bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasensitive bioassaying of HER-2 protein for diagnosis of breast cancer using reduced graphene oxide/chitosan as nanobiocompatible platform
Authors: Nasrollahpour Hassan , Isildak Ibrahim , Rashidi Mohammad-Reza , Hashemi Esmat Alsadat , Naseri Abdolhosein , Khalilzadeh Balal 
Published: May 2021

AbstractBackgroundIn this label-free bioassay, an electrochemiluminescence (ECL) immunosensor was developed for the quantification of breast cancer using HER-2 protein as a metastatic biomarker.MethodFor this purpose, the ECL emitter, [Ru(bpy)3]2+, was embedded into biocompatible chitosan (CS) polymer. The prepared bio-composite offered high ECL reading due to the depletion of human epidermal growth factor receptor 2 (HER-2) protein. Reduced graphene oxide (rGO) was used as substrate to increase signal stability and achieve greater sensitivity. For this, rGO was initially placed electrochemically on the glassy carbon electrode (GCE) surface by cyclic voltammetry (CV) technique. Next, the prepared CS/[Ru(bpy)3]2+biopolymer solution was coated on a drop of the modified electrode such that the amine groups of CS and the carboxylic groups of rGO could covalently interact. Using EDC/NHS chemistry, monoclonal antibodies (Abs) of HER-2 were linked to CS/[Ru(bpy)3]2+/rGO/GCE via amide bonds between the carboxylic groups of Ab molecules and amine groups of CS. The electrochemical behavior of the electrode was studied using different electrochemical techniques such as electrochemical impedance spectroscopy (EIS), differential pulse voltammetry (DPV) and square wave voltammetry (SWV) and also ECL tests.ResultsAfter passing all optimization steps, the lower limit of detection (LLOQ) and linear dynamic range (LDR) of HER-2 protein were practically obtained as 1 fM and 1 fM to 1 nM, individually. Importantly, the within and between laboratory precisions were performed and the suitable relative standard deviations (RSDs) were recorded as 3.1 and 3.5%, respectively.ConclusionsAs a proof of concept, the designed immunosensor was desirably applied for the quantification of HER-2 protein in breast cancer suffering patients. As a result, the designed ECL-based immunosensor has the capability of being used as a conventional test method in biomedical laboratories for early detection of HER-2 protein in biological fluids.Graphic Abstract
SPEAQeasy: a scalable pipeline for expression analysis and quantification for R/bioconductor-powered RNA-seq analyses
Authors: Eagles Nicholas J. , Burke Emily E. , Leonard Jacob , Barry Brianna K. , Stolz Joshua M. , Huuki Louise , Phan BaDoi N. , Serrato Violeta Larios , Gutiérrez-Millán Everardo , Aguilar-Ordoñez Israel , Jaffe Andrew E. , Collado-Torres Leonardo 
Published: May 2021

AbstractBackgroundRNA sequencing (RNA-seq) is a common and widespread biological assay, and an increasing amount of data is generated with it. In practice, there are a large number of individual steps a researcher must perform before raw RNA-seq reads yield directly valuable information, such as differential gene expression data. Existing software tools are typically specialized, only performing one step–such as alignment of reads to a reference genome–of a larger workflow. The demand for a more comprehensive and reproducible workflow has led to the production of a number of publicly available RNA-seq pipelines. However, we have found that most require computational expertise to set up or share among several users, are not actively maintained, or lack features we have found to be important in our own analyses.ResultsIn response to these concerns, we have developed a Scalable Pipeline for Expression Analysis and Quantification (SPEAQeasy), which is easy to install and share, and provides a bridge towards R/Bioconductor downstream analysis solutions. SPEAQeasy is portable across computational frameworks (SGE, SLURM, local, docker integration) and different configuration files are provided (http://research.libd.org/SPEAQeasy/).ConclusionsSPEAQeasy is user-friendly and lowers the computational-domain entry barrier for biologists and clinicians to RNA-seq data processing as the main input file is a table with sample names and their corresponding FASTQ files. The goal is to provide a flexible pipeline that is immediately usable by researchers, regardless of their technical background or computing environment.
A fast wavelet-based functional association analysis replicates several susceptibility loci for birth weight in a Norwegian population
Authors: Denault William R. P. , Romanowska Julia , Helgeland Øyvind , Jacobsson Bo , Gjessing Håkon K. , Jugessur Astanand 
Published: May 2021

Abstract
Background
Birth weight (BW) is one of the most widely studied anthropometric traits in humans because of its role in various adult-onset diseases. The number of loci associated with BW has increased dramatically since the advent of whole-genome screening approaches such as genome-wide association studies (GWASes) and meta-analyses of GWASes (GWAMAs). To further contribute to elucidating the genetic architecture of BW, we analyzed a genotyped Norwegian dataset with information on child’s BW (N=9,063) using a slightly modified version of a wavelet-based method by Shim and Stephens (2015) called WaveQTL.

