-483-5p in human cervical cancer cells (HeLa). The overexpression of FKBP4 in human granulosa cells (KGN) alleviated the apoptosis caused by CDDP and the overexpression of miR-483-5p . Furthermore, the overexpression of miR-483-5p in oocytes caused injury to the ovaries, and disrupted the levels of sex hormones in CDDP-POI mice (AMH: P <0.01; E 2 : P <0.01; FSH: P <0.01). Conclusions Analyses showed that miR-483-5p targets the FKBP4 protein in a mouse model of POI induced by CDDP. Elevated levels of miR-483-5p in oocytes aggravated POI induced by CDDP by targeting FKBP4. Overall, our data demonstrate that miR-483-5p was responsible for the underlying pathophysiology of POI induced by chemotherapeutic treatments, such as CDDP.