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Sample records for co-infection genetic analyses

  1. Co-infection and genetic diversity of tick-borne pathogens in roe deer from Poland.

    PubMed

    Welc-Falęciak, Renata; Werszko, Joanna; Cydzik, Krystian; Bajer, Anna; Michalik, Jerzy; Behnke, Jerzy M

    2013-05-01

    Wild species are essential hosts for maintaining Ixodes ticks and the tick-borne diseases. The aim of our study was to estimate the prevalence, the rate of co-infection with Babesia, Bartonella, and Anaplasma phagocytophilum, and the molecular diversity of tick-borne pathogens in roe deer in Poland. Almost half of the tested samples provided evidence of infection with at least 1 species. A. phagocytophilum (37.3%) was the most common and Bartonella (13.4%) the rarest infection. A total of 18.3% of all positive samples from roe deer were infected with at least 2 pathogens, and one-third of those were co-infected with A. phagocytophilum, Bartonella, and Babesia species. On the basis of multilocus molecular studies we conclude that: (1) Two different genetic variants of A. phagocytophilum, zoonotic and nonzoonotic, are widely distributed in Polish roe deer population; (2) the roe deer is the host for zoonotic Babesia (Bab. venatorum, Bab. divergens), closely related or identical with strains/species found in humans; (3) our Bab. capreoli and Bab. divergens isolates differed from reported genotypes at 2 conserved base positions, i.e., positions 631 and 663; and (4) this is the first description of Bart. schoenbuchensis infections in roe deer in Poland. We present 1 of the first complex epidemiological studies on the prevalence of Babesia, Bartonella, and A. phagocytophilum in naturally infected populations of roe deer. These game animals clearly have an important role as reservoir hosts of tick-borne pathogens, but the pathogenicity and zoonotic potential of the parasite genotypes hosted by roe deer requires further detailed investigation. PMID:23473225

  2. Phylogenetic and Genome-Wide Deep-Sequencing Analyses of Canine Parvovirus Reveal Co-Infection with Field Variants and Emergence of a Recent Recombinant Strain

    PubMed Central

    Pérez, Ruben; Calleros, Lucía; Marandino, Ana; Sarute, Nicolás; Iraola, Gregorio; Grecco, Sofia; Blanc, Hervé; Vignuzzi, Marco; Isakov, Ofer; Shomron, Noam; Carrau, Lucía; Hernández, Martín; Francia, Lourdes; Sosa, Katia; Tomás, Gonzalo; Panzera, Yanina

    2014-01-01

    Canine parvovirus (CPV), a fast-evolving single-stranded DNA virus, comprises three antigenic variants (2a, 2b, and 2c) with different frequencies and genetic variability among countries. The contribution of co-infection and recombination to the genetic variability of CPV is far from being fully elucidated. Here we took advantage of a natural CPV population, recently formed by the convergence of divergent CPV-2c and CPV-2a strains, to study co-infection and recombination. Complete sequences of the viral coding region of CPV-2a and CPV-2c strains from 40 samples were generated and analyzed using phylogenetic tools. Two samples showed co-infection and were further analyzed by deep sequencing. The sequence profile of one of the samples revealed the presence of CPV-2c and CPV-2a strains that differed at 29 nucleotides. The other sample included a minor CPV-2a strain (13.3% of the viral population) and a major recombinant strain (86.7%). The recombinant strain arose from inter-genotypic recombination between CPV-2c and CPV-2a strains within the VP1/VP2 gene boundary. Our findings highlight the importance of deep-sequencing analysis to provide a better understanding of CPV molecular diversity. PMID:25365348

  3. The rate of co-infection for piglet diarrhea viruses in China and the genetic characterization of porcine epidemic diarrhea virus and porcine kobuvirus.

    PubMed

    Zhao, Z-P; Yang, Z; Lin, W-D; Wang, W-Y; Yang, J; Jin, W-J; Qin, A-J

    2016-03-01

    Piglet diarrhea epidemics result in major economic losses for the swine industry. Four viruses are closely linked to porcine diarrhea: porcine kobuvirus (PKV), porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), and porcine rotavirus (PRoV). We have conducted an epidemiology study to determine the frequency of infection and co-infection with these viruses in China, and characterized the genetic variation of the isolated PEDV and PKV strains. Stool and intestinal samples (n = 314) were collected from piglets with diarrhea in China from years 2012 to 2014. RT-PCR was used to detect PKV, PEDV, TGEV, and PRoV. Phylogenetic relationships between reference strains and the isolated PEDV and PKV strains were determined based on the M and 3D gene sequence. The rates of infection with PKV, PEDV, TGEV and PRoV were 29.9%, 24.2%, 1.91%, and 0.31%, respectively. Co-infections with PKV and the other three viruses were very common. Co-infection of PKV and PEDV was detected in 15.0% (47/314) of the samples. Phylogenetic analysis of the PKV 3D gene indicated that there were some phylogenetic differences in the PKV strains across regions within China. However, according to the PEDV M gene, strains clustered into three groups and the primary group was distinct from the vaccine strain CV777. This study provides insights in to the prevalence of diarrhea viruses and their prevention and control in China. PMID:26982468

  4. Epidemiological investigation reveals genetic diversity and high co-infection rate of canine bocavirus strains circulating in Heilongjiang province, Northeast China.

    PubMed

    Guo, Donghua; Wang, Zhihui; Yao, Shuang; Li, Chunqiu; Geng, Yufei; Wang, Enyu; Zhao, Xiwen; Su, Mingjun; Wei, Shan; Wang, Xinyu; Feng, Li; Chang, Yung-Fu; Sun, Dongbo

    2016-06-01

    To trace evolution of CBoV in Northeast China, 201 fecal samples from rectal swabs of diarrheic dogs collected from May 2014 to April 2015 were investigated using PCR targeting partial NS1 gene (440bp). Furthermore, phylogenetic analysis of the identified CBoV strains was conducted using nucleotide sequences of the partial NS1 gene. The results indicated that 15 of 201 fecal samples (7.5%) were positive for CBoV; the partial NS1 genes of the 15 CBoV strains exhibited 83.1%-100% nucleotide identity, and 75.8%-100% amino acid identity; the entire VP2 gene of five selected CBoV strains exhibited 82.9%-96.8% nucleotide identity, and 90.4%-99.1% amino acid identity. The 15 CBoV strains exhibited high co-infection rates with CPV-2 (40%), CCoV (20%), and CaKV (26.67%). Phylogenetic analysis of the partial NS1 gene revealed that the 15 CBoV strains were divided into different subgroups of CBoV-2 when compared with CBoV-2 strains from South Korea, USA, Germany, and Hong Kong in China. Moreover, phylogenetic analysis of the VP2 gene indicated that five selected CBoV strains were divided into three different genetic groups of CBoV-2, involving in CBoV-2HK group, CBoV-2C group, and CBoV-2B group. The recombination analysis using the entire VP2 gene revealed three potential recombination events that occurred among five selected strains in our study. These data demonstrated that the CBoV strains circulating in Heilongjiang province, Northeast China showed genetic diversities, potential recombination events, and high co-infection rate. Further studies will be required to address the potential pathogenic role of these diverse CBoV strains. PMID:27234529

  5. Effects of genetic similarity on the life-history strategy of co-infecting trematodes: are parasites capable of intrahost kin recognition?

    PubMed

    Joannes, A; Lagrue, C; Poulin, R; Beltran-Bech, S

    2014-08-01

    For conspecific parasites sharing the same host, kin recognition can be advantageous when the fitness of one individual depends on what another does; yet, evidence of kin recognition among parasites remains limited. Some trematodes, like Coitocaecum parvum, have plastic life cycles including two alternative life-history strategies. The parasite can wait for its intermediate host to be eaten by a fish definitive host, thus completing the classical three-host life cycle, or mature precociously and produce eggs while still inside its intermediate host as a facultative shortcut. Two different amphipod species are used as intermediate hosts by C. parvum, one small and highly mobile and the other larger, sedentary, and burrow dwelling. Amphipods often harbour two or more C. parvum individuals, all capable of using one or the other developmental strategy, thus creating potential conflicts or cooperation opportunities over transmission routes. This model was used to test the kin recognition hypothesis according to which cooperation between two conspecific individuals relies on the individuals' ability to evaluate their degree of genetic similarity. First, data showed that levels of intrahost genetic similarity between co-infecting C. parvum individuals differed between host species. Second, genetic similarity between parasites sharing the same host was strongly linked to their likelihood of adopting identical developmental strategies. Two nonexclusive hypotheses that could explain this pattern are discussed: kin recognition and cooperation between genetically similar parasites and/or matching genotypes involving parasite genotype-host compatibility filters. PMID:24836164

  6. Host Genetic Factors and Dendritic Cell Responses Associated with the Outcome of Interferon/Ribavirin Treatment in HIV-1/HCV Co-Infected Individuals

    PubMed Central

    Sehgal, Mohit; Zeremski, Marija; Talal, Andrew H.; Khan, Zafar K.; Capocasale, Renold; Philip, Ramila; Jain, Pooja

    2015-01-01

    HIV-1/HCV co-infection is a significant health problem. Highly active antiretroviral treatment (HAART) against HIV-1 has proved to be fairly successful. On the other hand, direct acting antiviral drugs against HCV have improved cure rates but high cost and development of drug resistance are important concerns. Therefore PEGylated interferon (PEG-IFN) and ribavirin (RBV) still remain essential components of HCV treatment, and identification of host factors that predict IFN/RBV treatment response is necessary for effective clinical management of HCV infection. Impaired dendritic cell (DC) and T cell responses are associated with HCV persistence. It has been shown that IFN/RBV treatment enhances HCV-specific T cell functions and it is likely that functional restoration of DCs is the underlying cause. To test this hypothesis, we utilized an antibody cocktail (consisting of DC maturation, adhesion and other surface markers) to perform comprehensive phenotypic characterization of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in a cohort of HIV-1/HCV co-infected individuals undergoing IFN/RBV treatment. Our results show that pre-treatment frequencies of mDCs are lower in non-responders (NRs) compared to responders (SVRs) and healthy controls. Although, the treatment was able to restore the frequency of mDCs in NRs, it downregulated the frequency of CCR7+, CD54+ and CD62L+ mDCs. Pre-treatment frequencies of pDCs were lower in NRs and decreased further upon treatment. Compared to SVRs, NRs exhibited higher ratio of PD-L1+/CD86+ pDCs prior to treatment; and this ratio remained high even after treatment. These findings demonstrate that enumeration and phenotypic assessment of DCs before/during therapy can help predict the treatment outcome. We also show that before treatment, PBMCs from SVRs secrete higher amounts of IFN-γ compared to controls and NRs. Upon genotyping IFNL3 polymorphisms rs12979860, rs4803217 and ss469415590, we found rs12979860 to be a better predictor of

  7. HIV and co-infections

    PubMed Central

    Chang, Christina C; Crane, Megan; Zhou, JingLing; Mina, Michael; Post, Jeffrey J; Cameron, Barbara A; Lloyd, Andrew R; Jaworowski, Anthony; French, Martyn A; Lewin, Sharon R

    2013-01-01

    Summary Despite significant reductions in morbidity and mortality secondary to availability of effective combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) infection still accounts for 1.5 million deaths annually. The majority of deaths occur in sub-Saharan Africa where rates of opportunistic co-infections are disproportionately high. In this review, we discuss the immunopathogenesis of five common infections that cause significant morbidity in HIV-infected patients globally. These include co-infection with Mycobacterium tuberculosis, Cryptococcus neoformans, hepatitis B virus (HBV), hepatitis C virus (HCV), and Plasmodium falciparum. Specifically, we review the natural history of each co-infection in the setting of HIV, the specific immune defects induced by HIV, the effects of cART on the immune response to the co-infection, the pathogenesis of immune restoration disease (IRD) associated with each infection, and advances in the areas of prevention of each co-infection via vaccination. Finally, we discuss the opportunities and gaps for future research. PMID:23772618

  8. HIV and hepatitis C co-infection.

    PubMed

    Jones, R; Dunning, J; Nelson, M

    2005-09-01

    HIV/HCV co-infection is emerging as a major cause of morbidity and mortality in the 21st century. This editorial reviews the prevalence of co-infection, the factors involved in acquisition of HCV, and the influence of co-infection on disease progression. We examine the results of the major co-infection trials including APRICOT, ACTG 5071 and RIBAVIC. These trials, in association with emerging evidence for future therapies currently undergoing investigation, have led to increased hope of treatment success in co-infected individuals. PMID:16115185

  9. Analyses of genetic ancestry enable key insights for molecular ecology.

    PubMed

    Gompert, Zachariah; Buerkle, C Alex

    2013-11-01

    Gene flow and recombination in admixed populations produce genomes that are mosaic combinations of chromosome segments inherited from different source populations, that is, chromosome segments with different genetic ancestries. The statistical problem of estimating genetic ancestry from DNA sequence data has been widely studied, and analyses of genetic ancestry have facilitated research in molecular ecology and ecological genetics. In this review, we describe and compare different model-based statistical methods used to infer genetic ancestry. We describe the conceptual and mathematical structure of these models and highlight some of their key differences and shared features. We then discuss recent empirical studies that use estimates of genetic ancestry to analyse population histories, the nature and genetic basis of species boundaries, and the genetic architecture of traits. These diverse studies demonstrate the breadth of applications that rely on genetic ancestry estimates and typify the genomics-enabled research that is becoming increasingly common in molecular ecology. We conclude by identifying key research areas where future studies might further advance this field. PMID:24103088

  10. Genetic Analyses in Health Laboratories: Current Status and Expectations

    NASA Astrophysics Data System (ADS)

    Finotti, Alessia; Breveglieri, Giulia; Borgatti, Monica; Gambari, Roberto

    Genetic analyses performed in health laboratories involve adult patients, newborns, embryos/fetuses, pre-implanted pre-embryos, pre-fertilized oocytes and should meet the major medical needs of hospitals and pharmaceutical companies. Recent data support the concept that, in addition to diagnosis and prognosis, genetic analyses might lead to development of personalized therapy. Novel frontiers in genetic testing involve the development of single cell analyses and non-invasive assays, including those able to predict outcome of cancer pathologies by looking at circulating tumor cells, DNA, mRNA and microRNAs. In this respect, PCR-free diagnostics appears to be one of the most interesting and appealing approaches.

  11. A review of multivariate analyses in imaging genetics

    PubMed Central

    Liu, Jingyu; Calhoun, Vince D.

    2014-01-01

    Recent advances in neuroimaging technology and molecular genetics provide the unique opportunity to investigate genetic influence on the variation of brain attributes. Since the year 2000, when the initial publication on brain imaging and genetics was released, imaging genetics has been a rapidly growing research approach with increasing publications every year. Several reviews have been offered to the research community focusing on various study designs. In addition to study design, analytic tools and their proper implementation are also critical to the success of a study. In this review, we survey recent publications using data from neuroimaging and genetics, focusing on methods capturing multivariate effects accommodating the large number of variables from both imaging data and genetic data. We group the analyses of genetic or genomic data into either a priori driven or data driven approach, including gene-set enrichment analysis, multifactor dimensionality reduction, principal component analysis, independent component analysis (ICA), and clustering. For the analyses of imaging data, ICA and extensions of ICA are the most widely used multivariate methods. Given detailed reviews of multivariate analyses of imaging data available elsewhere, we provide a brief summary here that includes a recently proposed method known as independent vector analysis. Finally, we review methods focused on bridging the imaging and genetic data by establishing multivariate and multiple genotype-phenotype-associations, including sparse partial least squares, sparse canonical correlation analysis, sparse reduced rank regression and parallel ICA. These methods are designed to extract latent variables from both genetic and imaging data, which become new genotypes and phenotypes, and the links between the new genotype-phenotype pairs are maximized using different cost functions. The relationship between these methods along with their assumptions, advantages, and limitations are discussed

  12. Research on HIV Co-Infections

    MedlinePlus

    ... this page Get email updates Order publications Featured Research The Path to a Cure for Hepatitis C ... Skip Content Marketing Share this: Main Content Area Research on HIV Co-Infections HIV-infected people are ...

  13. A weighted U statistic for association analyses considering genetic heterogeneity.

    PubMed

    Wei, Changshuai; Elston, Robert C; Lu, Qing

    2016-07-20

    Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26833871

  14. Meta-analyses of genetic studies on major depressive disorder.

    PubMed

    López-León, S; Janssens, A C J W; González-Zuloeta Ladd, A M; Del-Favero, J; Claes, S J; Oostra, B A; van Duijn, C M

    2008-08-01

    The genetic basis of major depressive disorder (MDD) has been investigated extensively, but the identification of MDD genes has been hampered by conflicting results from underpowered studies. We review all MDD case-control genetic association studies published before June 2007 and perform meta-analyses for polymorphisms that had been investigated in at least three studies. The study selection and data extraction were performed in duplicate by two independent investigators. The 183 papers that met our criteria studied 393 polymorphisms in 102 genes. Twenty-two polymorphisms (6%) were investigated in at least three studies. Seven polymorphisms had been evaluated in previous meta-analyses, 5 of these had new data available. Hence, we performed meta-analyses for 20 polymorphisms in 18 genes. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistically significant associations were found for the APOE varepsilon2 (OR, 0.51), GNB3 825T (OR, 1.38), MTHFR 677T (OR, 1.20), SLC6A4 44 bp Ins/Del S (OR, 1.11) alleles and the SLC6A3 40 bpVNTR 9/10 genotype (OR, 2.06). To date, there is statistically significant evidence for six MDD susceptibility genes (APOE, DRD4, GNB3, MTHFR, SLC6A3 and SLC6A4). PMID:17938638

  15. Genetic and phenotypic analyses of carpel development in Arabidopsis.

    PubMed

    Balanzà, Vicente; Ballester, Patricia; Colombo, Monica; Fourquin, Chloé; Martínez-Fernández, Irene; Ferrándiz, Cristina

    2014-01-01

    Carpels are the female reproductive organs of the flower, organized in a gynoecium, which is arguably the most complex organ of a plant. The gynoecium provides protection for the ovules, helps to discriminate between male gametophytes, and facilitates successful pollination. After fertilization, it develops into a fruit, a specialized organ for seed protection and dispersal. To carry out all these functions, coordinated patterning and tissue specification within the developing gynoecium have to be achieved. In this chapter, we describe different methods to characterize defects in carpel patterning and morphogenesis associated with developmental mutations as well as a list of reporter lines that can be used to facilitate genetic analyses. PMID:24395260

  16. Genetic analyses of fancy rat-derived mutations.

    PubMed

    Kuramoto, Takashi; Yokoe, Mayuko; Yagasaki, Kayoko; Kawaguchi, Tatsuya; Kumafuji, Kenta; Serikawa, Tadao

    2010-01-01

    To collect rat mutations and increase the value of the rat model system, we introduced fancy-derived mutations to the laboratory and carried out genetic analyses. Six fancy rats were shipped from a fancy rat colony in the USA and used as founders. After initial crosses with a laboratory strain, TM/Kyo or PVG/Seac, inbreeding started and 6 partially inbred lines, including 2 sublines, were produced as Kyoto Fancy Rat Stock (KFRS) strains. During inbreeding, we isolated 9 mutations: 5 coat colors, American mink (am), Black eye (Be), grey (g), Pearl (Pel), siamese (sia); 1 coat pattern, head spot (hs); 2 coat textures, Rex (Re), satin (sat); and an ear pinnae malformation, dumbo (dmbo). Genetic analyses mapped 7 mutations to particular regions of the rat chromosomes (Chr): am to Chr 1, sia to Chr 1, sat to Chr 3, Re to Chr 7, g to Chr 8, dmbo to Chr 14, and hs to Chr 15. Candidate gene analysis revealed that a missense mutation in the tyrosinase gene, Ser79Pro, was responsible for sia. From mutant phenotypes and mapping positions, it is likely that all mutations isolated in this study were unique to the fancy rat. These findings suggest that fancy rat colonies are a good source for collecting rat mutations. The fancy-derived mutations, made available to biomedical research in the current study, will increase the scientific value of laboratory rats. PMID:20484848

  17. Co-infection alters population dynamics of infectious disease.

    PubMed

    Susi, Hanna; Barrès, Benoit; Vale, Pedro F; Laine, Anna-Liisa

    2015-01-01

    Co-infections by multiple pathogen strains are common in the wild. Theory predicts co-infections to have major consequences for both within- and between-host disease dynamics, but data are currently scarce. Here, using common garden populations of Plantago lanceolata infected by two strains of the pathogen Podosphaera plantaginis, either singly or under co-infection, we find the highest disease prevalence in co-infected treatments both at the host genotype and population levels. A spore-trapping experiment demonstrates that co-infected hosts shed more transmission propagules than singly infected hosts, thereby explaining the observed change in epidemiological dynamics. Our experimental findings are confirmed in natural pathogen populations-more devastating epidemics were measured in populations with higher levels of co-infection. Jointly, our results confirm the predictions made by theoretical and experimental studies for the potential of co-infection to alter disease dynamics across a large host-pathogen metapopulation. PMID:25569306

  18. HIV, HCV & Leprosy co-infection.

    PubMed

    George, A; Kanish, B

    2014-01-01

    In the era where Hansen's disease has achieved elimination status in India, co-infection with HIV can possibly cause a resurgence of this disease. A young intravenous drug abuser was found to have triple affliction, where HIV and HCV infection were discovered on testing after the patient was clinically diagnosed to have Hansen's disease. To our knowledge, there has been no case reported where leprosy was seen with HIV and HCV infection. We are reporting a patient with lepromatous Hansen's disease in type 2 reaction in whom HIV and HCV was incidentally diagnosed. PMID:26118224

  19. Impact of HIV co-infection on the evolution and transmission of multidrug-resistant tuberculosis.

    PubMed

    Eldholm, Vegard; Rieux, Adrien; Monteserin, Johana; Lopez, Julia Montana; Palmero, Domingo; Lopez, Beatriz; Ritacco, Viviana; Didelot, Xavier; Balloux, Francois

    2016-01-01

    The tuberculosis (TB) epidemic is fueled by a parallel Human Immunodeficiency Virus (HIV) epidemic, but it remains unclear to what extent the HIV epidemic has been a driver for drug resistance in Mycobacterium tuberculosis (Mtb). Here we assess the impact of HIV co-infection on the emergence of resistance and transmission of Mtb in the largest outbreak of multidrug-resistant TB in South America to date. By combining Bayesian evolutionary analyses and the reconstruction of transmission networks utilizing a new model optimized for TB, we find that HIV co-infection does not significantly affect the transmissibility or the mutation rate of Mtb within patients and was not associated with increased emergence of resistance within patients. Our results indicate that the HIV epidemic serves as an amplifier of TB outbreaks by providing a reservoir of susceptible hosts, but that HIV co-infection is not a direct driver for the emergence and transmission of resistant strains. PMID:27502557

  20. Understanding HIV-Mycobacteria synergism through comparative proteomics of intra-phagosomal mycobacteria during mono- and HIV co-infection

    PubMed Central

    Ganji, Rakesh; Dhali, Snigdha; Rizvi, Arshad; Rapole, Srikanth; Banerjee, Sharmistha

    2016-01-01

    Mycobacterium tuberculosis (Mtb) is the most common co-infection in HIV patients and a serious co-epidemic. Apart from increasing the risk of reactivation of latent tuberculosis (TB), HIV infection also permits opportunistic infection of environmental non-pathogenic mycobacteria. To gain insights into mycobacterial survival inside host macrophages and identify mycobacterial proteins or processes that influence HIV propagation during co-infection, we employed proteomics approach to identify differentially expressed intracellular mycobacterial proteins during mono- and HIV co-infection of human THP-1 derived macrophage cell lines. Of the 92 proteins identified, 30 proteins were upregulated during mycobacterial mono-infection and 40 proteins during HIV-mycobacteria co-infection. We observed down-regulation of toxin-antitoxin (TA) modules, up-regulation of cation transporters, Type VII (Esx) secretion systems, proteins involved in cell wall lipid or protein metabolism, glyoxalate pathway and branched chain amino-acid synthesis during co-infection. The bearings of these mycobacterial factors or processes on HIV propagation during co-infection, as inferred from the proteomics data, were validated using deletion mutants of mycobacteria. The analyses revealed mycobacterial factors that possibly via modulating the host environment, increased viral titers during co-infection. The study provides new leads for investigations towards hitherto unknown molecular mechanisms explaining HIV-mycobacteria synergism, helping address diagnostics and treatment challenges for effective co-epidemic management. PMID:26916387

  1. Understanding HIV-Mycobacteria synergism through comparative proteomics of intra-phagosomal mycobacteria during mono- and HIV co-infection.

    PubMed

    Ganji, Rakesh; Dhali, Snigdha; Rizvi, Arshad; Rapole, Srikanth; Banerjee, Sharmistha

    2016-01-01

    Mycobacterium tuberculosis (Mtb) is the most common co-infection in HIV patients and a serious co-epidemic. Apart from increasing the risk of reactivation of latent tuberculosis (TB), HIV infection also permits opportunistic infection of environmental non-pathogenic mycobacteria. To gain insights into mycobacterial survival inside host macrophages and identify mycobacterial proteins or processes that influence HIV propagation during co-infection, we employed proteomics approach to identify differentially expressed intracellular mycobacterial proteins during mono- and HIV co-infection of human THP-1 derived macrophage cell lines. Of the 92 proteins identified, 30 proteins were upregulated during mycobacterial mono-infection and 40 proteins during HIV-mycobacteria co-infection. We observed down-regulation of toxin-antitoxin (TA) modules, up-regulation of cation transporters, Type VII (Esx) secretion systems, proteins involved in cell wall lipid or protein metabolism, glyoxalate pathway and branched chain amino-acid synthesis during co-infection. The bearings of these mycobacterial factors or processes on HIV propagation during co-infection, as inferred from the proteomics data, were validated using deletion mutants of mycobacteria. The analyses revealed mycobacterial factors that possibly via modulating the host environment, increased viral titers during co-infection. The study provides new leads for investigations towards hitherto unknown molecular mechanisms explaining HIV-mycobacteria synergism, helping address diagnostics and treatment challenges for effective co-epidemic management. PMID:26916387

  2. Colony image acquisition and genetic segmentation algorithm and colony analyses

    NASA Astrophysics Data System (ADS)

    Wang, W. X.

