bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifunctional graphene metasurface to generate and steer vortex waves
Authors: Wang Mengyu , Zeng Qingsheng , Deng Li , Feng Botao , Xu Ping 
Published: November 2019

Abstract
Graphene, an innovated 2D material with atomic thickness, is a very promising candidate and has drawn great attentions in various applications. Graphene metasurface enables dynamic control of various wavefronts, achieving distinguished functionalities. The flexibility of graphene metasurface makes it possible to implement multifunctional devices with ease. In this work, a novel design of multifunctional graphene metasurface, which can combine the functionalities of generating and steering vortex waves, has been proposed. The multifunctional graphene metasurface consists of a large array of graphene reflective unit cells. Each unit cell is controlled independently by its size and external static gate voltage. By scrutinizing the reflective property of the graphene cell, the graphene metasurface is designed to realize multi-functionalities. Simulation results show that vortex wave can be generated and steered. This work can establish a methodology to design multifunctional graphene metasurfaces, and the tunability of graphene opens the gate to the design and fabrication of reconfigurable graphene devices.
Estrogen biosynthesis in cultured skeletal muscle cells (L6) induced by amino acids
Authors: Iresjö Britt-Marie , Landin Andreas , Ohlsson Claes , Lundholm Kent 
Published: November 2019

Abstract

Background
Previous investigations have indicated upregulation of gene expression in cellular pathways related to the biosynthesis of steroids in response to amino acids (AA) in skeletal muscle cells. This suggests AA as modulators of de novo synthesis of sex steroids for muscle growth and improved functional capacity. The aim of the present study was to investigate if increased availability of amino acids induced biosynthesis of sex steroids in skeletal muscles.

Methods
Confluent L6 muscle cells were cultured in media with various AA concentrations (0.3 or 9 mM AA or 2.1 mM branched-chain (BCAA) only), following pre-culture in serum-free medium. Sex steroids were quantified by gas chromatography-tandem mass spectrometry (GC-MS/MS). Mevalonate (diphospho-) decarboxylase enzyme (MVD) was quantified by Western blot.

Results
The experiments confirmed that estradiol and estrone increased in both L6 cell lysates and in conditioned media at the end of experiments on confluent cells, while progesterone or androgenic steroids were not detected in either cell lysates or culture media. Estradiol (+ 31 ± 3%) and estrone (+ 18 ± 4%) increased significantly in cells cultured at 9 mM AA (p < 0.001 vs. 0.3 mM AA, n = 10). Similarly, MVD protein increased at 9 mM AA (p < 0.001 vs. 0.3 mM AA, n = 17). An addition of BCAA alone to media increased MVD-protein levels to the same extent as all AA (p < 0.01 vs. 0.3 mM AA, n = 3).

Conclusion
Female sex steroids and MVD enzyme production increased significantly in response to amino acid availability. The results indicate a role of amino acids as modulators of local muscle estrogen synthesis in muscle cells from rats at feeding.
A novel approach to carotenoid accumulation in rice callus by mimicking the cauliflower Orange mutation via genome editing
Authors: Endo Akira , Saika Hiroaki , Takemura Miho , Misawa Norihiko , Toki Seiichi 
Published: November 2019

Abstract

Background
β-carotene (provitamin A) is an important target for biofortification of crops as a potential solution to the problem of vitamin A deficiency that is prevalent in developing countries. A previous report showed that dominant expression of splicing variants in the Orange (Or) gene causes β-carotene accumulation in cauliflower curd. In this study, we focused on a putative orthologue of the cauliflower or gene in rice, Osor, and attempt to accumulate β-carotene in rice callus by modification of the Osor gene via genome editing using CRISPR/Cas9.

Findings
CRISPR/Cas9 vectors for the Osor gene were constructed and transformed into rice calli. Some transformed calli showed orange color due to β-carotene hyper-accumulation. Molecular analyses suggest that orange-colored calli are due to an abundance of in-frame aberrant Osor transcripts, whereas out-of-frame mutations were not associated with orange color.

