bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptome analysis of the newly discovered insect vector of the pine wood nematode in China, revealing putative genes related to host plant adaptation
Authors: Hou Zehai , Shi Fengming , Ge Sixun , Tao Jing , Ren Lili , Wu Hao , Zong Shixiang 
Published: April 2021

Abstract
Background
In many insect species, the larvae/nymphs are unable to disperse far from the oviposition site selected by adults. The Sakhalin pine sawyer Monochamus saltuarius (Gebler) is the newly discovered insect vector of the pine wood nematode (Bursaphelenchus xylophilus) in China. Adult M. saltuarius prefers to oviposit on the host plant Pinus koraiensis, rather than P. tabuliformis. However, the genetic basis of adaptation of the larvae of M. saltuarius with weaken dispersal ability to host environments selected by the adult is not well understood.

Results
In this study, the free amino and fatty acid composition and content of the host plants of M. saltuarius larvae, i.e., P. koraiensis and P. tabuliformis were investigated. Compared with P. koraiensis, P. tabuliformis had a substantially higher content of various free amino acids, while the opposite trend was detected for fatty acid content. The transcriptional profiles of larval populations feeding on P. koraiensis and P. tabuliformis were compared using PacBio Sequel II sequencing combined with Illumina sequencing. The results showed that genes relating to digestion, fatty acid synthesis, detoxification, oxidation-reduction, and stress response, as well as nutrients and energy sensing ability, were differentially expressed, possibly reflecting adaptive changes of M. saltuarius in response to different host diets. Additionally, genes coding for cuticle structure were differentially expressed, indicating that cuticle may be a potential target for plant defense. Differential regulation of genes related to the antibacterial and immune response were also observed, suggesting that larvae of M. saltuarius may have evolved adaptations to cope with bacterial challenges in their host environments.

Conclusions
The present study provides comprehensive transcriptome resource of M. saltuarius relating to host plant adaptation. Results from this study help to illustrate the fundamental relationship between transcriptional plasticity and adaptation mechanisms of insect herbivores to host plants.
Evolutionary research on the expansin protein family during the plant transition to land provides new insights into the development of Tartary buckwheat fruit
Authors: Sun Wenjun , Yu Haomiao , Liu Moyang , Ma Zhaotang , Chen Hui 
Published: April 2021

AbstractBackgroundPlant transitions to land require robust cell walls for regulatory adaptations and to resist changing environments. Cell walls provide essential plasticity for plant cell division and defense, which are often conferred by the expansin superfamily with cell wall-loosening functions. However, the evolutionary mechanisms of expansin during plant terrestrialization are unclear.ResultsHere, we identified 323 expansin proteins in 12 genomes from algae to angiosperms. Phylogenetic evolutionary, structural, motif gain and loss and Ka/Ks analyses indicated that highly conserved expansin proteins were already present in algae and expanded and purified after plant terrestrialization. We found that the expansion of the FtEXPA subfamily was caused by duplication events and that the functions of certain duplicated genes may have differentiated. More importantly, we generated space-time expression profiles and finally identified five differentially expressedFtEXPsin both large and small fruit Tartary buckwheat that may regulate fruit size by responding to indoleacetic acid.ConclusionsA total of 323 expansin proteins from 12 representative plants were identified in our study during terrestrialization, and the expansin family that originated from algae expanded rapidly after the plants landed. The EXPA subfamily has more members and conservative evolution in angiosperms.FtEXPA1,FtEXPA11,FtEXPA12,FtEXPA19andFtEXPA24can respond to indole-3-acetic acid (IAA) signals and regulate fruit development. Our study provides a blueprint for improving the agronomic traits of Tartary buckwheat and a reference for defining the evolutionary history of the expansin family during plant transitions to land.
Meta-analysis suggests the microbiome responds to Evolve and Resequence experiments in Drosophila melanogaster
Authors: Henry Lucas P. , Ayroles Julien F. 
Published: April 2021

Abstract
Background
Experimental evolution has a long history of uncovering fundamental insights into evolutionary processes, but has largely neglected one underappreciated component--the microbiome. As eukaryotic hosts evolve, the microbiome may also respond to selection. However, the microbial contribution to host evolution remains poorly understood. Here, we re-analyzed genomic data to characterize the metagenomes from ten Evolve and Resequence (E&R) experiments in Drosophila melanogaster to determine how the microbiome changed in response to host selection.