    2012-01-01

    Colony anaysis is used in a large number of engineerings such as food, dairy, beverages, hygiene, environmental monitoring, water, toxicology, sterility testing. In order to reduce laboring and increase analysis acuracy, many researchers and developers have made efforts for image analysis systems. The main problems in the systems are image acquisition, image segmentation and image analysis. In this paper, to acquire colony images with good quality, an illumination box was constructed. In the box, the distances between lights and dishe, camra lens and lights, and camera lens and dishe are adjusted optimally. In image segmentation, It is based on a genetic approach that allow one to consider the segmentation problem as a global optimization,. After image pre-processing and image segmentation, the colony analyses are perfomed. The colony image analysis consists of (1) basic colony parameter measurements; (2) colony size analysis; (3) colony shape analysis; and (4) colony surface measurements. All the above visual colony parameters can be selected and combined together, used to make a new engineeing parameters. The colony analysis can be applied into different applications.

  3. Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected patients from Kolkata, India

    PubMed Central

    Sarkar, Jayeeta; Saha, Debraj; Bandyopadhyay, Bhaswati; Saha, Bibhuti; Kedia, Deepika; Guha Mazumder, D.N.; Chakravarty, Runu; Guha, Subhasish Kamal

    2016-01-01

    Background & objectives: Hepatitis B virus (HBV) and HIV co-infection has variable prevalence worldwide. In comparison to HBV mono-infection, the course of chronic HBV infection is accelerated in HIV/HBV co-infected patients. The present study was carried out to analyse the baseline characteristics (clinical, biochemical, serological and virological) of treatment naïve HIV/HBV co-infected and HIV mono-infected patients. Methods: Between July 2011 and January 2013, a total number of 1331 HIV-seropositive treatment naïve individuals, enrolled in the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono-infected and 78 HIV/HBV co-infected patients were characterized. The co-infected patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was quantified for all co-infected patients. HBV DNA was detected and quantified by real time-PCR amplification followed by HBV genotype determination. Results: HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The co-infected patients had significantly higher serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI). CD4 count was non-significantly lower in co-infected patients. Majority (61.5%) were HBeAg positive with higher HIV RNA (P<0.05), HBV DNA (P<0.001) and APRI (P<0.05) compared to those who were HBeAg negative. HBV/D was the predominant genotype (73.2%) and D2 (43.7%) was the commonest subgenotype. Interpretation & conclusions: HIV/HBV co-infected patients had significantly higher serum bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co-infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co-infected patients. Prior to initiation of antiretroviral treatment (ART) all patients should be screened for HBsAg to

  4. gPGA: GPU Accelerated Population Genetics Analyses

    PubMed Central

    Zhou, Chunbao; Lang, Xianyu; Wang, Yangang; Zhu, Chaodong

    2015-01-01

    Background The isolation with migration (IM) model is important for studies in population genetics and phylogeography. IM program applies the IM model to genetic data drawn from a pair of closely related populations or species based on Markov chain Monte Carlo (MCMC) simulations of gene genealogies. But computational burden of IM program has placed limits on its application. Methodology With strong computational power, Graphics Processing Unit (GPU) has been widely used in many fields. In this article, we present an effective implementation of IM program on one GPU based on Compute Unified Device Architecture (CUDA), which we call gPGA. Conclusions Compared with IM program, gPGA can achieve up to 52.30X speedup on one GPU. The evaluation results demonstrate that it allows datasets to be analyzed effectively and rapidly for research on divergence population genetics. The software is freely available with source code at https://github.com/chunbaozhou/gPGA. PMID:26248314

  5. Repeatable Population Dynamics among Vesicular Stomatitis Virus Lineages Evolved under High Co-infection.

    PubMed

    Williams, Elizabeth S C P; Morales, Nadya M; Wasik, Brian R; Brusic, Vesna; Whelan, Sean P J; Turner, Paul E

    2016-01-01

    Parasites and hosts can experience oscillatory cycles, where the densities of these interacting species dynamically fluctuate through time. Viruses with different replication strategies can also interact to produce cyclical dynamics. Frequent cellular co-infection can select for defective-interfering particles (DIPs): "cheater" viruses with shortened genomes that interfere with intracellular replication of full-length (ordinary) viruses. DIPs are positively selected when rare because they out-replicate ordinary viruses during co-infection, but DIPs are negatively selected when common because ordinary viruses become unavailable for intracellular exploitation via cheating. Here, we tested whether oscillatory dynamics of ordinary viruses were similar across independently evolved populations of vesicular stomatitis virus (VSV). Results showed identical cyclical dynamics across populations in the first 10 experimental passages, which transitioned to repeatable dampened oscillations by passage 20. Genomic analyses revealed parallel molecular substitutions across populations, particularly novel mutations that became dominant by passage 10. Our study showed that oscillatory dynamics and molecular evolution of interacting viruses were highly repeatable in VSV populations passaged under frequent co-infection. Furthermore, our data suggested that frequent co-infection with DIPs caused lowered performance of full-length viruses, by reducing their population densities by orders of magnitude compared to reproduction of ordinary viruses during strictly clonal infections. PMID:27065953

  6. Repeatable Population Dynamics among Vesicular Stomatitis Virus Lineages Evolved under High Co-infection

    PubMed Central

    Williams, Elizabeth S. C. P.; Morales, Nadya M.; Wasik, Brian R.; Brusic, Vesna; Whelan, Sean P. J.; Turner, Paul E.

    2016-01-01

    Parasites and hosts can experience oscillatory cycles, where the densities of these interacting species dynamically fluctuate through time. Viruses with different replication strategies can also interact to produce cyclical dynamics. Frequent cellular co-infection can select for defective-interfering particles (DIPs): “cheater” viruses with shortened genomes that interfere with intracellular replication of full-length (ordinary) viruses. DIPs are positively selected when rare because they out-replicate ordinary viruses during co-infection, but DIPs are negatively selected when common because ordinary viruses become unavailable for intracellular exploitation via cheating. Here, we tested whether oscillatory dynamics of ordinary viruses were similar across independently evolved populations of vesicular stomatitis virus (VSV). Results showed identical cyclical dynamics across populations in the first 10 experimental passages, which transitioned to repeatable dampened oscillations by passage 20. Genomic analyses revealed parallel molecular substitutions across populations, particularly novel mutations that became dominant by passage 10. Our study showed that oscillatory dynamics and molecular evolution of interacting viruses were highly repeatable in VSV populations passaged under frequent co-infection. Furthermore, our data suggested that frequent co-infection with DIPs caused lowered performance of full-length viruses, by reducing their population densities by orders of magnitude compared to reproduction of ordinary viruses during strictly clonal infections. PMID:27065953

  7. Genetic Analyses of Sorting of Paternally Transmitted Mitochondrial DNA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The organelles are maternally transmitted in the vast majority of eukaryotes. However paternal transmission of plastids and mitochondria occurs rarely in plants. Cucumber is a unique model plant for organellar genetics because its three genomes show differential transmission: maternal for chlorop...

  8. Behavioral Genetic Analyses of Prosocial Behavior in Adolescents

    ERIC Educational Resources Information Center

    Gregory, Alice M.; Light-Hausermann, Jade H.; Rijsdijk, Fruhling; Eley, Thalia C.

    2009-01-01

    Prosocial behavior is an important aspect of normal social and psychological development. Adult and child twin studies typically estimate the heritability of prosocial behavior to be between 30 and 50%, although relatively little is known about genetic and environmental influences upon prosocial behavior in adolescence. We therefore examined…

  9. Genetic Analyses of Soluble Carbohydrate Concentrations in Onion Bulbs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fructans are the primary soluble carbohydrate in onion (Allium cepa L.) bulbs and show significant correlations with dry weights and pungency. In this research, we estimated the genetic effects and interactions between two chromosome regions associated with higher amounts of soluble carbohydrates i...

  10. Phytochemical and genetic analyses of ancient cannabis from Central Asia

    PubMed Central

    Russo, Ethan B.; Jiang, Hong-En; Li, Xiao; Sutton, Alan; Carboni, Andrea; del Bianco, Francesca; Mandolino, Giuseppe; Potter, David J.; Zhao, You-Xing; Bera, Subir; Zhang, Yong-Bing; Lü, En-Guo; Ferguson, David K.; Hueber, Francis; Zhao, Liang-Cheng; Liu, Chang-Jiang; Wang, Yu-Fei; Li, Cheng-Sen

    2008-01-01

    The Yanghai Tombs near Turpan, Xinjiang-Uighur Autonomous Region, China have recently been excavated to reveal the 2700-year-old grave of a Caucasoid shaman whose accoutrements included a large cache of cannabis, superbly preserved by climatic and burial conditions. A multidisciplinary international team demonstrated through botanical examination, phytochemical investigation, and genetic deoxyribonucleic acid analysis by polymerase chain reaction that this material contained tetrahydrocannabinol, the psychoactive component of cannabis, its oxidative degradation product, cannabinol, other metabolites, and its synthetic enzyme, tetrahydrocannabinolic acid synthase, as well as a novel genetic variant with two single nucleotide polymorphisms. The cannabis was presumably employed by this culture as a medicinal or psychoactive agent, or an aid to divination. To our knowledge, these investigations provide the oldest documentation of cannabis as a pharmacologically active agent, and contribute to the medical and archaeological record of this pre-Silk Road culture. PMID:19036842

  11. Viral Co-infection and Leprosy Outcomes: A Cohort Study

    PubMed Central

    Machado, Paulo R. L.; Machado, Lídia M.; Shibuya, Mayume; Rego, Jamile; Johnson, Warren D.; Glesby, Marshall J.

    2015-01-01

    Background The role of the host immunity in determining leprosy clinical forms and complications is well recognized, implying that changes in the immune status may interfere with several aspects of the disease. Therefore, we hypothesized that the presence of viral co-infections and associated immunological changes will have a clinical impact on leprosy outcomes. The aim of our study was to determine the clinical impact of human immunodeficiency virus (HIV), human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection on the development of reactions, neuritis, neuropathy and relapses. Methodology/Principal Findings Cohort study in 245 leprosy subjects from Bahia, Brazil. Patients were followed from the time of diagnosis until at least the end of multidrug therapy. Viral co-infection was detected in 36 out of the 245 patients (14.7%). Specific co-infection rates were 10.6% for HBV, 2.9% for HIV, 2.5% for HTLV-1 and 0.8% for HCV. All four groups of co-infected patients had higher rates of neuritis and nerve function impairment compared to non co-infected leprosy subjects. The relapse rate was also higher in the co-infected group (8.3%) versus patients without co-infection (1.9%); relative risk 4.37, 95% confidence interval 1.02–18.74. Conclusions/Significance Leprosy patients should be screened for HBV, HCV, HIV and HTLV-1 co-infections. Besides contributing to better health care, this measure will facilitate the early detection of severe complications through targeting of higher risk patients. PMID:26267882

  12. Techniques and Approaches to Genetic Analyses in Nephrological Disorders.

    PubMed

    Willig, Laurel K

    2016-03-01

    Inherited renal disease is a leading cause of morbidity and mortality in pediatric nephrology. High throughput advancements in genomics have led to greater understanding of the biologic underpinnings of these diseases. However, the underlying genetic changes explain only part of the molecular biology that contributes to disease manifestation and progression. Other omics technologies will provide a more complete picture of these cellular processes. This review discusses these omics technologies in the context of pediatric renal disease. PMID:27617137

  13. Clinical Disease Severity of Respiratory Viral Co-Infection versus Single Viral Infection: A Systematic Review and Meta-Analysis

    PubMed Central

    Asner, Sandra A.; Science, Michelle E.; Tran, Dat; Smieja, Marek; Merglen, Arnaud; Mertz, Dominik

    2014-01-01

    Background Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. Methods We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. Results Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p<0.001) with viral co-infection as compared to other age groups (I2 for subgroup analysis 64%, p = 0.04). Conclusions No differences in clinical disease severity between viral co-infections and single respiratory infections were documented. The suggested increased risk of mortality observed amongst children with viral co-infections requires further investigation. PMID:24932493

  14. Hemosporidian parasites in forest birds from Venezuela: genetic lineage analyses.

    PubMed

    Mijares, Alfredo; Rosales, Romel; Silva-Iturriza, Adriana

    2012-09-01

    Avian hemosporidian parasites of the genera Haemoproteus, Plasmodium, and Leucocytozoon are transmitted by different dipteran vectors. In the present work, we looked for the presence of these parasites in 47 birds from 12 families, which were sampled in the migratory corridor Paso de Portachuelo, located at the Henri Pittier National Park, Venezuela. The presence of the parasites was evidenced by amplification of a region of 471 bp of their cytochrome b gene. This region of the marker presents enough polymorphism to identify most of the mitochondrial lineages. Therefore, the obtained amplicons were sequenced, not only to identify the genus of the parasites sampled, but also to analyze their genetic diversity in the study area. The overall parasite prevalence was low (11%). We reported, for the first time, Plasmodium in birds of the species Formicarius analis and Chamaeza campanisona (Formicariidae) and Haemoproteus in Geotrygon linearis (Columbidae). A phylogenetic tree was generated using the Haemoproteus, Plasmodium, and Leucocytozoon sequences obtained in this study, together with representative sequences from previous studies. The highest genetic diversities between the two Haemoproteus lineages (11.70%) and among the three Plasmodium lineages (7.86%) found in this study are also similar to those found when lineages reported in the literature were used. These results indicate that in the migratory corridor Paso de Portachuleo, representative parasite lineages are found, making this location an attractive location for future studies. PMID:23050478

  15. The epidemiological consequences of leprosy-tuberculosis co-infection.

    PubMed

    Hohmann, N; Voss-Böhme, A

    2013-02-01

    While in antiquity both leprosy and tuberculosis were prevalent in Europe, leprosy declined thereafter and, simultaneously, tuberculosis prevalence increased. Since both diseases are caused by mycobacterial infections, it has been suggested that there might be a causal relationship between both epidemics. Chaussinand observed the inverse prevalence of leprosy and tuberculosis and suggested that individuals with a latent tuberculosis infection are protected from acquiring leprosy. His cross-immunity hypothesis has been countered more recently by a co-infection hypothesis. The latter suggestion, proposed by Donoghue, states that people being infected with multi-bacillary leprosy are more susceptible to tuberculosis, which leads to increased mortality from the disease. This study utilizes mathematical modeling to explore the epidemiological consequences of the co-infection hypothesis for realistically confined parameter values. While the co-infection hypothesis appears plausible at first glance, a second thought reveals that it comprises also substantial consequences for tuberculosis epidemics: if co-infection raises the mortality rate above that of purely tuberculosis infected persons, then tuberculosis might as well be eradicated by leprosy. It is the specific interplay of both increased susceptibility towards tuberculosis and increased death rate when co-infected that determines the epidemiological fate. As a result of this analysis, it is shown that there is a large parameter region where the eventual disappearance of leprosy could indeed be explained by co-infection. This parameter region is considerably larger than that predicted by the cross-immunity hypothesis. This shows that the co-infection hypothesis should be considered a significant alternative to the cross-immunity hypothesis. The time scales at which the effects of co-infection are observed depend critically on the spatial distribution of the individuals but reach epidemiologically realistic values for

  16. Predicting Avian Influenza Co-Infection with H5N1 and H9N2 in Northern Egypt.

    PubMed

    Young, Sean G; Carrel, Margaret; Malanson, George P; Ali, Mohamed A; Kayali, Ghazi

    2016-01-01

    Human outbreaks with avian influenza have been, so far, constrained by poor viral adaptation to non-avian hosts. This could be overcome via co-infection, whereby two strains share genetic material, allowing new hybrid strains to emerge. Identifying areas where co-infection is most likely can help target spaces for increased surveillance. Ecological niche modeling using remotely-sensed data can be used for this purpose. H5N1 and H9N2 influenza subtypes are endemic in Egyptian poultry. From 2006 to 2015, over 20,000 poultry and wild birds were tested at farms and live bird markets. Using ecological niche modeling we identified environmental, behavioral, and population characteristics of H5N1 and H9N2 niches within Egypt. Niches differed markedly by subtype. The subtype niches were combined to model co-infection potential with known occurrences used for validation. The distance to live bird markets was a strong predictor of co-infection. Using only single-subtype influenza outbreaks and publicly available ecological data, we identified areas of co-infection potential with high accuracy (area under the receiver operating characteristic (ROC) curve (AUC) 0.991). PMID:27608035

  17. Choice of Reading Comprehension Test Influences the Outcomes of Genetic Analyses

    ERIC Educational Resources Information Center

    Betjemann, Rebecca S.; Keenan, Janice M.; Olson, Richard K.; DeFries, John C.

    2011-01-01

    Does the choice of test for assessing reading comprehension influence the outcome of genetic analyses? A twin design compared two types of reading comprehension tests classified as primarily associated with word decoding (RC-D) or listening comprehension (RC-LC). For both types of tests, the overall genetic influence is high and nearly identical.…

  18. High Prevalence of Co-Infections by Invasive and Non-Invasive Chlamydia trachomatis Genotypes during the Lymphogranuloma Venereum Outbreak in Spain

    PubMed Central

    Rodriguez-Dominguez, Mario; Gonzalez-Alba, Jose Maria; Puerta, Teresa; Menendez, Blanca; Sanchez-Diaz, Ana Maria; Canton, Rafael; del Romero, Jorge; Galan, Juan Carlos

    2015-01-01

    The evolution of Chlamydia trachomatis is mainly driven by recombination events. This fact can be fuelled by the coincidence in several European regions of the high prevalence of non-invasive urogenital genotypes and lymphogranuloma venereum (LGV) outbreaks. This scenario could modify the local epidemiology and favor the selection of new C. trachomatis variants. Quantifying the prevalence of co-infection could help to predict the potential risk in the selection of new variants with unpredictable results in pathogenesis or transmissibility. In the 2009-2013 period, 287 clinical samples with demonstrated presence of C. trachomatis were selected. They were divided in two groups. The first group was constituted by 137 samples with C. trachomatis of the LGV genotypes, and the second by the remaining 150 samples in which the presence of LGV genotypes was previously excluded. They were analyzed to detect the simultaneous presence of non-LGV genotypes based on pmpH and ompA genes. In the first group, co-infections were detected in 10.9% of the cases whereas in the second group the prevalence was 14.6%, which is the highest percentage ever described among European countries. Moreover, bioinformatic analyses suggested the presence among men who have sex with men of a pmpH-recombinant variant, similar to strains described in Seattle in 2002. This variant was the result of genetic exchange between genotypes belonging to LGV and members of G-genotype. Sequencing of other genes, phylogenetically related to pathotype, confirmed that the putative recombinant found in Madrid could have a common origin with the strains described in Seattle. Countries with a high prevalence of co-infections and high migration flows should enhance surveillance programs in at least their vulnerable population. PMID:25965545

  19. High Prevalence of Co-Infections by Invasive and Non-Invasive Chlamydia trachomatis Genotypes during the Lymphogranuloma Venereum Outbreak in Spain.

    PubMed

    Rodriguez-Dominguez, Mario; Gonzalez-Alba, Jose Maria; Puerta, Teresa; Menendez, Blanca; Sanchez-Diaz, Ana Maria; Canton, Rafael; del Romero, Jorge; Galan, Juan Carlos

    2015-01-01

    The evolution of Chlamydia trachomatis is mainly driven by recombination events. This fact can be fuelled by the coincidence in several European regions of the high prevalence of non-invasive urogenital genotypes and lymphogranuloma venereum (LGV) outbreaks. This scenario could modify the local epidemiology and favor the selection of new C. trachomatis variants. Quantifying the prevalence of co-infection could help to predict the potential risk in the selection of new variants with unpredictable results in pathogenesis or transmissibility. In the 2009-2013 period, 287 clinical samples with demonstrated presence of C. trachomatis were selected. They were divided in two groups. The first group was constituted by 137 samples with C. trachomatis of the LGV genotypes, and the second by the remaining 150 samples in which the presence of LGV genotypes was previously excluded. They were analyzed to detect the simultaneous presence of non-LGV genotypes based on pmpH and ompA genes. In the first group, co-infections were detected in 10.9% of the cases whereas in the second group the prevalence was 14.6%, which is the highest percentage ever described among European countries. Moreover, bioinformatic analyses suggested the presence among men who have sex with men of a pmpH-recombinant variant, similar to strains described in Seattle in 2002. This variant was the result of genetic exchange between genotypes belonging to LGV and members of G-genotype. Sequencing of other genes, phylogenetically related to pathotype, confirmed that the putative recombinant found in Madrid could have a common origin with the strains described in Seattle. Countries with a high prevalence of co-infections and high migration flows should enhance surveillance programs in at least their vulnerable population. PMID:25965545

  20. Biochemical and genetic analyses of acetoin catabolism in Alcaligenes eutrophus.

    PubMed Central

    Fründ, C; Priefert, H; Steinbüchel, A; Schlegel, H G

    1989-01-01

    In genetic studies on the catabolism of acetoin in Alcaligenes eutrophus, we used Tn5::mob-induced mutants which were impaired in the utilization of acetoin as the sole carbon source for growth. The transposon-harboring EcoRI restriction fragments from 17 acetoin-negative and slow-growing mutants (class 2a) and from six pleiotropic mutants of A. eutorphus, which were acetoin-negative and did not grow chemolithoautotrophically (class 2b), were cloned from pHC79 gene banks. The insertions of Tn5 were mapped on four different chromosomal EcoRI restriction fragments (A, C, D, and E) in class 2a mutants. The native DNA fragments were cloned from a lambda L47 or from a cosmid gene bank. Evidence is provided that fragments A (21 kilobase pairs [kb]) and C (7.7 kb) are closely linked in the genome; the insertions of Tn5 covered a region of approximately 5 kb. Physiological experiments revealed that this region encodes for acetoin:dichlorophenol-indophenol oxidoreductase, a fast-migrating protein, and probably for one additional protein that is as yet unknown. In mutants which were not completely impaired in growth on acetoin but which grew much slower and after a prolonged lag phase, fragments D (7.2 kb) and E (8.1 kb) were inactivated by insertion of Tn5::mob. No structural gene could be assigned to the D or E fragments. In class 2b mutants, insertions of Tn5 were mapped on fragment B (11.3 kb). This fragment complemented pleiotropic hno mutants in trans; these mutants were impaired in the formation of a rpoN-like protein. The expression of the gene cluster on fragments A and C seemed to be rpoN dependent. PMID:2556366

  1. Factors associated with HIV and syphilis co-infection among men who have sex with men in seven Chinese cities.

    PubMed

    Das, Aritra; Li, Jianjun; Zhong, Fei; Ouyang, Lin; Mahapatra, Tanmay; Tang, Weiming; Fu, Gengfeng; Zhao, Jinkou; Detels, Roger

    2015-03-01

    HIV-syphilis co-infection is often cited as a major reason behind recent resurgence in syphilis prevalence among men who have sex with men in China. Most published literatures explore factors associated with either HIV or syphilis, but not their co-infection. We analysed data from a cross-sectional survey on men who have sex with men in seven Chinese cities. Snowball sampling was used to recruit participants for the survey. Socio-demographic and behavioural predictors for HIV-syphilis mono/co-infection were examined using ordinal logistic regression. Factor scores were used to summarise (1) HIV-related knowledge and (2) access to HIV preventive services. Prevalence of HIV, syphilis, and their co-infection, among 2936 self-identified men who have sex with men, were 7.7%, 14.3%, and 2.6%, respectively. In the adjusted analysis, the significant positive correlates of poorer diagnoses (co-infection vs mono- and no infection or co- and mono-infection vs no infection) were: 30 to 39 years and ≥40 years age, education up to senior high school, unprotected anal intercourse, recent sexually transmitted infection symptoms, incorrect knowledge about routes of transmission, and access to preventive or counselling/testing services for HIV. For effective control of this dual epidemic, integrated HIV and syphilis surveillance and targeted intervention strategies for Chinese men who have sex with men are needed urgently. PMID:24737881

  2. Fine-scale genetic structure analyses suggest further male than female dispersal in mountain gorillas

    PubMed Central

    2014-01-01

    Background Molecular studies in social mammals rarely compare the inferences gained from genetic analyses with field information, especially in the context of dispersal. In this study, we used genetic data to elucidate sex-specific dispersal dynamics in the Virunga Massif mountain gorilla population (Gorilla beringei beringei), a primate species characterized by routine male and female dispersal from stable mixed-sex social groups. Specifically, we conducted spatial genetic structure analyses for each sex and linked our genetically-based observations with some key demographic and behavioural data from this population. Results To investigate the spatial genetic structure of mountain gorillas, we analysed the genotypes of 193 mature individuals at 11 microsatellite loci by means of isolation-by-distance and spatial autocorrelation analyses. Although not all males and females disperse, female gorillas displayed an isolation-by-distance pattern among groups and a signal of dispersal at short distances from their natal group based on spatial autocorrelation analyses. In contrast, male genotypes were not correlated with spatial distance, thus suggesting a larger mean dispersal distance for males as compared to females. Both within sex and mixed-sex pairs were on average genetically more related within groups than among groups. Conclusions Our study provides evidence for an intersexual difference in dispersal distance in the mountain gorilla. Overall, it stresses the importance of investigating spatial genetic structure patterns on a sex-specific basis to better understand the dispersal dynamics of the species under investigation. It is currently poorly understood why some male and female gorillas disperse while others remain in the natal group. Our results on average relatedness within and across groups confirm that groups often contain close relatives. While inbreeding avoidance may play a role in driving female dispersal, we note that more detailed dyadic genetic

  3. Fine-scale spatial genetic structure of eight tropical tree species as analysed by RAPDs.

    PubMed

    Degen, B; Caron, H; Bandou, E; Maggia, L; Chevallier, M H; Leveau, A; Kremer, A

    2001-10-01

    The fine-scale spatial genetic structure of eight tropical tree species (Chrysophyllum sanguinolentum, Carapa procera, Dicorynia guianensis, Eperua grandiflora, Moronobea coccinea, Symphonia globulifera, Virola michelii, Vouacapoua americana) was studied in populations that were part of a silvicultural trial in French Guiana. The species analysed have different spatial distribution, sexual system, pollen and seed dispersal agents, flowering phenology and environmental demands. The spatial position of trees and a RAPD data set for each species were combined using a multivariate genetic distance method to estimate spatial genetic structure. A significant spatial genetic structure was found for four of the eight species. In contrast to most observations in temperate forests, where spatial structure is not usually detected at distances greater than 50 m, significant genetic structure was found at distances up to 300 m. The relationships between spatial genetic structure and life history characteristics are discussed. PMID:11737299

  4. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network, and pathway analyses

    PubMed Central

    Kogelman, Lisette J. A.; Pant, Sameer D.; Fredholm, Merete; Kadarmideen, Haja N.

