Genetic Variants Associated with Serum Thyroid Stimulating Hormone (TSH) Levels in European Americans and African Americans from the eMERGE Network

Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10⁻¹⁷, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10⁻⁶, β = −0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = −0.09), VEGFA (rs11755845 p = 0.01, β = −0.13), and NFIA (rs334699 p = 1.50×10⁻³, β = −0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more diverse populations.     

Sandflies (Diptera: Psychodidae) in rural and urban environments in an endemic area of cutaneous leishmaniasis in southern Brazil

The high proportion of cases of cutaneous leishmaniasis reported amongst residents in the city of Bandeirantes, in the state of Paraná, Brazil, led the authors to investigate the phlebotomine fauna in both urban and rural environments. The sandflies were captured with automatic light traps from 07:00 pm-07:00 am fortnightly in 11 urban peridomiciles from April 2008-March 2009 and monthly in three ecotopes within four rural localities from April 2009-March 2010. In one of these latter localities, sandfly capture was conducted with white/black Shannon traps during each of three seasons: spring, summer and fall. A total of 5,729 sandflies of 17 species were captured. Nyssomyia neivai (46.7%) and Nyssomyia whitmani (35.3%) were the predominant species. In this study, 3,865 specimens were captured with automatic light traps: 22 (0.083 sandflies/trap) in the urban areas and 3,843 (26.69 sandflies/trap) in the rural areas. Ny. neivai was predominant in urban (68.2%) and rural (42.8%) areas. A total of 1,864 specimens were captured with the white/black Shannon traps and Ny. neivai (54.5%) and Ny. whitmani (31.4%) were the predominant species captured. The small numbers of sandflies captured in the urban areas suggest that the transmission of Leishmania has occurred in the rural area due to Ny. neivai and Ny. whitmani as the probable vectors.     

Cyclooxygenase-2 inhibition does not impair block bone grafts healing in rabbit model

Success of alveolar reconstructions using onlay autogenous block bone grafts depends on their adequate integration to the recipient bed influenced by a number of local molecules. Considering the fundamental role of cyclooxygenase (COX-2) in bone repair, the aim of this study was to analyze the effect of its inhibition in the integration of endochondral (EC) iliac crest, and intramembranous (IM) calvaria bone grafts. Thirty-two rabbits were divided into 4 groups: Calvaria Control (CC) and Iliac Control—treated with oral 0.9 % saline solution, and Calvarial-NSAID (C-NSAID) and Iliac-NSAID (I-NSAID) groups—treated with oral 6 mg/Kg non-steroidal anti-inflammatory drug etoricoxib. After 7, 14, 30 and 60 days the animals were euthanized and the specimens removed for histological, histomorphometric and immunohistochemistry analysis. At day 60, a tight integration of IM blocks could be seen with the presence of remodeling bone, whereas integration of EC grafts was mainly observed at the edges of the grafts. A significant higher percentage of bone matrix in the interface region of the CC grafts in comparison to C-NSAID only at day 14, whereas no differences were detected comparing the EC grafts. No differences were observed in Runx-2 and vascular endothelial growth factor (VEGF) immunolabeling when comparing CC and C-NSAID groups, while a significant weaker Runx-2 and VEGF labeling was detected in I-NSAID group at day 60. Although some influence was detected in osteogenesis, it is concluded that drug induced inhibition of COX-2 does not impair onlay bone grafts’ healing of both embryologic origins in rabbits.     

Modelling of sulphur amino acid requirements and nitrogen endogenous losses in kittens

