Monitoring Hip and Elbow Dysplasia Achieved Modest Genetic Improvement of 74 Dog Breeds over 40 Years in USA

Hip (HD) and Elbow Dysplasia (ED) are two common complex developmental disorders of dogs. In order to decrease their prevalence and severity, the Orthopedic Foundation for Animals (OFA) has a voluntary registry of canine hip and elbow conformation certified by boarded radiologists. However, the voluntarily reports have been severely biased against exposing dogs with problems, especially at beginning period. Fluctuated by additional influential factors such as age, the published raw scores barely showed trends of improvement. In this study, we used multiple-trait mixed model to simultaneously adjust these factors and incorporate pedigree to derive Estimated Breeding Values (EBV). A total of 1,264,422 dogs from 74 breeds were evaluated for EBVs from 760,455 hip scores and 135,409 elbow scores. These EBVs have substantially recovered the reporting bias and the other influences. Clear and steady trends of genetic improvement were observed over the 40 years since 1970. The total genetic improvements were 16.4% and 1.1% of the phenotypic standard deviation for HD and ED, respectively. The incidences of dysplasia were 0.83% and 2.08%, and the heritabilities were estimated as 0.22 and 0.17 for hip and elbow scores, respectively. The genetic correlation between them was 0.12. We conclude that EBV is more effective than reporting raw phenotype. The weak genetic correlation suggested that selection based on hip scores would also slightly improve elbow scores but it is necessary to allocate effort toward improvement of elbow scores alone.     

Influence of the nutritional conditions on haloalcohol dehalogenase HheC production by recombinant Escherichia coli P84A/MC1061

In this research, we first determined the three most significant nutrient factors affecting haloalcohol dehalogenase HheC production by Escherichia coli P84A/MC1061. These were glycerol, yeast extract, and ammonium sulfate. The steepest ascent method was then applied to obtain the optimal design intervals of the three factors. An application of center composite design was used, and the ingredients of the optimized medium were 1.8 g l^?1 glycerol, 48 g l^?1 yeast extract, 2.2 g l^?1 ammonium sulfate, 5 g l^?1 compound phosphate, 1 g l^?1 magnesium sulfate, and 1.19?×?10^?5?g l^?1 ferric sulfate. The enzyme activity reached 109,365 U ml^?1 under the most favorable conditions, which is a 277.7 % increase compared with the control group. Our study of cellular respiration parameters (oxygen uptake rate and carbon dioxide emission rate) revealed that the metabolic activity of the strain was strongly promoted under these optimal nutrient conditions and that yeast extract had a positive effect on respiratory intensity and the expression levels of HheC.     

A Genome-Wide Survey of Genetic Variation in Gorillas Using Reduced Representation Sequencing

All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. Whole genome assembly projects have provided an invaluable foundation for understanding genetics in all four genera, but to date genetic studies of multiple individuals within great ape species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,006,670 polymorphic sites in 14 individuals: 12 western lowland gorillas (Gorilla gorilla gorilla) and 2 eastern lowland gorillas (Gorilla beringei graueri). We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations.     

hOGG1 Ser326Cys Polymorphism and Risk of Hepatocellular Carcinoma among East Asians: A Meta-Analysis

Background

The hOGG1 gene encodes a DNA glycosylase enzyme responsible for DNA repair. The Ser326Cys polymorphism in this gene may influence its repair ability and thus plays a role in carcinogenesis. Several case-control studies have been conducted on this polymorphism and its relationship with the risk of hepatocellular carcinoma (HCC) among East Asians. However, their results are inconsistent.

Methods

We performed a meta-analysis of published case-control studies assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. PubMed, EMBASE, SCI, BIOSIS, CNKI and WanFang databases were searched. A random-effect model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses were conducted for additive, dominant and recessive genetic models.

Results

Eight studies were identified involving 2369 cases and 2442 controls assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. Applying a dominant genetic model, only in the Chinese population, the Cys allele was significantly associated with increased risk of HCC (OR 1.56, 95% CI 1.12–2.17). However, two studies influenced this finding according to sensitivity analysis. Furthermore, considerable heterogeneity and bias existed among Chinese studies.

Conclusion

There is limited evidence to support that the hOGG1 Ser326Cys polymorphism is associated with HCC risk among East Asians. Well-designed and large-sized studies are required to determine this relationship.     