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH) and differentially wired (DW) networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g., NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g., metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic) obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways that underlie

  5. Hepatitis Aand E Co-Infection with Worst Outcome.

    PubMed

    Saeed, Anjum; Cheema, Huma Arshad; Assiri, Asaad

    2016-06-01

    Infections are still a major problem in the developing countries like Pakistan because of poor sewage disposal and economic restraints. Acute viral hepatitis like Aand E are not uncommon in pediatric age group because of unhygienic food handling and poor sewage disposal, but majority recovers well without any complications. Co-infections are rare occurrences and physicians need to be well aware while managing such conditions to avoid worst outcome. Co-infection with hepatitis Aand E is reported occasionally in the literature, however, other concurrent infections such as hepatitis A with Salmonellaand hepatotropic viruses like viral hepatitis B and C are present in the literature. Co-infections should be kept in consideration when someone presents with atypical symptoms or unusual disease course like this presented case. We report here a girl child who had acute hepatitis A and E concurrent infections and presented with hepatic encephalopathy and had worst outcome, despite all the supportive measures being taken. PMID:27376213

  6. Impact of HIV co-infection on the evolution and transmission of multidrug-resistant tuberculosis

    PubMed Central

    Eldholm, Vegard; Rieux, Adrien; Monteserin, Johana; Lopez, Julia Montana; Palmero, Domingo; Lopez, Beatriz; Ritacco, Viviana; Didelot, Xavier; Balloux, Francois

    2016-01-01

    The tuberculosis (TB) epidemic is fueled by a parallel Human Immunodeficiency Virus (HIV) epidemic, but it remains unclear to what extent the HIV epidemic has been a driver for drug resistance in Mycobacterium tuberculosis (Mtb). Here we assess the impact of HIV co-infection on the emergence of resistance and transmission of Mtb in the largest outbreak of multidrug-resistant TB in South America to date. By combining Bayesian evolutionary analyses and the reconstruction of transmission networks utilizing a new model optimized for TB, we find that HIV co-infection does not significantly affect the transmissibility or the mutation rate of Mtb within patients and was not associated with increased emergence of resistance within patients. Our results indicate that the HIV epidemic serves as an amplifier of TB outbreaks by providing a reservoir of susceptible hosts, but that HIV co-infection is not a direct driver for the emergence and transmission of resistant strains. DOI: http://dx.doi.org/10.7554/eLife.16644.001 PMID:27502557

  7. Hepatitis B and Schistosoma co-infection in a non-endemic area.

    PubMed

    Cuenca-Gómez, J Á; Salas-Coronas, J; Lozano-Serrano, A B; Vázquez-Villegas, J; Soriano-Pérez, M J; Estévez-Escobar, M; Villarejo-Ordóñez, A; Cabezas-Fernández, M T

    2016-09-01

    Schistosomiasis is related to the development of liver fibrosis and portal hypertension. Chronic co-infection with HBV and Schistosoma has been associated in endemic areas with a higher risk for a more severe liver disease. However, no studies have assessed the real importance of this co-infection in non-endemic regions. This is a retrospective observational study of Sub-Saharan immigrants attending between October 2004 and February 2014. Patients with chronic HBV infection with and without evidence of schistosomal infection were compared. Epidemiological, analytical, and microbiological data were analysed. Likelihood of liver fibrosis based on APRI and FIB-4 indexes was established. A total of 507 patients were included in the study, 170 (33.5 %) of them harbouring evidence of schistosome infection. No differences were found in transaminase, GGT, and ALP levels. In fibrosis tests, a higher proportion of patients with HVB and S. mansoni detection reached possible fibrosis scores (F > 2) when compared to patients without schistosomiasis: 17.4 vs 14.2 % and 4.3 % vs 4.2 % (using high sensitivity and high specificity cut-offs respectively), although differences were not statistically significant (p = 0.69, p = 0.96). For possible cirrhosis (F4) score, similar results were observed: 4.3 % of co-infected patients vs 2.1 % of mono-infected ones, p = 0.46. According to these datas, in non-endemic regions the degree of hepatic fibrosis in patients with chronic hepatitis B is not substantially modified by schistosome co-infection. PMID:27272213

  8. Comparative genetic analyses of metric traits using diallel and factorial mating designs in bread wheat.

    PubMed

    Virk, D S; Khehra, A S; Virk, P S; Dhillon, B S

    1985-05-01

    For studying the inheritance of metric traits, diallel cross and factorial mating designs are commonly used. Since factorial mating design is less restrictive in crossing plans, the genetic information drawn from it was compared with that from a diallel cross. The comparison was made using graphical, genetic components and combining ability analyses for grain yield, grain weight and spike length in a field experiment of bread wheat (Triticum aestivum L.). Analyses were made on a nine parent diallel cross and a 4 ♀ × 5 ♂ factorial mating design which was sampled from the diallel cross. In general, there was a high degree of agreement between the results obtained from factorial mating design and diallel cross analyses showing thereby that the former provides almost equivalent genetic information to the latter. PMID:24253828

  9. Population Genetic and Admixture Analyses of Culex pipiens Complex (Diptera: Culicidae) Populations in California, United States

    PubMed Central

    Kothera, Linda; Nelms, Brittany M.; Reisen, William K.; Savage, Harry M.

    2013-01-01

    Microsatellite markers were used to genetically characterize 19 Culex pipiens complex populations from California. Two populations showed characteristics of earlier genetic bottlenecks. The overall FST value and a neighbor-joining tree suggested moderate amounts of genetic differentiation. Analyses using Structure indicated K = 4 genetic clusters: Cx. pipiens form pipiens L., Cx. quinquefasciatus Say, Cx. pipiens form molestus Forskäl, and a group of genetically similar individuals of hybrid origin. A Discriminant Analysis of Principal Components indicated that the latter group is a mixture of the other three taxa, with form pipiens and form molestus contributing somewhat more ancestry than Cx. quinquefasciatus. Characterization of 56 morphologically autogenous individuals classified most as Cx. pipiens form molestus, and none as Cx. pipiens form pipiens or Cx. quinquefasciatus. Comparison of California microsatellite data with those of Cx. pipiens pallens Coquillett from Japan indicated the latter does not contribute significantly to genotypes in California. PMID:23958909

  10. Choice of Reading Comprehension Test Influences the Outcomes of Genetic Analyses.

    PubMed

    Betjemann, Rebecca S; Keenan, Janice M; Olson, Richard K; Defries, John C

    2011-01-01

    Does the choice of test for assessing reading comprehension influence the outcome of genetic analyses? A twin design compared two types of reading comprehension tests classified as primarily associated with word decoding (RC-D) or listening comprehension (RC-LC). For both types of tests, the overall genetic influence is high and nearly identical. However, the tests differed significantly in how they covary with the genes associated with decoding and listening comprehension. Although Cholesky decomposition showed that both types of comprehension tests shared significant genetic influence with both decoding and listening comprehension, RC-D tests shared most genetic variance with decoding, and RC-LC tests shared most with listening comprehension. Thus, different tests used to measure the same construct may manifest very different patterns of genetic covariation. These results suggest that the apparent discrepancies among the findings of previous twin studies of reading comprehension could be due at least in part to test differences. PMID:21804757

  11. The Application and Performance of Single Nucleotide Polymorphism Markers for Population Genetic Analyses of Lepidoptera

    PubMed Central

    Coates, Brad Steven; Bayles, Darrell O.; Wanner, Kevin W.; Robertson, Hugh M.; Hellmich, Richard L.; Sappington, Thomas W.

    2011-01-01

    Microsatellite markers are difficult to apply within lepidopteran studies due to the lack of locus-specific PCR amplification and the high proportion of “null” alleles, such that erroneous estimations of population genetic parameters often result. Herein single nucleotide polymorphism (SNP) markers are developed from Ostrinia nubilalis (Lepidoptera: Crambidae) using next generation expressed sequence tag (EST) data. A total of 2742 SNPs were predicted within a reference assembly of 7414 EST contigs, and a subset of 763 were incorporated into 24 multiplex PCR reactions. To validate this pipeline, 5 European and North American sample sites were genotyped at 178 SNP loci, which indicated 84 (47.2%) were in Hardy–Weinberg equilibrium. Locus-by-locus FST, analysis of molecular variance, and STRUCTURE analyses indicate significant genetic differentiation may exist between European and North American O. nubilalis. The observed genetic diversity was significantly lower among European sites, which may result from genetic drift, natural selection, a genetic bottleneck, or ascertainment bias due to North American origin of EST sequence data. SNPs are an abundant source of mutation data for molecular genetic marker development in non-model species, with shared ancestral SNPs showing application within closely related species. These markers offer advantages over microsatellite markers for genetic and genomic analyses of Lepidoptera, but the source of mutation data may affect the estimation of population parameters and likely need to be considered in the interpretation of empirical data. PMID:22303334

  12. Association of CMV, HBV, or HCV co-infection with vaccine response in adults with well-controlled HIV infection.

    PubMed

    Troy, S B; Rossheim, A E B; Siik, J; Cunningham, T D; Kerry, J A

    2016-05-01

    Even after CD4 count recovery on antiretroviral therapy, HIV infection is associated with decreased response to most vaccines compared to the general population. Chronic infections with viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which are more prevalent in HIV-infected populations, have been linked to immune dysfunction and decreased vaccine response in the general population. However, whether co-infection with these other viruses contributes to the decreased vaccine response seen in adults with well-controlled HIV infection is unknown. We conducted a secondary analysis of data and serum from adults with well-controlled HIV infection from an inactivated polio vaccine trial (224 subjects) and a pneumococcal conjugate vaccine study (128 subjects). We evaluated the association of CMV, HBV, or HCV co-infection with post-vaccination antibody levels using both univariate and multivariate analyses, controlling for factors such as age, race, CD4 count, comorbidities, smoking status, and baseline antibody levels. Ninety-three percent, 7%, and 14% of subjects were co-infected with CMV, HBV, and HCV respectively. On both univariate and multivariate analysis, neither CMV nor HCV co-infection were significantly associated with post-vaccination antibody levels to either vaccine. HBV co-infection was significantly associated with post-vaccination antibody concentrations for pneumococcal serotype 7F on univariate analysis and 6A on multivariate analysis, but the association was with higher antibody concentrations. In conclusion, co-infection with CMV, HBV, or HCV does not appear to contribute to the decreased vaccine response seen in adults with well-controlled HIV infection. PMID:26751638

  13. Genetic analyses reveal unusually high diversity of infectious haematopoietic necrosis virus in rainbow trout aquaculture

    USGS Publications Warehouse

    Troyer, Ryan M.; LaPatra, Scott E.; Kurath, Gael

    2000-01-01

    Infectious haematopoietic necrosis virus (IHNV) is the most significant virus pathogen of salmon and trout in North America. Previous studies have shown relatively low genetic diversity of IHNV within large geographical regions. In this study, the genetic heterogeneity of 84 IHNV isolates sampled from rainbow trout (Oncorhynchus mykiss) over a 20 year period at four aquaculture facilities within a 12 mile stretch of the Snake River in Idaho, USA was investigated. The virus isolates were characterized using an RNase protection assay (RPA) and nucleotide sequence analyses. Among the 84 isolates analysed, 46 RPA haplotypes were found and analyses revealed a high level of genetic heterogeneity relative to that detected in other regions. Sequence analyses revealed up to 7·6% nucleotide divergence, which is the highest level of diversity reported for IHNV to date. Phylogenetic analyses identified four distinct monophyletic clades representing four virus lineages. These lineages were distributed across facilities, and individual facilities contained multiple lineages. These results suggest that co-circulating IHNV lineages of relatively high genetic diversity are present in the IHNV populations in this rainbow trout culture study site. Three of the four lineages exhibited temporal trends consistent with rapid evolution.

  14. Symbiodinium population genetics: testing for species boundaries and analysing samples with mixed genotypes.

    PubMed

    Wham, Drew C; LaJeunesse, Todd C

    2016-06-01

    Population genetic markers are increasingly being used to study the diversity, ecology and evolution of Symbiodinium, a group of eukaryotic microbes that are often mutualistic with reef-building corals. Population genetic markers can resolve individual clones, or strains, from samples of host tissue; however, samples may comprise different species that may confound interpretations of gene flow and genetic structure. Here, we propose a method for resolving species from population genetic data using tests for genetic recombination. Assigning individuals to genetically recombining populations prior to further analyses avoids critical errors in the interpretation of gene flow and dispersal. To demonstrate the effectiveness of the approach, we first apply this method to a simulated data set. We then use the method to resolve two species of host generalist Symbiodinium that commonly co-occur in reef-building corals collected from Indo-West Pacific reefs. We demonstrate that the method is robust even when some hosts contain genotypes from two distinct species. Finally, we examine population genetic data sets from two recently published papers in Molecular Ecology. We show that each strongly supports a two species interpretation, which significantly changes the original conclusions presented in these studies. When combined with available phylogenetic and ecological evidence, the use of population genetic data offers a robust method for unambiguously delimiting morphologically cryptic species. PMID:27118512

  15. Genetic analyses of elbow and hip dysplasia in the German shepherd dog.

    PubMed

    Stock, K F; Klein, S; Tellhelm, B; Distl, O

    2011-06-01

    Results from radiographic screening for canine hip dysplasia (CHD) and elbow dysplasia (CED) of 48 367 German shepherd dogs born in 2001-07 were used for the population genetic analyses. Available information included CHD scores for 47 730 dogs, CED scores for 28 011 dogs and detailed veterinary diagnoses of primary ED lesions for a subsample of 18 899 dogs. Quasi-continuous traits were CHD, CED and cases of CED without radiographically visible primary lesion (CED-ARTH). Binary coding was used for fragmented medial coronoid process of the ulna (FCP), borderline findings and mild to severe signs of dysplasia in hip and elbow joints. Genetic parameters were estimated in univariate threshold and multivariate linear and mixed linear-threshold models using Gibbs sampling. Correlations between univariately predicted breeding values (BV) indicated genetic differences between borderline and affected disease status for both CHD (r(BV) = 0.5) and CED (r(BV) = 0.3). Multivariate genetic analyses with separate consideration of borderline findings revealed moderate heritabilities of 0.2-0.3 for the quasi-continuous traits with positive additive genetic correlation of 0.3 between CHD and both CED and CED-ARTH. For FCP, heritability of 0.6 and additive genetic correlations of +0.1 to CHD and -0.1 to CED-ARTH were estimated. Results supported the relevant genetic determination of CHD and CED, argued for both diseases against interpretation of borderline findings as healthy and implied genetic heterogeneity of CED. Accordingly, future breeding strategies to reduce the prevalences of CHD and CED in the German shepherd dog should be most efficient when based on BV from multivariate genetic evaluation for CHD, CED-ARTH and FCP with use of the whole scale of categories for classification of CHD and CED. PMID:21554416

  16. The entry of cucumber mosaic virus into cucumber xylem is facilitated by co-infection with zucchini yellow mosaic virus.

    PubMed

    Mochizuki, Tomofumi; Nobuhara, Shinya; Nishimura, Miho; Ryang, Bo-Song; Naoe, Masaki; Matsumoto, Tadashi; Kosaka, Yoshitaka; Ohki, Satoshi T

    2016-10-01

    We investigated the synergistic effects of co-infection by zucchini yellow mosaic virus (ZYMV) and cucumber mosaic virus (CMV) on viral distribution in the vascular tissues of cucumber. Immunohistochemical observations indicated that ZYMV was present in both the phloem and xylem tissues. ZYMV-RNA was detected in both the xylem wash and guttation fluid of ZYMV-inoculated cucumber. Steam treatment at a stem internode indicated that ZYMV enters the xylem vessels and moves through them but does not cause systemic infection in the plant. CMV distribution in singly infected cucumbers was restricted to phloem tissue. By contrast, CMV was detected in the xylem tissue of cotyledons in plants co-infected with CMV and ZYMV. Although both ZYMV-RNA and CMV-RNA were detected in the xylem wash and upper internodes of steam-treated, co-infected cucumbers grown at 24 °C, neither virus was detected in the upper leaves using an ELISA assay. Genetically modified CMV harboring the ZYMV HC-Pro gene was distributed in the xylem and phloem tissues of singly inoculated cucumber cotyledons. These results indicate that the ZYMV HC-Pro gene facilitates CMV entry into the xylem vessels of co-infected cucumbers. PMID:27400992

  17. Chronic Lyme Disease and Co-infections: Differential Diagnosis.

    PubMed

    Berghoff, Walter

    2012-01-01

    In Lyme disease concurrent infections frequently occur. The clinical and pathological impact of co-infections was first recognized in the 1990th, i.e. approximately ten years after the discovery of Lyme disease. Their pathological synergism can exacerbate Lyme disease or induce similar disease manifestations. Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae. In contrast to the USA, human granulocytic anaplasmosis (HGA) and babesiosis are not of major importance in Europe. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease. This applies particularly to infections caused by Bartonella henselae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult. The diagnosis is even more complex when co-infections occur in association with Lyme disease. Treatment recommendations are based on individual expert opinions. In antibiotic therapy, the use of third generation cephalosporins should only be considered in cases of Lyme disease. The same applies to carbapenems, which however are used occasionally in infections caused by Yersinia enterocolitica. For the remaining infections predominantly tetracyclines and macrolides are used. Quinolones are for alternative treatment, particularly gemifloxacin. For Bartonella henselae, Chlamydia trachomatis, and Chlamydophila pneumoniae the combination with rifampicin is recommended. Erythromycin is the drug of choice for

  18. Chronic Lyme Disease and Co-infections: Differential Diagnosis

    PubMed Central

    Berghoff, Walter

    2012-01-01

    In Lyme disease concurrent infections frequently occur. The clinical and pathological impact of co-infections was first recognized in the 1990th, i.e. approximately ten years after the discovery of Lyme disease. Their pathological synergism can exacerbate Lyme disease or induce similar disease manifestations. Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae. In contrast to the USA, human granulocytic anaplasmosis (HGA) and babesiosis are not of major importance in Europe. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease. This applies particularly to infections caused by Bartonella henselae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult. The diagnosis is even more complex when co-infections occur in association with Lyme disease. Treatment recommendations are based on individual expert opinions. In antibiotic therapy, the use of third generation cephalosporins should only be considered in cases of Lyme disease. The same applies to carbapenems, which however are used occasionally in infections caused by Yersinia enterocolitica. For the remaining infections predominantly tetracyclines and macrolides are used. Quinolones are for alternative treatment, particularly gemifloxacin. For Bartonella henselae, Chlamydia trachomatis, and Chlamydophila pneumoniae the combination with rifampicin is recommended. Erythromycin is the drug of choice for

  19. The importance of molecular analyses for understanding the genetic diversity of Histoplasma capsulatum: an overview.

    PubMed

    Vite-Garín, Tania; Estrada-Bárcenas, Daniel Alfonso; Cifuentes, Joaquín; Taylor, Maria Lucia

    2014-01-01

    Advances in the classification of the human pathogen Histoplasma capsulatum (H. capsulatum) (ascomycete) are sustained by the results of several genetic analyses that support the high diversity of this dimorphic fungus. The present mini-review highlights the great genetic plasticity of H. capsulatum. Important records with different molecular tools, mainly single- or multi-locus sequence analyses developed with this fungus, are discussed. Recent phylogenetic data with a multi-locus sequence analysis using 5 polymorphic loci support a new clade and/or phylogenetic species of H. capsulatum for the Americas, which was associated with fungal isolates obtained from the migratory bat Tadarida brasiliensis. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). PMID:24252830

  20. Erysipelas Outbreaks in Flocks of Geese in Poland--Biochemical and Genetic Analyses of the Isolates.

    PubMed

    Bobrek, Kamila; Gaweł, Andrzej

    2015-09-01

    Erysipelothrix rhusiopathiae causes erysipelas in many vertebrate species. Severe disease outbreaks have been noted in many poultry species--chickens, ducks, emus, pheasants, pigeons, and geese. This article describes the biochemical and genetic analyses of six E. rhusiopathiae strains isolated from geese for meat production. The isolates came from birds kept in different poultry houses on one farm, and were collected during two erysipelas outbreaks. We analyzed and compared the isolates by random amplified polymorphic DNA with the use of NK6 primer and pulsed-field gel electrophoresis, with the restriction enzyme SmaI. Biochemical examination was performed with API Coryne test. Analyses showed that the three strains isolated during the first outbreak differed, whereas the three isolates from the second outbreak were identical to one another, but distinct from the isolates from the first outbreak. The results of biochemical and genetic analyses of E. rhusiopathiae strains isolated from geese suggest different sources of infection for the erysipelas outbreaks. PMID:26478164

  1. Systematic meta-analyses and field synopsis of genetic association studies of violence and aggression

    PubMed Central

    Vassos, E; Collier, D A; Fazel, S

    2014-01-01

    A large number of candidate gene studies for aggression and violence have been conducted. Successful identification of associations between genetic markers and aggression would contribute to understanding the neurobiology of antisocial behavior and potentially provide useful tools for risk prediction and therapeutic targets for high-risk groups of patients and offenders. We systematically reviewed the literature and assessed the evidence on genetic association studies of aggression and related outcomes in order to provide a field synopsis. We searched PubMed and Huge Navigator databases and sought additional data through reviewing reference lists and correspondence with investigators. Genetic association studies were included if outcome data on aggression or violent behavior either as a binary outcome or as a quantitative trait were provided. From 1331 potentially relevant investigations, 185 studies constituting 277 independent associations on 31 genes fulfilled the predetermined selection criteria. Data from variants investigated in three or more samples were combined in meta-analyses and potential sources of heterogeneity were investigated using subgroup analyses. In the primary analyses, which used relaxed inclusion criteria, we found no association between any polymorphism analyzed and aggression at the 5% level of significance. Subgroup analyses, including by severity of outcome, age group, characteristics of the sample and ethnicity, did not demonstrate any consistent findings. Current evidence does not support the use of such genes to predict dangerousness or as markers for therapeutic interventions. PMID:23546171

  2. Multicollinearity in spatial genetics: separating the wheat from the chaff using commonality analyses.

    PubMed

    Prunier, J G; Colyn, M; Legendre, X; Nimon, K F; Flamand, M C

    2015-01-01

    Direct gradient analyses in spatial genetics provide unique opportunities to describe the inherent complexity of genetic variation in wildlife species and are the object of many methodological developments. However, multicollinearity among explanatory variables is a systemic issue in multivariate regression analyses and is likely to cause serious difficulties in properly interpreting results of direct gradient analyses, with the risk of erroneous conclusions, misdirected research and inefficient or counterproductive conservation measures. Using simulated data sets along with linear and logistic regressions on distance matrices, we illustrate how commonality analysis (CA), a detailed variance-partitioning procedure that was recently introduced in the field of ecology, can be used to deal with nonindependence among spatial predictors. By decomposing model fit indices into unique and common (or shared) variance components, CA allows identifying the location and magnitude of multicollinearity, revealing spurious correlations and thus thoroughly improving the interpretation of multivariate regressions. Despite a few inherent limitations, especially in the case of resistance model optimization, this review highlights the great potential of CA to account for complex multicollinearity patterns in spatial genetics and identifies future applications and lines of research. We strongly urge spatial geneticists to systematically investigate commonalities when performing direct gradient analyses. PMID:25495950

  3. Co-infections and Pathogenesis of KSHV-Associated Malignancies

    PubMed Central

    Thakker, Suhani; Verma, Subhash C.

    2016-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpes virus 8 (HHV-8) is one of the several carcinogenic viruses that infect humans. KSHV infection has been implicated in the development of Kaposi’s sarcoma (KS), primary effusion lymphoma, and multicentric Castleman’s Disease. While KSHV infection is necessary for the development of KSHV associated malignancies, it is not sufficient to induce tumorigenesis. Evidently, other co-factors are essential for the progression of KSHV induced malignancies. One of the most important co-factors, necessary for the progression of KSHV induced tumors, is immune suppression that frequently arises during co-infection with HIV and also by other immune suppressants. In this mini-review, we discuss the roles of co-infection with HIV and other pathogens on KSHV infection and pathogenesis. PMID:26913028

  4. Septic arthritis due to tubercular and Aspergillus co-infection.

    PubMed

    Kumar, Mukesh; Thilak, Jai; Zahoor, Adnan; Jyothi, Arun

    2016-01-01

    Aspergillus septic arthritis is a rare and serious medical and surgical problem. It occurs mainly in immunocompromised patients. Aspergillus fumigatus is the most common causative organism followed by Aspergillus flavus. The most common site affected is knee followed by shoulder, ankle, wrist, hip and sacroiliac joint. Debridement and voriconazole are primary treatment of articular aspergilosis. To the best of our knowledge, there are no reported cases of co-infection of tuberculosis (TB) and Aspergillus infecting joints. We report a case of co-infection of TB and A. flavus of hip and knee of a 60-year-old male, with type 2 diabetes mellitus. He was treated with debridement, intravenous voriconazole, and antitubercular drugs. PMID:27293296

  5. Development, genetic and cytogenetic analyses of genetic sexing strains of the Mexican fruit fly, Anastrepha ludens Loew (Diptera: Tephritidae)

    PubMed Central

    2014-01-01

    Background Anastrepha ludens is among the pests that have a major impact on México's economy because it attacks fruits as citrus and mangoes. The Mexican Federal government uses integrated pest management to control A. ludens through the Programa Nacional Moscas de la Fruta [National Fruit Fly Program, SAGARPA-SENASICA]. One of the main components of this program is the sterile insect technique (SIT), which is used to control field populations of the pest by releasing sterile flies. Results To increase the efficiency of this technique, we have developed a genetic sexing strain (GSS) in which the sexing mechanism is based on a pupal colour dimorphism (brown-black) and is the result of a reciprocal translocation between the Y chromosome and the autosome bearing the black pupae (bp) locus. Ten strains producing wild-type (brown pupae) males and mutant (black pupae) females were isolated. Subsequent evaluations for several generations were performed in most of these strains. The translocation strain named Tapachula-7 showed minimal effect on survival and the best genetic stability of all ten strains. Genetic and cytogenetic analyses were performed using mitotic and polytene chromosomes and we succeeded to characterize the chromosomal structure of this reciprocal translocation and map the autosome breakpoint, despite the fact that the Y chromosome is not visible in polytene nuclei following standard staining. Conclusions We show that mitotic and polytene chromosomes can be used in cytogenetic analyses towards the development of genetic control methods in this pest species. The present work is the first report of the construction of GSS of Anastrepha ludens, with potential use in a future Moscafrut operational program. PMID:25472896

  6. Parasite virulence, co-infections and cytokine balance in malaria

    PubMed Central

    Gonçalves, Raquel Müller; Lima, Nathália Ferreira; Ferreira, Marcelo Urbano

    2014-01-01

    Strong early inflammatory responses followed by a timely production of regulatory cytokines are required to control malaria parasite multiplication without inducing major host pathology. Here, we briefly examine the homeostasis of inflammatory responses to malaria parasite species with varying virulence levels and discuss how co-infections with bacteria, viruses, and helminths can modulate inflammation, either aggravating or alleviating malaria-related morbidity. PMID:24854175

  7. Diagnosis & treatment of tuberculosis in HIV co-infected patients

    PubMed Central

    Padmapriyadarsini, C.; Narendran, G.; Swaminathan, Soumya

    2011-01-01

    Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection. PMID:22310818

  8. Syphilis and human immunodeficiency virus co-infection.

    PubMed Central

    Funnyé, Allen S.; Akhtar, Abbasi J.