Conclusions
We demonstrate that directed gene modification of the Osor gene via CRISPR/Cas9-mediated genome editing results in β-carotene fortification in rice calli. To date, golden rice, which accumulates β-carotene in rice endosperm, has been developed by conventional transgenic approaches. Our results suggest an alternative approach to enhancing β-carotene accumulation in crops.
An integrative methodology based on protein-protein interaction networks for identification and functional annotation of disease-relevant genes applied to channelopathies
Authors: Marín Milagros , Esteban Francisco J. , Ramírez-Rodrigo Hilario , Ros Eduardo , Sáez-Lara María José 
Published: November 2019

AbstractBackgroundBiologically data-driven networks have become powerful analytical tools that handle massive, heterogeneous datasets generated from biomedical fields. Protein-protein interaction networks can identify the most relevant structures directly tied to biological functions. Functional enrichments can then be performed based on these structural aspects of gene relationships for the study of channelopathies. Channelopathies refer to a complex group of disorders resulting from dysfunctional ion channels with distinct polygenic manifestations. This study presents a semi-automatic workflow using protein-protein interaction networks that can identify the most relevant genes and their biological processes and pathways in channelopathies to better understand their etiopathogenesis. In addition, the clinical manifestations that are strongly associated with these genes are also identified as the most characteristic in this complex group of diseases.ResultsIn particular, a set of nine representative disease-related genes was detected, these being the most significant genes in relation to their roles in channelopathies. In this way we attested the implication of some voltage-gated sodium (SCN1A, SCN2A, SCN4A, SCN4B, SCN5A, SCN9A) and potassium (KCNQ2, KCNH2) channels in cardiovascular diseases, epilepsies, febrile seizures, headache disorders, neuromuscular, neurodegenerative diseases or neurobehavioral manifestations. We also revealed the role of Ankyrin-G (ANK3) in the neurodegenerative and neurobehavioral disorders as well as the implication of these genes in other systems, such as the immunological or endocrine systems.ConclusionsThis research provides a systems biology approach to extract information from interaction networks of gene expression. We show how large-scale computational integration of heterogeneous datasets, PPI network analyses, functional databases and published literature may support the detection and assessment of possible potential therapeutic targets in the disease. Applying our workflow makes it feasible to spot the most relevant genes and unknown relationships in channelopathies and shows its potential as a first-step approach to identify both genes and functional interactions in clinical-knowledge scenarios of target diseases.MethodsAn initial gene pool is previously defined by searching general databases under a specific semantic framework. From the resulting interaction network, a subset of genes are identified as the most relevant through the workflow that includes centrality measures and other filtering and enrichment databases.
Proton pump inhibitors can reverse the YAP mediated paclitaxel resistance in epithelial ovarian cancer
Authors: He Jing , Shi Xiao-Yan , Li Zhi-min , Pan Xiao-hua , Li Ze-Lian , Chen Ying , Yan Shi-Jie , Xiao Lan 
Published: November 2019

Abstract

Background
Several reports indicated that the expression of Yes-associated protein (YAP) was associated with multi-drug resistance. Acidic microenvironment increased by the overexpression of vacuolar-ATPase (V-ATPase) was also observed in tumor growth and drug resistance. We hypothesize that proton pump inhibitors (PPIs), currently used in the anti-acid treatment of peptic disease, could inhibit the acidification of the tumor microenvironment and increase the sensitivity of tumor cells to cytotoxic agents. Thus, our objective is to explore the reversal of drug resistance by the inhibition of YAP through specific PPIs in the epithelial ovarian carcinoma (EOC) cells. .

Results
We found that V-ATPase D1 was a positive regulator of YAP. Sub-lethal doses of the proton pump inhibitor esomeprazole (EMSO) in combination with paclitaxel (PTX) increased the PTX sensitivity in PTX-resistant EOC cells, as compared to PTX single treatments by inhibiting YAP and reserving pH gradient created by the V-ATPase D1. Moreover, sub-lethal doses of EMSO combined with PTX decreased autophagy and improved caspases independent apoptosis of PTX-resistant EOC cells.

Conclusions
These results suggested that sub-lethal doses of esomeprazole reverse YAP-mediated PTX resistance through the inhibiting of both YAP expression and acidic tumor microenvironment created by the V-ATPase D1. Therefore, we think the use of PPIs represents a promising strategy to improve the effectiveness of anti-EOC.
Survival of Polyploid hybrid salamander embryos
Authors: Charney Noah D. , Kubel Jacob E. , Woodard Craig T. , Carbajal-González Blanca I. , Avis Samantha , Blyth Julia A. , Eiseman Charles S. , Castorino John , Malone John H. 
Published: November 2019

Abstract

Background
Animals with polyploid, hybrid nuclei offer a challenge for models of gene expression and regulation during embryogenesis. To understand how such organisms proceed through development, we examined the timing and prevalence of mortality among embryos of unisexual salamanders in the genus Ambystoma.

