bluuebunny/crossref_metadata_2025 huggingface dataset:
Imperfection sensitivity analysis for a composite bowed-out shell under axial compression
Authors: Li Zhun , Pan Guang , Shen Kechun
Published: November 2019

In this article, we present a systematic work to investigate the imperfection sensitivity of composite bowed-out shells with different layup patterns under axial compression. Two types of geometric imperfections, including eigenmode-shaped imperfections (produced by a first-order eigenmode imperfection approach and an N-order eigenmode imperfection approach) and dimple-shaped imperfections (produced by a single perturbation load approach and a multiple perturbation load approach), are introduced into the finite element model to predict their knock-down factors. For the eigenmode-shaped imperfections, we show that the knock-down factors predicted by the first-order eigenmode imperfection approach are riskier than the ones predicted by the N-order eigenmode imperfection approach. When adopting the single perturbation load approach, we reveal that the direction of a dimple on the shell makes a negligible effect on axial pressure bearing capacity, while the amplitude of a dimple on the shell plays a significant role in affecting the knock-down factors. Using the multiple perturbation load approach as an extension of the single perturbation load approach, we uncover that the knock-down factors predicted by the multiple perturbation load approach are more conservative than these achieved by the single perturbation load approach. In addition, we also find that the composite bowed-out shells are more sensitive to dimple-shaped imperfection than eigenmode-shaped imperfections. This work provides helpful findings for designing an airplane body and marine risers.
Quantifying the Impact of Influenza Among Persons With Type 2 Diabetes Mellitus: A New Approach to Determine Medical and Physical Activity Impact
Authors: Samson Sandrine I. , Konty Kevin , Lee Wei-Nchih , Quisel Tom , Foschini Luca , Kerr David , Liska Jan , Mills Henry , Hollingsworth Rosalind , Greenberg Michael , Beal Anne C.
Published: November 2019

Background:

We describe the impact of influenza on medical outcomes and daily activities among people with and without type 2 diabetes mellitus (T2DM).

Methods:

Retrospective cohort analysis of a US health plan offering a digital wellness platform connecting wearable devices capable of tracking steps, sleep, and heart rate. For the 2016 to 2017 influenza season, we compared adults with T2DM to age and gender matched controls. Medical claims were used to define cohorts and identify influenza events and outcomes. Digital tracking data were aggregated at time slices of minute-, day-, week-, and year-level. A pre-post study design compared the peri-influenza period (two weeks before and four weeks after influenza diagnosis) to the six-week preceding period (baseline).

Results:

A total of 54 656 T2DM and 113 016 non-DM controls were used for the study. People with T2DM had more influenza claims, vaccinations, and influenza antivirals per 100 people (1.96% vs 1.37%, 34.3% vs 24.3%, and 27.1 vs 22 respectively, P < .001). A total of 1086 persons with T2DM and 1567 controls had an influenza claim (47.4% male, median age 54, 6.4% vs 7.8% trackers, respectively). Glycemic events, pneumonia, and ischemic heart disease increased over baseline during the peri-influenza period for T2DM (1.74-, 7.4-, and 1.6-fold increase respectively, P < .01). In a device wearing subcohort, we observed 10 000 fewer steps surrounding the influenza event, with the lowest (5500 steps) two days postinfluenza. Average heart rate increased significantly (+5.5 beats per minute) one day prior to influenza.

Conclusion:

Influenza increases rates of pneumonia, heart disease, and abnormal glucose levels among people with T2DM, and negatively impacts daily activities compared to controls.
Down-regulation of miR-30b-5p protects cardiomyocytes against hypoxia-induced injury by targeting Aven
Authors: Zhang Lanfang , Jia Xinwei
Published: November 2019

Background

Ischemia/hypoxia-induced cardiomyocyte apoptosis has been considered as a main cause of myocardial infarction. Here, we aimed to investigate the functional role of miR-30b-5p in hypoxic cardiomyocytes.

Methods

AC16 human cardiomyocytes were cultured under hypoxia to simulate myocardial infarction. A qRT-PCR assay was performed to determine miR-30b-5p expression in hypoxic cardiomyocytes. Cell survival, injury and apoptosis were assessed by MTT, lactate dehydrogenase (LDH) release, and flow cytometry assays, respectively. The target gene of miR-30b-5p in hypoxic cardiomyocytes was validated by luciferase reporter assay and Western blotting.

Results

MiR-30b-5p expression was found to be significantly upregulated in hypoxic AC16 cells. The in vitro experiments showed that downregulation of miR-30b-5p effectively alleviated hypoxia-induced cardiomyocyte injury. Furthermore, Aven is a potential target gene of miR-30b-5p and its downregulation could partially reverse the influence of miR-30b-5p knockdown on AC16 cells under hypoxia.

Conclusions

Inhibition of miR-30b-5p could protect cardiomyocytes against hypoxia-induced injury by targeting Aven.
Functional Haplotype and eQTL Analyses of Genes Affecting Cadmium Content in Cultivated Rice
Authors: Lee Sang-Beom , Kim Gyeong-Jin , Kim Kyu-Won , Chu Sang-Ho , Shin Jung-Du , Lee Yu-Ji , Park Yong-Jin , Park Sang-Won
Published: November 2019

Background

Rice is a major food resource for Asian countries including Korea. However, most Asian countries are facing food safety problems due to cropland contamination by heavy metals. Thus, this study was conducted to investigate genetic factors affecting the expression of cadmium (Cd) gene, and to confirm differences in Cd translocation among cultivars because the current molecular understanding of Cd uptake-transport mechanisms remains insufficient. Associations between genotypes and gene expression level of Cd-related genes such as NRAMP, MTP, and HMA gene families in the rice core collection were analyzed at the genomic level.

