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| 1 | Genome-wide association studies of lactation yields of milk, fat, protein and somatic cell score in New Zealand dairy goats显示文摘Background: Identifying associations between genetic markers and traits of economic importance will provide practical benefits for the dairy goat industry, enabling genomic prediction of the breeding value of individuals, and facilitating discovery of the underlying genes and mutations. Genome-wide association studies were implemented to detect genetic regions that are significantly associated with effects on lactation yields of milk(MY), fat(FY),protein(PY) and somatic cell score(SCS) in New Zealand dairy goats.Methods: A total of 4,840 goats were genotyped with the Caprine 50 K SNP chip(Illumina Inc., San Diego, CA).After quality filtering, 3,732 animals and 41,989 SNPs were analysed assuming an additive linear model. Four GWAS models were performed, a single-SNP additive linear model and three multi-SNP Bayes C models. For the single-SNP GWAS, SNPs were fitted individually as fixed covariates, while the Bayes C models fit all SNPs simultaneously as random effects. A cluster of significant SNPs were used to define a haplotype block whose alleles were fitted as covariates in a Bayesian model. The corresponding diplotypes of the haplotype block were then fit as class variables in another Bayesian model.Results: Across all four traits, a total of 43 genome-wide significant SNPs were detected from the SNP GWAS. At a genome-wide significance level, the single-SNP analysis identified a cluster of variants on chromosome 19 associated with MY, FY, PY, and another cluster on chromosome 29 associated with SCS. Significant SNPs mapped in introns of candidate genes(45%), in intergenic regions(36%), were 0–5 kb upstream or downstream of the closest gene(14%) or were synonymous substitutions(5%). The most significant genomic window was located on chromosome 19 explaining up to 9.6% of the phenotypic variation for MY, 8.1% for FY, 9.1% for PY and 1% for SCS.Conclusions: The quantitative trait loci for yield traits on chromosome 19 confirms reported findings in other dairy goat populations. There is benefit to be gained from using these results for genomic selection to improve milk production in New Zealand dairy goats. | Megan Scholtens Andrew Jiang Ashley Smith Mathew Littlejohn Klaus Lehnert Russell Snell Nicolas Lopez-Villalobos Dorian Garrick Hugh Blair | 2020 | Journal of Animal Science and Biotechnology2020，11，4： | 2 |
| 2 | Gastric food retention at endoscopy is associated with severity of liver cirrhosis显示文摘BACKGROUND Gastrointestinal symptoms are prevalent in patients with cirrhosis.Cirrhotic patients have a known predilection to delayed gastric emptying compared to those without cirrhosis.However,the contributing factors have not been fully elucidated.Retained gastric food on esophagogastroduodenoscopy(EGD)has been used as a surrogate marker for delayed gastric emptying with reasonably high specificity.Therefore,we hypothesize that the frequency of retained gastric food contents at EGD will be higher in a cirrhotic population compared to a control population without liver disease.Additionally,we hypothesize that increased frequency of gastric food contents will be associated with increased severity of cirrhosis.AIM To determine the relative frequency of delayed gastric emptying among cirrhotics as compared to non-cirrhotics and to identify associated factors.METHODSWe performed a retrospective case-control study of cirrhotic subjects whounderwent EGD at an academic medical center between 2000 and 2015. Threehundred sixty-four patients with confirmed cirrhosis, who underwent a total of1044 EGDs for the indication of esophageal variceal screening or surveillance,were identified. During the same period, 519 control patients without liverdisease, who underwent a total of 881 EGDs for the indication of anemia, wereidentified. The presence of retained food on EGD was used as a surrogate fordelayed gastric emptying. The relative frequency of delayed gastric emptyingamong cirrhotics was compared