bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Variations at Three Different Positions of Prion Protein Coding Gene in Ethiopian Sheep Breeds and the Resistance/Susceptible Status to Classical and Atypical Scrapie
Authors: Teferedegn Eden Yitna , Yaman Yalcin , Un Cemal 
Published: December 2019

Abstract
Background: Classical Scrapie susceptibility in sheep has been linked to three polymorphisms at positions 136, 154, and 171 in the PRNP gene whereas atypical scrapie susceptibility is related to a polymorphism at position 141. Many other variants over the length of the prion protein coding gene were reported. Since infectious prion protein itself seems to be polymorphic, the identified novel PRNP gene variations may play a crucial role in fighting against the emergence of a new form of scrapie disease. Many studies conducted around the world to identify disease resistant status and new variants of PRNP gene in different breeds. However, such in-depth studies have never addressed the African continent’s sheep breeds. Therefore, genotyping native Ethiopian sheep breeds PRNP gene provides essential information to the current knowledge. This study aimed to identify potential novel variations in the Ethiopian sheep PRNP gene, thereby determine the uniqueness of the native breeds and predict scrapie status of sheep population based on the genotypes distribution. Results : Five novel variants were identified in the PRNP gene of native Ethiopian sheep. Four non-synonymous heterozygous substitutions at H99Q (CAC-->CAA), H99L (CAC-->CTA), A116E (GCA-->GAA), A116T (GCA-->ACA), and one synonymous N103N (AAC-->AAT) variants were detected. In addition to the novel variations, polymorphisms at 126,127,138,142,146,231, and 237 positions were also identified. The haplotype ARR was observed only in Menz and Afar breeds with frequencies 0.02 and 0.05 respectively. However, neither ARR/ARR nor VRQ/VRQ genotypes were identified in all of the breeds. Conclusion: Two of the novel variations at position 99 and 103 that are placed closer to the cleavage site and variant at 116 spotted in the palindrome region along with variants at position 127 in Glycine repeat domain may influence the conformational flexibility of prion protein. The low frequency of ARR haplotype and the sole variant 141L demonstrated that Ethiopian sheep are susceptible to classical scrapie and resistant to atypical scrapie. This study provides a valuable dataset that can be potentially integrated into selective breeding strategies against scrapie during inbreeding, crossbreeding and help to take precautious measures.
Prognostic value of an immune long non-coding RNA signature in liver hepatocellular carcinoma
Authors: kong rui , Wang Nan , Han Wei , Zheng Yuejuan , Lu Jie 
Published: December 2019

Abstract

Background: In recent years, long non-coding RNAs (lncRNAs) are emerging as crucial regulators in the immunological process of liver hepatocellular carcinoma (LIHC). Increasing studies have found that some lncRNAs could be used as a diagnostic or therapeutic target for clinical management, but little research has investigated the role of immune-related lncRNA in tumor prognosis. In this study, we aimed to develop an immune lncRNA signature for the precise diagnosis and prognosis of liver hepatocellular carcinoma. Methods: Gene expression profiles of LIHC samples obtained from TCGA were screened for immune-related genes using two reference gene sets. The optimal immune-related lncRNA signature was built via correlational analysis, univariate and multivariate cox analysis. Then the Kaplan-Meier plot, ROC curve, clinical analysis, gene set enrichment analysis, and principal component analysis were carried out to evaluate the capability of immune lncRNA signature as a prognostic indicator. Results: Six long non-coding RNA MSC−AS1, AC009005.1, AL117336.3, AL031985.3, AL365203.2, AC099850.3 were identified via correlation analysis and cox regression analysis considering their interactions with immune genes. Next, tumor samples were separated into two risk groups by the signature with different clinical outcomes. Stratification analysis showed the prognostic ability of this signature acted as an independent factor. The AUC value of ROC curve was 0.779. The Kaplan-Meier method was used in survival analysis and results showed a statistical difference between the two risk groups. The predictive performance of this signature was validated by principal component analysis (PCA). Data from gene set enrichment analysis (GSEA) further unveiled several potential biological processes of these biomarkers may involve in. Conclusion: In summary, the study demonstrated the potential role of the six-lncRNA signature served as an independent prognostic factor for LIHC patients.
Fusion transcript detection using spatial transcriptomics
Authors: Friedrich Stefanie , Sonnhammer Erik LL 
Published: December 2019