Results

Os01g0956700, Os05g0128400 and Os11g0485200 showed strong associations between expression level and genotype in the rice core collection, the regulatory factors that associated with these genes in cis and trans were founded. The association between the expression level and genotype of the candidate gene (Os01g0611300: metal tolerance protein) predicted to affect Cd content in rice by a previous genome-wide association study (GWAS) was also analyzed. Furthermore, as a result of the phylogeny and haplotype analyses of the candidate gene, high-Cd tolerance cultivars were selected. The correlations between Cd and other inorganic components (Mg, Mn, Fe, Cu and Zn) in the roots, stems, leaves and unpolished grain of selected rice cultivars were analyzed.

Conclusion

Therefore, these results may be useful for understanding the uptake-transport mechanisms of Cd and other inorganic components via molecular genetics and may help rice breeders develop new low-Cd cultivars in the near future.
Correction to: Use of genomic information to exploit genotype-by-environment interactions for body weight of broiler chicken in bio-secure and production environments
Authors: Chu Thinh T. , Bastiaansen John W. M. , Berg Peer , Romé Hélène , Marois Danye , Henshall John , Jensen Just
Published: November 2019

After publication of this work [1], we noticed that there was an error: the formula to calculate the standard error of the estimated correlation
Statistical analysis of variability in TnSeq data across conditions using zero-inflated negative binomial regression
Authors: Subramaniyam Siddharth , DeJesus Michael A. , Zaveri Anisha , Smith Clare M. , Baker Richard E. , Ehrt Sabine , Schnappinger Dirk , Sassetti Christopher M. , Ioerger Thomas R.
Published: November 2019

Background

Deep sequencing of transposon mutant libraries (or TnSeq) is a powerful method for probing essentiality of genomic loci under different environmental conditions. Various analytical methods have been described for identifying conditionally essential genes whose tolerance for insertions varies between two conditions. However, for large-scale experiments involving many conditions, a method is needed for identifying genes that exhibit significant variability in insertions across multiple conditions.

Results

In this paper, we introduce a novel statistical method for identifying genes with significant variability of insertion counts across multiple conditions based on Zero-Inflated Negative Binomial (ZINB) regression. Using likelihood ratio tests, we show that the ZINB distribution fits TnSeq data better than either ANOVA or a Negative Binomial (in a generalized linear model). We use ZINB regression to identify genes required for infection ofM. tuberculosisH37Rv in C57BL/6 mice. We also use ZINB to perform a analysis of genes conditionally essential in H37Rv cultures exposed to multiple antibiotics.

Conclusions

Our results show that, not only does ZINB generally identify most of the genes found by pairwise resampling (and vastly out-performs ANOVA), but it also identifies additional genes where variability is detectable only when the magnitudes of insertion counts are treated separately from local differences in saturation, as in the ZINB model.
SIMLIN: a bioinformatics tool for prediction of S-sulphenylation in the human proteome based on multi-stage ensemble-learning models
Authors: Wang Xiaochuan , Li Chen , Li Fuyi , Sharma Varun S. , Song Jiangning , Webb Geoffrey I.
Published: November 2019

Background

S-sulphenylation is a ubiquitous protein post-translational modification (PTM) where an S-hydroxyl (−SOH) bond is formed via the reversible oxidation on the Sulfhydryl group of cysteine (C). Recent experimental studies have revealed that S-sulphenylation plays critical roles in many biological functions, such as protein regulation and cell signaling. State-of-the-art bioinformatic advances have facilitated high-throughput in silico screening of protein S-sulphenylation sites, thereby significantly reducing the time and labour costs traditionally required for the experimental investigation of S-sulphenylation.

Results

In this study, we have proposed a novel hybrid computational framework, termedSIMLIN, for accurate prediction of protein S-sulphenylation sites using a multi-stage neural-network based ensemble-learning model integrating both protein sequence derived and protein structural features. Benchmarking experiments against the current state-of-the-art predictors for S-sulphenylation demonstrated thatSIMLINdelivered competitive prediction performance. The empirical studies on the independent testing dataset demonstrated thatSIMLINachieved 88.0% prediction accuracy and an AUC score of 0.82, which outperforms currently existing methods.

Conclusions

In summary,SIMLINpredicts human S-sulphenylation sites with high accuracy thereby facilitating biological hypothesis generation and experimental validation. The web server, datasets, and online instructions are freely available athttp://simlin.erc.monash.edu/ for academic purposes.
Analyses of inter-individual variations of sperm DNA methylation and their potential implications in cattle
Authors: Liu Shuli , Fang Lingzhao , Zhou Yang , Santos Daniel J.A. , Xiang Ruidong , Daetwyler Hans D. , Chamberlain Amanda J. , Cole John B. , Li Cong-jun , Yu Ying , Ma Li , Zhang Shengli , Liu George E.
Published: November 2019

Background

DNA methylation has been shown to be involved in many biological processes, including X chromosome inactivation in females, paternal genomic imprinting, and others.