Results
Our regional field surveys suggested that heightened rates of embryo mortality among unisexual salamanders begin in the earliest stages of embryogenesis. Although we expected elevated mortality after zygotic genome activation in the blastula stage, this is not what we found among embryos which we reared in the laboratory. Once embryos entered the first cleavage stage, we found no difference in mortality rates between unisexual salamanders and their bisexual hosts. Our results are consistent with previous studies showing high rates of unisexual mortality, but counter to reports that heightened embryo mortality continues throughout embryo development.

Conclusions
Possible causes of embryonic mortality in early embryogenesis suggested by our results include abnormal maternal loading of RNA during meiosis and barriers to insemination. The surprising survival rates of embryos post-cleavage invites further study of how genes are regulated during development in such polyploid hybrid organisms.
Electrochemical gradients are involved in regulating cytoskeletal patterns during epithelial morphogenesis in the Drosophila ovary
Authors: Weiß Isabel , Bohrmann Johannes 
Published: November 2019

AbstractBackgroundDuringDrosophilaoogenesis, the follicular epithelium differentiates into several morphologically distinct follicle-cell populations. Characteristic bioelectrical properties make this tissue a suitable model system for studying connections between electrochemical signals and the organisation of the cytoskeleton. Recently, we have described stage-specific transcellular antero-posterior and dorso-ventral gradients of intracellular pH (pHi) and membrane potential (Vmem) depending on the asymmetrical distribution and/or activity of various ion-transport mechanisms. In the present study, we analysed the patterns of basal microfilaments (bMF) and microtubules (MT) in relation to electrochemical signals.ResultsThe bMF- and MT-patterns in developmental stages 8 to 12 were visualised using labelled phalloidin and an antibody against acetylated α-tubulin as well as follicle-cell specific expression of GFP-actin and GFP-α-tubulin. Obviously, stage-specific changes of the pHi- and Vmem-gradients correlate with modifications of the bMF- and MT-organisation. In order to test whether cytoskeletal modifications depend directly on bioelectrical changes, we used inhibitors of ion-transport mechanisms that have previously been shown to modify pHiand Vmemas well as the respective gradients. We inhibited, in stage 10b, Na+/H+-exchangers and Na+-channels with amiloride, V-ATPases with bafilomycin, ATP-sensitive K+-channels with glibenclamide, voltage-dependent L-type Ca2+-channels with verapamil, Cl−-channels with 9-anthroic acid and Na+/K+/2Cl−-cotransporters with furosemide, respectively. The correlations between pHi, Vmem, bMF and MT observed in different follicle-cell types are in line with the correlations resulting from the inhibition experiments. While relative alkalisation and/or hyperpolarisation stabilised the parallel transversal alignment of bMF, acidification led to increasing disorder and to condensations of bMF. On the other hand, relative acidification as well as hyperpolarisation stabilised the longitudinal orientation of MT, whereas alkalisation led to loss of this arrangement and to partial disintegration of MT.ConclusionsWe conclude that the pHi- and Vmem-changes induced by inhibitors of ion-transport mechanisms simulate bioelectrical changes occurring naturally and leading to the cytoskeletal changes observed during differentiation of the follicle-cell epithelium. Therefore, gradual modifications of electrochemical signals can serve as physiological means to regulate cell and tissue architecture by modifying cytoskeletal patterns.
SNP eQTL status and eQTL density in the adjacent region of the SNP are associated with its statistical significance in GWA studies
Authors: Gorlov Ivan , Xiao Xiangjun , Mayes Maureen , Gorlova Olga , Amos Christopher 
Published: November 2019