Abstract
Background: Fusion transcripts are involved in tumourigenesis and play a crucial role in tumour heterogeneity, tumour evolution and cancer treatment resistance. However, fusion transcripts have not been studied at high spatial resolution in tissue sections due to the lack of full-length transcripts with spatial information. New high-throughput technologies like spatial transcriptomics measure the transcriptome of tissue sections on almost single-cell level. While this technique does not allow for direct detection of fusion transcripts, we show that they can be inferred using the relative poly(A) tail abundance of the involved parental genes. Method: We present a new method STfusion, which uses spatial transcriptomics to infer the presence and absence of poly(A) tails. A fusion transcript lacks a poly(A) tail for the 5´ gene and has an elevated number of poly(A) tails for the 3´ gene. Its expression level is defined by the upstream promoter of the 5´ gene. STfusion measures the difference between the observed and expected number of poly(A) tails with a novel C-score. Results: We verified the STfusion ability to predict fusion transcripts on HeLa cells with known fusions. STfusion and C-sore applied to clinical prostate cancer data revealed the spatial distribution of the cis-SAGe SLC45A3-ELK4 in 12 tissue sections with almost single-cell resolution. The cis-SAGe occured in the centre or periphery of inflamed, prostatic intraepithelial neoplastic, or cancerous areas, and occasionally in normal glands. Conclusions: STfusion detects fusion transcripts in cancer cell lines and clinical data, and distinguishes chimeric transcripts from chimeras caused by trans-splicing events. With STfusion and the use of C-scores, fusion transcripts can be localised in clinical tissue sections on almost single cell level.
Metformin and endometrial cancer risk: A Meta-analysis
Authors: Xie Weimin , Wen Dan 
Published: December 2019

Abstract
Objective: To assess the association between metformin and endometrial cancer risk by conducting a meta-analysis.Methods: A comprehensive search of electronic databases, conference abstracts, and clinical trial registers was performed to identify available evidence. Studies that evaluated the association between metformin use and endometrial cancer risk were considered. We pooled relative risk (RR) estimates with 95% confidence intervals (CIs) by using either a fixed-effects or a random-effects model.Results: Nine studies (1 randomized controlled trial, 5 cohort studies, and 3 case-control studies) involving more than 1.20 million participants and 7,762 cases of endometrial cancer met eligibility criteria. There was no evidence of an association between metformin use and endometrial cancer risk (RR, 0.96; 95% CI, 0.80 to 1.16). Similarly, the pooled data showed that metformin use was not significantly associated with endometrial cancer risk in patients with diabetes (RR, 0.93; 95% CI, 0.78 to 1.11). In subgroup analyses, the results were stable across different study designs and comparisons, and remained unchanged after adjusting for age and BMI or obesity.Conclusions: The current meta-analysis suggests that metformin has no chemopreventive effect against endometrial cancer.
The Promise of Whole-Exome Sequencing in Detecting Novel Variants of the MYO15A Gene in Two Iranian Pedigrees with Non-Syndromic Hearing Loss, A descriptive experimental study
Authors: khatami somayeh , Askari Masomeh , Bahreini Fatemeh , Chaleshtori Morteza Hashemzadeh , Asgharzadeh Samira 
Published: December 2019

Abstract
Background: Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods.Methods: This study was a report on two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families.Results: The implementation of WES to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) and its related variants was reported in the present study. Two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 were correspondingly identified and then segregations were confirmed using Sanger sequencing. According to online prediction tools, both identified variants seemed to have damaging effects.Conclusion: This study further supported the effectiveness of WES for genetic diagnosis of ARNSHL as a first approach.
Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival
Authors: Wang Danyang , Liu Qingmin , Ren Yanjun , Zhang Yan , Wang Xin , LIU BING 
Published: December 2019

Abstract
Background MicroRNAs have important roles in tumorigenesis. There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS has been described in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA-miRNA binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC.Methods We conducted a case-control study of 507 CRC cases recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′ untranslated region (3′ UTR) with CRC susceptibility and survival. Deaths and causes of death among the CRC cases were identified using the Hangzhou Cancer Registration System and Death Surveillance System. Genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′ UTR of KRAS were selected using the Haploview and HaploReg software. Results Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared with adjacent normal mucosa. The Rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with CRC susceptibility (adjusted odds ratio 2.414, 95% CI: 1.385–4.206). Among non-smokers, the miR-143 rs41291957 GA genotype and miR-145 rs74693964 CT genotype were borderline significantly associated with an increased risk of rectal cancer. However, there was no interaction effect between selected SNPs and smoking status. Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). CRC cases carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio 4.328, 95% CI: 1.236–15.147). Conclusions Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for CRC susceptibility and survival.
Precise annotation of tick mitochondrial genomes reveals multiple copy number variation of short tandem repeats and one transposon-like element
Authors: Chen Ze , Xu Xiaofeng , Yang Xiaolong , Yu Zhijun , Barker Stephen C. , Kelava Samuel , Chen Defu , Bu Wenjun , Liu Jingze , Gao Shan 
Published: December 2019