Treatment Outcomes in Undocumented Hispanic Immigrants with HIV Infection

Objective

Little is known about the treatment outcomes of undocumented Hispanic immigrants with HIV infection. We sought to compare the treatment outcomes of undocumented and documented patients 12-months after entering HIV care.

Methods

We conducted a retrospective cohort study of antiretroviral-naive patients 18 years and older attending their first visit at Thomas Street Health Center in Houston, Texas, between 1/1/2003 and 6/30/2008. The study population of 1,620 HIV-infected adults included 186 undocumented Hispanic, 278 documented Hispanic, 986 Black, and 170 White patients. The main outcome measures were retention in care (quarter years with at least one completed HIV primary care provider visit) and HIV suppression (HIV RNA <400 copies/mL), both measured 12-months after entering HIV care.

Results

Undocumented Hispanic patients had lower median initial CD₄ cell count (132 cells/mm³) than documented Hispanic patients (166 cells/mm³; P = 0.186), Black patients (226 cells/mm³; P<0.001), and White patients (264 cells/mm³; P = 0.001). However, once in care, undocumented Hispanic patients did as well or better than their documented counterparts. One year after entering HIV care, undocumented Hispanics achieved similar rates of retention in care and HIV suppression as documented Hispanic and White patients. Of note, black patients were significantly less likely to have optimal retention in care (adjusted odds ratio [aOR] 0.65, CI = 0.45–0.94) or achieve HIV suppression (aOR 0.32, CI = 0.17–0.61) than undocumented Hispanics.

Conclusions

Undocumented Hispanic persons with HIV infection enter care with more advanced disease than documented persons, suggesting testing and/or linkage to care efforts for this difficult-to-reach population need intensification. Once diagnosed, however, undocumented Hispanics have outcomes as good as or better than other racial/ethnic groups. Safety net providers for undocumented immigrants are vital for maintaining individual and public health.     

Design and Selection of a Camelid Single-Chain Antibody Yeast Two-Hybrid Library Produced De Novo for the Cap Protein of Porcine Circovirus Type 2 (PCV2)

Nanobodies (or variable domain of the heavy chain of the heavy-chain antibodies, VHHs) are single-domain antigen-binding fragments derived from camelid heavy chain antibodies. Their comparatively small size, monomeric behavior, high stability, high solubility, and ability to bind epitopes inaccessible to conventional antibodies make them especially suitable for many therapeutic and biotechnological applications. In this paper, for the first time, we created the immunized Camelus Bactrianus VHH yeast two-hybrid (Y2H) library according to the Clontech Mate & Plate library construction system. The transformation efficiency and titer of the VHH Y2H library were 7.26×10⁶ cfu/3 µg and 2×10⁹ cfu/ml, which met the demand for Y2H library screening. Using as an example the porcine circovirus type 2 (PCV2) Cap protein as bait, we screened 21 positive Cap-specific VHH sequences. Among these sequences, 7 of 9 randomly selected clones were strongly positive as indicated by enzyme-linked immunosorbent assay, either using PCV2 viral lysis or purified Cap protein as coated antigen. Additionally, the immunocytochemistry results further indicated that the screened VHHs could specifically detected PCV2 in the infected cells. All this suggests the feasibility of in vivo VHH throughput screening based on Y2H strategy.     

Trends in Population Blood Pressure and Prevalence,Awareness, Treatment,and Control of Hypertension among Middle-Aged and Older Adults in a Rural Area of Northwest China from 1982 to 2010

Objectives

To assess trends in average blood pressure levels and prevalence, awareness, treatment, and control of hypertension among adults in a rural area of Northwest China, and to determine associated risk factors.

Methods

Four cross-sectional population-based surveys were conducted between 1982 and 2010 among randomly selected adults in rural areas of Hanzhong, in Northwest China. Data on blood pressure, body mass index, family history of hypertension, and socio-demographic and lifestyle characteristics were collected in similar way by trained investigators in four surveys. Data of 8575 participants aged 35–64 years was analyzed. Averages and proportions were adjusted for age and sex.

Results

Average blood pressure in the population has increased since 1982 from 76.9 mm Hg to 79.6 mm Hg in 2010 (diastolic) and from 120.9 to 129.7 mm Hg (systolic). Prevalence of hypertension increased from 18.4% in 1982 to 30.5% in 2010, and awareness of hypertension increased from 16.8% to 38.4% in 2010. Treatment of hypertension increased from 1.0% in 1982 to 17.4% in 2010, and control of hypertension increased from 0.1% in 1982 to 3.5% in 2010. All these gradients were statistically significant (P<0.01 for trend). Population blood pressure and prevalence, awareness and treatment of hypertension were positively associated with increasing age, body mass index and having family history of hypertension.