Results

Based on the correlation patterns of methylation levels of neighboring CpG sites among 28 sperm whole genome bisulfite sequencing (WGBS) data (486 × coverage), we obtained 31,272 methylation haplotype blocks (MHBs). Among them, we defined conserved methylated regions (CMRs), variably methylated regions (VMRs) and highly variably methylated regions (HVMRs) among individuals, and showed that HVMRs might play roles in transcriptional regulation and function in complex traits variation and adaptive evolution by integrating evidence from traditional and molecular quantitative trait loci (QTL), and selection signatures. Using a weighted correlation network analysis (WGCNA), we also detected a co-regulated module of HVMRs that was significantly associated with reproduction traits, and enriched for glycosyltransferase genes, which play critical roles in spermatogenesis and fertilization. Additionally, we identified 46 VMRs significantly associated with reproduction traits, nine of which were regulated by cis-SNPs, implying the possible intrinsic relationships among genomic variations, DNA methylation, and phenotypes. These significant VMRs were co-localized (± 10 kb) with genes related to sperm motility and reproduction, includingZFP36L1,CRISP2andHGF. We provided further evidence that rs109326022 within a predominant QTL on BTA18 might influence the reproduction traits through regulating the methylation level of nearby genesJOSD2andASPDHin sperm.

Conclusion

In summary, our results demonstrated associations of sperm DNA methylation with reproduction traits, highlighting the potential of epigenomic information in genomic improvement programs for cattle.
Spatial organization of endometrial gene expression at the onset of embryo attachment in pigs
Authors: Zeng Shuqin , Ulbrich Susanne E. , Bauersachs Stefan
Published: November 2019

Background

During the preimplantation phase in the pig, the conceptus trophoblast elongates into a filamentous form and secretes estrogens, interleukin 1 beta 2, interferons, and other signaling molecules before attaching to the uterine epithelium. The processes in the uterine endometrium in response to conceptus signaling are complex. Thus, the objective of this study was to characterize transcriptome changes in porcine endometrium during the time of conceptus attachment considering the specific localization in different endometrial cell types.

Results

Low-input RNA-sequencing was conducted for the main endometrial compartments, luminal epithelium (LE), glandular epithelium (GE), blood vessels (BV), and stroma. Samples were isolated from endometria collected on Day 14 of pregnancy and the estrous cycle (each groupn = 4) by laser capture microdissection. The expression of 12,000, 11,903, 11,094, and 11,933 genes was detectable in LE, GE, BV, and stroma, respectively. Differential expression analysis was performed between the pregnant and cyclic group for each cell type as well as for a corresponding dataset for complete endometrium tissue samples. The highest number of differentially expressed genes (DEGs) was found for LE (1410) compared to GE, BV, and stroma (800, 1216, and 384). For the complete tissue, 3262 DEGs were obtained. The DEGs were assigned to Gene Ontology (GO) terms to find overrepresented functional categories and pathways specific for the individual endometrial compartments. GO classification revealed that DEGs in LE were involved in ‘biosynthetic processes’, ‘related to ion transport’, and ‘apoptotic processes’, whereas ‘cell migration’, ‘cell growth’, ‘signaling’, and ‘metabolic/biosynthetic processes’ categories were enriched for GE. For blood vessels, categories such as ‘focal adhesion’, ‘actin cytoskeleton’, ‘cell junction’, ‘cell differentiation and development’ were found as overrepresented, while for stromal samples, most DEGs were assigned to ‘extracellular matrix’, ‘gap junction’, and ‘ER to Golgi vesicles’.

Conclusions

The localization of differential gene expression to different endometrial cell types provided a significantly improved view on the regulation of biological processes involved in conceptus implantation, such as the control of uterine fluid secretion, trophoblast attachment, growth regulation by Wnt signaling and other signaling pathways, as well as the modulation of the maternal immune system.
The genomes of two parasitic wasps that parasitize the diamondback moth
Authors: Shi Min , Wang Zhizhi , Ye Xiqian , Xie Hongqing , Li Fei , Hu Xiaoxiao , Wang Zehua , Yin Chuanlin , Zhou Yuenan , Gu Qijuan , Zou Jiani , Zhan Leqing , Yao Yuan , Yang Jian , Wei Shujun , Hu Rongmin , Guo Dianhao , Zhu Jiangyan , Wang Yanping , Huang Jianhua , Pennacchio Francesco , Strand Michael R. , Chen Xuexin
Published: November 2019

Background

Parasitic insects are well-known biological control agents for arthropod pests worldwide. They are capable of regulating their host’s physiology, development and behaviour. However, many of the molecular mechanisms involved in host-parasitoid interaction remain unknown.

Results

We sequenced the genomes of two parasitic wasps (Cotesia vestalis, andDiadromus collaris) that parasitize the diamondback mothPlutella xylostellausing Illumina and Pacbio sequencing platforms. Genome assembly using SOAPdenovo produced a 178 Mb draft genome forC. vestalisand a 399 Mb draft genome forD. collaris. A total set that contained 11,278 and 15,328 protein-coding genes forC. vestalisandD. collaris, respectively, were predicted using evidence (homology-based and transcriptome-based) and de novo prediction methodology. Phylogenetic analysis showed that the braconidC. vestalisand the ichneumonidD. collarisdiverged approximately 124 million years ago. These two wasps exhibit gene gains and losses that in some cases reflect their shared life history as parasitic wasps and in other cases are unique to particular species. Gene families with functions in development, nutrient acquisition from hosts, and metabolism have expanded in each wasp species, while genes required for biosynthesis of some amino acids and steroids have been lost, since these nutrients can be directly obtained from the host. Both wasp species encode a relative higher number of neprilysins (NEPs) thus far reported in arthropod genomes while several genes encoding immune-related proteins and detoxification enzymes were lost in both wasp genomes.