Abstract
Background: Annotation of mitochondrial (mt) genomes is indispensable for fundamental research in many fields, including mt biochemistry, physiology, and the molecular phylogenetics and evolution of animals. Moreover, high-resolution annotation of animal mt genomes can be used to investigate RNA processing, maturation, degradation, and even the regulation of gene expression. In this study, we used long-PCR amplification combined with Next-Generation Sequencing (NGS) to obtain complete mt genomes of individual ticks and performed precise annotation of these mt genomes. We aimed to: (1) develop a simple, cost-effective and accurate method for the study of extremely high AT-content mt genomes within an individual animal containing miniscule DNA; (2) provide a high-quality reference genome for D. silvarum with precise annotation and also for future studies of other tick mt genomes; and (3) use these mt genomes containing two Control Regions (CRs) to confirm our previous findings from those containing one CR. Results: Based on these mt genome annotations, most of our findings were consistent with those from previous studies. Moreover, two new and important findings were reported for the first time, contributing fundamental knowledge to mt biology. The first was the discovery of a transposon-like element that may eventually reveal much about mechanisms of gene rearrangements in mt genomes. Another finding was that Copy Number Variation (CNV) of Short Tandem Repeats (STRs) account for mitochondrial sequence diversity (heterogeneity) within an individual tick, insect, mouse or human. All the detected DNA variations within a single human cell were CNV of STRs, whereas SNPs were not detected. The CNV of STRs in the protein-coding genes resulted in frameshift mutations in the proteins, which can cause deleterious effects. Mitochondria containing these deleterious STR mutations accumulate in cells and could produce deleterious proteins. Conclusions: We proposed that the accumulation of CNV of STRs in mitochondria causes aging or diseases. Our study will lead to the reconsideration of the importance of STRs and a unified study of CNV of STRs with longer and shorter repeat units (particularly polynucleotides) in both nuclear and mt genomes.
Genome-wide association study (GWAS) reveals genetic loci of lead (Pb) tolerance during seedling establishment in rapeseed (Brassica napus L.)
Authors: Zhang Fugui , Xiao Xin , Xu Kun , Cheng Xi , Xie Ting , Hu Jihong , Wu Xiaoming 
Published: December 2019

Abstract
Background Lead (Pb) pollution in soil has become one of the major environmental threats to plant growth and human health. Safe utilization of Pb contaminated soil by phytoremediation require Pb tolerant rapeseed ( Brassica napus L.) accessions. However, breeding of new B. napus cultivars tolerance to Pb stress has been restricted by limited knowledge on molecular mechanisms involved in Pb tolerance. This work was carried out to identify genetic loci related to Pb tolerance during seedling establishment in rapeseed.Results Pb tolerance, which was assessed by quantifying radicle length (RL) under 0 or 100 mg/L Pb stress condition, shown an extensive variation in 472 worldwide-collected rapeseed accessions. Based on the criterion of relative RL>80%, six Pb tolerant genotypes were selected. Four quantitative trait loci (QTL) associated with Pb tolerance were identified by Genome-wide association study. The expression level of nine promising candidate genes, including GSTUs , BCATs , UBP13 , TBR and HIPP01 , located in these four QTL regions, were significantly higher or induced by Pb in Pb tolerant accessions in comparison to Pb sensitive accessions.Conclusion To our knowledge, this is the first study on Pb tolerant germplasms and genomic loci in B. napus . The findings can provide valuable genetic resources for the breeding of Pb tolerant B. napus cultivar and understanding of Pb tolerance mechanism in Brassica species.
Evaluation of antioxidant and antimicrobial activities of chloroformic and methanolic extracts of 6 important medicinal plants collected from Northern of Iran
Authors: Ghahari Somayeh , Hadadi Zahra , Nematzadeh Ghorban Ali 
Published: December 2019