AbstractBackgroundOver the relatively short history of Genome Wide Association Studies (GWASs), hundreds of GWASs have been published and thousands of disease risk-associated SNPs have been identified. Summary statistics from the conducted GWASs are often available and can be used to identify SNP features associated with the level of GWAS statistical significance. Those features could be used to select SNPs from gray zones (SNPs that are nominally significant but do not reach the genome-wide level of significance) for targeted analyses.MethodsWe used summary statistics from recently published breast and lung cancer and scleroderma GWASs to explore the association between the level of the GWAS statistical significance and the expression quantitative trait loci (eQTL) status of the SNP. Data from the Genotype-Tissue Expression Project (GTEx) were used to identify eQTL SNPs.ResultsWe found that SNPs reported as eQTLs were more significant in GWAS (higher -log10p) regardless of the tissue specificity of the eQTL. Pan-tissue eQTLs (those reported as eQTLs in multiple tissues) tended to be more significant in the GWAS compared to those reported as eQTL in only one tissue type. eQTL density in the ±5 kb adjacent region of a given SNP was also positively associated with the level of GWAS statistical significance regardless of the eQTL status of the SNP. We found that SNPs located in the regions of high eQTL density were more likely to be located in regulatory elements (transcription factor or miRNA binding sites).When SNPs were stratified by the level of statistical significance, the proportion of eQTLs was positively associated with the mean level of statistical significance in the group. The association curve reaches a plateau around -log10p ≈ 5. The observed associations suggest that quasi-significant SNPs (10− 5 < p < 5 × 10− 8) and SNPs at the genome wide level of statistical significance (p < 5 × 10− 8) may have a similar proportions of risk associated SNPs.ConclusionsThe results of this study indicate that the SNP’s eQTL status, as well as eQTL density in the adjacent region are positively associated with the level of statistical significance of the SNP in GWAS.
Genetic analysis of novel phenotypes for farm animal resilience to weather variability
Authors: Sánchez-Molano Enrique , Kapsona Vanessa V. , Ilska Joanna J. , Desire Suzanne , Conington Joanne , Mucha Sebastian , Banos Georgios 
Published: November 2019

Abstract

Background
Climate change is expected to have a negative impact on food availability. While most efforts have been directed to reducing greenhouse gas emissions, complementary strategies are necessary to control the detrimental effects of climate change on farm animal performance. The objective of this study was to develop novel animal resilience phenotypes using reaction norm slopes, and examine their genetic and genomic parameters. A closely monitored dairy goat population was used for this purpose.

Results
Individual animals differed in their response to changing atmospheric temperature and a temperature-humidity index. Significant genetic variance and heritability estimates were derived for these animal resilience phenotypes. Furthermore, some resilience traits had a significant unfavourable genetic correlation with animal performance. Genome-wide association analyses identified several candidate genes related to animal resilience to environment change.

Conclusions
Heritable variation exists among dairy goats in their production response to fluctuating weather variables. Results may inform future breeding programmes aimed to ensure efficient animal performance under changing climatic conditions.
Characterization and discovery of miRNA and miRNA targets from apomictic and sexual genotypes of Eragrostis curvula
Authors: Garbus Ingrid , Selva Juan Pablo , Pasten María Cielo , Bellido Andrés Martín , Carballo José , Albertini Emidio , Echenique Viviana 
Published: November 2019

AbstractBackgroundWeeping lovegrass (Eragrostis curvula[Shrad.] Nees) is a perennial grass found in semi-arid regions that is well adapted for growth in sandy soils and drought conditions.E. curvulaconstitutes a polymorphic complex that includes cytotypes with different ploidy levels (from 2x to 8x), where most polyploids are facultative apomicts, although both sexual reproduction and full apomixis have been reported in this species. Apomixis is thought to be associated with silencing of the sexual pathway, which would involve epigenetic mechanisms. However, a correlation between small RNAs and apomixis has not yet been conclusively established.ResultsAiming to contribute to the elucidation of their role in the expression of apomixis, we constructed small RNA libraries from sexual and apomicticE. curvulagenotypes via Illumina technology, characterized the small RNA populations, and conducted differential expression analysis by comparing these small RNAs with theE. curvulareference transcriptome. We found that the expression of two genes is repressed in the sexual genotype, which is associated with specific microRNA expression.ConclusionOur results support the hypothesis that inE. curvulathe expression of apomixis leads to sexual repression.
Identification of loci associated with conception rate in primiparous Holstein cows
Authors: Kiser Jennifer N. , Clancey Erin , Moraes Joao G. N. , Dalton Joseph , Burns Gregory W. , Spencer Thomas E. , Neibergs Holly L. 
Published: November 2019