Results
Bacterial diversity was significantly different in 5/10 studies, primarily in traits associated with metabolism or immunity. Duration of selection did not significantly influence bacterial diversity, highlighting the importance of associations with specific host traits.

Conclusions
Our genomic re-analysis suggests the microbiome often responds to host selection; thus, the microbiome may contribute to the response of Drosophila in E&R experiments. We outline important considerations for incorporating the microbiome into E&R experiments. The E&R approach may provide critical insights into host-microbiome interactions and fundamental insight into the genomic basis of adaptation.
N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways
Authors: Yan Xinyu , Han Han , Zhang Shizhen , Lu Yanzhu , Ren Linghuan , Tang Yufei , Li Xiaolong , Jian Fan , Wang Yan , Long Hu , Lai Wenli 
Published: April 2021

Abstract
Background
Nociceptin/orphanin FQ (N/OFQ) has been revealed to play bidirectional roles in orofacial pain modulation. Calcitonin gene-related peptide (CGRP) is a well-known pro-nociceptive molecule that participates in the modulation of orofacial pain. We aimed to determine the effects of N/OFQ on the modulation of orofacial pain and on the release of CGRP.

Methods
Orofacial pain model was established by ligating springs between incisors and molars in rats for the simulation of tooth movement. The expression level of N/OFQ was determined and pain level was scored in response to orofacial pain. Both agonist and antagonist of N/OFQ receptor were administered to examine their effects on pain and the expression of CGRP in trigeminal ganglia (TG). Moreover, gene therapy based on the overexpression of N/OFQ was delivered to validate the modulatory role of N/OFQ on pain and CGRP expression.

Results
Tooth movement elicited orofacial pain and an elevation in N/OFQ expression. N/OFQ exacerbated orofacial pain and upregulated CGRP expression in TG, while UFP-101 alleviated pain and downregulated CGRP expression. N/OFQ-based gene therapy was successful in overexpressing N/OFQ in TG, which resulted in pain exacerbation and elevation of CGRP expression in TG.

Conclusions
N/OFQ exacerbated orofacial pain possibly through upregulating CGRP.
Knockout of the entire family of AITR genes in Arabidopsis leads to enhanced drought and salinity tolerance without fitness costs
Authors: Chen Siyu , Zhang Na , Zhou Ganghua , Hussain Saddam , Ahmed Sajjad , Tian Hainan , Wang Shucai 
Published: April 2021

Abstract
Backgorund
Environmental stresses including abiotic stresses and biotic stresses limit yield of plants. Stress-tolerant breeding is an efficient way to improve plant yield under stress conditions. Genome editing by CRISPR/Cas9 can be used in molecular breeding to improve agronomic traits in crops, but in most cases, with fitness costs. The plant hormone ABA regulates plant responses to abiotic stresses via signaling transduction. We previously identified AITRs as a family of novel transcription factors that play a role in regulating plant responses to ABA and abiotic stresses. We found that abiotic stress tolerance was increased in the single, double and triple aitr mutants. However, it is unclear if the increased abiotic stress tolerance in the mutants may have fitness costs.

Results
We report here the characterization of AITRs as suitable candidate genes for CRISPR/Cas9 editing to improve plant stress tolerance. By using CRISPR/Cas9 to target AITR3 and AITR4 simultaneously in the aitr256 triple and aitr1256 quadruple mutants respectively, we generated Cas9-free aitr23456 quintuple and aitr123456 sextuple mutants. We found that reduced sensitivities to ABA and enhanced tolerance to drought and salt were observed in these mutants. Most importantly, plant growth and development was not affected even in the aitr123456 sextuple mutants, in whom the entire AITR family genes have been knocked out, and the aitr123456 sextuple mutants also showed a wild type response to the pathogen infection.