    2003-01-01

    Co-infection of syphilis and AIDS has profound implications for the African American community. The purpose of this review is to: evaluate the historical background of HIV and syphilis and their similarities in pathogenesis; review the epidemiology of syphilis and HIV co-infection, and implications for continued prevention efforts; examine the effect of syphilis on HIV transmission and acquisition; and, to examine the effects of HIV infection on syphilis transmission, diagnostic and serologic changes, clinical course, and treatment. The prevalence of HIV is higher in those with syphilis; moreover, the prevalence of HIV and syphilis co-infection is highest in African Americans. There may be humoral and cellular immune similarities. HIV may affect the transmission of syphilis, alter its serologic diagnosis, and accelerate and change the clinical course and response to treatment. In conclusion, combined infection of HIV and syphilis may alter the clinical presentation and course of either disease. There are historical and immunologic similarities and the high prevalence in African Americans compared to other groups is of great importance for prevention efforts. PMID:12793793

  9. [Noonan syndrome can be diagnosed clinically and through molecular genetic analyses].

    PubMed

    Henningsen, Marie Krab; Jelsig, Anne Marie; Andersen, Helle; Brusgaard, Klaus; Ousager, Lilian Bomme; Hertz, Jens Michael

    2015-08-01

    Noonan syndrome is part of the group of RASopathies caused by germ line mutations in genes involved in the RAS/MAPK pathway. There is substantial phenotypic overlap among the RASopathies. Diagnosis of Noonan syndrome is often based on clinical features including dysmorphic facial features, short stature and congenital heart disease. Rapid advances in sequencing technology have made molecular genetic analyses a helpful tool in diagnosing and distinguishing Noonan syndrome from other RASopathies. PMID:26321587

  10. Recommendations for utilizing and reporting population genetic analyses: the reproducibility of genetic clustering using the program STRUCTURE.

    PubMed

    Gilbert, Kimberly J; Andrew, Rose L; Bock, Dan G; Franklin, Michelle T; Kane, Nolan C; Moore, Jean-Sébastien; Moyers, Brook T; Renaut, Sébastien; Rennison, Diana J; Veen, Thor; Vines, Timothy H

    2012-10-01

    Reproducibility is the benchmark for results and conclusions drawn from scientific studies, but systematic studies on the reproducibility of scientific results are surprisingly rare. Moreover, many modern statistical methods make use of 'random walk' model fitting procedures, and these are inherently stochastic in their output. Does the combination of these statistical procedures and current standards of data archiving and method reporting permit the reproduction of the authors' results? To test this, we reanalysed data sets gathered from papers using the software package STRUCTURE to identify genetically similar clusters of individuals. We find that reproducing structure results can be difficult despite the straightforward requirements of the program. Our results indicate that 30% of analyses were unable to reproduce the same number of population clusters. To improve this, we make recommendations for future use of the software and for reporting STRUCTURE analyses and results in published works. PMID:22998190

  11. Influenza promotes pneumococcal growth during co-infection by providing host sialylated substrates as a nutrient source

    PubMed Central

    Siegel, Steven J.; Roche, Aoife M.; Weiser, Jeffrey N.

    2014-01-01

    Summary Much of the mortality attributed to influenza virus is due to secondary bacterial pneumonia, particularly from Streptococcus pneumoniae. However, mechanisms underlying this co-infection are incompletely understood. We find that prior influenza infection enhances pneumococcal colonization of the murine nasopharynx, which in-turn promotes bacterial spread to the lungs. Influenza accelerates bacterial replication in vivo, and sialic acid, a major component of airway glycoconjugates, is identified as the host-derived metabolite that stimulates pneumococcal proliferation. Influenza infection increases sialic acid and sialylated mucin availability, and enhances desialylation of host glycoconjugates. Pneumococcal genes for sialic acid catabolism are required for influenza to promote bacterial growth. Decreasing sialic acid availability in vivo by genetic deletion of the major airway mucin Muc5ac or mucolytic treatment limits influenza-induced pneumococcal replication. Our findings suggest that higher rates of disease during co-infection could stem from influenza-provided sialic acid, which increases pneumococcal proliferation, colonization and aspiration. PMID:25011108

  12. Genetic analyses of chromosome 12 loci in Crohn's disease

    PubMed Central

    Lesage, S; Zouali, H; Colombel, J; Belaiche, J; Cezard, J; Tysk, C; Almer, S; Gassull, M; Binder, V; Chamaillard, M; Le Gall, I; Thomas, G; Hugot, J

    2000-01-01

    BACKGROUND AND AIMS—Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, both of which are multifactorial diseases involving the interaction of genetic and environmental factors. A region on chromosome 12 centred around the marker locus D12S83 has previously been associated with IBD predisposition. The aim of the study was to investigate this genetic region in an independent panel of European families affected by Crohn's disease.
METHODS—A sample of 95 families with two or more affected relatives and 75 simplex nuclear families were genotyped for 19 microsatellite loci located on chromosome 12. A search for linkage and linkage disequilibrium was performed using non-parametric two point and multipoint analyses with the Analyze and Genehunter packages.
RESULTS—No evidence of linkage or linkage disequilibrium was observed for any of the marker loci, including D12S83 (p=0.35 for the two point linkage test). Multipoint linkage analysis also failed to reveal positive linkage on chromosome 12. Power calculations allowed us to reject the hypothesis that the genetic region of chromosome 12 centred on D12S83 contains a susceptibility locus with a relative risk (λs) equal to or greater than 2.0 in these families.
CONCLUSION—Failure to detect linkage or linkage disequilibrium in these families suggests that the chromosome 12 locus previously reported to be associated with genetic predisposition to IBD does not play a role in all European family samples. This observation is compatible with heterogeneity in the genetic basis of susceptibility to the disease and/or exposure to various environmental factors among Caucasian families.


Keywords: chromosome 12; inflammatory bowel disease; Crohn's disease; linkage analyses; replication study PMID:11076876

  13. Clinical Indicators for Bacterial Co-Infection in Ghanaian Children with P. falciparum Infection

    PubMed Central

    Nielsen, Maja Verena; Amemasor, Solomon; Agyekum, Alex; Loag, Wibke; Marks, Florian; Sarpong, Nimako; Dekker, Denise; Adu-Sarkodie, Yaw; May, Jürgen

    2015-01-01

    Differentiation of infectious causes in severely ill children is essential but challenging in sub- Saharan Africa. The aim of the study was to determine clinical indicators that are able to identify bacterial co-infections in P. falciparum infected children in rural Ghana. In total, 1,915 severely ill children below the age of 15 years were recruited at Agogo Presbyterian Hospital in Ghana between May 2007 and February 2011. In 771 (40%) of the children malaria parasites were detected. This group was analyzed for indicators of bacterial co-infections using bivariate and multivariate regression analyses with 24 socio-economic variables, 16 terms describing medical history and anthropometrical information and 68 variables describing clinical symptoms. The variables were tested for sensitivity, specificity, positive predictive value and negative predictive value. In 46 (6.0%) of the children with malaria infection, bacterial co-infection was detected. The most frequent pathogens were non-typhoid salmonellae (45.7%), followed by Streptococcus spp. (13.0%). Coughing, dehydration, splenomegaly, severe anemia and leukocytosis were positively associated with bacteremia. Domestic hygiene and exclusive breastfeeding is negatively associated with bacteremia. In cases of high parasitemia (>10,000/μl), a significant association with bacteremia was found for splenomegaly (OR 8.8; CI 1.6–48.9), dehydration (OR 18.2; CI 2.0–166.0) and coughing (OR 9.0; CI 0.7–118.6). In children with low parasitemia, associations with bacteremia were found for vomiting (OR 4.7; CI 1.4–15.8), severe anemia (OR 3.3; CI 1.0–11.1) and leukocytosis (OR 6.8 CI 1.9–24.2). Clinical signs of impaired microcirculation were negatively associated with bacteremia. Ceftriaxone achieved best coverage of isolated pathogens. The results demonstrate the limitation of clinical symptoms to determine bacterial co-infections in P. falciparum infected children. Best clinical indicators are dependent on the

  14. Co-infection of classic swine H1N1 influenza virus in pigs persistently infected with porcine rubulavirus.

    PubMed

    Rivera-Benitez, José Francisco; De la Luz-Armendáriz, Jazmín; Saavedra-Montañez, Manuel; Jasso-Escutia, Miguel Ángel; Sánchez-Betancourt, Ivan; Pérez-Torres, Armando; Reyes-Leyva, Julio; Hernández, Jesús; Martínez-Lara, Atalo; Ramírez-Mendoza, Humberto

    2016-02-29

    Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV. PMID:26854342

  15. New Genetic and Linguistic Analyses Show Ancient Human Influence on Baobab Evolution and Distribution in Australia

    PubMed Central

    Rangan, Haripriya; Bell, Karen L.; Baum, David A.; Fowler, Rachael; McConvell, Patrick; Saunders, Thomas; Spronck, Stef; Kull, Christian A.; Murphy, Daniel J.

    2015-01-01

    This study investigates the role of human agency in the gene flow and geographical distribution of the Australian baobab, Adansonia gregorii. The genus Adansonia is a charismatic tree endemic to Africa, Madagascar, and northwest Australia that has long been valued by humans for its multiple uses. The distribution of genetic variation in baobabs in Africa has been partially attributed to human-mediated dispersal over millennia, but this relationship has never been investigated for the Australian species. We combined genetic and linguistic data to analyse geographic patterns of gene flow and movement of word-forms for A. gregorii in the Aboriginal languages of northwest Australia. Comprehensive assessment of genetic diversity showed weak geographic structure and high gene flow. Of potential dispersal vectors, humans were identified as most likely to have enabled gene flow across biogeographic barriers in northwest Australia. Genetic-linguistic analysis demonstrated congruence of gene flow patterns and directional movement of Aboriginal loanwords for A. gregorii. These findings, along with previous archaeobotanical evidence from the Late Pleistocene and Holocene, suggest that ancient humans significantly influenced the geographic distribution of Adansonia in northwest Australia. PMID:25830225

  16. New genetic and linguistic analyses show ancient human influence on baobab evolution and distribution in Australia.

    PubMed

    Rangan, Haripriya; Bell, Karen L; Baum, David A; Fowler, Rachael; McConvell, Patrick; Saunders, Thomas; Spronck, Stef; Kull, Christian A; Murphy, Daniel J

    2015-01-01

    This study investigates the role of human agency in the gene flow and geographical distribution of the Australian baobab, Adansonia gregorii. The genus Adansonia is a charismatic tree endemic to Africa, Madagascar, and northwest Australia that has long been valued by humans for its multiple uses. The distribution of genetic variation in baobabs in Africa has been partially attributed to human-mediated dispersal over millennia, but this relationship has never been investigated for the Australian species. We combined genetic and linguistic data to analyse geographic patterns of gene flow and movement of word-forms for A. gregorii in the Aboriginal languages of northwest Australia. Comprehensive assessment of genetic diversity showed weak geographic structure and high gene flow. Of potential dispersal vectors, humans were identified as most likely to have enabled gene flow across biogeographic barriers in northwest Australia. Genetic-linguistic analysis demonstrated congruence of gene flow patterns and directional movement of Aboriginal loanwords for A. gregorii. These findings, along with previous archaeobotanical evidence from the Late Pleistocene and Holocene, suggest that ancient humans significantly influenced the geographic distribution of Adansonia in northwest Australia. PMID:25830225

  17. Co-infections in Visceral Pentastomiasis, Democratic Republic of the Congo

    PubMed Central

    Sulyok, Mihály; Riu, Therese; Rózsa, Lajos; Bodó, Imre; Schoen, Christoph; Muntau, Birgit; Babocsay, Gergely; Hardi, Richard

    2016-01-01

    Snakeborne Armillifer pentastomiasis is an emerging human parasitic infection in rural tropical areas where snake meat is eaten. After a series of severe ocular A. grandis larval infections and anecdotal abdominal infection in Sankuru District, Democratic Republic of the Congo, during 2014–2015, we systematically investigated possible pentastomid etiology in patients who underwent surgery in the region. Histologic and molecular analyses by established pentastomid 18S rDNA- and newly developed Armillifer-specific cytochrome oxidase PCRs revealed larval pentastomid lesions in 3.7% of patients. Some persons had A. armillatus and A. grandis co-infections. Another pentastomid larva, Raillietiella sp., was molecularly detected in 1 patient who had concomitant A. grandis and A. armillatus infection. The PCRs used were suitable for detecting pentastomid species even in highly necrotic tissues. Phylogenetic analyses of Armillifer cytochrome oxidase genes detected multiple local strains. PMID:27434739

  18. Co-infections in Visceral Pentastomiasis, Democratic Republic of the Congo.

    PubMed

    Tappe, Dennis; Sulyok, Mihály; Riu, Therese; Rózsa, Lajos; Bodó, Imre; Schoen, Christoph; Muntau, Birgit; Babocsay, Gergely; Hardi, Richard

    2016-08-01

    Snakeborne Armillifer pentastomiasis is an emerging human parasitic infection in rural tropical areas where snake meat is eaten. After a series of severe ocular A. grandis larval infections and anecdotal abdominal infection in Sankuru District, Democratic Republic of the Congo, during 2014-2015, we systematically investigated possible pentastomid etiology in patients who underwent surgery in the region. Histologic and molecular analyses by established pentastomid 18S rDNA- and newly developed Armillifer-specific cytochrome oxidase PCRs revealed larval pentastomid lesions in 3.7% of patients. Some persons had A. armillatus and A. grandis co-infections. Another pentastomid larva, Raillietiella sp., was molecularly detected in 1 patient who had concomitant A. grandis and A. armillatus infection. The PCRs used were suitable for detecting pentastomid species even in highly necrotic tissues. Phylogenetic analyses of Armillifer cytochrome oxidase genes detected multiple local strains. PMID:27434739

  19. [A meningitis case of Brucella and tuberculosis co-infection].

    PubMed

    Karsen, Hasan; Karahocagil, Mustafa Kasim; Irmak, Hasan; Demiröz, Ali Pekcan

    2008-10-01

    Turkey is located at an endemic area for brusellosis and tuberculosis which are both important public health problems. Meningitis caused by Brucella and Mycobacterium spp. may be confused since the clinical and laboratory findings are similar. In this report, a meningitis case with Brucella and tuberculosis co-infection has been presented. A 19-years-old woman was admitted to our clinic with severe headache, fever, vomiting, meningeal irritation symptoms, confusion and diplopia. The patient was initially diagnosed as Brucella meningitis based on her history (stockbreeding, consuming raw milk products, clinical symptoms concordant to brucellosis lasting for 4-5 months), physical examination and laboratory findings of cerebrospinal fluid (CSF). Standard tube agglutination test for brucellosis was positive at 1/80 titer in CSF and at 1/640 titer in serum, whereas no growth of Brucella spp. was detected in CSF and blood cultures. Antibiotic therapy with ceftriaxone, rifampicin and doxycyclin was started, however, there was no clinical improvement and agitation and confusion of the patient continued by the end of second day of treatment. Repeated CSF examination yielded acid-fast bacteria. The patient was then diagnosed as meningitis with double etiology and the therapy was changed to ceftriaxone, streptomycin, morphozinamide, rifampicin and isoniazid for thirty days. Tuberculosis meningitis was confirmed with the growth of Mycobacterium tuberculosis on the 14th day of cultivation (BACTEC, Becton Dickinson, USA) of the CSF sample. On the 30th day of treatment she was discharged on anti-tuberculous treatment with isoniazid and rifampicin for 12 months. The follow-up of the patient on the first and third months of treatment revealed clinical and laboratory improvement. Since this was a rare case of Brucella and tuberculosis co-infection, this report emphasizes that such co-infections should be kept in mind especially in the endemic areas for tuberculosis and brucellosis

  20. Electron microscopic, genetic and protein expression analyses of Helicobacter acinonychis strains from a Bengal tiger.

    PubMed

    Tegtmeyer, Nicole; Rivas Traverso, Francisco; Rohde, Manfred; Oyarzabal, Omar A; Lehn, Norbert; Schneider-Brachert, Wulf; Ferrero, Richard L; Fox, James G; Berg, Douglas E; Backert, Steffen

    2013-01-01

    Colonization by Helicobacter species is commonly noted in many mammals. These infections often remain unrecognized, but can cause severe health complications or more subtle host immune perturbations. The aim of this study was to isolate and characterize putative novel Helicobacter spp. from Bengal tigers in Thailand. Morphological investigation (Gram-staining and electron microscopy) and genetic studies (16SrRNA, 23SrRNA, flagellin, urease and prophage gene analyses, RAPD DNA fingerprinting and restriction fragment polymorphisms) as well as Western blotting were used to characterize the isolated Helicobacters. Electron microscopy revealed spiral-shaped bacteria, which varied in length (2.5-6 µm) and contained up to four monopolar sheathed flagella. The 16SrRNA, 23SrRNA, sequencing and protein expression analyses identified novel H. acinonychis isolates closely related to H. pylori. These Asian isolates are genetically very similar to H. acinonychis strains of other big cats (cheetahs, lions, lion-tiger hybrid and other tigers) from North America and Europe, which is remarkable in the context of the great genetic diversity among worldwide H. pylori strains. We also found by immunoblotting that the Bengal tiger isolates express UreaseA/B, flagellin, BabA adhesin, neutrophil-activating protein NapA, HtrA protease, γ-glutamyl-transpeptidase GGT, Slt lytic transglycosylase and two DNA transfer relaxase orthologs that were known from H. pylori, but not the cag pathogenicity island, nor CagA, VacA, SabA, DupA or OipA proteins. These results give fresh insights into H. acinonychis genetics and the expression of potential pathogenicity-associated factors and their possible pathophysiological relevance in related gastric infections. PMID:23940723

  1. Electron Microscopic, Genetic and Protein Expression Analyses of Helicobacter acinonychis Strains from a Bengal Tiger

    PubMed Central

    Tegtmeyer, Nicole; Rivas Traverso, Francisco; Rohde, Manfred; Oyarzabal, Omar A.; Lehn, Norbert; Schneider-Brachert, Wulf; Ferrero, Richard L.; Fox, James G.; Berg, Douglas E.; Backert, Steffen

    2013-01-01

    Colonization by Helicobacter species is commonly noted in many mammals. These infections often remain unrecognized, but can cause severe health complications or more subtle host immune perturbations. The aim of this study was to isolate and characterize putative novel Helicobacter spp. from Bengal tigers in Thailand. Morphological investigation (Gram-staining and electron microscopy) and genetic studies (16SrRNA, 23SrRNA, flagellin, urease and prophage gene analyses, RAPD DNA fingerprinting and restriction fragment polymorphisms) as well as Western blotting were used to characterize the isolated Helicobacters. Electron microscopy revealed spiral-shaped bacteria, which varied in length (2.5–6 µm) and contained up to four monopolar sheathed flagella. The 16SrRNA, 23SrRNA, sequencing and protein expression analyses identified novel H. acinonychis isolates closely related to H. pylori. These Asian isolates are genetically very similar to H. acinonychis strains of other big cats (cheetahs, lions, lion-tiger hybrid and other tigers) from North America and Europe, which is remarkable in the context of the great genetic diversity among worldwide H. pylori strains. We also found by immunoblotting that the Bengal tiger isolates express UreaseA/B, flagellin, BabA adhesin, neutrophil-activating protein NapA, HtrA protease, γ-glutamyl-transpeptidase GGT, Slt lytic transglycosylase and two DNA transfer relaxase orthologs that were known from H. pylori, but not the cag pathogenicity island, nor CagA, VacA, SabA, DupA or OipA proteins. These results give fresh insights into H. acinonychis genetics and the expression of potential pathogenicity-associated factors and their possible pathophysiological relevance in related gastric infections. PMID:23940723

  2. Diversity Array Technology Markers: Genetic Diversity Analyses and Linkage Map Construction in Rapeseed (Brassica napus L.)

    PubMed Central

    Raman, Harsh; Raman, Rosy; Nelson, Matthew N.; Aslam, M.N.; Rajasekaran, Ravikesavan; Wratten, Neil; Cowling, Wallace A.; Kilian, A.; Sharpe, Andrew G.; Schondelmaier, Joerg

    2012-01-01

    We developed Diversity Array Technology (DArT) markers for application in genetic studies of Brassica napus and other Brassica species with A or C genomes. Genomic representation from 107 diverse genotypes of B. napus L. var. oleifera (rapeseed, AACC genomes) and B. rapa (AA genome) was used to develop a DArT array comprising 11 520 clones generated using PstI/BanII and PstI/BstN1 complexity reduction methods. In total, 1547 polymorphic DArT markers of high technical quality were identified and used to assess molecular diversity among 89 accessions of B. napus, B. rapa, B. juncea, and B. carinata collected from different parts of the world. Hierarchical cluster and principal component analyses based on genetic distance matrices identified distinct populations clustering mainly according to their origin/pedigrees. DArT markers were also mapped in a new doubled haploid population comprising 131 lines from a cross between spring rapeseed lines ‘Lynx-037DH’ and ‘Monty-028DH’. Linkage groups were assigned on the basis of previously mapped simple sequence repeat (SSRs), intron polymorphism (IP), and gene-based markers. The map consisted of 437 DArT, 135 SSR, 6 IP, and 6 gene-based markers and spanned 2288 cM. Our results demonstrate that DArT markers are suitable for genetic diversity analysis and linkage map construction in rapeseed. PMID:22193366

  3. Diversity array technology markers: genetic diversity analyses and linkage map construction in rapeseed (Brassica napus L.).

    PubMed

    Raman, Harsh; Raman, Rosy; Nelson, Matthew N; Aslam, M N; Rajasekaran, Ravikesavan; Wratten, Neil; Cowling, Wallace A; Kilian, A; Sharpe, Andrew G; Schondelmaier, Joerg

    2012-01-01

    We developed Diversity Array Technology (DArT) markers for application in genetic studies of Brassica napus and other Brassica species with A or C genomes. Genomic representation from 107 diverse genotypes of B. napus L. var. oleifera (rapeseed, AACC genomes) and B. rapa (AA genome) was used to develop a DArT array comprising 11 520 clones generated using PstI/BanII and PstI/BstN1 complexity reduction methods. In total, 1547 polymorphic DArT markers of high technical quality were identified and used to assess molecular diversity among 89 accessions of B. napus, B. rapa, B. juncea, and B. carinata collected from different parts of the world. Hierarchical cluster and principal component analyses based on genetic distance matrices identified distinct populations clustering mainly according to their origin/pedigrees. DArT markers were also mapped in a new doubled haploid population comprising 131 lines from a cross between spring rapeseed lines 'Lynx-037DH' and 'Monty-028DH'. Linkage groups were assigned on the basis of previously mapped simple sequence repeat (SSRs), intron polymorphism (IP), and gene-based markers. The map consisted of 437 DArT, 135 SSR, 6 IP, and 6 gene-based markers and spanned 2288 cM. Our results demonstrate that DArT markers are suitable for genetic diversity analysis and linkage map construction in rapeseed. PMID:22193366

  4. Will an "island" population of voles be recolonized if eradicated? Insights from molecular genetic analyses

    USGS Publications Warehouse

    Miller, M.P.; Haig, S.M.; Ledig, D.B.; Vander Heyden, M. F.; Bennett, G.

    2011-01-01

    We performed genetic analyses of Microtus longicaudus populations within the Crook Point Unit of the Oregon Islands National Wildlife Refuge. A M. longicaudus population at Saddle Rock (located approx. 65 m off-shore from the Crook Point mainland) is suspected to be partially responsible for declines of a Leach's storm-petrel colony at this important nesting site. Using Amplified Fragment Length Polymorphism markers and mitochondrial DNA, we illustrate that Saddle Rock and Crook Point function as separate island and mainland populations despite their close proximity. In addition to genetic structure, we also observed reduced genetic diversity at Saddle Rock, suggesting that little individual movement occurs between populations. If local resource managers decide to perform an eradication at Saddle Rock, we conclude that immediate recolonization of the island by M. longicaudus would be unlikely. Because M. longicaudus is native to Oregon, we also consider the degree with which the differentiation of Saddle Rock signifies the presence of a unique entity that warrants conservation rather than eradication. ?? The Wildlife Society, 2011.