Results
WaveQTL uses wavelet regression for regional testing and offers a more flexible functional modeling framework compared to conventional GWAS methods. To further improve WaveQTL, we added a novel feature termed “zooming strategy” to enhance the detection of associations in typically small regions. The modified WaveQTL replicated five out of the 133 loci previously identified by the largest GWAMA of BW to date by Warrington et al. (2019), even though our sample size was 26 times smaller than that study and 18 times smaller than the second largest GWAMA of BW by Horikoshi et al. (2016). In addition, the modified WaveQTL performed better in regions of high LD between SNPs.

Conclusions
This study is the first adaptation of the original WaveQTL method to the analysis of genome-wide genotypic data. Our results highlight the utility of the modified WaveQTL as a complementary tool for identifying loci that might escape detection by conventional genome-wide screening methods due to power issues. An attractive application of the modified WaveQTL would be to select traits from various public GWAS repositories to investigate whether they might benefit from a second analysis.
Genome-wide analysis of ATP-binding cassette transporter provides insight to genes related to bioactive metabolite transportation in Salvia miltiorrhiza
Authors: Yan Li , Zhang Jianhong , Chen Hongyu , Luo Hongmei 
Published: May 2021

Abstract
Background
ATP-binding cassette (ABC) transporters have been found to play important roles in metabolic transport in plant cells, influencing subcellular compartmentalisation and tissue distribution of these metabolic compounds. Salvia miltiorrhiza Bunge, known as Danshen in traditional Chinese medicine, is a highly valued medicinal plant used to treat cardiovascular and cerebrovascular diseases. The dry roots and rhizomes of S. miltiorrhiza contain biologically active secondary metabolites of tanshinone and salvianolic acid. Given an assembled and annotated genome and a set of transcriptome data of S. miltiorrhiza, we analysed and identified the candidate genes that likely involved in the bioactive metabolite transportation of this medicinal plant, starting with the members of the ABC transporter family.

Results
A total of 114 genes encoding ABC transporters were identified in the genome of S. miltiorrhiza. All of these ABC genes were divided into eight subfamilies: 3ABCA, 31ABCB, 14ABCC, 2ABCD, 1ABCE, 7ABCF, 46ABCG, and 10 ABCI. Gene expression analysis revealed tissue-specific expression profiles of these ABC transporters. In particular, we found 18 highly expressed transporters in the roots of S. miltiorrhiza, which might be involved in transporting the bioactive compounds of this medicinal plant. We further investigated the co-expression profiling of these 18 genes with key enzyme genes involved in tanshinone and salvianolic acid biosynthetic pathways using quantitative reverse transcription polymerase chain reaction (RT-qPCR). From this RT-qPCR validation, we found that three ABC genes (SmABCG46, SmABCG40, and SmABCG4) and another gene (SmABCC1) co-expressed with the key biosynthetic enzymes of these two compounds, respectively, and thus might be involved in tanshinone and salvianolic acid transport in root cells. In addition, we predicted the biological functions of S. miltiorrhiza ABC transporters using phylogenetic relationships and analysis of the transcriptome to find biological functions.

Conclusions
Here, we present the first systematic analysis of ABC transporters in S. miltiorrhiza and predict candidate transporters involved in bioactive compound transportation in this important medicinal plant. Using genome-wide identification, transcriptome profile analysis, and phylogenetic relationships, this research provides a new perspective on the critical functions of ABC transporters in S. miltiorrhiza.
Basic leucine zipper (bZIP) transcription factor genes and their responses to drought stress in ginseng, Panax ginseng C.A. Meyer
Authors: Li Hongjie , Chen Jing , Zhao Qi , Han Yilai , Li Li , Sun Chunyu , Wang Kangyu , Wang Yanfang , Zhao Mingzhu , Chen Ping , Lei Jun , Wang Yi , Zhang Meiping 
Published: May 2021

Abstract
Background
Ginseng is an important medicinal herb in Asia and Northern America. The basic leucine zipper (bZIP) transcription factor genes play important roles in many biological processes and plant responses to abiotic and biotic stresses, such as drought stress. Nevertheless, the genes remain unknown in ginseng.