Conclusions
Our results suggest that knockout of the AITR family genes in Arabidopsis enhanced abiotic stress tolerance without fitness costs. Considering that knock-out a few AITRs will lead to enhanced abiotic stress tolerance, that AITRs are widely distributed in angiosperms with multiple encoding genes, AITRs may be targeted for molecular breeding to improve abiotic stress tolerance in plants including crops.
Poplar protease inhibitor expression differs in an herbivore specific manner
Authors: Eberl Franziska , Fabisch Thomas , Luck Katrin , Köllner Tobias G. , Vogel Heiko , Gershenzon Jonathan , Unsicker Sybille B. 
Published: April 2021

Abstract
Background
Protease inhibitors are defense proteins widely distributed in the plant kingdom. By reducing the activity of digestive enzymes in insect guts, they reduce the availability of nutrients and thus impair the growth and development of the attacking herbivore. One well-characterized class of protease inhibitors are Kunitz-type trypsin inhibitors (KTIs), which have been described in various plant species, including Populus spp. Long-lived woody perennials like poplar trees encounter a huge diversity of herbivores, but the specificity of tree defenses towards different herbivore species is hardly studied. We therefore aimed to investigate the induction of KTIs in black poplar (P. nigra) leaves upon herbivory by three different chewing herbivores, Lymantria dispar and Amata mogadorensis caterpillars, and Phratora vulgatissima beetles.

Results
We identified and generated full-length cDNA sequences of 17 KTIs that are upregulated upon herbivory in black poplar leaves, and analyzed the expression patterns of the eight most up-regulated KTIs via qRT-PCR. We found that beetles elicited higher transcriptional induction of KTIs than caterpillars, and that both caterpillar species induced similar KTI expression levels. Furthermore, KTI expression strongly correlated with the trypsin-inhibiting activity in the herbivore-damaged leaves, but was not dependent on damage severity, i.e. leaf area loss, for most of the genes.

Conclusions
We conclude that the induction of KTIs in black poplar is controlled at the transcriptional level in a threshold-based manner and is strongly influenced by the species identity of the herbivore. However, the underlying molecular mechanisms and ecological consequences of these patterns remain to be investigated.
Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression
Authors: Wen Caihong , Feng Xiaoqing , Yuan Honggang , Gong Yong , Wang Guangsheng 
Published: April 2021

Abstract
Background
Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation.

Methods
Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot.

Results
Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p.

Conclusion
Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.
Gene expression and immune infiltration in melanoma patients with different mutation burden
Authors: Wang Liwei , Chen Fu , Liu Rui , Shi Lei , Zhao Guosheng , Yan Zhengjian 
Published: April 2021

Abstract
Background
Immunotherapy is a vital component in cancer treatment. However, due to the complex genetic bases of cancer, a clear prediction index for efficacy has not been established. Tumor mutation burden (TMB) is one of the essential factors that affect immunotherapeutic efficacies, but it has not been determined whether the mutation is associated with the survival of Skin Cutaneous Melanoma (SKCM) patients. This study aimed at evaluating the correlation between TMB and immune infiltration.

Methods
Somatic mutation profiles (n = 467), transcriptome data (n = 471), and their clinical information (n = 447) of all SKCM samples were downloaded from The Cancer Genome Atlas (TCGA) database. For each sample, TMB was calculated as the number of variants per megabase. Based on K-M survival analysis, they were allocated into the high-TMB and low-TMB groups (the optimal cutoff was determined by the ‘surv_cutpoint’ algorithm of survival R package). Then, Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) were performed, with immune-associated biological pathways found to be significantly enriched in the low-TMB group. Therefore, immune genes that were differentially expressed between the two groups were evaluated in Cox regression to determine their prognostic values, and a four-gene TMB immune prognostic model (TMB-IP) was constructed.

