Effect of reproductive tract scoring on reproductive efficiency in beef heifers bred by timed insemination and natural service versus only natural service

The objective was to determine the effects of reproductive tract score (RTS) on reproductive performance in beef heifers bred by timed artificial insemination followed by natural service (AI-NS) or by natural service only (NSO). Angus cross beef heifers (n = 2660) in the AI-NS group were artificially inseminated at a fixed time (5- or 7-day CO-Synch + controlled internal drug release protocol) once, then exposed to bulls 2 weeks later (bull-to-heifer ratio = 1:40–1:50) for the reminder of the 85-day breeding season. Angus cross beef heifers (n = 1381) in NSO group were submitted to bulls (bull-to-heifer ratio = 1:20–1:25) for the entire 85-day breeding season. Heifers were reproductive tract scored from 1 (prepubertal) to 5 (cyclic) 4 weeks before, and were body condition scored (BCS) from 1 (emaciated) to 9 (obese) at the beginning of breeding season. Pregnancy diagnosis was performed 70 days after AI for AI-NS group and 2 months after the end of breeding season for both groups. Heifers in both groups were well managed and of similar age (14.9 ± 0.4 [AI-NS] and 14.7 ± 0.8 [NSO] months). Pregnancy rates (PRs) and number of days to become pregnant were calculated using PROC GLIMMIX and PROC LIFETEST procedures of SAS. Adjusting for BCS (P = 0.07), expressed estrus (P < 0.05), year (P < 0.05), and BCS by year interaction (P < 0.05), the AI-PR was greater for heifers in AI-NS group with higher RTS (P < 0.0001; 40.7%, 48.3%, 57.6%, and 64.6% for RTS of 2 or less, 3, 4, and 5, respectively). Controlling for BCS (P < 0.05), year (P < 0.05) and the breeding season pregnancy rates (BS-PRs) were greater for heifers in the AI-NS group with higher RTS (P < 0.01; 81.2%, 86.5%, 90.4%, and 95.2% for RTS of 2 or less, 3, 4, and 5, respectively). Similarly, adjusting for BCS, year (P < 0.05), the BS-PR was greater for heifers in NSO group with higher RTS (P < 0.01; 79.7%, 84.3%, 88.4%, and 90.2% for RTS of 2 or less, 3, 4, and 5, respectively). Heifers with higher RTS in both groups became pregnant earlier in the breeding season compared with heifers with lower RTS (log-rank statistics: P < 0.0001). Heifers in the AI-NS group become pregnant at a faster rate compared with those in the NSO group (P < 0.01). The BS-PR for heifers with RTS 5 was different between AI-NS and NSO groups (P < 0.0001). In conclusion, the RTS influenced both the number of beef heifers that became pregnant during the breeding season and the time at which they become pregnant. Furthermore, irrespective of RTS, heifers bred by NSO required more time to become pregnant than their counterparts in herds that used timed AI. The application of RTS system is reliant on the use of synchronization protocol. The application of RTS for selection may plausibly remove precocious females with lower RTS. On the contrary, application of RTS would help select heifers that will become pregnant earlier in breeding season.     

Kiwifruit extracts inhibit cytokine production by lipopolysaccharide-activated macrophages, and intestinal epithelial cells isolated from IL10 gene deficient mice

Inflammatory bowel disease (IBD) is a chronic, inflammatory disorder of the gastrointestinal tract involving an inappropriate immune response to commensal microorganisms in a genetically susceptible host. This study examined the effects of aqueous and ethyl acetate extracts of gold kiwifruit (Actinidia chinensis) or green kiwifruit (Actinidia deliciosa) using in vitro models of IBD. These models comprised primary macrophages and intestinal epithelial cells isolated from C57BL/5J and interleukin-10 gene deficient (Il10^−/−) mice and RAW 264.7, a murine macrophage-like cell line. All four kiwifruit extracts reduced the activation of these models after lipopolysaccharide stimulation, decreasing nitric oxide and cytokine secretion by both Il10^−/− and wild-type cells. The ethyl acetate extracts exhibited the highest anti-inflammatory activity, with almost complete suppression of lipopolysaccharide-stimulated macrophage activation. These results suggest that kiwifruit extracts have significant anti-inflammatory activity relevant to IBD. We suggest that the Il10^−/− mouse is a suitable model for further study of these compounds.     