Results
Here, we report 91 bZIP genes identified from ginseng, designated PgbZIP genes. These PgbZIP genes were alternatively spliced into 273 transcripts. Phylogenetic analysis grouped the PgbZIP genes into ten groups, including A, B, C, D, E, F, G, H, I and S. Gene Ontology (GO) categorized the PgbZIP genes into five functional subcategories, suggesting that they have diversified in functionality, even though their putative proteins share a number of conserved motifs. These 273 PgbZIP transcripts expressed differentially across 14 tissues, the roots of different ages and the roots of different genotypes. However, the transcripts of the genes expressed coordinately and were more likely to form a co-expression network. Furthermore, we studied the responses of the PgbZIP genes to drought stress in ginseng using a random selection of five PgbZIP genes, including PgbZIP25, PgbZIP38, PgbZIP39, PgbZIP53 and PgbZIP54. The results showed that all five PgbZIP genes responded to drought stress in ginseng, indicating that the PgbZIP genes play important roles in ginseng responses to drought stress.

Conclusions
These results provide knowledge and gene resources for deeper functional analysis of the PgbZIP genes and molecular tools for enhanced drought tolerance breeding in ginseng.
Identification and characterization of HAK/KUP/KT potassium transporter gene family in barley and their expression under abiotic stress
Authors: Cai Kangfeng , Zeng Fanrong , Wang Junmei , Zhang Guoping 
Published: May 2021

Abstract
Background
HAK/KUP/KT (High-affinity K+ transporters/K+ uptake permeases/K+ transporters) is the largest potassium transporter family in plants, and plays pivotal roles in K+ uptake and transport, as well as biotic and abiotic stress responses. However, our understanding of the gene family in barley (Hordeum vulgare L.) is quite limited.

Results
In the present study, we identified 27 barley HAK/KUP/KT genes (hereafter called HvHAKs) through a genome-wide analysis. These HvHAKs were unevenly distributed on seven chromosomes, and could be phylogenetically classified into four clusters. All HvHAK protein sequences possessed the conserved motifs and domains. However, the substantial difference existed among HAK members in cis-acting elements and tissue expression patterns. Wheat had the most orthologous genes to barley HAKs, followed by Brachypodium distachyon, rice and maize. In addition, six barley HAK genes were selected to investigate their expression profiling in response to three abiotic stresses by qRT-PCR, and their expression levels were all up-regulated under salt, hyperosmotic and potassium deficiency treatments.

Conclusion
Twenty seven HAK genes (HvHAKs) were identified in barley, and they differ in tissue expression patterns and responses to salt stress, drought stress and potassium deficiency.
RNA sequencing-based analysis of the magnum tissues revealed the novel genes and biological pathways involved in the egg-white formation in the laying hen
Authors: Sah Nirvay , Kuehu Donna Lee , Khadka Vedbar Singh , Deng Youping , Jha Rajesh , Wasti Sanjeev , Mishra Birendra 
Published: May 2021

Abstract
Background
The mechanism of egg formation in the oviduct of laying hens is tightly controlled; each segment of the oviduct contributes a unique component of the egg. Several genes/proteins are involved in the synthesis of a completely healthy egg. This implies a time- and tissue-specific expression of genes and proteins in the different oviductal segments. We used hens at different physiological stages and time points to understand the transcriptional regulation of egg-white (albumen) synthesis and secretion onto the eggs in the magnum of laying hens. This study used Next-Generation Sequencing and quantitative real-time PCR (qPCR) to detect the novel genes and the cognate biological pathways that regulate the major events during the albumen formation.