  5. Systematic meta-analyses of gene-specific genetic association studies in prostate cancer

    PubMed Central

    Hao, Qiang; Wei, Dong; Zhang, Yaoguang; Chen, Xin; Yang, Fan; Yang, Ze; Zhu, Xiaoquan; Wang, Jianye

    2016-01-01

    In the past twenty-five years, over 700 case-control association studies on the risk of prostate cancer have been published worldwide, but their results were largely inconsistent. To facilitate following and explaining these findings, we performed a systematic meta-analysis using allelic contrasts for gene-specific SNVs from at least three independent population-based case-control studies, which were published in the field of prostate cancer between August 1, 1990 and August 1, 2015. Across 66 meta-analyses, a total of 20 genetic variants involving 584,100 subjects in 19 different genes (KLK3, IGFBP3, ESR1, SOD2, CAT, CYP1B1, VDR, RFX6, HNF1B, SRD5A2, FGFR4, LEP, HOXB13, FAS, FOXP4, SLC22A3, LMTK2, EHBP1 and MSMB) exhibited significant association with prostate cancer. The average summary OR was 1.33 (ranging from: 1.016–3.788) for risk alleles and 0.838 (ranging from: 0.757–0.896) for protective alleles. Of these positive variants, FOXP4 rs1983891, LMTK2 rs6465657 and RFX6 rs339331 had not been previously meta-analyzed. Further analyses with sufficient power design and investigations of the potential biological roles of these genetic variants in prostate cancer should be conducted. PMID:26967244

  6. Genetic variability and evolutionary analyses of the coat protein gene of Tomato mosaic virus.

    PubMed

    Rangel, E A; Alfaro-Fernández, A; Font-San-Ambrosio, M I; Luis-Arteaga, M; Rubio, L

    2011-12-01

    Tomato mosaic virus (ToMV), a member of the genus Tobamovirus, infects several ornamental and horticultural crops worldwide. In this study, the nucleotide sequences of the coat protein gene of worldwide ToMV isolates were analyzed to estimate the genetic structure and diversity of this virus and the involved evolutionary forces. The phylogenetic analysis showed three clades with high bootstrap support: Clade I contained three ToMV isolates from Brazil collected from pepper, Clade II comprised one Brazilian ToMV isolate from pepper, and Clade III was composed of ToMV isolates collected from different plant hosts (pepper, tomato, eggplant, lilac, camellia, dogwood, red spruce, etc.) and water (from melting ice, lakes and streams) from different countries: USA, Brazil, Korea, Germany, Spain, Denmark (Greenland), China, Taiwan, Malaysia, Iran, and Kazakhstan. With the exception of Brazil, nucleotide diversity within and between different geographic regions was very low, although statistical analyses suggested some gene flow between most of these regions. Our analyses also suggested a strong negative selection which could have contributed to the genetic stability of ToMV. PMID:21881940

  7. Can novel genetic analyses help to identify low-dispersal marine invasive species?

    PubMed Central

    Teske, Peter R; Sandoval-Castillo, Jonathan; Waters, Jonathan M; Beheregaray, Luciano B

    2014-01-01

    Genetic methods can be a powerful tool to resolve the native versus introduced status of populations whose taxonomy and biogeography are poorly understood. The genetic study of introduced species is presently dominated by analyses that identify signatures of recent colonization by means of summary statistics. Unfortunately, such approaches cannot be used in low-dispersal species, in which recently established populations originating from elsewhere in the species' native range also experience periods of low population size because they are founded by few individuals. We tested whether coalescent-based molecular analyses that provide detailed information about demographic history supported the hypothesis that a sea squirt whose distribution is centered on Tasmania was recently introduced to mainland Australia and New Zealand through human activities. Methods comparing trends in population size (Bayesian Skyline Plots and Approximate Bayesian Computation) were no more informative than summary statistics, likely because of recent intra-Tasmanian dispersal. However, IMa2 estimates of divergence between putatively native and introduced populations provided information at a temporal scale suitable to differentiate between recent (potentially anthropogenic) introductions and ancient divergence, and indicated that all three non-Tasmanian populations were founded during the period of European settlement. While this approach can be affected by inaccurate molecular dating, it has considerable (albeit largely unexplored) potential to corroborate nongenetic information in species with limited dispersal capabilities. PMID:25165524

  8. Can novel genetic analyses help to identify low-dispersal marine invasive species?

    PubMed

    Teske, Peter R; Sandoval-Castillo, Jonathan; Waters, Jonathan M; Beheregaray, Luciano B

    2014-07-01

    Genetic methods can be a powerful tool to resolve the native versus introduced status of populations whose taxonomy and biogeography are poorly understood. The genetic study of introduced species is presently dominated by analyses that identify signatures of recent colonization by means of summary statistics. Unfortunately, such approaches cannot be used in low-dispersal species, in which recently established populations originating from elsewhere in the species' native range also experience periods of low population size because they are founded by few individuals. We tested whether coalescent-based molecular analyses that provide detailed information about demographic history supported the hypothesis that a sea squirt whose distribution is centered on Tasmania was recently introduced to mainland Australia and New Zealand through human activities. Methods comparing trends in population size (Bayesian Skyline Plots and Approximate Bayesian Computation) were no more informative than summary statistics, likely because of recent intra-Tasmanian dispersal. However, IMa2 estimates of divergence between putatively native and introduced populations provided information at a temporal scale suitable to differentiate between recent (potentially anthropogenic) introductions and ancient divergence, and indicated that all three non-Tasmanian populations were founded during the period of European settlement. While this approach can be affected by inaccurate molecular dating, it has considerable (albeit largely unexplored) potential to corroborate nongenetic information in species with limited dispersal capabilities. PMID:25165524

  9. Genetic Associations with Diabetes: Meta-Analyses of 10 Candidate Polymorphisms

    PubMed Central

    Wang, Qinwen; Xu, Leiting; Bu, Shizhong; Huang, Yi; Zhang, Cheng; Ye, Huadan; Xu, Xuting; Liu, Qiong; Ye, Meng; Mai, Yifeng; Duan, Shiwei

    2013-01-01

    Aims The goal of our study is to investigate the combined contribution of 10 genetic variants to diabetes susceptibility. Methods Bibliographic databases were searched from 1970 to Dec 2012 for studies that reported on genetic association study of diabetes. After a comprehensive filtering procedure, 10 candidate gene variants with informative genotype information were collected for the current meta-anlayses. Using the REVMAN software, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the combined contribution of the selected genetic variants to diabetes. Results A total of 37 articles among 37,033 cases and 54,716 controls were involved in the present meta-analyses of 10 genetic variants. Three variants were found to be significantly associated with type 1 diabetes (T1D): NLRP1 rs12150220 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01), IL2RA rs11594656 (OR = 0.86, 95% CI = 0.82–0.91, P<0.00001), and CLEC16A rs725613 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01). APOA5 −1131T/C polymorphism was shown to be significantly associated with of type 2 diabetes (T2D, OR = 1.27, 95% CI = 1.03–1.57, P = 0.03). No association with diabetes was showed in the meta-analyses of other six genetic variants, including SLC2A10 rs2335491, ATF6 rs2070150, KLF11 rs35927125, CASQ1 rs2275703, GNB3 C825T, and IL12B 1188A/C. Conclusion Our results demonstrated that IL2RA rs11594656 and CLEC16A rs725613 are protective factors of T1D, while NLRP1 rs12150220 and APOA5 −1131T/C are risky factors of T1D and T2D, respectively. PMID:23922971

  10. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

    PubMed

    Lill, Christina M; Roehr, Johannes T; McQueen, Matthew B; Kavvoura, Fotini K; Bagade, Sachin; Schjeide, Brit-Maren M; Schjeide, Leif M; Meissner, Esther; Zauft, Ute; Allen, Nicole C; Liu, Tian; Schilling, Marcel; Anderson, Kari J; Beecham, Gary; Berg, Daniela; Biernacka, Joanna M; Brice, Alexis; DeStefano, Anita L; Do, Chuong B; Eriksson, Nicholas; Factor, Stewart A; Farrer, Matthew J; Foroud, Tatiana; Gasser, Thomas; Hamza, Taye; Hardy, John A; Heutink, Peter; Hill-Burns, Erin M; Klein, Christine; Latourelle, Jeanne C; Maraganore, Demetrius M; Martin, Eden R; Martinez, Maria; Myers, Richard H; Nalls, Michael A; Pankratz, Nathan; Payami, Haydeh; Satake, Wataru; Scott, William K; Sharma, Manu; Singleton, Andrew B; Stefansson, Kari; Toda, Tatsushi; Tung, Joyce Y; Vance, Jeffery; Wood, Nick W; Zabetian, Cyrus P; Young, Peter; Tanzi, Rudolph E; Khoury, Muin J; Zipp, Frauke; Lehrach, Hans; Ioannidis, John P A; Bertram, Lars

    2012-01-01

    More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P  =  1.3 × 10(-8)). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies. PMID:22438815

  11. COMPLEMENTARY PROTEOMIC AND GENETIC ANALYSES OF RICE RESPONSE TO RICE CHALLENGE BY THE FUNGAL PATHOGEN RHIZOCTONIA SOLANI

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice (Oryza sativa L.) is considered a model crop plant due to its importance worldwide as a food source, a small diploid genome suitable for genetic and proteomic analyses, and completion of the rice genome sequence. The objective of our research was to utilize both proteomic and genetic approaches...

  12. Response to antiretroviral therapy in occult hepatitis B and HIV co-infection in West Africa.

    PubMed

    Chadwick, David; Stanley, Alastair; Sarfo, Stephen; Appiah, Lambert; Ankcorn, Michael; Foster, Geraldine; Schwab, Uli; Phillips, Richard; Geretti, Anna M

    2013-01-01

    This study evaluated the outcome of first-line antiretroviral therapy among 35 Ghanaians with occult HBV/HIV co-infection, comparing them over 2 years to 120 patients with HBsAg+ HBV/HIV co-infection and 230 patients without HBV co-infection. Increases in CD4 cell count and BMI were similar, whereas elevations of hepatic transaminases were more frequent in both the occult HBV and HBsAg+ patients. Occult HBV/HIV co-infection appears not to impact adversely on response to antiretroviral therapy in Ghana. PMID:22874516

  13. Helminths and malaria co-infections are associated with elevated serum IgE

    PubMed Central

    2014-01-01

    Background Both helminth and malaria infections result in a highly polarized immune response characterized by IgE production. This study aimed to investigate the total serum IgE profile in vivo as a measure of Th2 immune response in malaria patients with and without helminth co-infection. Methods A cross sectional observational study composed of microscopically confirmed malaria positive (N = 197) and malaria negative (N = 216) apparently healthy controls with and without helminth infection was conducted at Wondo Genet Health Center, Southern Ethiopia. A pre-designed structured format was utilized to collect socio-demographic and clinical data of the subjects. Detection and quantification of helminths, malaria parasites and determination of serum IgE levels were carried out following standard procedures. Results Irrespective of helminth infection, individuals infected by malaria showed significantly high levels of serum IgE compared with malaria free apparently healthy controls (with and without helminth infections). Moreover, malaria patients co-infected with intestinal helminths showed high level of serum IgE compared with those malaria patients without intestinal helminths (2198 IU/ml versus 1668 IU/ml). A strong statistically significant association was observed between malaria parasite density and elevated serum IgE levels (2047 IU/ml versus 1778 IU/ml; P = 0.001) with high and low parasitaemia (parasite density >50,000 parasite/μl of blood), respectively. Likewise, helminth egg loads were significantly associated with elevated serum IgE levels (P = 0.003). Conclusions The elevated serum IgE response in malaria patients irrespective of helminth infection and its correlation with malaria parasite density and helminth egg intensity support that malaria infection is also a strong driver of IgE production as compared to helminths. PMID:24886689

  14. Prediction Formulas for Individual Opioid Analgesic Requirements Based on Genetic Polymorphism Analyses

    PubMed Central

    Yoshida, Kaori; Nishizawa, Daisuke; Ichinomiya, Takashi; Ichinohe, Tatsuya; Hayashida, Masakazu; Fukuda, Ken-ichi; Ikeda, Kazutaka

    2015-01-01

    Background The analgesic efficacy of opioids is well known to vary widely among individuals, and various factors related to individual differences in opioid sensitivity have been identified. However, a prediction model to calculate appropriate opioid analgesic requirements has not yet been established. The present study sought to construct prediction formulas for individual opioid analgesic requirements based on genetic polymorphisms and clinical data from patients who underwent cosmetic orthognathic surgery and validate the utility of the prediction formulas in patients who underwent major open abdominal surgery. Methods To construct the prediction formulas, we performed multiple linear regression analyses using data from subjects who underwent cosmetic orthognathic surgery. The dependent variable was 24-h postoperative or perioperative fentanyl use, and the independent variables were age, gender, height, weight, pain perception latencies (PPL), and genotype data of five single-nucleotide polymorphisms (SNPs). To examine the utility of the prediction formulas, we performed simple linear regression analyses using subjects who underwent major open abdominal surgery. Actual 24-h postoperative or perioperative analgesic use and the predicted values that were calculated using the multiple regression equations were incorporated as dependent and independent variables, respectively. Results Multiple linear regression analyses showed that the four SNPs, PPL, and weight were retained as independent predictors of 24-h postoperative fentanyl use (R2 = 0.145, P = 5.66 × 10-10) and the two SNPs and weight were retained as independent predictors of perioperative fentanyl use (R2 = 0.185, P = 1.99 × 10-15). Simple linear regression analyses showed that the predicted values were retained as an independent predictor of actual 24-h postoperative analgesic use (R2 = 0.033, P = 0.030) and perioperative analgesic use (R2 = 0.100, P = 1.09 × 10-4), respectively. Conclusions We

  15. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers

    PubMed Central

    Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega del Vecchyo, Vicente Diego; Chiang, Charleston W. K.; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M.; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

    2015-01-01

    We report ~17.6M genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from prior sequencing-based compilations and enriched for predicted functional consequence. Furthermore, ~76K variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. Fourteen signals, including two major new loci, were observed for lipid levels, and 19, including two novel loci, for inflammatory markers. New associations would be missed in analyses based on 1000 Genomes data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

  16. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers.

    PubMed

    Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Porcu, Eleonora; Naitza, Silvia; Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega Del Vecchyo, Vicente Diego; Chiang, Charleston W K; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

    2015-11-01

    We report ∼17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, ∼76,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

  17. Comparative sequence and genetic analyses of asparagus BACs reveal no microsynteny with onion or rice.

    PubMed

    Jakse, Jernej; Telgmann, Alexa; Jung, Christian; Khar, Anil; Melgar, Sergio; Cheung, Foo; Town, Christopher D; Havey, Michael J

    2006-12-01

    The Poales (includes the grasses) and Asparagales [includes onion (Allium cepa L.) and asparagus (Asparagus officinalis L.)] are the two most economically important monocot orders. The Poales are a member of the commelinoid monocots, a group of orders sister to the Asparagales. Comparative genomic analyses have revealed a high degree of synteny among the grasses; however, it is not known if this synteny extends to other major monocot groups such as the Asparagales. Although we previously reported no evidence for synteny at the recombinational level between onion and rice, microsynteny may exist across shorter genomic regions in the grasses and Asparagales. We sequenced nine asparagus BACs to reveal physically linked genic-like sequences and determined their most similar positions in the onion and rice genomes. Four of the asparagus BACs were selected using molecular markers tightly linked to the sex-determining M locus on chromosome 5 of asparagus. These BACs possessed only two putative coding regions and had long tracts of degenerated retroviral elements and transposons. Five asparagus BACs were selected after hybridization of three onion cDNAs that mapped to three different onion chromosomes. Genic-like sequences that were physically linked on the cDNA-selected BACs or genetically linked on the M-linked BACs showed significant similarities (e < -20) to expressed sequences on different rice chromosomes, revealing no evidence for microsynteny between asparagus and rice across these regions. Genic-like sequences that were linked in asparagus were used to identify highly similar (e < -20) expressed sequence tags (ESTs) of onion. These onion ESTs mapped to different onion chromosomes and no relationship was observed between physical or genetic linkages in asparagus and genetic linkages in onion. These results further indicate that synteny among grass genomes does not extend to a sister order in the monocots and that asparagus may not be an appropriate smaller genome

  18. Hepatitis C virus/human T lymphotropic virus 1/2 co-infection: Regional burden and virological outcomes in people who inject drugs

    PubMed Central

    Castro, Erika; Roger, Elena

    2016-01-01

    This review analyses current data concerning co-infection with hepatitis C virus (HCV) and human T lymphotropic virus (HTLV)-1/2 in people who inject drugs (PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the ongoing and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the PubMed literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes. PMID:27175351

  19. Hepatitis C virus/human T lymphotropic virus 1/2 co-infection: Regional burden and virological outcomes in people who inject drugs.

    PubMed

    Castro, Erika; Roger, Elena

    2016-05-12

    This review analyses current data concerning co-infection with hepatitis C virus (HCV) and human T lymphotropic virus (HTLV)-1/2 in people who inject drugs (PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the ongoing and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the PubMed literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes. PMID:27175351

  20. Correlation of Klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model.

    PubMed

    Fodah, Ramy A; Scott, Jacob B; Tam, Hok-Hei; Yan, Pearlly; Pfeffer, Tia L; Bundschuh, Ralf; Warawa, Jonathan M

    2014-01-01

    Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models. In this study, we performed sequencing of the ATCC 43816 genome to support future efforts characterizing genetic elements required for disease. Furthermore, we performed comparative genetic analyses to the previously sequenced genomes from NTUH-K2044 and MGH 78578 to gain an understanding of the conservation of known virulence determinants amongst the three strains. We found that ATCC 43816 and NTUH-K2044 both possess the known virulence determinant for yersiniabactin, as well as a Type 4 secretion system (T4SS), CRISPR system, and an acetonin catabolism locus, all absent from MGH 78578. While both NTUH-K2044 and MGH 78578 are clinical isolates, little is known about the disease potential of these strains in cell culture and animal models. Thus, we also performed functional analyses in the murine macrophage cell lines RAW264.7 and J774A.1 and found that MGH 78578 (K52 serotype) was internalized at higher levels than ATCC 43816 (K2) and NTUH-K2044 (K1), consistent with previous characterization of the antiphagocytic properties of K1 and K2 serotype capsules. We also examined the three K. pneumoniae strains in a novel BALB/c respiratory disease model and found that ATCC 43816 and NTUH-K2044 are highly virulent (LD50<100 CFU) while MGH 78578 is relatively avirulent. PMID:25203254

  1. Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

    PubMed

    Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

    2016-09-01

    Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. PMID:27241629

  2. A Weighted U Statistic for Genetic Association Analyses of Sequencing Data

    PubMed Central

    Wei, Changshuai; Li, Ming; He, Zihuai; Vsevolozhskaya, Olga; Schaid, Daniel J.; Lu, Qing

    2014-01-01

    With advancements in next generation sequencing technology, a massive amount of sequencing data are generated, which offers a great opportunity to comprehensively investigate the role of rare variants in the genetic etiology of complex diseases. Nevertheless, the high-dimensional sequencing data poses a great challenge for statistical analysis. The association analyses based on traditional statistical methods suffer substantial power loss because of the low frequency of genetic variants and the extremely high dimensionality of the data. We developed a weighted U statistic, referred to as WU-SEQ, for the high-dimensional association analysis of sequencing data. Based on a non-parametric U statistic, WU-SEQ makes no assumption of the underlying disease model and phenotype distribution, and can be applied to a variety of phenotypes. Through simulation studies and an empirical study, we showed that WU-SEQ outperformed a commonly used SKAT method when the underlying assumptions were violated (e.g., the phenotype followed a heavy-tailed distribution). Even when the assumptions were satisfied, WU-SEQ still attained comparable performance to SKAT. Finally, we applied WU-SEQ to sequencing data from the Dallas Heart Study (DHS), and detected an association between ANGPTL 4 and very low density lipoprotein cholesterol. PMID:25331574

  3. Genetic and functional properties of uncultivated MCG archaea assessed by metagenome and gene expression analyses

    PubMed Central

    Meng, Jun; Xu, Jun; Qin, Dan; He, Ying; Xiao, Xiang; Wang, Fengping

    2014-01-01

    The Miscellaneous Crenarchaeota group (MCG) Archaea is one of the predominant archaeal groups in anoxic environments and may have significant roles in the global biogeochemical cycles. However, no isolate of MCG has been cultivated or characterized to date. In this study, we investigated the genetic organization, ecophysiological properties and evolutionary relationships of MCG archaea with other archaeal members using metagenome information and the result of gene expression experiments. A comparison of the gene organizations and similarities around the 16S rRNA genes from all available MCG fosmid and cosmid clones revealed no significant synteny among genomic fragments, demonstrating that there are large genetic variations within members of the MCG. Phylogenetic analyses of large-subunit+small-subunit rRNA, concatenated ribosomal protein genes and topoisomerases IB gene (TopoIB) all demonstrate that MCG constituted a sister lineage to the newly proposed archaeal phylum Aigarchaeota and Thaumarchaeota. Genes involved in protocatechuate degradation and chemotaxis were found in a MCG fosmid 75G8 genome fragment, suggesting that this MCG member may have a role in the degradation of aromatic compounds. Moreover, the expression of a putative 4-carboxymuconolactone decarboxylase was observed when the sediment was supplemented with protocatechuate, further supporting the hypothesis that this MCG member degrades aromatic compounds. PMID:24108328

  4. Sample richness and genetic diversity as drivers of chimera formation in nSSU metagenetic analyses

    PubMed Central

    Fonseca, V. G.; Nichols, B.; Lallias, D.; Quince, C.; Carvalho, G. R.; Power, D. M.; Creer, S.

    2012-01-01

    Eukaryotic diversity in environmental samples is often assessed via PCR-based amplification of nSSU genes. However, estimates of diversity derived from pyrosequencing environmental data sets are often inflated, mainly because of the formation of chimeric sequences during PCR amplification. Chimeras are hybrid products composed of distinct parental sequences that can lead to the misinterpretation of diversity estimates. We have analyzed the effect of sample richness, evenness and phylogenetic diversity on the formation of chimeras using a nSSU data set derived from 454 Roche pyrosequencing of replicated, large control pools of closely and distantly related nematode mock communities, of known intragenomic identity and richness. To further investigate how chimeric molecules are formed, the nSSU gene secondary structure was analyzed in several individuals. For the first time in eukaryotes, chimera formation proved to be higher in both richer and more genetically diverse samples, thus providing a novel perspective of chimera formation in pyrosequenced environmental data sets. Findings contribute to a better understanding of the nature and mechanisms involved in chimera formation during PCR amplification of environmentally derived DNA. Moreover, given the similarities between biodiversity analyses using amplicon sequencing and those used to assess genomic variation, our findings have potential broad application for identifying genetic variation in homologous loci or multigene families in general. PMID:22278883

  5. Interspecific Chromosome Substitution Lines as Genetic Resources for Improvement, Trait Analyses and Genomic Inference

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three of the research areas likely to very significantly impact genetic improvement of cotton are interspecific introgression, genetic dissection of complex traits and sequencing of [AD] genomes. Interspecific introgression is expected to increase genetic diversity of breeding germplasm, creating op...

  6. Serum adiponectin in HIV-1 and hepatitis C virus mono- and co-infected Kenyan injection drug users

    PubMed Central

    Ndombi, Eric M; Budambula, Valentine; Webale, Mark K; Musumba, Francis O; Wesongah, Jesca O; Mibei, Erick; Ahmed, Aabid A; Lihana, Raphael; Were, Tom

    2015-01-01

    Adiponectin is an important marker of anthropometric profiles of adipose tissue. However, association of adiponectin and adiposity in HIV mono- and co-infected and hepatitis (HCV) injection drug users (IDUs) has not been elucidated. Therefore, the relationship of total adiponectin levels with anthropometric indices of adiposity was examined in HIV mono-infected (anti-retroviral treatment, ART-naive, n=16 and -experienced, n=34); HCV mono-infected, n=36; HIV and HCV co-infected (ART-naive, n=5 and -experienced, n=13); uninfected, n=19 IDUs; and healthy controls, n=16 from coastal Kenya. Anthropometric indices of adiposity were recorded and total circulating adiponectin levels were measured in serum samples using enzyme-linked immunosorbent assay. Adiponectin levels differed significantly amongst the study groups (P<0.0001). Post-hoc analyses revealed decreased levels in HIV mono-infected ART-naive IDUs in comparison to uninfected IDUs (P<0.05) and healthy controls (P<0.05). However, adiponectin levels were elevated in HCV mono-infected IDUs relative to HIV mono-infected ART-naive (P<0.001) and -experienced (P<0.001) as well as HIV and HCV co-infected ART-naive (P<0.05) IDUs. Furthermore, adiponectin correlated with weight (ρ=0.687; P=0.003) and BMI (ρ=0.598; P=0.014) in HIV mono-infected ART-naive IDUs; waist circumference (ρ=−0.626; P<0.0001), hip (ρ=−0.561; P=0.001) circumference, and bust-to-waist ratio (ρ=0.561; P=0.001) in HIV mono-infected ART-experienced IDUs; waist girth (ρ=0.375; P=0.024) in HCV mono-infected IDUs; and waist-to-hip ratio (ρ=−0.872; P=0.048) in HIV and HCV co-infected ART-naive IDUs. Altogether, these results suggest suppression of adiponectin production in treatment-naive HIV mono-infected IDUs and that circulating adiponectin is a useful surrogate marker of altered adiposity in treatment-naive and -experienced HIV and HCV mono- and co-infected IDUs. PMID:26306727

  7. Malaria-Cutaneous Leishmaniasis Co-infection: Influence on Disease Outcomes and Immune Response

    PubMed Central

    Pinna, Raquel A.; Silva-dos-Santos, Danielle; Perce-da-Silva, Daiana S.; Oliveira-Ferreira, Joseli; Villa-Verde, Dea M. S.; De Luca, Paula M.; Banic, Dalma M.