Conclusions

We present the annotated genome sequence of two parasitic waspsC. vestalisandD. collaris, which parasitize a common host, the diamondback moth,P. xylostella. These data will provide a fundamental source for studying the mechanism of host control and will be used in parasitoid comparative genomics to study the origin and diversification of the parasitic lifestyle.
Transcriptome sequencing of a keystone aquatic herbivore yields insights on the temperature-dependent metabolism of essential lipids
Authors: Windisch Heidrun S. , Fink Patrick
Published: November 2019

Background

Nutritional quality of phytoplankton is a major determinant of the trophic transfer efficiency at the plant-herbivore interface in freshwater food webs. In particular, the phytoplankton’s content of the essential polyunsaturated omega-3 fatty acid eicosapentaenoic acid (EPA) has been repeatedly shown to limit secondary production in the major zooplankton herbivore genusDaphnia. Despite extensive research efforts on the biological model organismDaphnia, and the availability of severalDaphniagenomes, little is known regarding the molecular mechanisms underlying the limitations inDaphniarelated to dietary EPA availability.

Results

We used RNA-seq to analyse the transcriptomic response ofDaphnia magnawhich were fed with two different diets — each with or without supplementation of EPA — at two different temperature levels (15 and 20 °C). The transcripts were mapped to theD. magnagenome assembly version 2.4, containing 26,646 translations. WhenD. magnafed on green alga, changing the temperature provoked a differential expression of 2001 transcripts, and in cyanobacteria-fed daphnia, 3385 transcripts were affected. The supplementation of EPA affected 1635 (on the green algal diet), or 175 transcripts (on the cyanobacterial diet), respectively. Combined effects for diet and temperature were also observed (669 for the green algal and 128 transcripts for the cyanobacterial diet). Searching for orthologous genes (COG-analysis) yielded a functional overview of the altered transcriptomes. Cross-matched transcript sets from both feed types were compiled to illuminate core responses to the factors temperature and EPA-supplementation.

Conclusions

Our highly controlled eco-physiological experiments revealed an orchestrated response of genes involved in the transformation and signalling of essential fatty acids, including eicosanoid-signalling pathways with potential immune functions. We provide an overview of downstream-regulated genes, which contribute to enhance growth and reproductive output. We also identified numerous EPA-responsive candidate genes of yet unknown function, which constitute new targets for future studies on the molecular basis of EPA-dependent effects at the freshwater plant-herbivore interface.
Blp1 protein shows virulence-associated features and elicits protective immunity to Acinetobacter baumannii infection
Authors: Skerniškytė Jūratė , Karazijaitė Emilija , Deschamps Julien , Krasauskas Renatas , Armalytė Julija , Briandet Romain , Sužiedėlienė Edita
Published: November 2019

Background

Multidrug resistant Acinetobacter baumannii is one of the major infection agents causing nosocomial pneumonia. Therefore, new therapeutic approaches against this bacterium are needed. Surface-exposed proteins from bacterial pathogens are implicated in a variety of virulence-related traits and are considered as promising candidates for vaccine development.

Results

We show in this study that a large Blp1 protein from opportunistic pathogen A. baumannii is encoded in all examined clinical strains of globally spread international clonal lineages I (IC I) and II (IC II). The two blp1 gene variants exhibit lineage-specific distribution profile. By characterization of blp1 deletion mutants and their complementation with blp1 alleles we show that blp1 gene is required for A. baumannii biofilm formation and adhesion to epithelial cells in IC I strain but not in the IC II strain. Nevertheless both alleles are functional in restoring the deficient phenotypes of IC I strain. Moreover, the blp1 gene is required for the establishing of A. baumannii virulence phenotype in nematode and murine infection models. Additionally, we demonstrate that C-terminal 711 amino acid fragment of Blp1 elicits an efficient protection to lethal A. baumannii infection in a murine model using active and passive immunization approaches. Antiserum obtained against Blp1-specific antigen provides opsonophagocytic killing of A. baumannii in vitro.

Conclusions

Lineage-specific variants of surface-exposed components of bacterial pathogens complicate the development of new therapeutic approaches. Though we demonstrated different impact of Blp1 variants on adherence of IC I and IC II strains, Blp1-specific antiserum neutralized A. baumannii strains of both clonal lineages. Together with the observed increased survival rate in vaccinated mice these results indicate that A. baumannii Blp1 protein could be considered as a new vaccine candidate.
Characterization of a highly divergent Sugarcane mosaic virus from Canna indica L. by deep sequencing
Authors: Li Yongqiang , Xia Fei , Wang Yixuan , Yan Chenge , Jia Anning , Zhang Yongjiang
Published: November 2019

Background

Cannas are popular ornamental plants and widely planted for the beautiful foliage and flower. Viral disease is a major threaten to canna horticulture industry. In the city of Beijing, mosaic disease in canna was frequently observed, but the associated causal agent and its biological characterization is still unknown.

