A comparison of founder-only and all-pedigree-members genotype-expression association by regression analysis

Genotype-expression association analysis using linear regression may produce different test results depending on whether founders only or all pedigreed members are used. This difference is not due to the correlation of samples within a pedigree, because linear mixed models have been applied to account for that correlation. We investigated the possibility that the difference is due to a dependence of expression levels on, among other things, the generation number in the pedigree. Indeed, of the 30 or so studied expression quantitative traits, several of them show significant dependence on the generation number. We propose to use all pedigree members in genotype-expression association analyses whenever the complete genotyping information is available

Construction and Application of a Korean Reference Panel for Imputing Classical Alleles and Amino Acids of Human Leukocyte Antigen Genes

Genetic variations of human leukocyte antigen (HLA) genes within the major histocompatibility complex (MHC) locus are strongly associated with disease susceptibility and prognosis for many diseases, including many autoimmune diseases. In this study, we developed a Korean HLA reference panel for imputing classical alleles and amino acid residues of several HLA genes. An HLA reference panel has potential for use in identifying and fine-mapping disease associations with the MHC locus in East Asian populations, including Koreans. A total of 413 unrelated Korean subjects were analyzed for single nucleotide polymorphisms (SNPs) at the MHC locus and six HLA genes, including HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1. The HLA reference panel was constructed by phasing the 5,858 MHC SNPs, 233 classical HLA alleles, and 1,387 amino acid residue markers from 1,025 amino acid positions as binary variables. The imputation accuracy of the HLA reference panel was assessed by measuring concordance rates between imputed and genotyped alleles of the HLA genes from a subset of the study subjects and East Asian HapMap individuals. Average concordance rates were 95.6% and 91.1% at 2-digit and 4-digit allele resolutions, respectively. The imputation accuracy was minimally affected by SNP density of a test dataset for imputation. In conclusion, the Korean HLA reference panel we developed was highly suitable for imputing HLA alleles and amino acids from MHC SNPs in East Asians, including Koreans

Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review

Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis

Lactic acid bacteria affect serum cholesterol levels, harmful fecal enzyme activity, and fecal water content

<p>Abstract</p> <p>Background</p> <p>Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as lower cholesterol. Although present in many foods, most trials have been in spreads or dairy products. Here we tested whether <it>Bifidobacteria </it>isolates could lower cholesterol, inhibit harmful enzyme activities, and control fecal water content.</p> <p>Methods</p> <p><it>In vitro </it>culture experiments were performed to evaluate the ability of <it>Bifidobacterium </it>spp. isolated from healthy Koreans (20~30 years old) to reduce cholesterol-levels in MRS broth containing polyoxyethanylcholesterol sebacate. Animal experiments were performed to investigate the effects on lowering cholesterol, inhibiting harmful enzyme activities, and controlling fecal water content. For animal studies, 0.2 ml of the selected strain cultures (10⁸~10⁹CFU/ml) were orally administered to SD rats (fed a high-cholesterol diet) every day for 2 weeks.</p> <p>Results</p> <p><it>B. longum </it>SPM1207 reduced serum total cholesterol and LDL levels significantly (<it>p </it>< 0.05), and slightly increased serum HDL. <it>B. longum </it>SPM1207 also increased fecal LAB levels and fecal water content, and reduced body weight and harmful intestinal enzyme activities.</p> <p>Conclusion</p> <p>Daily consumption of <it>B. longum </it>SPM1207 can help in managing mild to moderate hypercholesterolemia, with potential to improve human health by helping to prevent colon cancer and constipation.</p

Phylogenetic analysis and characterization of Korean orf virus from dairy goats: case report

An outbreak of orf virus infection in dairy goats in Korea was investigated. Suspected samples of the skin and lip of affected goats were sent to the laboratory for more exact diagnosis. Orf virus was detected by electron microscopy and viral DNA was identified by PCR. To reveal the genetic characteristics of the Korean strain (ORF/09/Korea), the sequences of the major envelope protein (B2L) and orf virus interferon resistance (VIR) genes were determined and then compared with published reference sequences. Phylogenetic analysis revealed that the ORF/09/Korea strain was closest to the isolates (Taiping) from Taiwan. This is believed to be the first report on the molecular characterization of orf virus in Korea

Prevalence and characteristics of foodborne pathogens from slaughtered pig carcasses in Korea

The introduction of bacteria into slaughterhouses can lead to microbial contamination in carcasses during slaughter, and the initial level of bacteria in carcasses is important because it directly affects spoilage and the shelf life. This study was conducted to investigate the microbiological quality, and the prevalence of foodborne pathogens in 200 carcasses from 20 pig slaughterhouses across Korea. Distribution of microbial counts were significantly higher for aerobic bacteria at 3.01–4.00 log10 CFU/cm2 (42.0%) and 2.01–3.00 log10 CFU/cm2 (28.5%), whereas most of Escherichia coli showed the counts under 1.00 log10 CFU/cm2 (87.0%) (P &lt; 0.05). The most common pathogen isolated from 200 carcasses was Staphylococcus aureus (11.5%), followed by Yersinia enterocolitica (7.0%). In total, 17 S. aureus isolates from four slaughterhouses were divided into six pulsotypes and seven spa types, and showed the same or different types depending on the slaughterhouses. Interestingly, isolates from two slaughterhouses carried only LukED associated with the promotion of bacterial virulence, whereas, isolates from two other slaughterhouses carried one or more toxin genes associated with enterotoxins including sen. In total, 14 Y. enterocolitica isolates from six slaughterhouses were divided into nine pulsotypes, 13 isolates belonging to biotype 1A or 2 carried only ystB, whereas one isolate belonging to bio-serotype 4/O:3 carried both ail and ystA. This is the first study to investigate microbial quality and the prevalence of foodborne pathogens in carcasses from slaughterhouses nationally, and the findings support the need for ongoing slaughterhouse monitoring to improve the microbiological safety of pig carcasses