Dose-dependent effects of the caspase inhibitor Q-VD-OPh on different apoptosis-related processes

The effects of the pan-caspase inhibitor Q-VD-OPh on caspase activity, DNA fragmentation, PARP cleavage, 7A6 exposition, and cellular adhesivity to fibronectin were analyzed in detail in three different apoptotic systems involving two cell lines (JURL-MK1 and HL60) and two apoptosis inducers (imatinib mesylate and suberoylanilide hydroxamic acid). Q-VD-OPh fully inhibited caspase-3 and -7 activity at 0.05 μM concentration as indicated both by the measurement of the rate of Ac-DEVD-AFC cleavage and anti-caspase immunoblots. Caspase-8 was also inhibited at low Q-VD-OPh concentrations. On the other hand, significantly higher Q-VD-OPh dose (10 μM) was required to fully prevent the cleavage of PARP-1. DNA fragmentation and disruption of the cell membrane functionality (Trypan blue exclusion test) were both prevented at 2 μM Q-VD-OPh while 10 μM inhibitor was needed to inhibit the drug-induced loss of cellular adhesivity to fibronectin which was observed in JURL-MK1 cells. The exposition of the mitochondrial antigen 7A6 occurred independently of Q-VD-OPh addition and may serve to the detection of cumulative incidence of the cells which have initiated the apoptosis. Our results show that Q-VD-OPh efficiency in the inhibition of caspase-3 activity and DNA fragmentation in the whole-cell environment is about two orders of magnitude higher than that of z-VAD-fmk. This difference is not due to a slow permeability of the latter through the cytoplasmic membrane.     

复合凝乳酶对功能性消化不良儿童营养状态和摄食行为的影响

目的:观察复合凝乳酶胶囊对不同亚型功能性消化不良儿童临床表现、营养状态和摄食行为的影响及安全性。方法:以2017年8月至2018年9月在湖北省妇幼保健院儿童消化内科就诊的功能性消化不良(Functional dyspepsia,FD)儿童为研究对象进行问卷调查,观察治疗前和复合凝乳酶治疗2 w后患儿临床症状变化及药物相关不良反应的发生情况,监测患儿身高和体重,进行膳食情况的调查。结果:共163例儿童纳入研究,发生餐后不适综合征(Postprandial distress syndrome, PDS)66例,上腹痛综合征(Epigastric pain syndrome, EPS)97例。治疗前,PDS组儿童症状总分明显高于EPS儿童(6.9±2.7 vs 3.6±1.7,t=5.90,P=0.00)。PDS组儿童WAZ、WHZ、HAZ、身高别体质量Z值(weight for height Z score,WHZ)、年龄别身高Z值(height for age Z score,HAZ)、年龄别体质量Z值(weight for age Z score,WAZ)、体质量指数(body mass index,BMI)、膳食多样化分数(Dietary diversity score, DDS)均明显低于EPS组(P均0.05)。治疗2 w后,PDS儿童症状总分明显降低(P=0.00),改善程度依次为:厌食早饱腹痛嗳气恶心腹胀。EPS儿童症状总分无明显变化(P=0.11)。PDS儿童WAZ、WHZ、DDS均有明显升高(P均0.05)。EPS儿童DDS无明显变化(t=0.22,P=0.30)。研究期间未见明显药物相关不良反应。结论:复合凝乳酶胶囊可改善PDS患儿的临床症状、营养状态和膳食多样性,且安全性高。     

Strong influence of dietary intake and physical activity on body fatness in elderly Japanese men: age-associated loss of polygenic resistance against obesity

Genome-wide association studies identified single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) in middle-aged populations; however, it is unclear whether these SNPs are associated with body fatness in elderly people. We examined the association between genetic risk score (GRS) from BMI-associated SNPs and body fatness in elderly Japanese men. We also examined the contribution of GRS, dietary macronutrient intake, and physical activity to body fatness by different age groups. GRS was calculated from 10 BMI-associated SNPs in 84 middle-aged (30–64 years) and 97 elderly (65–79 years) Japanese men; subjects were divided into low, middle, and high GRS groups. Dietary macronutrient intake was assessed using a questionnaire, and physical activity was evaluated using both a questionnaire and an accelerometer. The middle-aged individuals with a high GRS had greater BMI; waist circumference; and total abdominal fat, visceral fat, and subcutaneous fat areas than the middle-aged individuals with low GRS, whereas the indicators were not different between the GRS groups in elderly individuals. Multiple linear regression analysis showed that GRS was the strongest predictor of BMI, total abdominal fat, and visceral fat in the middle-aged group, whereas fat, alcohol, and protein intakes or vigorous-intensity physical activity were more strongly associated with these indicators than was GRS in the elderly group. These results suggest that GRS from BMI-associated SNPs is not predictive of body fatness in elderly Japanese men. The stronger contribution of dietary macronutrient intake and physical activity to body fatness may attenuate the genetic predisposition in elderly men.     

High-resolution CT scoring system-based grading scale predicts the clinical outcomes in patients with idiopathic pulmonary fibrosis

Background

The 2011 idiopathic pulmonary fibrosis (IPF) guidelines are based on the diagnosis of IPF using only high-resolution computed tomography (HRCT). However, few studies have thus far reviewed the usefulness of the HRCT scoring system based on the grading scale provided in the guidelines. We retrospectively studied 98 patients with respect to assess the prognostic value of changes in HRCT findings using a new HRCT scoring system based on the grading scale published in the guidelines.

Methods

Consecutive patients with IPF who were diagnosed using HRCT alone between January 2008 and January 2012 were evaluated. HRCT examinations and pulmonary function tests were performed at six-month intervals for the first year after diagnosis. The HRCT findings were evaluated using the new HRCT scoring system (HRCT fibrosis score) over time. The findings and survival rates were analyzed using a Kaplan-Meier analysis.