    2016-01-01

    Malaria and Cutaneous Leishmaniasis (CL) are co-endemic throughout large regions in tropical countries and co-infection may impact the evolution of host-parasite interactions. In the present study, we evaluate Malaria/Leishmaniasis disease outcome, Th1/Th2 cytokine levels and the CD4 and CD8 T-cell profiles in a co-infection murine model (BALB/c) of Plasmodium yoelii 17XNL (Py) and Leishmania amazonensis (La) or L. braziliensis (Lb). Malaria parasitaemia was assessed through blood strains stained with Giemsa. Leishmania lesions were monitored with a digital caliper and parasite loads determined by limiting-dilution assay. Serum levels of IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10, and IL-17 were determined using multiplexed bead assay and expression of CD3, CD4, and CD8 T-cells markers were determined by Flow Cytometry in the thymus, spleens and lymph nodes. Parasitaemia in Lb+Py co-infected group was lower than in Py single-infected group, suggesting a protective effect of Lb co-infection in Malaria progression. In contrast, La+Py co-infection increased parasitaemia, patent infection and induced mortality in non-lethal Malaria infection. Regarding Leishmaniasis, Lb+Py co-infected group presented smaller lesions and less ulceration than Lb single-infected animals. In contrast, La+Py co-infected group presented only a transitory delay on the development of lesions when compared to La single-infected mice. Decreased levels of IFN-γ, TNF, IL-6, and IL-10 were observed in the serum of co-infected groups, demonstrating a modulation of Malaria immune response by Leishmania co-infections. We observed an intense thymic atrophy in Py single-infected and co-infected groups, which recovered earlier in co-infected animals. The CD4 and CD8 T cell profiles in thymus, spleens and lymph nodes did not differ between Py single and co-infected groups, except for a decrease in CD4+CD8+ T cells which also increased faster in co-infected mice. Our results suggest that Py and Leishmania co-infection

  8. Human immunodeficiency virus and hepatitis C co-infection in sub-Saharan West Africa.

    PubMed

    Mboto, C I; Davies, A; Fielder, M; Jewell, A P

    2006-01-01

    Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is becoming a major global problem, leading to increased morbidity and mortality in developed countries. Co-existence in sub-Saharan West Africa of a high prevalence of HIV and HCV, which share similar behavioural risk factors and modes of transmission, must be seen in the broader context of an emerging third epidemic of HIV and HCV co-infection, as many factors that may affect the spread of HIV and HCV co-infection are endemic in the continent, including host factors such as sexual behaviour, presence of other sexually transmitted diseases, female and male circumcision status, percutaneous and perinatal exposure, and poverty. This review examines the epidemiology, risk factors and transmission of HIV and HCV co-infection and draws attention to the possible emergence of an epidemic of HIV and HCV co-infection in the region. PMID:16613141

  9. Genetic Analyses of a Three Generation Family Segregating Hirschsprung Disease and Iris Heterochromia.

    PubMed

    Cui, Long; Wong, Emily Hoi-Man; Cheng, Guo; Firmato de Almeida, Manoel; So, Man-Ting; Sham, Pak-Chung; Cherny, Stacey S; Tam, Paul Kwong-Hang; Garcia-Barceló, Maria-Mercè

    2013-01-01

    We present the genetic analyses conducted on a three-generation family (14 individuals) with three members affected with isolated-Hirschsprung disease (HSCR) and one with HSCR and heterochromia iridum (syndromic-HSCR), a phenotype reminiscent of Waardenburg-Shah syndrome (WS4). WS4 is characterized by pigmentary abnormalities of the skin, eyes and/or hair, sensorineural deafness and HSCR. None of the members had sensorineural deafness. The family was screened for copy number variations (CNVs) using Illumina-HumanOmni2.5-Beadchip and for coding sequence mutations in WS4 genes (EDN3, EDNRB, or SOX10) and in the main HSCR gene (RET). Confocal microscopy and immunoblotting were used to assess the functional impact of the mutations. A heterozygous A/G transition in EDNRB was identified in 4 affected and 3 unaffected individuals. While in EDNRB isoforms 1 and 2 (cellular receptor) the transition results in the abolishment of translation initiation (M1V), in isoform 3 (only in the cytosol) the replacement occurs at Met91 (M91V) and is predicted benign. Another heterozygous transition (c.-248G/A; -predicted to affect translation efficiency-) in the 5'-untranslated region of EDN3 (EDNRB ligand) was detected in all affected individuals but not in healthy carriers of the EDNRB mutation. Also, a de novo CNVs encompassing DACH1 was identified in the patient with heterochromia iridum and HSCR Since the EDNRB and EDN3 variants only coexist in affected individuals, HSCR could be due to the joint effect of mutations in genes of the same pathway. Iris heterochromia could be due to an independent genetic event and would account for the additional phenotype within the family. PMID:23840513

  10. High prevalence of trypanosome co-infections in freshwater fishes.

    PubMed

    Grybchuk-Ieremenko, Anastasiia; Losev, Alexander; Kostygov, Alexei Yu; Lukeš, Julius; Yurchenko, Vyacheslav

    2014-12-01

    One thousand three hundred seventy three fish specimens of eight different species from the vicinity of Kyiv, Ukraine, were examined for the presence of trypanosomes and 921 individuals were found to be infected. The prevalence of infection ranged from 24% in freshwater bream, Abramis brama (Linnaeus), to 100% in spined loach, Cobitis 'taenia' Linnaeus. The level of parasitaemia also varied significantly between generally mild infections in pikeperch, Sander lucioperca (Linnaeus), and heavy ones in C. 'taenia'. In most cases the infections with trypanosomes were asymptomatic. Cases of co-infection with species of Trypanoplasma Laveran et Mesnil, 1901 were documented for five out of eight examined host species. Molecular analysis of the 18S rDNA sequences revealed that four hosts, namely northern pike, Esox lucius Linnaeus, freshwater bream, spined loach and European perch, Perca fluviatilis Linnaeus, were simultaneously infected with two different trypanosome species. Our findings advocate the view that to avoid the risk posed by mixed infections, subsequent molecular taxonomic studies should be performed on clonal lines derived from laboratory cultures of fish trypanosomes. PMID:25651690

  11. Co-infection by human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1): does immune activation lead to a faster progression to AIDS?

    PubMed Central

    2009-01-01

    Background Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1. Methods We enrolled 29 patients co-infected by HTLV-1 and HIV (co-infected), 59 patients mono-infected by HIV (HIV) and 16 healthy controls (HC), respectively. For phenotypic analysis, cells were stained with the following fluorochrome-labeled anti-human monoclonal antibodies CD4-APC, CD8-PerCP, CD25-PE, CD62L-FITC, CD45RA-FITC. CD45RO-PE, CD38-PE; being analysed by four-colour flow cytometry. Results We initially found that CD4+ T cell counts were significantly higher in co-infected, as compared to HIV groups. Moreover, CD4+ T Lymphocytes from co-infected patients presented significantly higher levels of CD45RO and CD25, but lower levels of CD45RA and CD62L, strongly indicating that CD4+ T cells are more activated under HTLV-1 plus HIV co-infection. Conclusion Our data indicate that HTLV-1/HIV co-infected patients progress with higher CD4+ T cell counts and higher levels of activation markers. In this context, it is conceivable that in co-infected individuals, these higher levels of activation may account for a faster progression to AIDS. PMID:20028500

  12. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

    PubMed Central

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves

    2016-01-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  13. Increased susceptibility to Strongyloides venezuelensis in mice due to Mycobacterium bovis co-infection which modulates production of Th2 cytokines.

    PubMed

    Carmo, A M; Vicentini, M A; Dias, A T; Alves, L L; Alves, C C S; Brandi, J S; De Paula, M L; Fernandes, A; Barsante, M M; Souza, M A; Teixeira, H C; Negrão-Corrêa, D; Ferreira, A P

    2009-09-01

    An estimated quarter of the world's population possesses an infection caused by gastrointestinal nematodes, which induce a Th2 type immune response. Concomitant infection of nematodes with Mycobacterium tuberculosis, which induces a predominantly Th1 type response, is very frequent in tropical and subtropical regions. This study examined immune responses of BALB/c mice infected with Strongyloides venezuelensis and then co-infected with Mycobacterium bovis. The number of worms in the intestine, eggs in feces, cytokine production in lungs and intestine and the expression of CD80, CD86, CTLA-4 and CD28 cell markers on pulmonary cells were analysed. Our results indicate that co-infected mice had an increased parasite burden, which correlates with elevated IFN-gamma and IL-10 cytokine production and decreased IL-4 and IL-13. Moreover, decreased expression of CD80 and increased expression of CTLA-4 were observed in co-infected mice. Our data point out that susceptibility to Strongyloides venezuelensis infection is increased by Mycobacterium bovis co-infection, resulting in higher parasite survival. PMID:19660155

  14. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure.

    PubMed

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; Almeida, Adilson José de; Pelajo-Machado, Marcelo; Castro, Tatiana Xavier de; Nascimento, Jussara Pereira do; Brown, Kevin E; Pinto, Marcelo Alves

    2016-04-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  15. Transcription and genetic analyses of a putative N-acetylmuramyl-L-alanine amidase in Borrelia burgdorferi

    PubMed Central

    Yang, Yu; Li, Chunhao

    2010-01-01

    In this study, a putative N-acetylmuramyl-L-alanine amidase gene (bb0666) was identified in the genome of the Lyme disease spirochete Borrelia burgdorferi. This protein shares c. 30% identity with its counterparts from other bacteria. Reverse transcriptase-PCR analysis showed that bb0666 along with two other genes (bb0665 and bb0667) are cotranscribed with the motility and chemotaxis genes. This newly identified operon is termed as pami. Sequence and primer extension analyses showed that pami was regulated by a σ70-like promoter, which is designated as Pami. Transcriptional analysis using a gene encoding green fluorescence protein as a reporter demonstrated that Pami functions in both Escherichia coli and B. burgdorferi. Genetic studies showed that the Δbb0666 mutant grows in long chains of unseparated cells, whose phenotype is similar to its counterparts in E. coli. Taken together, these results demonstrate that bb0666 is a homolog of MurNac-LAAs that contributes to the cell division of B. burgdorferi. PMID:19025570

  16. Genetic diversity at the Dhn3 locus in Turkish Hordeum spontaneum populations with comparative structural analyses

    PubMed Central

    Uçarlı, Cüneyt; McGuffin, Liam J.; Çaputlu, Süleyman; Aravena, Andres; Gürel, Filiz

    2016-01-01

    We analysed Hordeum spontaneum accessions from 21 different locations to understand the genetic diversity of HsDhn3 alleles and effects of single base mutations on the intrinsically disordered structure of the resulting polypeptide (HsDHN3). HsDHN3 was found to be YSK2-type with a low-frequency 6-aa deletion in the beginning of Exon 1. There is relatively high diversity in the intron region of HsDhn3 compared to the two exon regions. We have found subtle differences in K segments led to changes in amino acids chemical properties. Predictions for protein interaction profiles suggest the presence of a protein-binding site in HsDHN3 that coincides with the K1 segment. Comparison of DHN3 to closely related cereals showed that all of them contain a nuclear localization signal sequence flanking to the K1 segment and a novel conserved region located between the S and K1 segments [E(D/T)DGMGGR]. We found that H. vulgare, H. spontaneum, and Triticum urartu DHN3s have a greater number of phosphorylation sites for protein kinase C than other cereal species, which may be related to stress adaptation. Our results show that the nature and extent of mutations in the conserved segments of K1 and K2 are likely to be key factors in protection of cells. PMID:26869072

  17. German cohort of HCV mono-infected and HCV/HIV co-infected patients reveals relative under-treatment of co-infected patients

    PubMed Central

    2014-01-01

    Background Current German and European HIV guidelines recommend early evaluation of HCV treatment in all HIV/HCV co-infected patients. However, there are still considerable barriers to initiate HCV therapy in everyday clinical practice. This study evaluates baseline characteristics, “intention-to-treat” pattern and outcome of therapy of HCV/HIV co-infected patients in direct comparison to HCV mono-infected patients in a “real-life” setting. Methods A large, single-center cohort of 172 unselected HCV patients seen at the Infectious Diseases Unit at the University Medical Center Hamburg-Eppendorf from 2000–2011, 88 of whom HCV/HIV co-infected, was retrospectively analyzed by chart review with special focus on demographic, clinical and virologic aspects as well as treatment outcome. Results Antiviral HCV combination therapy with PEG-interferon plus weight-adapted ribavirin was initiated in 88/172 (52%) patients of the entire cohort and in n = 36 (40%) of all HCV/HIV co-infected patients (group A) compared to n = 52 (61%) of the HCV mono-infected group (group B) (p = 0.006). There were no significant differences of the demographics or severity of the liver disease between the two groups with the exception of slightly higher baseline viral loads in group A. A sustained virologic response (SVR) was observed in 50% (n = 18) of all treated HIV/HCV co-infected patients versus 52% (n = 27) of all treated HCV mono-infected patients (p = 0.859). Genotype 1 was the most frequent genotype in both groups (group A: n = 37, group B: n = 49) and the SVR rates for these patients were only slightly lower in the group of co-infected patients (group A: n = 33%, group B: 40% p = 0.626). During the course of treatment HCV/HIV co-infected patients received less ribavirin than mono-infected patients. Conclusion Overall, treatment was only initiated in half of the patients of the entire cohort and in an even smaller proportion of HCV/HIV co-infected

  18. Co-infection of Long-Term Carriers of Plasmodium falciparum with Schistosoma haematobium Enhances Protection from Febrile Malaria: A Prospective Cohort Study in Mali

    PubMed Central

    Sangala, Jules; Li, Shanping; Doumtabe, Didier; Kone, Younoussou; Traoré, Abdrahamane; Bathily, Aboudramane; Sogoba, Nafomon; Coulibaly, Michel E.; Huang, Chiung-Yu; Ongoiba, Aissata; Kayentao, Kassoum; Diallo, Mouctar; Dramane, Zongo; Nutman, Thomas B.; Crompton, Peter D.; Doumbo, Ogobara; Traore, Boubacar

    2014-01-01

    needed to determine whether co-infection induces immunomodulatory mechanisms that protect against febrile malaria or whether genetic, behavioral, or environmental factors not accounted for here explain these findings. PMID:25210876

  19. Co-infection of human parvovirus B19 with Plasmodium falciparum contributes to malaria disease severity in Gabonese patients

    PubMed Central

    2013-01-01

    Background High seroprevalence of parvovirus B19 (B19V) coinfection with Plasmodium falciparum has been previously reported. However, the impact of B19V-infection on the clinical course of malaria is still elusive. In this study, we investigated the prevalence and clinical significance of B19V co-infection in Gabonese children with malaria. Methods B19V prevalence was analyzed in serum samples of 197 Gabonese children with P. falciparum malaria and 85 healthy controls using polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and direct DNA-sequencing. Results B19V was detected in 29/282 (10.28%) of Gabonese children. B19V was observed more frequently in P. falciparum malaria patients (14.21%) in comparison to healthy individuals (1.17%) (P<0.001). Notably, the mild-malaria group revealed significantly lower hematocrit levels in B19V/P. falciparum co-infection than in P. falciparum mono-infection (P<0.05). Genetic analysis revealed a predominance of B19V genotype-1 (71.43%) in the studied population. However, B19V-genotype 2 was observed significantly more often in children with severe-malaria than in mild-malaria (P=0.04). Conclusion Our findings reveal that B19V-infection is frequent in Gabonese children with P. falciparum malaria and signifies a possible contribution of B19V on the clinical course of malaria in a genotype-dependent manner. B19V co-infection should be considered as a additional diagnostic measure in malaria patients with life threatening anemia. PMID:23945350

  20. Mutation analyses of molecularly cloned satellite tobacco mosaic virus during serial passage in plants: evidence for hotspots of genetic change.

    PubMed

    Kurath, G; Dodds, J A

    1995-07-01

    The high level of genetic diversity and rapid evolution of viral RNA genomes are well documented, but few studies have characterized the rate and nature of ongoing genetic change over time under controlled experimental conditions, especially in plant hosts. The RNA genome of satellite tobacco mosaic virus (STMV) was used as an effective model for such studies because of advantageous features of its genome structure and because the extant genetic heterogeneity of STMV has been characterized previously. In the present study, the process of genetic change over time was studied by monitoring multiple serial passage lines of STMV populations for changes in their consensus sequences. A total of 42 passage lines were initiated by inoculation of tobacco plants with a helper tobamovirus and one of four STMV RNA inocula that were transcribed from full-length infectious STMV clones or extracted from purified STMV type strain virions. Ten serial passages were carried out for each line and the consensus genotypes of progeny STMV populations were assessed for genetic change by RNase protection analyses of the entire 1,059-nt STMV genome. Three different types of genetic change were observed, including the fixation of novel mutations in 9 of 42 lines, mutation at the major heterogeneity site near nt 751 in 5 of the 19 lines inoculated with a single genotype, and selection of a single major genotype in 6 of the 23 lines inoculated with mixed genotypes. Sequence analyses showed that the majority of mutations were single base substitutions. The distribution of mutation sites included three clusters in which mutations occurred at or very near the same site, suggesting hot spots of genetic change in the STMV genome. The diversity of genetic changes in sibling lines is clear evidence for the important role of chance and random sampling events in the process of genetic diversification of STMV virus populations. PMID:7489510

  1. Genetic structure of wild boar (Sus scrofa) populations from East Asia based on microsatellite loci analyses

    PubMed Central

    2014-01-01

    Background Wild boar, Sus scrofa, is an extant wild ancestor of the domestic pig as an agro-economically important mammal. Wild boar has a worldwide distribution with its geographic origin in Southeast Asia, but genetic diversity and genetic structure of wild boar in East Asia are poorly understood. To characterize the pattern and amount of genetic variation and population structure of wild boar in East Asia, we genotyped and analyzed microsatellite loci for a total of 238 wild boar specimens from ten locations across six countries in East and Southeast Asia. Results Our data indicated that wild boar populations in East Asia are genetically diverse and structured, showing a significant correlation of genetic distance with geographic distance and implying a low level of gene flow at a regional scale. Bayesian-based clustering analysis was indicative of seven inferred genetic clusters in which wild boars in East Asia are geographically structured. The level of genetic diversity was relatively high in wild boars from Southeast Asia, compared with those from Northeast Asia. This gradient pattern of genetic diversity is consistent with an assumed ancestral population of wild boar in Southeast Asia. Genetic evidences from a relationship tree and structure analysis suggest that wild boar in Jeju Island, South Korea have a distinct genetic background from those in mainland Korea. Conclusions Our results reveal a diverse pattern of genetic diversity and the existence of genetic differentiation among wild boar populations inhabiting East Asia. This study highlights the potential contribution of genetic variation of wild boar to the high genetic diversity of local domestic pigs during domestication in East Asia. PMID:25034725

  2. The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses

    PubMed Central

    2014-01-01

    Background There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. Methods In a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year program to collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center. Results Over 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children’s or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the

  3. Alternative models in genetic analyses of carcass traits measured by ultrasonography in Guzerá cattle: A Bayesian approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to study alternative models for genetic analyses of carcass traits assessed by ultrasonography in Guzerá cattle. Data from 947 measurements (655 animals) of Rib-eye area (REA), rump fat thickness (RFT) and backfat thickness (BFT) were used. Finite polygenic models (FPM), infinitesi...

  4. Genetic diversity of Chikungunya virus, India 2006-2010: evolutionary dynamics and serotype analyses.

    PubMed

    Sumathy, K; Ella, Krishna M

    2012-03-01

    The genetic diversity of Chikungunya virus (CHIKV) causing recurring outbreaks in India since 2006 was studied. The 2006 epidemic was caused by a virus strain of the East, Central and South African (ECSA) genotype with 226A in the E1 glycoprotein. The variant strain with E1-A226V mutation caused outbreaks since 2007 in the state of Kerala where Aedes albopictus is the abundant mosquito vector. Molecular epidemiology data since 2007 is scarce from other regions of the country. RT-PCR, sequencing and phylogenetic analyses of CHIKV isolates from the 2009 to 2010 epidemics in the States of Tamil Nadu and Andhra Pradesh placed them in a separate clade within the ECSA lineage. The isolates of the study had 226A in the E1 glycoprotein. The isolates had a novel E1-K211E mutation that was under significant positive selection. E1-211E is highly conserved in the Asian genotype of the virus circulated by Aedes aegypti. Unique mutations in E2 glycoprotein were identified. The two sub-lineages of ECSA genotype circulating in India parallel the abundance of Ae. albopictus and Ae. aegypti. Novel mutations in the envelope glycoproteins suggest adaptive evolution of the virus to local vector abundance. Cross neutralization of the virus isolates from recurring Indian epidemics indicated that no distinct serotypes had evolved. The study has provided insights into the origin, distribution and evolutionary adaptation of the virus to local vector abundance in the region that has reportedly, the highest incidence of CHIKV infection in the world. PMID:22246833

  5. Population Genetic Analyses of Helicobacter pylori Isolates from Gambian Adults and Children

    PubMed Central

    Secka, Ousman; Moodley, Yoshan; Antonio, Martin; Berg, Douglas E.; Tapgun, Mary; Walton, Robert; Worwui, Archibald; Thomas, Vivat; Corrah, Tumani; Thomas, Julian E.; Adegbola, Richard A.

    2014-01-01

    The gastric pathogen Helicobacter pylori is one of the most genetically diverse of bacterial species. Much of its diversity stems from frequent mutation and recombination, preferential transmission within families and local communities, and selection during persistent gastric mucosal infection. MLST of seven housekeeping genes had identified multiple distinct H. pylori populations, including three from Africa: hpNEAfrica, hpAfrica1 and hpAfrica2, which consists of three subpopulations (hspWAfrica, hspCAfrica and hspSAfrica). Most detailed H. pylori population analyses have used strains from non-African countries, despite Africa's high importance in the emergence and evolution of humans and their pathogens. Our concatenated sequences from seven H. pylori housekeeping genes from 44 Gambian patients (MLST) identified 42 distinct sequence types (or haplotypes), and no clustering with age or disease. STRUCTURE analysis of the sequence data indicated that Gambian H. pylori strains belong to the hspWAfrica subpopulation of hpAfrica1, in accord with Gambia's West African location. Despite Gambia's history of invasion and colonisation by Europeans and North Africans during the last millennium, no traces of Ancestral Europe1 (AE1) population carried by those people were found. Instead, admixture of 17% from Ancestral Europe2 (AE2) was detected in Gambian strains; this population predominates in Nilo-Saharan speakers of North-East Africa, and might have been derived from admixture of hpNEAfrica strains these people carried when they migrated across the Sahara during the Holocene humid period 6,000–9,000 years ago. Alternatively, shared AE2 ancestry might have resulted from shared ancestral polymorphisms already present in the common ancestor of sister populations hpAfrica1 and hpNEAfrica. PMID:25310300

  6. Efficacy of integrated school based de-worming and prompt malaria treatment on helminths -Plasmodium falciparum co-infections: A 33 months follow up study

    PubMed Central

    2011-01-01

    Background The geographical congruency in distribution of helminths and Plasmodium falciparum makes polyparasitism a common phenomenon in Sub Saharan Africa. The devastating effects of helminths-Plasmodium co-infections on primary school health have raised global interest for integrated control. However little is known on the feasibility, timing and efficacy of integrated helminths-Plasmodium control strategies. A study was conducted in Zimbabwe to evaluate the efficacy of repeated combined school based antihelminthic and prompt malaria treatment. Methods A cohort of primary schoolchildren (5-17 years) received combined Praziquantel, albendazole treatment at baseline, and again during 6, 12 and 33 months follow up surveys and sustained prompt malaria treatment. Sustained prompt malaria treatment was carried out throughout the study period. Children's infection status with helminths, Plasmodium and helminths-Plasmodium co-infections was determined by parasitological examinations at baseline and at each treatment point. The prevalence of S. haematobium, S. mansoni, STH, malaria, helminths-Plasmodium co-infections and helminths infection intensities before and after treatment were analysed. Results Longitudinal data showed that two rounds of combined Praziquantel and albendazole treatment for schistosomiasis and STHs at 6 monthly intervals and sustained prompt malaria treatment significantly reduced the overall prevalence of S. haematobium, S. mansoni, hookworms and P. falciparum infection in primary schoolchildren by 73.5%, 70.8%, 67.3% and 58.8% respectively (p < 0.001, p < 0.001, p < 0.001, p < 0.001 respectively). More importantly, the prevalence of STH + schistosomes, P. f + schistosomes, and P. f + STHs + schistosomes co-infections were reduced by 68.0%, 84.2%, and 90.7%, respectively. The absence of anti-helminthic treatment between the 12 mth and 33 mth follow-up surveys resulted in the sharp increase in STHs + schistosomes co-infection from 3.3% at 12 months

  7. TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo

    PubMed Central

    Kaboru, Berthollet Bwira; Ogwang, Brenda. A.; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

    2013-01-01

    Background: HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. Methods: A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Results: Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases’ control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. Conclusion: HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region. PMID:24596866

  8. Albendazole treatment of HIV-1 and helminth co-infection: A randomized, double blind, placebo-controlled trial

    PubMed Central

    Walson, Judd L.; Otieno, Phelgona A.; Mbuchi, Margaret; Richardson, Barbra A.; Lohman-Payne, Barbara; Macharia, Steve Wanyee; Overbaugh, Julie; Berkley, James; Sanders, Eduard J.; Chung, Michael; John-Stewart, Grace C.

    2009-01-01

    OBJECTIVE Several co-infections have been shown to impact the progression of HIV-1 infection. We sought to determine if treatment of helminth co-infection in HIV-1 infected adults impacted markers of HIV-1 disease progression. DESIGN To date there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression. METHODS A randomized, double-blind, placebo-controlled trial of albendazole (400mg daily for three days) in antiretroviral-naïve HIV-1 infected adults (CD4 >200 cells/mm3) with soil-transmitted helminth infection was conducted at ten sites in Kenya (Clinical Trials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values. RESULTS Of 1,551 HIV-1 infected individuals screened for helminth-infection, 299 were helminth-infected. 234 adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 count was 557 cells/mm3 and mean plasma viral load was 4.75 log10 copies/mL at enrolment. Albendazole therapy resulted in significantly higher CD4 counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow up (+109 cells/mm3; 95% CI +38.9 to +179.0, p=0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (p=0.09). These effects were not seen with treatment of other species of soil-transmitted helminths. CONCLUSIONS Treatment of A. lumbricoides with albendazole in HIV-1 co-infected adults resulted in significantly increased CD4 counts during 3-month follow-up. Given the high prevalence of A. lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression. PMID:18670219

  9. Co-infection patterns and geographic distribution of a complex pathosystem targeted by pathogen-resistant plants.

    PubMed

    Biddle, J M; Linde, C; Godfree, R C

    2012-01-01

    Increasingly, pathogen-resistant (PR) plants are being developed to reduce the agricultural impacts of disease. However PR plants also have the potential to result in increased invasiveness of nontarget host populations and so pose a potential threat to nontarget ecosystems. In this paper we use a new framework to investigate geographical variation in the potential risk associated with unintended release of genetically modified alfalfa mosaic virus (AMV)-resistant Trifolium repens (white clover) into nontarget host populations containing AMV, clover yellow vein virus (ClYVV), and white clover mosaic virus (WCIMV) in southeastern Australia. Surveys of 213 sites in 37 habitat types over a 300 000-km2 study region showed that T. repens is a significant weed of many high-conservation-value habitats in southeastern Australia and that AMV, ClYVV, and WClMV occur in 15-97% of nontarget host populations. However, T. repens abundance varied with site disturbance, habitat conservation value, and proximity to cropping, and all viral pathogens had distinct geographic distributions and infection patterns. Virus species frequently co-infected host plants and displayed nonindependent distributions within host populations, although co-infection patterns varied across the study region. Our results clearly illustrate the complexity of conducting environmental risk assessments that involve geographically widespread, invasive pasture species and demonstrate the general need for targeted, habitat- and pathosystem-specific studies prior to the process of tiered risk assessment. PMID:22471074

  10. The Role of Co-Infections in Mother-to-Child Transmission of HIV§

    PubMed Central

    King, Caroline C.; Ellington, Sascha R.; Kourtis, Athena P.