Results
Magnum tissues collected from laying (n = 5 each at 3 h post-ovulation, p.o. and 15–20 h p.o.), non-laying (n = 4), and molting (n = 5) hens were used for differential gene expression analyses. A total of 540 genes (152 upregulated and 388 down-regulated) were differentially expressed at 3 h p.o. in the magnum of laying hens. Kyoto Encyclopedia of Genes and Genomes pathways analysis of the 152 upregulated genes revealed that glycine, serine, and threonine metabolism was the most-enriched biological pathway. Furthermore, the top two most enriched keywords for the upregulated genes were amino-acid biosynthesis and proteases. Nine candidate genes associated with albumen formation were validated with qPCR to have differential expression in laying, non-laying, and molting hens. Proteases such as TMPRSS9, CAPN2, MMP1, and MMP9 (protein maturation, ECM degradation, and angiogenesis); enzymes such as PSPH, PHGDH, and PSAT1 (amino-acid biosynthesis); RLN3, ACE, and REN (albumen synthesis, secretion and egg transport); and AVD, AvBD11, and GPX3 (antimicrobial and antioxidants) were recognized as essential molecules linked to albumen deposition in the magnum.

Conclusions
This study revealed some novel genes that participate in the signaling pathways for egg-white synthesis and secretion along with some well-known functional genes. These findings help to understand the mechanisms involved in albumen biosynthesis.
Prevalence and antibiotics susceptibility profiles of Streptococcus pyogenes among pediatric patients with acute pharyngitis at Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia
Authors: Kebede Destaw , Admas Alemale , Mekonnen Daniel 
Published: May 2021

Abstract
Background
Streptococcus pyogenes (S. pyogenes) is a Gram positive bacterium which is a leading cause of pharyngitis, skin and soft tissue infection and post streptococcal syndromes. Due to lack of β-lactamase enzyme production, it was considered universally susceptible to penicillin group and later generation of β-lactam antibiotics. As such, empirical treatment was common which might leads to development of antibiotics resistance. Therefore, the aims of this study were to determine the prevalence, antibiotics susceptibility profile; and associated factors of S. pyogenes among pediatric patients with acute pharyngitis in Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Northwest Ethiopia.

Methods
Hospital based cross-sectional study was carried out on 154 pediatric patients, whose age ranged from 0 to 18 years old using consecutive convenient sampling technique from 1st February to 19th June 2020 at FHCSH. S. pyogenes were identified by throat swab culture on 5% sheep blood agar with an overnight incubation at 37 °C in candle jar containing 5% CO2. Gram stain, catalase test and bacitracin test were used to identify S. pyogenes. Then,the data were entered into EpiData version 3.1 and analyzed by SPSS version 20 software. Finally, stepwise, bivariable and multivariable logistic regressions were carried out for identifyying factors having significant ssociation (p<0.05) with acute pharyngitis.

Results
From the total throat swabs, 14 (9.1%) with (95% CI; 4.5–14.3) were culture positive for S. pyogenes. From these, all isolates were sensitive to penicillin and ampicillin. On the otherhand, 4 (35.7%), 4 (35.5%), 3 (21.4%), 2 (14.3%), 1 (7.1%), 7 (50.0%) and 1 (7.1%) isolates were resistant for ceftriaxone, vancomycin, erythromycin, tetracycline, chloramphenicol, clindamycin and levofloxacin, respectively. The presence of any smoker in home showed significant association with S. pyogenes acute pharyngitis. Furthermore, having tender lymphadenopathy and recurrence were clinical predictors for S. pyogenes acute pharyngitis (P < 0.05).

Conclusion
The prevalence of S. pyogenes was guaged at 9.1% which is considered as low prevalence. All S. pyogenes isolats remain sensitive to penicillin. However, resistance was reported to clindamycin 7 (50.0%), ceftriaxone 5 (35.7%) and erythromycin 3 (21.4%). The current practice of giving erythromycin, clindamycin instead of penicillin and ampicillin is againest the microbiology result. Therefore, current empirical treatment of acute pharyngitis shall take in to account the current evidences. Continuous surveillance of antibiotics resistance pattern of S. pyogenes for acute pharyngitis must be strengthen to improve the use of antibiotics in hospitals.
Comparative genome analysis of multidrug-resistant Pseudomonas aeruginosa JNQH-PA57, a clinically isolated mucoid strain with comprehensive carbapenem resistance mechanisms
Authors: Hao Mingju , Ma Wanshan , Dong Xiutao , Li Xiaofeng , Cheng Fang , Wang Yujiao 
Published: May 2021