Results

The HRCT fibrosis scores at six and 12 months after diagnosis were significantly increased compared to those observed at the initial diagnosis (p < 0.001). The patients with an elevated HRCT fibrosis score at six months based on a receiver operating characteristic (ROC) curves analysis had a poor prognosis (log-rank, hazard ratio [HR] 2.435, 95% CI 1.196-4.962; p = 0.0142). Furthermore, among the patients without marked changes in %FVC, those with an elevated score above the cut-off value had a poor prognosis (HR 2.192, 95% CI 1.003-4.791; p = 0.0491).

Conclusions

Our data demonstrate that the HRCT scoring system based on the grading scale is useful for predicting the clinical outcomes of IPF and identifying patients with an adverse prognosis when used in combination with spirometry.     

A feature selection method for classification within functional genomics experiments based on the proportional overlapping score

Background

Microarray technology, as well as other functional genomics experiments, allow simultaneous measurements of thousands of genes within each sample. Both the prediction accuracy and interpretability of a classifier could be enhanced by performing the classification based only on selected discriminative genes. We propose a statistical method for selecting genes based on overlapping analysis of expression data across classes. This method results in a novel measure, called proportional overlapping score (POS), of a feature’s relevance to a classification task.

Results

We apply POS, along‐with four widely used gene selection methods, to several benchmark gene expression datasets. The experimental results of classification error rates computed using the Random Forest, k Nearest Neighbor and Support Vector Machine classifiers show that POS achieves a better performance.

Conclusions

A novel gene selection method, POS, is proposed. POS analyzes the expressions overlap across classes taking into account the proportions of overlapping samples. It robustly defines a mask for each gene that allows it to minimize the effect of expression outliers. The constructed masks along‐with a novel gene score are exploited to produce the selected subset of genes.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2105-15-274) contains supplementary material, which is available to authorized users.     

On the association of common and rare genetic variation influencing body mass index: a combined SNP and CNV analysis

Background

As the architecture of complex traits incorporates a widening spectrum of genetic variation, analyses integrating common and rare variation are needed. Body mass index (BMI) represents a model trait, since common variation shows robust association but accounts for a fraction of the heritability. A combined analysis of single nucleotide polymorphisms (SNP) and copy number variation (CNV) was performed using 1850 European and 498 African-Americans from the Study of Addiction: Genetics and Environment. Genetic risk sum scores (GRSS) were constructed using 32 BMI-validated SNPs and aggregate-risk methods were compared: count versus weighted and proxy versus imputation.

Results

The weighted SNP-GRSS constructed from imputed probabilities of risk alleles performed best and was highly associated with BMI (p = 4.3×10⁻¹⁶) accounting for 3% of the phenotypic variance. In addition to BMI-validated SNPs, common and rare BMI/obesity-associated CNVs were identified from the literature. Of the 84 CNVs previously reported, only 21-kilobase deletions on 16p12.3 showed evidence for association with BMI (p = 0.003, frequency = 16.9%), with two CNVs nominally associated with class II obesity, 1p36.1 duplications (OR = 3.1, p = 0.009, frequency 1.2%) and 5q13.2 deletions (OR = 1.5, p = 0.048, frequency 7.7%). All other CNVs, individually and in aggregate, were not associated with BMI or obesity. The combined model, including covariates, SNP-GRSS, and 16p12.3 deletion accounted for 11.5% of phenotypic variance in BMI (3.2% from genetic effects). Models significantly predicted obesity classification with maximum discriminative ability for morbid-obesity (p = 3.15×10⁻¹⁸).

Conclusion

Results show that incorporating validated effect sizes and allelic probabilities improve prediction algorithms. Although rare-CNVs did not account for significant phenotypic variation, results provide a framework for integrated analyses.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-368) contains supplementary material, which is available to authorized users.     

LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias

We report the design of a targeted resequencing panel for monogenic dyslipidemias, LipidSeq, for the purpose of replacing Sanger sequencing in the clinical detection of dyslipidemia-causing variants. We also evaluate the performance of the LipidSeq approach versus Sanger sequencing in 84 patients with a range of phenotypes including extreme blood lipid concentrations as well as additional dyslipidemias and related metabolic disorders. The panel performs well, with high concordance (95.2%) in samples with known mutations based on Sanger sequencing and a high detection rate (57.9%) of mutations likely to be causative for disease in samples not previously sequenced. Clinical implementation of LipidSeq has the potential to aid in the molecular diagnosis of patients with monogenic dyslipidemias with a high degree of speed and accuracy and at lower cost than either Sanger sequencing or whole exome sequencing. Furthermore, LipidSeq will help to provide a more focused picture of monogenic and polygenic contributors that underlie dyslipidemia while excluding the discovery of incidental pathogenic clinically actionable variants in nonmetabolism-related genes, such as oncogenes, that would otherwise be identified by a whole exome approach, thus minimizing potential ethical issues.