Results

After small RNA deep sequencing, 36,776 contigs were assembled and 16 of them shared high sequence identities with the different proteins of Sugarcane mosaic virus (SCMV) of the size ranging from 86 to 1911 nt. The complete genome of SCMV isolate (canna) was reconstructed by sequencing all cDNA clones obtained from RT-PCR and 5′\3′ RACE amplifications. SCMV-canna isolate showed to have a full RNA genome of 9579 nt in length and to share 78% nt and 85% aa sequence identities with SCMV isolates from other hosts. The phylogenetic tree constructed based on the full genome sequence of SCMV isolates allocated separately the canna-isolate in a distinct clade, indicating a new strain. Recombination analyses demonstrated that SCMV-canna isolate was a recombinant originating from a sugarcane-infecting isolate (major parent, acc. no. AJ310103) and a maize-infecting isolate (minor parent, acc. no. AJ297628). Pathogenicity test showed SCMV-canna could cause typical symptoms of mosaic and necrosis in some tested plants with varying levels of severity but was less virulent than the isolate SCMV-BJ. Field survey showed that the virus was widely distributed.

Conclusions

This study identified SCMV as the major agent causing the prevalent mosaic symptom in canna plants in Beijing and its genomic and biological characterizations were further explored. All these data enriched the knowledge of the viruses infecting canna and would be helpful in effective disease management in canna.
Seasonal and diurnal patterns of non-structural carbohydrates in source and sink tissues in field maize
Authors: Liang Xiao-Gui , Gao Zhen , Zhang Li , Shen Si , Zhao Xue , Liu Yun-Peng , Zhou Li-Li , Paul Matthew J. , Zhou Shun-Li
Published: November 2019

Background

Carbohydrate partitioning and utilization is a key determinant of growth rate and of yield in plants and crops. There are few studies on crops in field conditions. In Arabidopsis, starch accumulation in leaves is a negative indicator of growth rate.

Results

Here, we wished to establish if starch accumulation in leaves could potentially be a marker for growth rate and yield in crops such as maize. We characterized daily patterns of non-structural carbohydrate (NSC) at different growth stages over two seasons for maize hybrids in the field. In 27 commercial hybrids, we found a significant negative relationship between residual starch in leaves and plant growth, but not with final yield and biomass. We then focused on three typical hybrids and established a method for calculation of C turnover in photosynthetic leaves that took into account photosynthesis, leaf area and NSC accumulation. The ratios of stored NSC decreased from approximately 15% to less than 4% with ongoing ontogeny changes from V7 to 28 days after pollination.

Conclusion

The proportion rather than absolute amount of carbon partitioned to starch in leaves at all stages of development related well with yield and biomass accumulation. It is proposed that screening plants at an early vegetative growth stage such as V7 for partitioning into storage may provide a prospective method for maize hybrid selection. Our study provides the basis for further validation as a screening tool for yield.
Whole-transcriptome RNA sequencing reveals the global molecular responses and ceRNA regulatory network of mRNAs, lncRNAs, miRNAs and circRNAs in response to copper toxicity in Ziyang Xiangcheng (Citrus junos Sieb. Ex Tanaka)
Authors: Fu Xing-Zheng , Zhang Xiao-Yong , Qiu Jie-Ya , Zhou Xue , Yuan Meng , He Yi-Zhong , Chun Chang-Pin , Cao Li , Ling Li-Li , Peng Liang-Zhi
Published: November 2019

Background

Copper (Cu) toxicity has become a potential threat for citrus production, but little is known about related mechanisms. This study aims to uncover the global landscape of mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in response to Cu toxicity so as to construct a regulatory network of competing endogenous RNAs (ceRNAs) and to provide valuable knowledge pertinent to Cu response in citrus.

Results

Tolerance of four commonly used rootstocks to Cu toxicity was evaluated, and ‘Ziyang Xiangcheng’ (Citrus junos) was found to be the most tolerant genotype. Then the roots and leaves sampled from ‘Ziyang Xiangcheng’ with or without Cu treatment were used for whole-transcriptome sequencing. In total, 5734 and 222 mRNAs, 164 and 5 lncRNAs, 45 and 17 circRNAs, and 147 and 130 miRNAs were identified to be differentially expressed (DE) in Cu-treated roots and leaves, respectively, in comparison with the control. Gene ontology enrichment analysis showed that most of the DEmRNAs and targets of DElncRNAs and DEmiRNAs were annotated to the categories of ‘oxidation-reduction’, ‘phosphorylation’, ‘membrane’, and ‘ion binding’. The ceRNA network was then constructed with the predicted pairs of DEmRNAs-DEmiRNAs and DElncRNAs-DEmiRNAs, which further revealed regulatory roles of these DERNAs in Cu toxicity.

Conclusions

A large number of mRNAs, lncRNAs, circRNAs, and miRNAs in ‘Ziyang Xiangcheng’ were altered in response to Cu toxicity, which may play crucial roles in mitigation of Cu toxicity through the ceRNA regulatory network in this Cu-tolerant rootstock.
Identification of quantitative trait loci for increased α-tocopherol biosynthesis in wild soybean using a high-density genetic map
Authors: Park Cheolwoo , Dwiyanti Maria Stefanie , Nagano Atsushi J. , Liu Baohui , Yamada Tetsuya , Abe Jun
Published: November 2019

Background

Soybean is one of the most important crop sources of tocopherols (Toc). However, the content of α-Toc, an isoform with the highest vitamin E activity in humans, is low in most cultivars. With the aim of broadening genetic variability, we performed quantitative trait locus (QTL) analysis for a high seed α-Toc trait detected in a wild soybean and characterized the sequence polymorphisms and expression profiles of γ-tocopherol methyltransferase (γ-TMT) genes as potential candidates.