ABSTRACT

The objective of this study was to estimate the sulphur amino acid (methionine + cystine) requirements and nitrogen endogenous losses in kittens aged 150 to 240 d. Thirty-six cats were distributed in six treatments (six cats per treatment) consisting of different concentrations of methionine + cystine (M + C): T1, 6.5 g/kg; T2, 8.8 g/kg; T3, 11.3 g/kg; T4, 13.6 g/kg; T5, 16.0 g/kg; and control, 6.5 g/kg. Diets were formulated by serial dilution of T5 (a diet relatively deficient in M + C but containing high protein concentrations) with a minimal nitrogen diet (MND). Thus, crude protein and amino acid concentrations in diets T1–T5 decreased by the same factor. The control diet was the T1 diet supplemented with adequate concentrations of M + C (6.5 g/kg; 8.8 g/kg; 11.3 g/kg; 13.6 g/kg and 16.0 g/kg). All diets were based on ingredients commonly used in extruded cat diets. Digestibility assays were performed for the determination of nitrogen balance. Nitrogen intake (NI) and nitrogen excretion (NEX) results data were fitted with an exponential equation to estimate nitrogen maintenance requirement (NMR), theoretical maximum for daily nitrogen retention (NR_maxT), and protein quality (b). M + C requirements were calculated from the limiting amino acid intake (LAAI) equation assuming a nitrogen retention of 45 to 65% NR_maxT. The NMR of kittens aged 150, 195, and 240 d was estimated at 595, 559, and 455 mg/kg body weight (BW)^0.67 per day, respectively, and M + C requirements were estimated at 517, 664, and 301 mg/kg BW^0.67 per day, respectively.     

Lawsone,a 2-hydroxy-1,4-naphthoquinone from Lawsonia inermis (henna), produces mitochondrial dysfunctions and triggers mitophagy in Saccharomyces cerevisiae

Molecular Biology Reports - Lawsone is a natural naphthoquinone present in the henna leaf extract with several cytotoxic activities and used as precursor for synthesis of various pharmaceutical...     

SNP interaction detection with random forests in high-dimensional genetic data

ABSTRACT: BACKGROUND: Identifying variants associated with complex human traits in high-dimensional data is a central goal of genome-wide association studies. However, complicated etiologies such as gene-gene interactions are ignored by the univariate analysis usually applied in these studies. Random Forests (RF) are a popular data-mining technique that can accommodate a large number of predictor variables and allow for complex models with interactions. RF analysis produces measures of variable importance that can be used to rank the predictor variables. Thus, single nucleotide polymorphism (SNP) analysis using RFs is gaining popularity as a potential filter approach that considers interactions in high-dimensional data. However, the impact of data dimensionality on the power of RF to identify interactions has not been thoroughly explored. We investigate the ability of rankings from variable importance measures to detect gene-gene interaction effects and their potential effectiveness as filters compared to p-values from univariate logistic regression, particularly as the data becomes increasingly high-dimensional. RESULTS: RF effectively identifies interactions in low dimensional data. As the total number of predictor variables increases, probability of detection declines more rapidly for interacting SNPs than for non-interacting SNPs, indicating that in high-dimensional data the RF variable importance measures are capturing marginal effects rather than capturing the effects of interactions. CONCLUSIONS: While RF remains a promising data-mining technique that extends univariate methods to condition on multiple variables simultaneously, RF variable importance measures fail to detect interaction effects in high-dimensional data in the absence of a strong marginal component, and therefore may not be useful as a filter technique that allows for interaction effects in genome-wide data.     

A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of S?o Paulo,Brazil

We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.     

Complexity,polymorphism, and recombination of mouse T-cell receptor α gene families

Genomic DNA from a large panel of inbred strains of mice were hybridized sequentially with 15 V_α, 2 V_δ, 1 C_α, and 1 C_δ probes. Most of the V_α probes detected a high degree of plymorphism and have allowed the definition of five mouse T-cell receptor α (Tcr _α) haplotypes. One of these haplotypes (Tcr _α ^e ) appears to arise from a recombination between theTcr _α ^b andTcr _α ^a haplotypes, the latter being the most frequently found in the conventional inbred strains. This recombination event clearly indicates that the members of at least 11 V_α subfamilies are not closely linked but highly interspersed with one another on chromosome 14.     

13C NMR spectroscopy of neolignans

The ¹³C NMR spectra of 15 neolignans of several structural types and two lignans were analyzed and their carbon shifts assigned. The shifts of pyrogallol ether and ethyl phenyl carbinyl ether models were used in this connection. The stereochemistry of a dimeric sideproduct in the preparation of the latter models was determined by ¹³C NMR analysis.