Prognostic Value of Metastatic Tumoral Caveolin-1 Expression in Patients with Resected Gastric Cancer

Objective. Caveolin-1 (Cav-1), as the main component of caveolae, has complex roles in tumourigenesis in human malignancies. We investigated Cav-1 in primary and metastatic tumor cells of gastric cancer (GC) and its association with clinical outcomes. Methods. We retrieved 145 cases of GC who had undergone curative gastrectomy. The expression levels of Cav-1 was evaluated by immunohistochemistry, and its association with clinicopathological parameters and patient survival was analyzed. Results. High expression of Cav-1 protein of the GC in the stomach and metastatic lymph node was 12.4% (18/145) and 16.5% (15/91). In the multivariate analysis, tumoral Cav-1 protein in metastatic lymph node showed prognostic significance for relapse-free survival (RFS, HR, 3.934; 95% CI, 1.882–8.224; P=0.001) and cancer-specific survival outcome (CSS, HR, 2.681; 95% CI, 1.613–8.623; P=0.002). Among the GCs with metastatic lymph node, it remained as a strong indicator of poor prognosis for RFS (HR, 3.136; 95% CI, 1.444–6.810; P=0.004) and CSS (HR, 2.509; 95% CI, 1.078–5.837; P=0.032). Conclusion. High expression of tumoral Cav-1 protein in metastatic lymph node is associated with unfavorable prognosis of curative resected GC, indicating the potential of novel prognostic markers

Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects

<p>Abstract</p> <p>Background</p> <p>Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.</p> <p>Methods</p> <p>Melanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.</p> <p>Results</p> <p>SPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.</p> <p>Conclusions</p> <p>Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.</p

Funding structures for Build-to-Suit developments in Brazil: advantages and risks

Empreendimentos build-to-suit são aqueles em que o locador desenvolve um imóvel sob medida para o locatário, que o ocupará pelo prazo previsto em contrato. Dadas as peculiaridades desse tipo de contrato no contexto do real estate, o objetivo deste artigo é analisar as diferentes origens de recursos (fontes de funding) e a forma como eles são empregados (estruturas de funding) para desenvolver os empreendimentos, e discutir as vantagens e riscos dessas estruturas de funding do ponto de vista do empreendedor, que também é o locador. De forma a desenvolver este estudo e formatar as estruturas de funding apresentadas, parte-se de uma revisão das\ud práticas atuais do mercado imobiliário brasileiro (através de notícias veiculadas\ud na mídia e de prospectos de negócios realizados), da literatura brasileira sobre o tema e do conhecimento gerado no Grupo de Real Estate da Escola Politécnica da USP. De maneira a verificar a validade legal das soluções, é realizada uma checagem com\ud base na legislação brasileira e nas normas da Comissão de Valores Mobiliários.\ud Considera-se fontes de funding aquelas tratadas (1) como equity: capital próprio do empreendedor, capital de parceiros (e sócios) no empreendimento na forma de dinheiro ou imóveis (notadamente, o terreno onde será construído o empreendimento), ou investimento de Fundo de Investimento Imobiliário (FII); e (2) como dívida: financiamento bancário, securitização dos recebíveis de aluguéis com CRI ou debêntures. As estruturas de funding apresentadas serão combinações dessas fontes. A análise evidencia que estruturas com financiamento por securitização e emissão de CRI são as mais adequadas de forma geral para os negócios, assim como o investimento completo por FII para negócios de maior porte e nos quais o FII é proprietário direto do empreendimento. \ud Palavras-chave: real estate, build-to-suit, locação, funding, project financeBuild-to-suit real estate assets are tailor made developments for the tenant purposes, who occupies and operates the property for the duration agreed. Given the peculiarities of these contracts and the specificities of the property, this article aims at analyzing the sources of capital and how these funds are mixed and structured for the developments. The article discusses the risks and benefits of each of these funding\ud structures assuming the role of developer. In order to do this study and establish the funding structures shown, the research starts with a review of the current practices in Brazilian real estate market (based on press releases and prospects of deals), of local research papers, and will use the knowledge created at the Real Estate Research Group at Escola Politécnica at Universidade de São Paulo. Since it’s necessary to validate\ud the solutions proposed, Brazilian laws and Comissão de Valores Mobiliários (CVM) norms\ud are reviewed. Funding sources considered will be treated as (1) equity: developers own funds, partnership (via capital or real state – mainly land – investment), or Fundo de Investimento Imobiliário (Brazilian investment structure comparable to REITs); or as (2) debt: banks traditional credit lines, securitization of receivables with CRI emissions\ud , and debt bond emissions. The funding structures presented are mixes of these sources. The analysis shows that the structures best suited for this purpose are those with debt by securitization with CRI emissions, along with the complete investment by a FII but only with large emissions and having the FII as the sole owner of the real estate. \ud Keywords: real estate, build-to-suit, rent, funding, project financ

Follicular Dendritic Cell Sarcoma of the Abdomen: the Imaging Findings

Follicular dendritic cell sarcoma is a rare neoplasm that originates from follicular dendritic cells in lymphoid follicles. This disease usually involves the lymph nodes, and especially the head and neck area. Rarely, extranodal sites may be affected, including tonsil, the oral cavity, liver, spleen and the gastrointestinal tract. We report here on the imaging findings of follicular dendritic cell sarcoma of the abdomen that involved the retroperitoneal lymph nodes and colon. It shows as a well-defined, enhancing homogenous mass with internal necrosis and regional lymphadenopathy