Results

A recombinant inbred line population was developed from a cross between the low α-Toc breeding line TK780 and the high α-Toc wild accession B04009. The α-Toc content in seeds correlated strongly with the ratio of α-Toc to γ-Toc contents. QTL analysis using a high-density map constructed with 7710 single nucleotide polymorphisms (SNPs) generated by restriction site-associated DNA sequencing detected six QTLs involved in α-Toc biosynthesis. Of these, three in chromosomes (Chr) 9, 11, and 12 produced consistent effects during a 2-year trial. B04009 allele at QTLs in Chr9 and Chr12 and TK780 allele at the QTL in Chr11 each promoted the conversion of γ-Toc to α-Toc, which elevated the seed α-Toc content. SNPs and indels were detected between the parents in three γ-TMT genes (γ-TMT1, γ-TMT2, and γ-TMT3) co-located in the QTLs in Chr9 and Chr12, of which some existed in the cis-regulatory elements associated with seed development and functions. In immature cotyledons, γ-TMT3 was expressed at higher levels in B04009 than TK780, irrespective of two thermal conditions tested, whereas the expression of γ-TMT2 was markedly upregulated under higher temperatures, particularly in B04009.

Conclusions

We identified QTLs consistently controlling α-Toc biosynthesis in wild soybean seeds in 2-year trials. The QTL on Chr9 had been previously identified in soybean, whereas the QTLs on Chr11 and Chr12 were novel. Further molecular dissections and characterization of the QTLs may facilitate the use of high α-Toc alleles from wild soybean in soybean breeding and an understanding of the molecular mechanisms underlying α-Toc biosynthesis in soybean seeds.
Multiplex nucleotide editing by high-fidelity Cas9 variants with improved efficiency in rice
Authors: Xu Wen , Song Wei , Yang Yongxing , Wu Ying , Lv Xinxin , Yuan Shuang , Liu Ya , Yang Jinxiao
Published: November 2019

Background

Application of the CRISPR/Cas9 system or its derived base editors enables targeted genome modification, thereby providing a programmable tool to exploit gene functions and to improve crop traits.

Results

We report that PmCDA1 is much more efficient than rAPOBEC1 when fused to CRISPR/Cas9 nickase for the conversion of cytosine (C) to thymine (T) in rice. Three high-fidelity SpCas9 variants, eSpCas9(1.1), SpCas9-HF2 and HypaCas9, were engineered to serve with PmCDA1 (pBEs) as C-to-T base editors. These three high-fidelity editors had distinct multiplex-genome editing efficiencies. To substantially improve their base-editing efficiencies, a tandemly arrayed tRNA-modified single guide RNA (sgRNA) architecture was applied. The efficiency of eSpCas9(1.1)-pBE was enhanced up to 25.5-fold with an acceptable off-target effect. Moreover, two- to five-fold improvement was observed for knock-out mutation frequency by these high-fidelity Cas9s under the direction of the tRNA-modified sgRNA architecture.

Conclusions

We have engineered a diverse toolkit for efficient and precise genome engineering in rice, thus making genome editing for plant research and crop improvement more flexible.
Does depressed persons with non-cardiovascular morbidity have a higher risk of CVD? A population-based cohort study in Sweden
Authors: Almas Aysha , Moller Jette , Iqbal Romaina , Lundin Andreas , Forsell Yvonne
Published: November 2019

Background

Depression often co-exists with non-cardiovascular morbid conditions. Whether this comorbidity increases the risk of cardiovascular disease has so far not been studied. Thus, the aim of this study was to determine if non-cardiovascular morbidity modifies the effect of depression on future risk of CVD.

Methods

Data was derived from the PART study (acronym in Swedish for: Psykisk hälsa, Arbete och RelaTioner: Mental Health, Work and Relationships), a longitudinal cohort study on mental health, work and relations, including 10,443 adults (aged 20–64 years). Depression was assessed using the Major Depression Inventory (MDI) and self-reported data on non-cardiovascular morbidity was assessed in 1998–2000. Outcomes of CVD were assessed using the National Patient Register during 2001–2014.

Results

Both depression (HR 1.5 (95% CI, 1.1, 2.0)) and non-cardiovascular morbidity (HR 2.0 (95% CI, 1.8, 2.6)) were associated with an increased future risk of CVD. The combined effect of depression and non-cardiovascular comorbidity on future CVD was HR 2.1 (95%, CI 1.3, 3.4) after adjusting for age, gender and socioeconomic position. Rather similar associations were seen after further adjustment for hypertension, diabetes and unhealthy lifestyle factors.

Conclusion

Persons affected by depression in combination with non-cardiovascular morbidity had a higher risk of CVD compared to those without non-cardiovascular morbidity or depression alone.
Changes in primary care provider utilization by phase of care for women diagnosed with breast cancer: a CanIMPACT longitudinal cohort study
Authors:   for the Canadian Team to Improve Community-Based Cancer Care Along the Continuum (CanIMPACT), Decker K. , Moineddin R. , Kendell C. , Urquhart R. , Biswanger N. , Groome P. , McBride M. L. , Winget M. , Whitehead M. , Grunfeld E.
Published: November 2019

Background

Primary care providers (PCPs) have always played an important role in cancer diagnosis. There is increasing awareness of the importance of their role during treatment and survivorship. We examined changes in PCP utilization from pre-diagnosis to survival for women diagnosed with breast cancer, factors associated with being a high user of primary care, and variation across four Canadian provinces.

Methods

The cohorts included women 18+ years of age diagnosed with stage I-III invasive breast cancer in years 2007–2012 in British Columbia (BC), Manitoba (MB), Ontario (ON), and Nova Scotia (NS) who had surgery plus adjuvant chemotherapy and were alive 30+ months after diagnosis (N = 19,589). We compared the rate of PCP visits in each province across phases of care (pre-diagnosis, diagnosis, treatment, and survival years 1 to 4).