to non-cirrhotics. Characteristics of patients withand without retained food on EGD were compared using univariable andmultivariable logistic regression analysis to identify associated factors.RESULTSOverall, 40 (4.5%) patients had evidence of retained food on EGD. Cirrhotics weremore likely to have retained food on EGD than non-cirrhotics (9.1% vs 1.4%, P <0.001). Characteristics associated with retained food on univariable analysisincluded age less than 60 years (12.6% vs 5.2%, P = 0.015), opioid use (P = 0.004),Child-Pugh class C (24.1% Child-Pugh class C vs 6.4% Child-Pugh class A, P =0.007), and lower platelet count (P = 0.027). On multivariate logistic regressionanalysis, in addition to the presence of cirrhosis (adjusted OR = 5.83;95%CI: 2.32-14.7, P < 0.001), diabetes mellitus (types 1 and 2 combined) (OR = 2.34;95%CI:1.08-5.06, P = 0.031), opioid use (OR = 3.08;95%CI: 1.29-7.34, P = 0.011), andChild-Pugh class C (OR = 4.29;95%CI: 1.43-12.9, P = 0.01) were also associatedwith a higher likelihood of food retention on EGD.CONCLUSIONCirrhotics have a higher frequency of retained food at EGD than non-cirrhotics.Decompensated cirrhosis, defined by Child-Pugh class C, is associated with ahigher likelihood of delayed gastric emptying. | David B Snell Shirley Cohen-Mekelburg Russell Weg Gaurav Ghosh Adam P Buckholz Amit Mehta Xiaoyue Ma Paul J Christos Arun B Jesudian | 2019 | World Journal of Hepatology2019，11，11： | 2 |
| 3 | Why some tumours trigger neovascularisation and others don't:the story thus far显示文摘Background:Angiogenesis is not essential for tumours to develop and expand,as cancer can also grow in a nonangiogenic fashion,but why this type of growth occurs is unknown.Surprisingly,our data from mRNA transcription profiling did not show any differences in the classical angiogenic pathways,but differences were observed in mitochondrial metabolic pathways,suggesting a key role for metabolic reprogramming.We then validated these results with mRNA profiling by investigating differential protein expression via immunohistochemistry in angiogenic and non-angiogenic non-small cell lung cancers(NSCLCs).Methods:Immunohistochemical staining for 35 angiogenesis- and hypoxia-related biomarkers were performed on a collection of 194 angiogenic and 73 non-angiogenic NSCLCs arranged on tissue microarrays.Sequencing of P53 was performed with frozen tissue samples of NSCLC.Results:The non-angiogenic tumours were distinguished from the angiogenic ones by having higher levels of proteins associated with ephrin pathways,mitochondria,cell biogenesis,and hypoxia-inducible factor 1(HIF1) regulation by oxygen and transcription of HIF-controlled genes but lower levels of proteins involved in the stroma,cell-cell signaling and adhesion,integrins,and Delta-Notch and epidermal growth factor(EGF)-related signaling.However,proteins classically associated with angiogenesis were present in both types of tumours at very comparable levels.Cytoplasmic expression of P53 was strongly associated with non-angiogenic tumours.A pilot investigation showed that P53 mutations were observed in 32.0%of angiogenic cases but in 71.4%of non-angiogenic tumours.Conclusions:Our observations thus far indicate that both angiogenic and non-angiogenic tumours experience hypoxia/HIF and vascular endothelial growth factor(VEGF) pathway protein expression in a comparable fashion.However,angiogenesis does not ensue in the non-angiogenic tumours.Surprisingly,metabolic reprogramming seems to distinguish these two types of neoplastic growth.On the basis of these results,we raise the hypothesis that in some,but not in all cases,initial tissue remodeling and/or inflammation could be one of the secondary steps necessary to trigger angiogenesis.In the non-angiogenic tumours,in which neovascularisation fails to occur,HIF pathway activation could be the driving force toward metabolic reprogramming. | Omanma Adighibe Russell D.Leek Marta Fernandez-Mercado Jiangting Hu Cameron Snell Kevin C.Gatter Adrian L.Harris Francesco Pezzella | 2016 | Chinese Journal of Cancer2016，35，2： | 0 |
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