Results
Elevated TMB levels were associated with better survival outcomes in SKCM patients. Based on the cutoff value in OS analysis, they were divided into high-TMB and low-TMB groups. GSEA revealed that the low-TMB group was associated with immunity while intersection analysis revealed that there were 38 differentially expressed immune-related genes between the two groups. Four TMB-associated immune genes were used to construct a TMB-IP model. The AUC of the ROC curve of this model reached a maximum of 0.75 (95%CI, 0.66–0.85) for OS outcomes. Validation in each clinical subgroup confirmed the efficacy of the model to distinguish between high and low TMB-IP score patients.

Conclusions
In SKCM patients, low TMB was associated with worse survival outcomes and enriched immune-associated pathways. The four TMB-associated immune genes model can effectively distinguish between high and low-risk patients.
Association of ST6GAL1 and CYP19A1 polymorphisms in the 3′-UTR with astrocytoma risk and prognosis in a Chinese Han population
Authors: Wang Tuo , Sun Yao , Xiong Zichao , Wu Jiamin , Ding Xiaoying , Guo Xiaoye , Shao Yuan 
Published: April 2021

Abstract
Background
Astrocytoma is a common type of central nervous system tumor. In this study, we investigated the correlation between ST6GAL1 and CYP19A1 polymorphisms and the risk and prognosis of astrocytoma.

Methods
A total of 365 astrocytoma patients and 379 healthy controls were genotyped using the Agena MassARRAY system. The correlation between ST6GAL1 and CYP19A1 variants and astrocytoma risk was calculated using logistic regression. The survival rate of patients with astrocytoma was analyzed to evaluate prognosis.

Results
We found that the ST6GAL1-rs2239611 significantly decreased the risk of astrocytoma in the codominant model (p = 0.044) and dominant model (p = 0.049). In stratified analyses, CYP19A1-rs2255192 might be associated with a higher risk of astrocytoma among the low-grade subgroup under recessive (p = 0.034) and additive (p = 0.030) models. However, CYP19A1-rs4646 had a risk-decreasing effect on the high-grade subgroup in the codominant model (p = 0.044). The results of Cox regression analysis showed that the CYP19A1-rs2239611 and -rs1042757 polymorphisms were significantly correlated with the prognosis of astrocytoma.

Conclusion
Our results suggest that ST6GAL1 and CYP19A1 genes may be a potential biomarker of genetic susceptibility and prognosis to astrocytoma in the Chinese Han population.
A data-driven approach for the discovery of biomarkers associated with thyroid eye disease
Authors: Zou Huihui , Xu Weiwei , Wang Ying , Wang Zhihong 
Published: April 2021

Abstract
Background
Thyroid eye disease (TED) is the most common autoimmune disease and usually occurs in patients with hyperthyroidism. In this disease, eye-related tissue, such as eye muscles, eyelids, tear glands, etc., become inflated, which causes the eyes and eyelids to become red, swollen, and uncomfortable. The pathophysiology of this disease is still poorly known.

Aim
This study aims to discover potential biomarkers and regulatory pathways of TED which will not only help to diagnose the disease and understand orbital involvement in thyroid dysfunction but also provide an insight for better therapeutics.

Methods
We applied a data-driven approach by combining gene biomarkers both from published literature and computationally predicted from microarray gene expression data. Further, the DAVID tool is used for Gene Ontology-based enrichment analysis.

Results
We obtained a total of 22 gene biomarkers, including 18 semi-automatically curated from the literature and 4 predicted using data-driven approaches, involved in the pathogenesis of TED that can be used as potential information for therapeutic targets. Further, we constructed a regulatory pathway of TED biomarkers comprises of 310 connected components, and 1134 interactions using four prominent interaction databases.