Results

PCP use was greatest during treatment and decreased with each successive survival year in all provinces. The unadjusted difference in PCP use between treatment and pre-diagnosis was most pronounced in BC where PCP use was six times higher during treatment than pre-diagnosis. Factors associated with being a high user of primary care during treatment included comorbidity and being a high user of care pre-diagnosis in all provinces. These factors were also associated with being a higher user of care during diagnosis and survival.

Conclusions

Contrary to the traditional view that PCPs focus primarily on cancer prevention and early detection, we found that PCPs are involved in the care of women diagnosed with breast cancer across all phases of care.
Elevated serum triglyceride and low-density lipoprotein cholesterol promotes the formation of colorectal polyps
Authors: Xie Chenxi , Wen Pingwu , Su Jingling , Li Qin , Ren Yandan , Liu Yueyu , Shen Renze , Ren Jianlin
Published: November 2019

Background

Hyperlipidaemia may be a potential risk factor for the occurrence of intestinal polyps. This study aimed to evaluate correlation between lipidaemia and the formation of colorectal polyps.

Methods

One hundred and fourteen patients with colorectal polyps and forty-eight healthy controls were included in this study. Colonoscopies were performed for all patients and controls within 1 week before blood samples were taken. The concentrations of serum lipids and lipoproteins were measured simultaneously using an automatic biochemical analyser. The colorectal lesions were classified based on pathological characteristics, and four types were identified in the study: hyperplastic polyp (HP), tubular adenoma (TA), tubulovillous adenoma (TVA) and adenoma with high-grade dysplasia (A-HGD). Advanced adenoma was classified according to the number, size and histological type of polyps.

Results

The value of low-density lipoprotein cholesterol (LDL-C) was significantly higher in the group with advanced adenoma than in the controls (p < 0.05). Moreover, the LDL-C values in the HP and TA groups were higher when compared to that of controls (p < 0.05). Obesity, age, and increased TG and LDL-C were independent risk factors for the formation of colorectal polyps. The cut-off values of triglyceride (TG) and LDL-C to distinguish polyp patients from healthy controls were 0.96 mmol/L (AUC = 0.604, p = 0.036) and 3.05 mmol/L (AUC = 0.654, p = 0.002). The combined use of increased LDL-C and TG levels to distinguish polyp patients was effective, with a sensitivity of 50.0% and a specificity of 89.6% (AUC = 0.733, p < 0.01).

Conclusions

Colorectal polyps are more often found in obese and older patients. Increased LDL-C and TG were correlated with the occurrence of polyps. Combination of the two serum indicators was useful to assess risk of colorectal lesions, maybe more effective in screening hyperplastic polyp, tubular adenoma and advanced adenoma.
Validation of the clinical frailty score (CFS) in French language
Authors: Abraham Paul , Courvoisier Delphine S. , Annweiler Cedric , Lenoir Cliff , Millien Thomas , Dalmaz Francoise , Flaatten Hans , Moreno Rui , Christensen Steffen , de Lange Dylan W. , Guidet Bertrand , Bendjelid Karim , Walder Bernhard , Bollen Pinto Bernardo
Published: November 2019

Background

Very old critical ill patients are a rapid expanding group. To better understand the magnitude of the challenges involved in intensive care practice for an ageing population and discuss a rational allocation of resources, healthcare practitioners need a reliable evaluation of frailty. In order to promote the adequate use of the Clinical Frailty Scale (CFS) in a wider panel of countries, we aimed to develop, validate and characterise a French (FR) version from the original English (EN) CFS.

Methods

We included participants recruited prospectively for the observational “The very old intensive care patient: A multinational prospective observation study” (VIP Study) at Geneva University Hospitals (FR speaking hospital). A FR version of the CFS was obtained by translation (EN- > FR) and back translation (FR- > EN). The final CFS-FR was then evaluated twice on the same participants with at least a 2-week interval by FR-speaking doctors and nurses.

Results

Inter-rater reliability was 0.87 (95%CI: 0.76–0.93) between doctors for the original CFS version and 0.76 (95%CI: 0.57–0.87) between nurses for the FR version. Inter-rater variability between doctor and nurse was 0.75 (95%CI: 0.56–0.87) for the original version, and 0.73 (95%CI: 0.52–0.85) for the FR version.

Test-retest (stability) with the original vs the FR version was 0.86 (95%CI: 0.72–0.93) for doctors and 0.87 (95%CI: 0.76–0.93) for nurses.

Differences between the evaluations of the CFS-EN and CSF-FR were not different from 0, with a mean difference of 0.06 (95%CI -0.24, 0.36) for the EN version and − 0.03 (95%CI -0.47, 0.41) for the FR version. Average original version ratings were slightly lower than FR version ratings, though this difference did not reach significance: -0.29 (95%CI -0.54, 0.04).

Conclusion

In this prospective cohort of very old intensive care participants we developed and tested the basic psychometric properties (internal consistency, reproducibility) of a French version of the CFS. This manuscript provides clinically meaningful psychometric properties that have not been previously reported in any other language, including in the original EN version.