Abstract
Background: The plant essential oils and extracts are possible sources of natural bioactive molecules and have been selected globally for new antimicrobial compounds, food preservatives, and alternatives to treat infectious disease.Methods: In this research, antimicrobial activities of chloroformic and methanolic extracts of Sophora flavescens, Rhaponticum repens, Alhagi maurorum, Melia azedarach, Peganum harmala, and Juncus conglomeratus were evaluated against 8 bacteria (S. aureus, B. subtilis, R. toxicus, P. aeruginosa, E. coli, P. syringae, X. campestris, P. viridiflava) and 3 fungi (Pyricularia oryzae, Fusarium oxysporum and Botrytis cinerea) through disc diffusion method. Furthermore, the essential oil of plants with the highest antibacterial activity was analyzed utilizing GC/MS. Moreover, tested plants were exposed to screening for possible antioxidant effect utilizing DPPH test, guaiacol peroxidas, and catalase enzymes. Besides, the amount of total phenol and flavonoid of these plants was measured. Results: Among tested plants, methanolic and chloroformic extracts of P. harmala fruits showed the highest antibacterial activity against tested bacteria. Also, the investigation of free radical scavenging effects of the tested plants indicated the highest DPPH, protein, guaiacol peroxidase, and catalase in P. harmala, M. azedarach, J. conglomeratus fruits, and J. conglomeratus fruits, respectively. In addition, the phytochemical analysis demonstrated the greatest amounts of total phenolic, and flavonoid compositions in J. conglomeratus and P. harmala. Conclusion: The results indicated that these plants can act as a promising antimicrobial agent due to its short killing time.
Safety assessment of cerium oxide nanoparticles: Combined repeated-dose toxicity with reproductive/developmental toxicity screening and biodistribution in rats
Authors: Lee Jinsoo , Jeong Ji-Seong , Kim Sang Yun , Lee Seung-Jin , Shin Young-Jun , Im Wan-Jung , Kim Sung-Hwan , Park Kwangsik , Jeong Eun Ju , Nam Sang-Yoon , Yu Wook-Joon 
Published: December 2019

Abstract
Background Cerium oxide nanoparticles (CeO 2 NPs) are widely used in various commercial applications because of their characteristic properties. CeO 2 NPs can be easily exposed to humans in real life, but the safety assessment of CeO 2 NPs has not been fully investigated. Therefore, in this study, we conducted a combined repeated-dose and reproductive/developmental toxicity screening study to investigate the potential effects on general health hazards, including reproductive/developmental functions, after repeated CeO 2 NPs oral exposure. In addition, tissues from parental animals and their pups were collected to analyze the internal accumulation of cerium. CeO 2 NPs were orally administered to Sprague-Dawley rats at doses of 0, 100, 300 and 1000 mg/kg during their pre-mating, mating, gestation and early lactation periods. Results In the general systemic and reproductive/developmental examinations, no marked toxicities were observed in any of in-life and terminal observation parameters in this study. In the biodistribution analysis, cerium was not detected in either parental or pup tissues (blood, liver, lungs and kidneys). Conclusion Repeated oral exposure of CeO 2 NPs did not induce marked toxicities affecting general systemic and reproductive/developmental functions up to the dose level of 1000 mg/kg and the CeO 2 NPs were not systemically absorbed in parental animals or their pups. This result could be used to risk assessment for human, and additional toxicity studies with CeO 2 NPs will be necessary considering various physicochemical properties and exposure probabilities of this nanoparticles.
An accelerometer-based navigation system provides acetabular cup orientation accuracy comparable to that of computed tomography-based navigation during total hip arthroplasty in the supine position
Authors: Tetsunaga Tomonori , Yamada Kazuki , Tetsunaga Tomoko , Sanki Tomoaki , Kawamura Yoshi , Ozaki Toshifumi 
Published: December 2019

Abstract
Background: Inadequate acetabular component orientation is associated with postoperative impingement, dislocation, and accelerated polyethylene wear. Computed tomography (CT)-based navigation systems provide accuracy for total hip arthroplasty (THA) but are not available in all facilities. Accelerometer-based navigation systems are inexpensive, but their accuracy remains undetermined. This study compares the accuracy of cup orientation in THA using CT-based and accelerometer-based navigation systems. Methods: This retrospective study included 35 consecutive patients (11 males, 24 females; mean age, 65 years) who underwent primary cementless THA via an anterolateral approach in the supine position. Both CT-based and accelerometer-based navigation systems were used simultaneously. The accuracy of cup orientation was compared between the two systems using postoperative CT. Results: The accuracy of cup inclination was 2.7° ± 2.0° in the CT-based group and 3.3° ± 2.4° in the accelerometer-based group. The accuracy of cup anteversion was 2.8° ± 2.6° in the CT-based group and 3.4° ± 2.2° in the accelerometer-based group. No significant difference was observed in cup inclination ( p = 0.29) or cup anteversion ( p = 0.34) between CT-based and accelerometer-based navigation. Conclusions: The accuracy of cup positioning did not differ significantly between CT-based and accelerometer-based navigation systems.