    2015-01-01

    In HIV-infected women, co-infections that target the placenta, fetal membranes, genital tract, and breast tissue, as well as systemic maternal and infant infections, have been shown to increase the risk for mother-to-child transmission of HIV (MTCT). Active co-infection stimulates the release of cytokines and inflammatory agents that enhance HIV replication locally or systemically and increase tissue permeability, which weakens natural defenses to MTCT. Many maternal or infant co-infections can affect MTCT of HIV, and particular ones, such as genital tract infection with herpes simplex virus, or systemic infections such as hepatitis B, can have substantial epidemiologic impact on MTCT. Screening and treatment for co-infections that can make infants susceptible to MTCT in utero, peripartum, or postpartum can help reduce the incidence of HIV infection among infants and improve the health of mothers and infants worldwide. PMID:23305198

  11. Resource limitation alters the consequences of co-infection for both hosts and parasites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most animals are concurrently infected with multiple parasites and live in environments with fluctuating resource availability. Compelling evidence from humans, laboratory model systems, and wildlife suggests that interactions among co-infecting parasites can influence disease dynamics, individual h...

  12. The Effect of Malaria and HIV Co-Infection on Anemia: A Meta-Analysis.

    PubMed

    Naing, Cho; Sandhu, Nisha Kaur; Wai, Victor Nyunt

    2016-04-01

    Malaria and human immunodeficiency virus (HIV) infections are globally important public health concerns. The objectives of this study were (i) to determine the prevalence of malaria and HIV co-infections in people living in endemic countries, and (ii) to assess the effect of co-infection on anemia.Studies were searched on electronic databases including PubMed, Embase, Medline, Google Scholar, and African Journals Online. Observational studies, assessing the prevalence of co-infection and reporting its association with anemia, were included. The methodological quality of included studies was assessed using a tool called the risk of bias assessment for non-randomized studies. Heterogeneity among studies was investigated with the I-square test. Pooled prevalence of the co-infection and its 95% confidence interval (CI) were estimated using the random-effect model, reflected on heterogeneity among studies. Summary odds ratio (OR), summary standardized mean difference (SMD), and their corresponding 95% CIs were estimated, as appropriate. Subgroup analysis and meta-regression were performed for robustness of results. Publication bias was assessed by visualization of a funnel plot.Twenty-three studies were included in the present study. Overall, the pooled prevalence of co-infection was 19% (95% CI: 15-23%, I: 98.1%), showing 26% (95% CI: 20-32%, I: 98.7%) in adults, 12% (95% CI: 7-17%, I: 95.0) in pregnant women, and 9% (95% CI: 6-11%, I: 68.6%) in children. Anemia was comparable between the monoinfected and co-infected adults (summary OR: 1.49, 95% CI: 0.93-2.37) and increased by 49% in co-infected pregnant women (summary OR: 1.49, 95% CI: 1.14-1.94). The mean hemoglobin concentration was significantly lower in the co-infected group than the monoinfected group (summary SMD: -0.47, 95% CI: -0.61 to -0.33). The results of meta-regression on the prevalence of co-infection using the publication year and total population as covariates showed the I value remained high implying

  13. The consequences of co-infections for parasite transmission in the mosquito Aedes aegypti.

    PubMed

    Duncan, Alison B; Agnew, Philip; Noel, Valérie; Michalakis, Yannis

    2015-03-01

    Co-infections may modify parasite transmission opportunities directly as a consequence of interactions in the within-host environment, but also indirectly through changes in host life history. Furthermore, host and parasite traits are sensitive to the abiotic environment with variable consequences for parasite transmission in co-infections. We investigate how co-infection of the mosquito Aedes aegypti with two microsporidian parasites (Vavraia culicis and Edhazardia aedis) at two levels of larval food availability affects parasite transmission directly, and indirectly through effects on host traits. In a laboratory infection experiment, we compared how co-infection, at low and high larval food availability, affected the probability of infection, within-host growth and the transmission potential of each parasite, compared to single infections. Horizontal transmission was deemed possible for both parasites when infected hosts died harbouring horizontally transmitting spores. Vertical transmission was judged possible for E. aedis when infected females emerged as adults. We also compared the total input number of spores used to seed infections with output number, in single and co-infections for each parasite. The effects of co-infection on parasite fitness were complex, especially for V. culicis. In low larval food conditions, co-infection increased the chances of mosquitoes dying as larvae or pupae, thus increasing opportunities for V. culicis' horizontal transmission. However, co-infection reduced larval longevity and hence time available for V. culicis spore production. Overall, there was a negative net effect of co-infection on V. culicis, whereby the number of spores produced was less than the number used to seed infection. Co-infections also negatively affected horizontal transmission of the more virulent parasite, E. aedis, through reduced longevity of pre-adult hosts. However, its potential transmission suffered less relative to V. culicis. Our results

  14. Tuberculosis and HIV co-infection in children

    PubMed Central

    2014-01-01

    uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV. Conclusion Data on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings. PMID:24564453

  15. Genetic analyses benefit from using less heterogeneous phenotypes: An illustration with the Hospital Anxiety and Depression Scale (HADS)

    PubMed Central

    Laurin, Charles A.; Hottenga, Jouke-Jan; Willemsen, Gonneke; Boomsma, Dorret I.; Lubke, Gitta H.

    2015-01-01

    Phenotypic heterogeneity of depression has been cited as one of causes of the limited success to detect genetic variants in genome-wide studies. The 7-item Hospital Anxiety and Depression Scale (HADS-D) was developed to detect depression in individuals with physical health problems. An initial psychometric analysis showed that a short version (“HADS-4”) is less heterogeneous and hence more reliable than the full scale, and correlates equally strong with a DSM-oriented depression scale. We compared the HADS-D and the HADS-4 to assess the benefits of using less heterogeneous phenotype measures in genetic analyses. We compared HADS-D and HADS-4 in three separate analyses: (1) twin- and family-based heritability estimation, (2) SNP-based heritability estimation using the software GCTA, and (3) a genome-wide association study (GWAS). The twin study resulted in heritability estimates between 18 and 25%, with additive genetic variance being the largest component. There was also evidence for assortative mating and a dominance component of genetic variance, with HADS-4 having slightly lower estimates of assortment. Importantly, when estimating heritability from SNPs, the HADS-D did not show a significant genetic variance component, while for the HADS-4, a statistically significant amount of heritability was estimated. Moreover, the HADS-4 had substantially more SNPs with small p-values in the GWAS analysis than did the HADS-D. Our results underline the benefits of using more homogeneous phenotypes in psychiatric genetic analyses. Homogeneity can be increased by focusing on core symptoms of disorders, thus reducing the noise in aggregate phenotypes caused by substantially different symptom profiles. PMID:25832296

  16. Classical and molecular genetic analyses of his-3 mutants of Neurospora crassa. II. Southern blot analyses and molecular mechanisms of mutagenicity.

    PubMed

    Dubins, J S; Overton, L K; Cobb, R R; de Serres, F J

    1989-11-01

    Previous studies (Overton et al., Mutation Res., 1989) on specific revertibility of 81 his-3 mutants have shown a correlation between complementation pattern and presumed genetic alteration similar to that shown by ad-3B mutants. In the present study, restriction enzyme analyses were used to further characterize the genetic alterations in individual his-3 mutants. The restriction fragment banding patterns of the majority of mutants were identical with that shown by wild-type 74-OR23-1A and were consistent with expectations based on previous data suggesting that they resulted from single base-pair alterations (Overton et al., Mutation Res., 1989). His-3 mutants with altered banding patterns were only found among those with polarized complementation patterns or noncomplementing mutants. One of the mutants with a polarized complementation pattern, 1-189-83, and another noncomplementing mutant, 1-189-85, are associated with genetic alterations proximal to the his-3 locus. In one other mutant, 1-226-565 (with a polarized complementation pattern), an insertion of approx. 2 kb has occurred in the proximal region of the his-3 locus. Two other mutants, 1-155-270 and 1-155-276 (both noncomplementing), contained a large insertion of approx. 12.8 kb in the proximal region of the his-3 locus. PMID:2530448

  17. Predictors of pneumococcal co-infection for patients with pandemic (H1N1) 2009.

    PubMed

    Masiá, Mar; Padilla, Sergio; Antequera, Pedro; Ramos, José Manuel; Ruiz, Montserrat; Gutiérrez, Félix

    2011-08-01

    We conducted a systematic investigation of pneumococcal co-infection in patients with a diagnosis of pandemic (H1N1) 2009 and any risk factor for complications or with severity criteria. We found 14% prevalence, with one third of patients having nonpneumonic infections. A severity assessment score >1 and high C-reactive protein levels were predictors of pneumococcal co-infection. PMID:21801627

  18. Co-infection of Plasmodium vivax Malaria and Cytomegalovirus in an Immunocompetent Neonate.

    PubMed

    Chandelia, Sudha; Jain, Sarika

    2014-12-01

    Co-infections when occur can pose substantial diagnostic and treatment challenges for clinicians. In this case report we describe a neonate with co infection of plasmodium vivax malaria with Cytomegalovirus and discuss whether it can be the result of reactivation of one by the other infection postnatally or if these infections can affect and facilitate the transplacental transmission of each other from the mother. PMID:25653999

  19. Phylogeographic analyses of submesophotic snappers Etelis coruscans and Etelis "marshi" (family Lutjanidae) reveal concordant genetic structure across the Hawaiian Archipelago.

    PubMed

    Andrews, Kimberly R; Moriwake, Virginia N; Wilcox, Christie; Grau, E Gordon; Kelley, Christopher; Pyle, Richard L; Bowen, Brian W

    2014-01-01

    The Hawaiian Archipelago has become a natural laboratory for understanding genetic connectivity in marine organisms as a result of the large number of population genetics studies that have been conducted across this island chain for a wide taxonomic range of organisms. However, population genetic studies have been conducted for only two species occurring in the mesophotic or submesophotic zones (30+m) in this archipelago. To gain a greater understanding of genetic connectivity in these deepwater habitats, we investigated the genetic structure of two submesophotic fish species (occurring ∼200-360 m) in this archipelago. We surveyed 16 locations across the archipelago for submesophotic snappers Etelis coruscans (N = 787) and E. "marshi" (formerly E. carbunculus; N = 770) with 436-490 bp of mtDNA cytochrome b and 10-11 microsatellite loci. Phylogeographic analyses reveal no geographic structuring of mtDNA lineages and recent coalescence times that are typical of shallow reef fauna. Population genetic analyses reveal no overall structure across most of the archipelago, a pattern also typical of dispersive shallow fishes. However some sites in the mid-archipelago (Raita Bank to French Frigate Shoals) had significant population differentiation. This pattern of no structure between ends of the Hawaiian range, and significant structure in the middle, was previously observed in a submesophotic snapper (Pristipomoides filamentosus) and a submesophotic grouper (Hyporthodus quernus). Three of these four species also have elevated genetic diversity in the mid-archipelago. Biophysical larval dispersal models from previous studies indicate that this elevated diversity may result from larval supplement from Johnston Atoll, ∼800 km southwest of Hawaii. In this case the boundaries of stocks for fishery management cannot be defined simply in terms of geography, and fishery management in Hawaii may need to incorporate external larval supply into management plans. PMID

  20. Host infection history modifies co-infection success of multiple parasite genotypes.

    PubMed

    Klemme, Ines; Louhi, Katja-Riikka; Karvonen, Anssi

    2016-03-01

    Co-infections by multiple parasite genotypes are common and have important implications for host-parasite ecology and evolution through within-host interactions. Typically, these infections take place sequentially, and therefore, the outcome of co-infection may be shaped by host immune responses triggered by previous infections. For example, in vertebrates, specific immune responses play a central role in protection against disease over the course of life, but co-infection research has mostly focused on previously uninfected individuals. Here, we investigated whether sequential exposure and activation of host resistance in rainbow trout Oncorhynchus mykiss affects infection success and interactions between co-infecting parasite genotypes of the trematode eye-fluke Diplostomum pseudospathaceum. In accordance with earlier results, we show that a simultaneous attack of two parasite genotypes facilitates parasite establishment in previously uninfected hosts. However, we find for the first time that this facilitation in co-infection is lost in hosts with prior infection. We conclude that vertebrate host infection history can affect the direction of within-host-parasite interactions. Our results may have significant implications for the evolution of co-infections and parasite transmission strategies. PMID:26589834

  1. Insights into human immunodeficiency virus-hepatitis B virus co-infection in India

    PubMed Central

    Chakravarty, Runu; Pal, Ananya

    2015-01-01

    Shared routes of transmission lead to frequent human immunodeficiency virus (HIV)-hepatitis B virus (HBV) co-infection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liver diseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV co-infection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome (genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study. PMID:26279986

  2. Analyses of genetic diversity in five Canadian dairy breeds using pedigree data.

    PubMed

    Melka, M G; Stachowicz, K; Miglior, F; Schenkel, F S

    2013-12-01

    The issue of loss of animal genetic diversity, worldwide in general and in Canada in particular, has become noteworthy. The objective of this study was to analyze the trend in within-breed genetic diversity and identify the major causes of loss of genetic diversity in five Canadian dairy breeds. Pedigrees were analyzed using the software EVA (evolutionary algorithm) and CFC (contribution, inbreeding, coancestry), and a FORTRAN package for pedigree analysis suited for large populations (PEDIG). The average rate of inbreeding in the last generation analyzed (2003 to 2007) was 0.93, 1.07, 1.26, 1.09 and 0.80% for Ayrshire, Brown Swiss, Canadienne, Guernsey and Milking Shorthorn, respectively, and the corresponding estimated effective population sizes were 54, 47, 40, 46 and 66, respectively. Based on coancestry coefficients, the estimated effective population sizes in the last generation were 62, 76, 43, 61 and 76, respectively. The estimated percentage of genetic diversity lost within each breed over the last four decades was 6, 7, 11, 8 and 5%, respectively. The relative proportion of genetic diversity lost due to random genetic drift in the five breeds ranged between 59.3% and 89.7%. The results indicate that each breed has lost genetic diversity over time and that the loss is gaining momentum due to increasing rates of inbreeding and reduced effective population sizes. Therefore, strategies to decrease rate of inbreeding and increase the effective population size are advised. PMID:24079800

  3. Functional connectivity analyses in imaging genetics: considerations on methods and data interpretation.

    PubMed

    Bedenbender, Johannes; Paulus, Frieder M; Krach, Sören; Pyka, Martin; Sommer, Jens; Krug, Axel; Witt, Stephanie H; Rietschel, Marcella; Laneri, Davide; Kircher, Tilo; Jansen, Andreas

    2011-01-01

    Functional magnetic resonance imaging (fMRI) can be combined with genotype assessment to identify brain systems that mediate genetic vulnerability to mental disorders ("imaging genetics"). A data analysis approach that is widely applied is "functional connectivity". In this approach, the temporal correlation between the fMRI signal from a pre-defined brain region (the so-called "seed point") and other brain voxels is determined. In this technical note, we show how the choice of freely selectable data analysis parameters strongly influences the assessment of the genetic modulation of connectivity features. In our data analysis we exemplarily focus on three methodological parameters: (i) seed voxel selection, (ii) noise reduction algorithms, and (iii) use of additional second level covariates. Our results show that even small variations in the implementation of a functional connectivity analysis can have an impact on the connectivity pattern that is as strong as the potential modulation by genetic allele variants. Some effects of genetic variation can only be found for one specific implementation of the connectivity analysis. A reoccurring difficulty in the field of psychiatric genetics is the non-replication of initially promising findings, partly caused by the small effects of single genes. The replication of imaging genetic results is therefore crucial for the long-term assessment of genetic effects on neural connectivity parameters. For a meaningful comparison of imaging genetics studies however, it is therefore necessary to provide more details on specific methodological parameters (e.g., seed voxel distribution) and to give information how robust effects are across the choice of methodological parameters. PMID:22220190

  4. Lack of Genetic Variation of Bursaphelenchus xylophilus in Portugal Revealed by RAPD-PCR Analyses.

    PubMed

    Vieira, Paulo; Burgermeister, Wolfgang; Mota, Manuel; Metge, Kai; Silva, Gonçalo

    2007-06-01

    Random Amplified Polymorphic DNA (RAPD-PCR) technique was used to assess the level of genetic variability and genetic relationships among 24 Portuguese isolates of pinewood nematode, Bursaphelenchus xylophilus. The isolates represent the main infested areas of Portugal. Two additional isolates of B. xylophilus representing North America and East Asia were included, and B. mucronatus was used as out-group. Twenty-eight random primers generated a total of 640 DNA fragments. The Nei and Li similarity index revealed a high genetic similarity among the Portuguese isolates (above 90%). Hierarchical cluster analysis was performed to illustrate the relatedness among the isolates. No indication for separate groups among the Portuguese isolates was obtained, and the low level of genetic diversity strongly suggests that they were dispersed recently from a single introduction. The lack of apparent relationship between the genetic and the geographic matrices of the Portuguese isolates limits the use of this technique for following recent pathways of distribution. Genetic distance of the Portuguese isolates towards an isolate from China was much lower as compared to an isolate from the USA. This confirmed previous results suggesting an East Asian origin of the Portuguese B. xylophilus. PMID:19259480

  5. Borrelia burgdorferi sensu lato and co-infections with Anaplasma phagocytophilum and Rickettsia spp. in Ixodes ricinus in Hamburg, Germany.

    PubMed

    May, K; Jordan, D; Fingerle, V; Strube, C

    2015-12-01

    To obtain initial data on Borrelia burgdorferi sensu lato (Spirochaetales: Spirochaetaceae) in Ixodes ricinus (Ixodida: Ixodidae) ticks in Hamburg, Germany, 1400 questing ticks were collected by flagging at 10 different public recreation areas in 2011 and analysed using probe-based quantitative real-time polymerase chain reaction. The overall rate of infection with B. burgdorferi s.l. was 34.1%; 30.0% of adults were infected (36.7% of females and 26.0% of males), as were 34.5% of nymphs. Significant differences in tick infection rates were observed between the spring and summer/autumn months, as well as among sampling locations. Borrelia genospecies identification by reverse line blotting was successful in 43.6% of positive tick samples. The most frequent genospecies was Borrelia garinii/Borrelia bavariensis, followed by Borrelia afzelii, Borrelia valaisiana, B. burgdorferi sensu stricto, Borrelia spielmanii, Borrelia bissettii and Borrelia lusitaniae. Based on previously published data, co-infection of Borrelia and Rickettsiales spp. was determined in 25.8% of ticks. Overall, 22.9% of ticks were co-infected with Rickettsia spp. (Rickettsiales: Rickettsiaceae), 1.7% with Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae), and 1.2% with both pathogens. Study results show a high prevalence of Borrelia-positive ticks in recreation areas in the northern German city of Hamburg and the potential health risk to humans in these areas should not be underestimated. PMID:26096626

  6. Staphylococcus aureus and Pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes.

    PubMed

    Limoli, D H; Yang, J; Khansaheb, M K; Helfman, B; Peng, L; Stecenko, A A; Goldberg, J B

    2016-06-01

    Cystic fibrosis-related diabetes (CFRD) patients suffer from accelerated rates of pulmonary decline compared to cystic fibrosis (CF) patients with normal glucose tolerance (NGT). However, the mechanisms underlying this difference are unknown. While CFRD is associated with increased respiratory infections, a link between infection and enhanced pulmonary dysfunction remains unclear. The development of glucose intolerance is spectral, resulting in impaired glucose tolerance (IGT) prior to the diagnosis of CFRD. Inclusion of IGT patients within the NGT group may diminish the ability to identify correlations with CFRD. With this in mind, this study aimed to determine if the association between CFRD and respiratory infections is correlated with pulmonary decline. Respiratory cultures from 234 CF patients with confirmed diagnosis of NGT or CFRD were analyzed to measure rates of infection, focusing on the two most prevalent bacteria in CF, Staphylococcus aureus and Pseudomonas aeruginosa. Infection status was correlated with pulmonary function and confounding clinical variables including age, gender, blood glucose levels, and CF transmembrane conductance regulator (CFTR) phenotype were considered in multivariate analyses. CFRD patients, particularly those with extremely high blood glucose levels, were more likely than NGT patients to be co-infected with S. aureus and P. aeruginosa, compared to infection with only one pathogen. Co-infection was associated with decreased lung function and increased frequency of pulmonary exacerbations, even after adjustment for confounding variables. Alterations in the microbial community composition, as opposed to the presence of a single pathogen, may account for greater pulmonary decline in CFRD patients. PMID:26993289

  7. MicroRNAs, Hepatitis C Virus, and HCV/HIV-1 Co-Infection: New Insights in Pathogenesis and Therapy

    PubMed Central

    Gupta, Archana; Swaminathan, Gokul; Martin-Garcia, Julio; Navas-Martin, Sonia

    2012-01-01

    MicroRNAs (miRNAs) can exert a profound effect on Hepatitis C virus (HCV) replication. The interaction of HCV with the highly liver-enriched miRNA, miR-122 represents one such unique example of viruses having evolved mechanism(s) to usurp the host miRNA machinery to support viral life cycle. Furthermore, HCV infection can also trigger changes in the cellular miRNA profile, which may ultimately contribute to the outcome of viral infection. Accumulating knowledge on HCV-host miRNA interactions has ultimately influenced the design of therapeutic interventions against chronic HCV infection. The importance of microRNA modulation in Human Immunodeficiency Virus (HIV-1) replication has been reported, albeit only in the context of HIV-1 mono-infection. The development of HCV infection is dramatically influenced during co-infection with HIV-1. Here, we review the current knowledge on miRNAs in HCV mono-infection. In addition, we discuss the potential role of some miRNAs, identified from the analyses of public data, in HCV/HIV-1 co-infection. PMID:23202492

  8. Common mental disorders in TB/HIV co-infected patients in Ethiopia

    PubMed Central

    2010-01-01

    Background- The relationship between TB/HIV co-infection and common mental disorders (CMD) has been scarcely investigated. In this study, we compared the occurrence of CMD in TB/HIV co-infected and non-co-infected HIV patients in Ethiopia. Methods- We conducted a cross sectional study in three hospitals in Ethiopia from February to April, 2009. The study population consisted of 155 TB/HIV co-infected and 465 non-co-infected HIV patients. CMD was assessed through face to face interviews by trained clinical nurses using the Kessler 10 scale. Several risk factors for CMD were assessed using a structured questionnaire. Results- TB/HIV co-infected patients had significantly (p = 0.001) greater risk of CMD (63.7%) than the non-co-infected patients (46.7%). When adjusted for the effect of potential confounding variables, the odds of having CMD for TB/HIV co-infected individuals was 1.7 times the odds for non-co-infected patients [OR = 1.7, (95%CI: 1.0, 2.9)]. Individuals who had no source of income [OR = 1.7, (95%CI: 1.1, 2.8)], and day labourers [OR = 2.4, 95%CI: 1.2, 5.1)] were more likely to have CMD as compared to individuals who had a source of income and government employees respectively. Patients who perceived stigma [OR = 2.2, 95%CI: 1.5, 3.2)] and who rate their general health as "poor" [OR = 10.0, 95%CI: 2.8, 35.1)] had significantly greater risk of CMD than individual who did not perceive stigma or who perceived their general health to be "good". Conclusion- TB/HIV control programs should develop guidelines to screen and treat CMD among TB/HIV co-infected patients. Screening programs should focus on individuals with no source of income, jobless people and day labourers. PMID:20618942

  9. Human Helminth Co-Infection: Analysis of Spatial Patterns and Risk Factors in a Brazilian Community

    PubMed Central

    Pullan, Rachel L.; Bethony, Jeffrey M.; Geiger, Stefan M.; Cundill, Bonnie; Correa-Oliveira, Rodrigo; Quinnell, Rupert J.; Brooker, Simon

    2008-01-01

    Background Individuals living in areas endemic for helminths are commonly infected with multiple species. Despite increasing emphasis given to the potential health impacts of polyparasitism, few studies have investigated the relative importance of household and environmental factors on the risk of helminth co-infection. Here, we present an investigation of exposure-related risk factors as sources of heterogeneity in the distribution of co-infection with Necator americanus and Schistosoma mansoni in a region of southeastern Brazil. Methodology Cross-sectional parasitological and socio-economic data from a community-based household survey were combined with remotely sensed environmental data using a geographical information system. Geo-statistical methods were used to explore patterns of mono- and co-infection with N. americanus and S. mansoni in the region. Bayesian hierarchical models were then developed to identify risk factors for mono- and co-infection in relation to community-based survey data to assess their roles in explaining observed heterogeneity in mono and co-infection with these two helminth species. Principal Findings The majority of individuals had N. americanus (71.1%) and/or S. mansoni (50.3%) infection; 41.0% of individuals were co-infected with both helminths. Prevalence of co-infection with these two species varied substantially across the study area, and there was strong evidence of household clustering. Hierarchical multinomial models demonstrated that relative socio-economic status, household crowding, living in the eastern watershed and high Normalized Difference Vegetation Index (NDVI) were significantly associated with N. americanus and S. mansoni co-infection. These risk factors could, however, only account for an estimated 32% of variability between households. Conclusions Our results demonstrate that variability in risk of N. americanus and S. mansoni co-infection between households cannot be entirely explained by exposure-related risk

  10. BAYESIAN METHODS FOR GENETIC ASSOCIATION ANALYSIS WITH HETEROGENEOUS SUBGROUPS: FROM META-ANALYSES TO GENE-ENVIRONMENT INTERACTIONS

    PubMed Central

    Wen, Xiaoquan; Stephens, Matthew

    2015-01-01

    Genetic association analyses often involve data from multiple potentially-heterogeneous subgroups. The expected amount of heterogeneity can vary from modest (e.g. a typical meta-analysis), to large (e.g. a strong gene-environment interaction). However, existing statistical tools are limited in their ability to address such heterogeneity. Indeed, most genetic association meta-analyses use a “fixed effects” analysis, which assumes no heterogeneity. Here we develop and apply Bayesian association methods to address this problem. These methods are easy to apply (in the simplest case, requiring only a point estimate for the genetic effect, and its standard error, from each subgroup), and effectively include standard frequentist meta-analysis methods, including the usual “fixed effects” analysis, as special cases. We apply these tools to two large genetic association studies: one a meta-analysis of genome-wide association studies from the Global Lipids consortium, and the second a cross-population analysis for expression quantitative trait loci (eQTLs). In the Global Lipids data we find, perhaps surprisingly, that effects are generally quite homogeneous across studies. In the eQTL study we find that eQTLs are generally shared among different continental groups, and discuss consequences of this for study design. PMID:26413181

  11. A severe case of co-infection with Enterovirus 71 and vaccine-derived Poliovirus type II.

    PubMed

    Ma, Shaohui; Du, Zengqing; Feng, Min; Che, Yanchun; Li, Qihan

    2015-11-01

    Enterovirus 71 (EV71) is often identified as the primary pathogen that directly leads to severe cases of HFMD, whereas the association between other enteroviruses and EV71 infection remains largely unclear. Here we report a rare case of a 5-year-old boy co-infected with EV71 and vaccine-derived Poliovirus (VDPV) type II, which were identified based on PCR and sequence analysis results and clinical symptoms and were characterized on CT. We determined that the EV71 strain belongs to the C4 subtype, and the VDPV II strain was closely genetically related to the reference Sabin type II strain. This report may improved our understanding of the clinical significance of the associations between clinical signs and the infectious properties of the involved pathogens. PMID:26361010

  12. Genetic heterogeneity in psoriasis vulgaris based on linkage analyses of a large family material

    SciTech Connect

    Wahlstroem, J.; Swanbeck, G.; Inerot, A.