Abstract

Background
Subfertility is a major issue facing the dairy industry as the average US Holstein cow conception rate (CCR) is approximately 35%. The genetics underlying the physiological processes responsible for CCR, the proportion of cows able to conceive and maintain a pregnancy at each breeding, are not well characterized. The objectives of this study were to identify loci, positional candidate genes, and transcription factor binding sites (TFBS) associated with CCR and determine if there was a genetic correlation between CCR and milk production in primiparous Holstein cows. Cows were bred via artificial insemination (AI) at either observed estrus or timed AI and pregnancy status was determined at day 35 post-insemination. Additive, dominant, and recessive efficient mixed model association expedited (EMMAX) models were used in two genome-wide association analyses (GWAA). One GWAA focused on CCR at first service (CCR1) comparing cows that conceived and maintained pregnancy to day 35 after the first AI (n = 494) to those that were open after the first AI (n = 538). The second GWAA investigated loci associated with the number of times bred (TBRD) required for conception in cows that either conceived after the first AI (n = 494) or repeated services (n = 472).

Results
The CCR1 GWAA identified 123, 198, and 76 loci associated (P < 5 × 10− 08) in additive, dominant, and recessive models, respectively. The TBRD GWAA identified 66, 95, and 33 loci associated (P < 5 × 10− 08) in additive, dominant, and recessive models, respectively. Four of the top five loci were shared in CCR1 and TBRD for each GWAA model. Many of the associated loci harbored positional candidate genes and TFBS with putative functional relevance to fertility. Thirty-six of the loci were validated in previous GWAA studies across multiple breeds. None of the CCR1 or TBRD associated loci were associated with milk production, nor was their significance with phenotypic and genetic correlations to 305-day milk production.

Conclusions
The identification and validation of loci, positional candidate genes, and TFBS associated with CCR1 and TBRD can be utilized to improve, and further characterize the processes involved in cattle fertility.
Subsets of mononuclear phagocytes are enriched in the inflamed colons of patients with IBD
Authors: Liu Hong , Dasgupta Suryasarathi , Fu Yu , Bailey Brandi , Roy Christian , Lightcap Eric , Faustin Benjamin 
Published: November 2019

Abstract

Background
Myeloid cells, especially mononuclear phagocytes, which include monocytes, macrophages and dendritic cells (DC), play vital roles in innate immunity, and in the initiation and maintenance of adaptive immunity. While T cell-associated activation pathways and cytokines have been identified and evaluated in inflammatory bowel disease (IBD) patients (Neurath, Nat Rev Gastroenterol Hepatol 14:269–78, 1989), the role of mononuclear phagocytes are less understood. Recent reports support the crucial role of DC subsets in the development of acute colitis models (Arimura et al., Mucosal Immunol 10:957–70, 2017), and suggest they may contribute to the pathogenesis of ulcerative colitis (UC) by inducing Th1/Th2/Th17 responses (Matsuno et al., Inflamm Bowel Dis 23:1524–34, 2017).

Results
We performed in silico analysis and evaluated the enrichment of immune cells, with a focus on mononuclear phagocytes in IBD patient colonic biopsies. Samples were from different gut locations, with different levels of disease severity, and with treatment response to current therapies. We observe enrichment of monocytes, M1 macrophages, activated DCs (aDCs) and plasmacytoid dendritic cells (pDCs) in inflamed tissues from various gut locations. This enrichment correlates with disease severity. Additionally, the same mononuclear phagocytes subsets are among the top enriched cell types in both infliximab and vedolizumab treatment non-responder samples. We further investigated the enrichment of selected DC and monocyte subsets based on gene signatures derived from a DC- and monocyte-focused single cell RNA-seq (scRNA-seq) study (Villani et al., Science 356:eaah4573, 2017), and verified enrichment in both inflamed tissues and those with treatment resistance. Moreover, we validated an increased mononuclear phagocyte subset abundance in a Dextran Sulphate Sodium (DSS) induced colitis model in C57Bl/6 mice representative of chronic inflammation.

Conclusions
We conducted an extensive analysis of immune cell populations in IBD patient colonic samples and identified enriched subsets of monocytes, macrophages and dendritic cells in inflamed tissues. Understanding how they interact with other immune cells and other cells in the colonic microenvironment such as epithelial and stromal cells will help us to delineate disease pathogenesis.