Abstract
Background
The prevalence of clinical multidrug-resistant (MDR) Pseudomonas aeruginosa has been increasing rapidly worldwide over the years and responsible for a wide range of acute and chronic infections with high mortalities. Although hundreds of complete genomes of clinical P. aeruginosa isolates have been sequenced, only a few complete genomes of mucoid strains are available, limiting a comprehensive understanding of this important group of opportunistic pathogens. Herein, the complete genome of a clinically isolated mucoid strain P. aeruginosa JNQH-PA57 was sequenced and assembled using Illumina and Oxford nanopore sequencing technologies. Genomic features, phylogenetic relationships, and comparative genomics of this pathogen were comprehensively analyzed using various bioinformatics tools. A series of phenotypic and molecular-genetic tests were conducted to investigate the mechanisms of carbapenem resistance in this strain.

Results
Several genomic features of MDR P. aeruginosa JNQH-PA57 were identified based on the whole-genome sequencing. We found that the accessory genome of JNQH-PA57 including several prophages, genomic islands, as well as a PAPI-1 family integrative and conjugative element (ICE), mainly contributed to the larger genome of this strain (6,747,067 bp) compared to other popular P. aeruginosa strains (with an average genome size of 6,445,223 bp) listed in Pseudomonas Genome Database. Colony morphology analysis and biofilm crystal staining assay respectively demonstrated an enhanced alginate production and a thicker biofilm formation capability of JNQH-PA57. A deleted mutation at nt 424 presented in mucA gene, resulted in the upregulated expression of a sigma-factor AlgU and a GDP mannose dehydrogenase AlgD, which might explain the mucoid phenotype of this strain. As for the carbapenem resistance mechanisms, our results revealed that the interplay between impaired OprD porin, chromosomal β-lactamase OXA-488 expression, MexAB-OprM and MexXY-OprM efflux pumps overexpression, synergistically with the alginates-overproducing protective biofilm, conferred the high carbapenem resistance to P. aeruginosa JNQH-PA57.

Conclusion
Based on the genome analysis, we could demonstrate that the upregulated expression of algU and algD, which due to the truncation variant of MucA, might account for the mucoid phenotype of JNQH-PA57. Moreover, the resistance to carbapenem in P. aeruginosa JNQH-PA57 is multifactorial. The dataset presented in this study provided an essential genetic basis for the comprehensive cognition of the physiology, pathogenicity, and carbapenem resistance mechanisms of this clinical mucoid strain.
Oxytocin ameliorates impaired social behavior in a Chd8 haploinsufficiency mouse model of autism
Authors: Cherepanov Stanislav M. , Gerasimenko Maria , Yuhi Teruko , Furuhara Kazumi , Tsuji Chiharu , Yokoyama Shigeru , Nakayama Keiichi I. , Nishiyama Masaaki , Higashida Haruhiro 
Published: May 2021

Abstract
Background
Autism spectrum disorder (ASD) is characterized by the core symptoms of impaired social interactions. Increasing evidence suggests that ASD has a strong genetic link with mutations in chromodomain helicase DNA binding protein 8 (CHD8), a gene encoding a chromatin remodeler. It has previously been shown that Chd8 haplodeficient male mice manifest ASD-like behavioral characteristics such as anxiety and altered social behavior. Along with that, oxytocin (OT) is one of the main neuropeptides involved in social behavior. Administration of OT has shown improvement of social behavior in genetic animal models of ASD. The present study was undertaken to further explore behavioral abnormalities of Chd8 haplodeficient mice of both sexes, their link with OT, and possible effects of OT administration. First, we performed a battery of behavioral tests on wild-type and Chd8+/∆SL female and male mice. Next, we measured plasma OT levels and finally studied the effects of intraperitoneal OT injection on observed behavioral deficits.

Results
We showed general anxiety phenotype in Chd8+/∆SL mice regardless of sex, the depressive phenotype in Chd8+/∆SL female mice only and bidirectional social deficit in female and male mice. We observed decreased level of OT in Chd+/∆SL mice, possibly driven by males. Mice injected by OT demonstrated recovery of social behavior, while reduced anxiety was observed only in male mice.

Conclusions
Here, we demonstrated that abnormal social behaviors were observed in both male and female Chd8+/∆SL mice. The ability of peripheral OT administration to affect such behaviors along with altered plasma OT levels indicated a possible link between Chd8 + /∆SL and OT in the pathogenesis of ASD as well as the possible usefulness of OT as a therapeutic tool for ASD patients with CHD8 mutations.