The French cultural adaptation of this CFS has adequate psychometric properties for doctors or nurses to evaluate frailty in very old intensive care patients.
Being the next of kin of an older person living in a nursing home: an interview study about quality of life
Authors: Rosén Helena , Behm Lina , Wallerstedt Birgitta , Ahlström Gerd
Published: November 2019

Background

The length of stay in nursing homes before death in Sweden has significantly decreased, and nearly one-third of people die within 6 weeks of entering a nursing home. Support for the next of kin is one of the cornerstones of palliative care, but the principles are not always adhered to as recommended when caring for the elderly, which can affect the quality of life of their next of kin. The aim of this study was to explore the experiences of quality of life among the next of kin of older persons who live in nursing homes before an educational intervention of palliative care.

Methods

This is an explorative qualitative interview study with 40 next of kin using qualitative content analysis performed at baseline before the implementation of the principles of palliative care in nursing homes.

Results

The next of kin’s experiences of quality of life were expressed in three themes: Orientation to the new life situation, Challenges in their relationship and the Significance of the quality of care in the nursing home. The next of kin experienced a sense of relief, although the older person was constantly on their minds, and they could feel lonely. The difference in the couple’slife situations was experienced as burdensome by the next of kin. The challenges in the relationship were described as stressful, related to a guilty conscience and the older person’s vulnerability. The nursing home could be a context facilitating good relations. The perceptions of quality of care in terms of person-centredness affected the quality of life of the next of kin.

Conclusions

The findings show that four factors are decisive for the quality of life of next of kin: the relationships within the family, the degree of relief that nursing home care entails as compared to home care, the older person’s health status and whether the care is person-centred. Increased knowledge and education regarding palliative care in nursing homes are needed to better meet the needs of next of kin. Implementation of palliative care should take into account the need for support for next of kin.

Trial registration

NCT02708498, 15 March 2016.
Disability incidence and functional decline among older adults with major chronic diseases
Authors: Fong Joelle H.
Published: November 2019

Background

More than 80% of elderly Americans have at least one chronic disease. While past studies have shown that hierarchical patterns of functional loss may differ by gender and institutional settings, little is known about whether such patterns differ in relation to chronic health condition. The aim of this study is to investigate the pattern of functional loss among older adults with major chronic illnesses, and to compare their onset and ordering of incident ADL disability with those of persons without such conditions.

Methods

We use a nationally representative sample of persons aged 80+ from the 1998–2014 Asset and Health Dynamics of the Oldest Old survey. The group with major noncommunicable diseases (including cardiovascular disease, cancer, chronic respiratory disease, and diabetes) comprises 3,514,052 subjects, while the comparison group comprises 1,073,263 subjects. Self-reports of having difficulty with six distinct ADLs are used to estimate disability incidence rate. Nonparametric statistical methods are used to derive median onset ages and ADL loss sequence separately for each group.

Results

Older adults with major chronic diseases have higher rates of incident disability across all ADL items. Estimated median onset ages of ADL disabilities for the full sample range from 91.5 to 95.6. Disability occurs earlier for chronically ill persons (onset ages 91.1–95.0) than for those in the comparison group (onset ages 93.5–98.1). Among those with major chronic diseases, the ADL loss sequence ordered by median ages of disability onset is bathing, walking, dressing, toileting, transferring and eating. The activities are also distinctly separated into an early-loss cluster and a late-loss cluster. Although the loss sequence derived for the comparison group is largely similar, disability progression for those with major chronic diseases is compressed within a shorter timeframe and the timing gaps between adjacent disabilities are smaller.

Conclusions

Older Americans with major noncommunicable diseases face an earlier and steeper slope of functional decline. Chronic care delivery programs should adapt to dynamic changes in older patients’ functional status. Health interventions to help patients delay disability onset and optimize functional autonomy within emerging models of chronic care should especially target early-loss activities such as bathing, dressing, and walking.
Magnitude of Rotavirus A and Campylobacter jejuni infections in children with diarrhea in Twin cities of Rawalpindi and Islamabad, Pakistan
Authors: Sadiq Asma , Bokhari Habib , Noreen Zobia , Asghar Rai Muhammad , Bostan Nazish
Published: November 2019

Background

Acute diarrhea is a leading cause of morbidity and mortality in children particularly in developing countries of Asia and Africa. The present study was conducted to detect the two most important pathogens, rotavirus and Campylobacter Jejuni in children suffering with diarrhea in Rawalpindi and Islamabad, Pakistan in 2014. The clinical and epidemiological aspects of the disease were also investigated.

Methods

A total of 500 stool samples were collected from children presented with clinical signs and symptoms of acute diarrhea. The samples were initially screened for the presence of rotavirus A (RVA) via ELISA (Enzyme-linked immunosorbent assay) and RT-PCR (Reverse Transcriptase PCR) and then were analysed for C. jejuni by using species specific PCR assay.

Results

The detection rate of RVA was 26.4% (132/500) while, Campylobacter was detected in 52% (260/500) of samples with C. jejuni accounted for 48.2% (241/500) of all study cases. Co-infection of C. jejuni with RVA was identified in 21.8% of all cases. Children with RVA and C. jejuni co-infection showed a higher probability (p = 0.01) to be dehydrated. A significant association (p = 0.02) was found between C. jejuni positive status and fever in children. The median age of children with both RVA and C. jejuni infection was 6–11 months. The RVA detection rate was high in winter months of the year while, C. jejuni infections were documented high in summer over 1 year study period.

Conclusions

The overall results have demonstrated the high prevalence of C. jejuni in Rawalpindi, Islamabad, Pakistan in 2014. The results of present study will not only help to calculate disease burden caused by C. jejuni and rotavirus but also will provide critical information to health authorities in planning public health care strategies against these pathogens.