Conclusions

Average blood pressure levels and the prevalence, awareness, treatment and control of hypertension among adults in rural areas of Hanzhong have increased since 1982. However, awareness, treatment and control rates remain low. Public health programs and practical strategies are required to improve prevention and control of hypertension in rural Northwest China. In particular, attention should be given to the elderly and obese, and to those with a family history of hypertension, while raising awareness and treatment among younger adults.     

Association of Genetic Variants in the Adiponectin Gene with Metabolic Syndrome: A Case-Control Study and a Systematic Meta-Analysis in the Chinese Population

Background

The prevalence of metabolic syndrome has been rising worldwide, including in China, but knowledge on specific genetic determinants of metabolic syndrome is very limited. A number of studies have reported that polymorphisms in the ADIPOQ gene are associated with metabolic syndrome in Chinese Han populations. However, data is still conflicting. The objective of this study was to examine the associations of the adiponectin genetic variants with metabolic syndrome by a case-control study and meta-analyses in Chinese.

Methods

We first investigated the association of ADIPOQ rs2241766 (+45T>G in exon 2), rs266729 (−11377C>G in promoter) and rs1501299 (+276G>T in intron 2) polymorphisms with metabolic syndrome in a Hubei Han Chinese population with 322 metabolic syndrome patients and 161 normal controls recruited from the Yichang, Hubei. Then we comprehensively reviewed the association between ADIPOQ rs2241766/rs266729/rs1501299 and metabolic syndrome in the Chinese populations via a meta-analysis. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CI).

Results

The G allele frequency of rs2241766 in metabolic syndrome patients was significantly higher than those of controls group (29.8% vs 23.3%, OR = 1.40, P = 0.033). The logistic regression analysis adjusted by gender and age showed a nominally significant association for rs2241766 GG+GT genotype (P = 0.065, OR = 1.55) and rs1501299 GG genotype in recessive model (OR = 1.54, P = 0.066). However, no association was observed for rs266729 in our sample. We identified thirteen studies for rs2241766 (2,684 metabolic syndrome patients and 2,864 controls), three studies for rs266729, and eleven studies for rs1501299 (2,889 metabolic syndrome patients and 3,304 controls) in Chinese. Meta-analysis indicated significant associations for the rs2241766 G allele (OR = 1.14, 95%CI = 1.05–1.24, P = 0.003), rs266729 GG+GT genotypes (OR = 0.80, 95%CI = 0.68–0.92, P = 0.003) and rs1501299 GG+TG genotypes (OR = 1.42, 95%CI 1.16–1.75, P = 0.001).

Conclusions

Our results demonstrated ADIPOQ as a pleiotropic locus for metabolic syndrome and its components in the Han Chinese population.     

Differential Regulation of MAPK Phosphorylation in the Dorsal Hippocampus in Response to Prolonged Morphine Withdrawal-Induced Depressive-Like Symptoms in Mice

Depression is one of the most frequent neuropsychiatric comorbidities associated with opiate addiction. Mitogen activated protein kinase (MAPK) and MAPK phosphatase (MKP) are involved in drug addiction and depression. However, the potential role of MAPK and MKP in depression caused by morphine withdrawal remains unclear. We utilized a mouse model of repeated morphine administration to examine the molecular mechanisms that contribute to prolonged withdrawal induced depressive-like behaviors. Depressive-like behaviors were significant at 1 week after withdrawal and worsened over time. Phospho-ERK (extracellular signal-regulated protein kinase) was decreased and MKP-1 was elevated in the hippocampus, and JNK (c-Jun N-terminal protein kinase), p38 (p38 protein kinase) and MKP-3 were unaffected. A pharmacological blockade of MKP-1 by intra-hippocampal sanguinarine (SA) infusion prevented the development of depressive-like behaviors and resulted in relatively normal levels of MKP-1 and phospho-ERK after withdrawal. Our findings support the association between hippocampal MAPK phosphorylation and prolonged morphine withdrawal-induced depression, and emphasize the MKP-1 as an negative regulator of the ERK phosphorylation that contributes to depression.