Conclusion
This constructed pathway can be further utilized for disease dynamics and simulation studies.
Determinants of student’s physical activity: a 12-month follow-up study in Ningxia province
Authors: Huang Wei , Shi Xiangrong , Wang Yujie , Li Xiaoling , Gao Pengpeng , Lu Jieguo , Zhuang Jie 
Published: April 2021

Abstract
Background
Physical activity has many health benefits for children and adolescents. However, the prevalence of physical inactivity in school-aged children and adolescents remains high in China. Many factors impact the levels of moderate and vigorous physical activity (MVPA) among students. This study investigated the factors associated with students’ MVPA levels and the determinants of changes in their MVPA behaviour.

Methods
This is a longitudinal study with a 12-month follow-up. The study samples were obtained from 2016 and 2017 Physical Activity and Fitness in China—The Youth Study, and they included 1597 students (aged 9–18 years) from 31 primary, junior high, and high schools in Ningxia Province. Factors related to the individual (Age, Sex, BMI and attitude to PA), school (school exercise facility, PE class, teacher support, PA time and PA environment) and neighbourhood (free skill training, sport events, sport organization, sport facility) factors were measured via questionnaire at baseline and after 12 months. Multiple logistic regression was performed to examine the factors that impact students’ MVPA level and the determinants of changes in students’ MVPA behaviour.

Results
There was no difference in students’ MVPA levels between 2016 and 2017. Boys were more physically active than girls at baseline (RR 1.55, 95% CI 1.10, 2.20). Neighbourhood factors associated students’ MVPA levels were significant, but all of these factors (neighbourhood sport events, organizations, facilities, etc.) were removed from the longitudinal model. Individual and school factors were important for students’ MVPA maintenance and positive development (e.g., gender, attitude, school PE class and PA time).

Conclusions
In conclusion, both neighbourhood and school factors may affect students’ MVPA, but school appears to plays a more critical role in maintaining and promoting students’ MVPA levels. In addition, individual factors may be more important than school and neighbourhood factors in influencing students’ MVPA levels. Our research demonstrates that students’ attitudes towards PA and school factors should be considered targets for future intervention programmes to promote MVPA. More education programmes may help enhance students’ attitudes towards PA, but more studies with large samples and objective assessments are needed to explore the determinants of MVPA.
Ethnic inequalities in older adults bowel cancer awareness: findings from a community survey conducted in an ethnically diverse region in England
Authors: Kerrison Robert S. , Prentice Andrew , Marshall Sarah , Choglay Sameer , Levitan Michael , Alter Marsha , Ghanouni Alex , McGregor Lesley , von Wagner Christian 
Published: April 2021

Abstract
Background
To date, research exploring the public’s awareness of bowel cancer has taken place with predominantly white populations. To enhance our understanding of how bowel cancer awareness varies between ethnic groups, and inform the development of targeted interventions, we conducted a questionnaire study across three ethnically diverse regions in Greater London, England.

Methods
Data were collected using an adapted version of the bowel cancer awareness measure. Eligible adults were individuals, aged 60+ years, who were eligible for screening. Participants were recruited and surveyed, verbally, by staff working at 40 community pharmacies in Northwest London, the Harrow Somali association, and St. Mark’s Bowel Cancer Screening Centre. Associations between risk factor, symptom and screening awareness scores and ethnicity were assessed using multivariate regression.

Results
1013 adults, aged 60+ years, completed the questionnaire; half were of a Black, Asian or Minority ethnic group background (n = 507; 50.0%). Participants recognised a mean average of 4.27 of 9 symptoms and 3.99 of 10 risk factors. Symptom awareness was significantly lower among all ethnic minority groups (all p’s < 0.05), while risk factor awareness was lower for Afro-Caribbean and Somali adults, specifically (both p’s < 0.05). One in three adults (n = 722; 29.7%) did not know there is a Bowel Cancer Screening Programme. Bowel screening awareness was particularly low among Afro-Caribbean and Somali adults (both p’s < 0.05).

Conclusion
Awareness of bowel cancer symptoms, risk factors and screening varies by ethnicity. Interventions should be targeted towards specific groups for whom awareness of screening and risk factors is low.