    1994-09-01

    Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscore over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.

  13. Viral hepatitis and human immunodeficiency virus co-infections in Asia

    PubMed Central

    Utsumi, Takako; Lusida, Maria I

    2015-01-01

    Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) affect many people in Asian countries, although there are geographic differences. Both HBV and HIV (HBV/HIV) and HCV/HIV co-infections are highly prevalent in Asia. Hetero- and homosexual, injection drug use, and geographic area are strong predictors of HBV, HCV, and HIV serostatus. In HBV endemic regions, the prevalence and genotype distribution of HBV/HIV co-infection is almost comparable with that in the general population. In Japan, where HBV has low endemicity, the prevalence of HBV/HIV co-infection is approximately 10-fold higher than that in the general population, and HBV Ae is the most common subgenotype among HIV infected individuals. Highly active antiretroviral therapy (HAART) is an effective treatment for HIV/Acquired Immune Deficiency Syndrome. Lamivudine, a component of HAART, is an effective treatment for HBV, HIV, and HBV/HIV co-infection; however, cost, emerging drug resistance, antiretroviral-associated liver toxicity and liver-related morbidity due to HCV progression are particular concerns. HCV/HIV co-infection may accelerate the clinical progression of both HCV and HIV. The high prevalence of HBV/HIV and HCV/HIV co-infections in Asia underscores the need to improve prevention and control measures, as fewer evidence-based prevention strategies are available (compared with Western countries). In this review, the most recent publications on the prevalence of HBV/HIV and HCV/HIV co-infections and related issues, such as therapy and problems in Asia, are updated and summarized. PMID:25964874

  14. Clonorchis sinensis Co-infection Could Affect the Disease State and Treatment Response of HBV Patients

    PubMed Central

    Huang, Yan; Chen, Tingjin; Kong, Xiangzhan; Sun, Hengchang; Yu, Xinbing; Xu, Jin

    2016-01-01

    Background Clonorchis sinensis (C. sinensis) is considered to be an important parasitic zoonosis because it infects approximately 35 million people, while approximately 15 million were distributed in China. Hepatitis B virus (HBV) infection is a major public health issue. Two types of pathogens have the potential to cause human liver disease and eventually hepatocellular carcinoma. Concurrent infection with HBV and C. sinensis is often observed in some areas where C. sinensis is endemic. However, whether C. sinensis could impact HBV infection or vice versa remains unknown. Principal Findings Co-infection with C. sinensis and HBV develops predominantly in males. Co-infected C. sinensis and HBV patients presented weaker liver function and higher HBV DNA titers. Combination treatment with antiviral and anti-C. sinensis drugs in co-infected patients could contribute to a reduction in viral load and help with liver function recovery. Excretory-secretory products (ESPs) may, in some ways, increase HBV viral replication in vitro. A mixture of ESP and HBV positive sera could induce peripheral blood mononuclear cells (PBMCs) to produce higher level of Th2 cytokines including IL-4, IL-6 and IL-10 compared to HBV alone, it seems that due to presence of ESP, the cytokine production shift towards Th2. C. sinensis/HBV co-infected patients showed higher serum IL-6 and IL-10 levels and lower serum IFN-γ levels. Conclusions/Significance Patients with concomitant C. sinensis and HBV infection presented weaker liver function and higher HBV DNA copies. In co-infected patients, the efficacy of anti-viral treatment was better in patients who were prescribed with entecavir and praziquantel than entecavir alone. One possible reason for the weaker response to antiviral therapies in co-infected patients was the shift in cytokine production from Th1 to Th2 that may inhibit viral clearance. C. sinensis/HBV co-infection could exacerbate the imbalance of Th1/Th2 cytokine. PMID:27348302

  15. ToRCH "co-infections" are associated with increased risk of abortion in pregnant women.

    PubMed

    Rasti, Sima; Ghasemi, Fatemeh Sadat; Abdoli, Amir; Piroozmand, Ahmad; Mousavi, Seyed Gholam Abbas; Fakhrie-Kashan, Zohreh

    2016-03-01

    ToRCH infections (toxoplasmosis, rubella, cytomegalovirus and Herpes simplex virus) have long been known to be associated with bad obstetric outcomes. However, little information is available about the impact of ToRCH co-infections on the outcome of pregnancy. Hence, we tested the IgG and IgM antibodies to Toxoplasma gondii, Rubella, Cytomegalovirus and Herpes Simplex Virus among 81 pregnant women with abortion (case group) and 98 pregnant women with normal delivery (control group). In the single-infection model, only CMV-IgM seropositivity was significantly increased in case than control group (25.9% in case and 12.2 % in control, OR = 2.5, P = 0.019). In the co-infection model, 14 patterns were recognized, but two patterns were significantly increased in the case than the control group. Co-infection of T. gondii IgG + CMV IgM was 9.1-fold increased in the case than the control group (8.6% in the case and 1% in control, OR = 9.1; P = 0.024). Also, co-infection of T. gondii IgG + HSV IgG + CMV IgM was 7.7-fold increased in case than the control group (7.4% in case and 1 % in control, OR = 7.7; P = 0.04). Although the OR of other co-infections was higher in the case than the control group, the difference was not statistically significant. These findings indicate that ToRCH co-infections are associated with increased risk of abortion than single infection. Hence, the rates of co-infections should be considered in prenatal screening of ToRCH infections. PMID:26499091

  16. Genetic and genomic analyses as a basis for new diagnostic nosologies

    PubMed Central

    Gershon, Elliot S.; Grennan, Kay S.

    2015-01-01

    For schizophrenia, bipolar disorder, and autism, clinical descriptions are precise and reliable, but there is great overlap among diagnoses in associated genetic polymorphisms and rare variants, treatment response, and other phenomenological findings such as brain imaging. It is widely hoped that new diagnostic categories can be developed which are more precise and predictive of important features of illness, particularly response to pharmacological agents. It is the intent of this paper to describe the diagnostic implications of some current genetic findings, and to describe how the genetic associations with diagnosis may be teased apart into new associations with biologically coherent diagnostic entities and scales, based on the various functional aspects of the associated genes and functional genomic data. PMID:25987865

  17. Genetics of Central Valley O. mykiss populations: drainage and watershed scale analyses

    USGS Publications Warehouse

    Nielsen, Jennifer L.; Pavey, Scott A.; Wiacek, Talia; Williams, Ian S.

    2005-01-01

    Genetic variation at 11 microsatellite loci described population genetic structure for Oncorhynchus mykiss in the Central Valley, California. Spatial and temporal variation was examined as well as relationships between hatchery and putative natural spawning anadromous stocks. Genetic diversity was analyzed at two distinct spatial scales: fine-scale within drainage for five populations on Clear Creek; between and among drainage diversity for 23 populations. Significant regional spatial structure was apparent, both within Clear Creek and among rainbow trout populations throughout the Central Valley. Significant differences in allelic frequencies were found among most river or drainage systems. Less than 1% of the molecular variance could be attributed to differences found between drainages. Hatchery populations were shown to carry similar genetic diversity to geographically proximate wild populations. Central Valley M = 0.626 (below the M < 0.68 threshold) supported recent population reductions within the Central Valley. However, average estimated effective population size was relatively high (Ne = 5066). Significant allelic differences were found in rainbow trout collected above and below impassable dams on the American, Yuba, Stanislaus and Tuolumne rivers. Rainbow trout sampled in Spring Creek were extremely bottlenecked with allelic variation at only two loci and an estimated effective population size of 62, suggesting some local freshwater O. mykiss stocks may be declining rapidly. These data support significant genetic population structure for steelhead and rainbow trout populations within the Central Valley across multiple scales. Careful consideration of this genetic diversity and its distribution across the landscape should be part of future conservation and restoration efforts. 

  18. Marshes as “Mountain Tops”: Genetic Analyses of the Critically Endangered São Paulo Marsh Antwren (Aves: Thamnophilidae)

    PubMed Central

    de Camargo, Crisley; Gibbs, H. Lisle; Costa, Mariellen C.; Del-Rio, Glaucia; Silveira, Luís F.

    2015-01-01

    Small populations of endangered species can be impacted by genetic processes such as drift and inbreeding that reduce population viability. As such, conservation genetic analyses that assess population levels of genetic variation and levels of gene flow can provide important information for managing threatened species. The São Paulo Marsh Antwren (Formicivora paludicola) is a recently-described and critically endangered bird from São Paulo State (Brazil) whose total estimated population is around 250–300 individuals, distributed in only 15 isolated marshes around São Paulo metropolitan region. We used microsatellite DNA markers to estimate the population genetic characteristics of the three largest remaining populations of this species all within 60 km of each other. We detected a high and significant genetic structure between all populations (overall FST = 0.103) which is comparable to the highest levels of differentiation ever documented for birds, (e.g., endangered birds found in isolated populations on the tops of African mountains), but also evidence for first-generation immigrants, likely from small local unsampled populations. Effective population sizes were small (between 28.8–99.9 individuals) yet there are high levels of genetic variability within populations and no evidence for inbreeding. Conservation implications of this work are that the high levels of genetic structure suggests that translocations between populations need to be carefully considered in light of possible local adaptation and that remaining populations of these birds should be managed as conservation units that contain both main populations studied here but also small outlying populations which may be a source of immigrants. PMID:26447791

  19. Marshes as "Mountain Tops": Genetic Analyses of the Critically Endangered São Paulo Marsh Antwren (Aves: Thamnophilidae).

    PubMed

    de Camargo, Crisley; Gibbs, H Lisle; Costa, Mariellen C; Del-Rio, Glaucia; Silveira, Luís F; Wasko, Adriane P; Francisco, Mercival R

    2015-01-01

    Small populations of endangered species can be impacted by genetic processes such as drift and inbreeding that reduce population viability. As such, conservation genetic analyses that assess population levels of genetic variation and levels of gene flow can provide important information for managing threatened species. The São Paulo Marsh Antwren (Formicivora paludicola) is a recently-described and critically endangered bird from São Paulo State (Brazil) whose total estimated population is around 250-300 individuals, distributed in only 15 isolated marshes around São Paulo metropolitan region. We used microsatellite DNA markers to estimate the population genetic characteristics of the three largest remaining populations of this species all within 60 km of each other. We detected a high and significant genetic structure between all populations (overall FST = 0.103) which is comparable to the highest levels of differentiation ever documented for birds, (e.g., endangered birds found in isolated populations on the tops of African mountains), but also evidence for first-generation immigrants, likely from small local unsampled populations. Effective population sizes were small (between 28.8-99.9 individuals) yet there are high levels of genetic variability within populations and no evidence for inbreeding. Conservation implications of this work are that the high levels of genetic structure suggests that translocations between populations need to be carefully considered in light of possible local adaptation and that remaining populations of these birds should be managed as conservation units that contain both main populations studied here but also small outlying populations which may be a source of immigrants. PMID:26447791

  20. Simulation, prediction, and genetic analyses of daily methane emissions in dairy cattle.

    PubMed

    Yin, T; Pinent, T; Brügemann, K; Simianer, H; König, S

    2015-08-01

    This study presents an approach combining phenotypes from novel traits, deterministic equations from cattle nutrition, and stochastic simulation techniques from animal breeding to generate test-day methane emissions (MEm) of dairy cows. Data included test-day production traits (milk yield, fat percentage, protein percentage, milk urea nitrogen), conformation traits (wither height, hip width, body condition score), female fertility traits (days open, calving interval, stillbirth), and health traits (clinical mastitis) from 961 first lactation Brown Swiss cows kept on 41 low-input farms in Switzerland. Test-day MEm were predicted based on the traits from the current data set and 2 deterministic prediction equations, resulting in the traits labeled MEm1 and MEm2. Stochastic simulations were used to assign individual concentrate intake in dependency of farm-type specifications (requirement when calculating MEm2). Genetic parameters for MEm1 and MEm2 were estimated using random regression models. Predicted MEm had moderate heritabilities over lactation and ranged from 0.15 to 0.37, with highest heritabilities around DIM 100. Genetic correlations between MEm1 and MEm2 ranged between 0.91 and 0.94. Antagonistic genetic correlations in the range from 0.70 to 0.92 were found for the associations between MEm2 and milk yield. Genetic correlations between MEm with days open and with calving interval increased from 0.10 at the beginning to 0.90 at the end of lactation. Genetic relationships between MEm2 and stillbirth were negative (0 to -0.24) from the beginning to the peak phase of lactation. Positive genetic relationships in the range from 0.02 to 0.49 were found between MEm2 with clinical mastitis. Interpretation of genetic (co)variance components should also consider the limitations when using data generated by prediction equations. Prediction functions only describe that part of MEm which is dependent on the factors and effects included in the function. With high

  1. Preliminary genetic analyses of important musculoskeletal conditions of Thoroughbred racehorses in Hong Kong☆

    PubMed Central

    Welsh, Claire E.; Lewis, Thomas W.; Blott, Sarah C.; Mellor, Dominic J.; Lam, Kenneth H.; Stewart, Brian D.; Parkin, Timothy D.H.

    2013-01-01

    A retrospective cohort study of important musculoskeletal conditions of Thoroughbred racehorses was conducted using health records generated over a 15 year period (n = 5062, 1296 sires). The prevalence of each condition in the study population was: fracture, 13%; osteoarthritis, 10%; suspensory ligament injury, 10%; and tendon injury, 19%. Linear and logistic sire and animal regression models were built to describe the binary occurrence of these musculoskeletal conditions, and to evaluate the significance of possible environmental risk factors. The heritability of each condition was estimated using residual maximum likelihood (REML). Bivariate mixed models were used to generate estimates of genetic correlations between each pair of conditions. Heritability estimates of fracture, osteoarthritis, suspensory ligament and tendon injury were small to moderate (range: 0.01–0.20). Fracture was found to be positively genetically correlated with both osteoarthritis and suspensory ligament injury. These results suggest that there is a significant genetic component involved in the risk of the studied conditions. Due to positive genetic correlations, a reduction in prevalence of one of the correlated conditions may effect a reduction in risk of the other condition. PMID:23746478

  2. Genetic and Environmental Influences on Conduct Disorder: Symptom, Domain and Full-Scale Analyses

    ERIC Educational Resources Information Center

    Gelhorn, Heather L.; Stallings, Michael C.; Young, Susan E.; Corley, Robin P.; Rhee, Soo Hyun; Hewitt, John K.

    2005-01-01

    Background: We used variable threshold models which accounted for age and gender differences to investigate the genetic and environmental influences on DSM-IV conduct disorder (CD) at the level of symptoms, aggressive versus non-aggressive domains, and full-scale. Method: A community sample of 1100 twin pairs (age 11-18) was interviewed using the…

  3. The application and performance of single nucleotide polymorphism markers for population genetic analyses of Lepidoptera

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single nucleotide polymorphisms (SNPs) are nucleotide substitution mutations that tend to be at high densities within eukaryotic genomes. The development of assays that detect allelic variation at SNP loci is attractive for genome mapping, population genetics, and phylogeographic applications. A p...

  4. High acceptance of an early dyslexia screening test involving genetic analyses in Germany.

    PubMed

    Wilcke, Arndt; Müller, Bent; Schaadt, Gesa; Kirsten, Holger; Boltze, Johannes

    2016-02-01

    Dyslexia is a developmental disorder characterized by severe problems in the acquisition of reading and writing skills. It has a strong neurobiological basis. Genetic influence is estimated at 50-70%. One of the central problems with dyslexia is its late diagnosis, normally not before the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics. Our aim was to determine the acceptance of such a future test among parents. We conducted a representative survey in Germany with 1000 parents of children aged 3-7 years, with and without experience of dyslexia. 88.7% of the parents supported the introduction of an early test for dyslexia based on EEG and genetics; 82.8% would have their own children tested, and 57.9% were willing to pay for the test if health insurance did not cover the costs. Test acceptance was significantly higher if parents had prior experience with dyslexia. The perceived benefits of such a test were early recognition and remediation and, preventing deficits. Concerns regarded the precision of the test, its potentially stigmatizing effect and its costs. The high overall support for the test leads to the conclusion that parents would accept a test for dyslexia based on EEG and genetics. PMID:26036858

  5. Development and genetic analyses of early season cold tolerant sorghum germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sorghum is one of the most versatile & resilient crop species with vast genetic diversity. To date sorghum provides commodity products for grain, forage & bioenergy industries. It is also well-known for excellent drought and high temperature tolerance; and is considered as water and climate susta...

  6. Genetic polymorphism analyses of 30 InDels in Chinese Xibe ethnic group and its population genetic differentiations with other groups

    PubMed Central

    Meng, Hao-Tian; Zhang, Yu-Dang; Shen, Chun-Mei; Yuan, Guo-Lian; Yang, Chun-Hua; Jin, Rui; Yan, Jiang-Wei; Wang, Hong-Dan; Liu, Wen-Juan; Jing, Hang; Zhu, Bo-Feng

    2015-01-01

    In the present study, we obtained population genetic data and forensic parameters of 30 InDel loci in Chinese Xibe ethnic group from northwestern China and studied the genetic relationships between the studied Xibe group and other reference groups. The observed heterozygosities ranged from 0.1704 at HLD118 locus to 0.5247 at HLD92 locus while the expected heterozygosities ranged from 0.1559 at HLD118 locus to 0.4997 at HLD101 locus. The cumulative power of exclusion and total probability of discrimination power in the studied group were 0.9867 and 0.9999999999902 for the 30 loci, respectively. Analyses of structure, PCA, interpopulation differentiations and phylogenetic tree revealed that the Xibe group had close genetic relationships with South Korean, Beijing Han and Guangdong Han groups. The results indicated that these 30 loci should only be used as a complement for autosomal STRs in paternity cases but could provide an acceptable level of discrimination in forensic identification cases in the studied Xibe group. Further studies should be conducted for better understanding of the Xibe genetic background. PMID:25651970

  7. Genetic polymorphism analyses of 30 InDels in Chinese Xibe ethnic group and its population genetic differentiations with other groups.

    PubMed

    Meng, Hao-Tian; Zhang, Yu-Dang; Shen, Chun-Mei; Yuan, Guo-Lian; Yang, Chun-Hua; Jin, Rui; Yan, Jiang-Wei; Wang, Hong-Dan; Liu, Wen-Juan; Jing, Hang; Zhu, Bo-Feng

    2015-01-01

    In the present study, we obtained population genetic data and forensic parameters of 30 InDel loci in Chinese Xibe ethnic group from northwestern China and studied the genetic relationships between the studied Xibe group and other reference groups. The observed heterozygosities ranged from 0.1704 at HLD118 locus to 0.5247 at HLD92 locus while the expected heterozygosities ranged from 0.1559 at HLD118 locus to 0.4997 at HLD101 locus. The cumulative power of exclusion and total probability of discrimination power in the studied group were 0.9867 and 0.9999999999902 for the 30 loci, respectively. Analyses of structure, PCA, interpopulation differentiations and phylogenetic tree revealed that the Xibe group had close genetic relationships with South Korean, Beijing Han and Guangdong Han groups. The results indicated that these 30 loci should only be used as a complement for autosomal STRs in paternity cases but could provide an acceptable level of discrimination in forensic identification cases in the studied Xibe group. Further studies should be conducted for better understanding of the Xibe genetic background. PMID:25651970

  8. Epidemiological and clinical correlates of malaria-helminth co-infections in southern Ethiopia

    PubMed Central

    2013-01-01

    Background In many areas of the world, including Ethiopia, malaria and helminths are co-endemic, therefore, co-infections are common. However, little is known how concurrent infections affect the epidemiology and/or pathogenesis of each other. Therefore, this study was conducted to assess the effects of intestinal helminth infections on the epidemiology and clinical patterns of malaria in southern Ethiopia where both infections are prevalent. Methods A cross-sectional study was conducted in 2006 at Wondo Genet Health Center and Bussa Clinic, southern Ethiopia. Consecutive blood film positive malaria patients (N=230) and malaria negative asymptomatic individuals (N=233) were recruited. Malaria parasite detection and quantification was diagnosed using Giemsa-stained thick and thin blood films, respectively. Helminths were detected using direct microscopy and formol-ether concentration techniques. Coarse quantification of helminths ova was made using Kato Katz method. Results The over all magnitude of intestinal parasitic infection was high irrespective of malaria infection (67% among malaria positive patients versus 53.1% among malaria non-infected asymptomatic individuals). Trichuris trichiura infection was associated with increased malaria prevalence while increased worm burden of helminths as expressed by egg intensity was associated with increased malaria parasitaemia which could be a potential factor for development of severe malarial infection with the course of the disease. Majority (77%) of the subjects had multiple helminths infection. T. trichiura, Ascaris lumbricoides, Schistosoma mansoni, and hookworm infestation accounted for 64.5, 57.7 %, 28.4%, and 12.2% of the infections, respectively. Conclusions Populations in malaria-endemic areas of southern Ethiopia are multi-parasitized with up to four helminths. Mass deworming may be a simple practical approach in endemic areas in reducing the risk of severe malarial attack particularly for those at high risk

  9. HBV and HIV co-infection: Impact on liver pathobiology and therapeutic approaches

    PubMed Central

    Parvez, Mohammad Khalid

    2015-01-01

    The consequences of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection on progression of severe liver diseases is a serious public health issue, worldwide. In the co-infection cases, about 90% of HIV-infected population is seropositive for HBV where approximately 5%-40% individuals are chronically infected. In HIV co-infected individuals, liver-related mortality is estimated over 17 times higher than those with HBV mono-infection. The spectrum of HIV-induced liver diseases includes hepatitis, steatohepatitis, endothelialitis, necrosis, granulomatosis, cirrhosis and carcinoma. Moreover, HIV co-infection significantly alters the natural history of hepatitis B, and therefore complicates the disease management. Though several studies have demonstrated impact of HIV proteins on hepatocyte biology, only a few data is available on interactions between HBV and HIV proteins. Thus, the clinical spectrum as well as the complexity of the co-infection offers challenging fronts to study the underlying molecular mechanisms, and to design effective therapeutic strategies. PMID:25625003

  10. Interaction between unrelated viruses during in vivo co-infection to limit pathology and immunity.

    PubMed

    McAfee, Megan S; Huynh, Trung P; Johnson, John L; Jacobs, Bertram L; Blattman, Joseph N

    2015-10-01

    Great progress has been made in understanding immunity to viral infection. However, infection can occur in the context of co-infection by unrelated pathogens that modulate immune responses and/or disease. We have studied immunity and disease during co-infection with two unrelated viruses: Ectromelia virus (ECTV) and Lymphocytic Choriomeningitis virus (LCMV). ECTV infection can be a lethal in mice due in part to the blockade of Type I Interferons (IFN-I). We show that ECTV/LCMV co-infection results in decreased ECTV viral load and amelioration of ECTV-induced disease, likely due to IFN-I induction by LCMV, as rescue is not observed in IFN-I receptor deficient mice. However, immune responses to LCMV in ECTV co-infected mice were also lower compared to mice infected with LCMV alone and potentially biased toward effector-memory cell generation. Thus, we provide evidence for bi-directional effects of viral co-infection that modulate disease and immunity. PMID:26099694

  11. Distribution, diversity and drivers of blood-borne parasite co-infections in Alaskan bird populations.

    PubMed

    Oakgrove, Khouanchy S; Harrigan, Ryan J; Loiseau, Claire; Guers, Sue; Seppi, Bruce; Sehgal, Ravinder N M

    2014-09-01

    Avian species are commonly infected by multiple parasites, however few studies have investigated the environmental determinants of the prevalence of co-infection over a large scale. Here we believe that we report the first, detailed ecological study of the prevalence, diversity and co-infections of four avian blood-borne parasite genera: Plasmodium spp., Haemoproteus spp., Leucocytozoon spp. and Trypanosoma spp. We collected blood samples from 47 resident and migratory bird species across a latitudinal gradient in Alaska. From the patterns observed at collection sites, random forest models were used to provide evidence of associations between bioclimatic conditions and the prevalence of parasite co-infection distribution. Molecular screening revealed a higher prevalence of haematozoa (53%) in Alaska than previously reported. Leucocytozoons had the highest diversity, prevalence and prevalence of co-infection. Leucocytozoon prevalence (35%) positively correlated with Trypanosoma prevalence (11%), negatively correlated with Haemoproteus prevalence (14%) and had no correlation with Plasmodium prevalence (7%). We found temperature, precipitation and tree cover to be the primary environmental drivers that show a relationship with the prevalence of co-infection. The results provide insight into the impacts of bioclimatic drivers on parasite ecology and intra-host interactions, and have implications for the study of infectious diseases in rapidly changing environments. PMID:25014331

  12. Triple NF-kB binding sites and LTR sequence similarities in HIV-1C isolates irrespective of helminth co-infection

    PubMed Central

    2014-01-01

    Background Helminth infections as well as structural alternations in the long-terminal repeat (LTR) regions of HIV-1 are known to contribute to elevated HIV RNA level and enhance HIV-1 diseases progression. However, the impact of helminths infections on the occurrences of triple NF-κB and genetic variability in LTR region of HIV-1C isolates is not known. We aimed to examine the presence of genetic variability in the LTR region of HIV-1C isolates during chronic HIV-helminth co-infection. Methods HIV-1C infected Ethiopians with (n = 22) and without (n = 20) helminth infection were included. The LTR region of HIV was amplified and sequenced. Sequences were aligned with reference set from the Los Alamos HIV database. Phylogenetic analysis and frequency of polymorphic changes was performed by the neighbour-joining method using Geneious Basic software. Results All LTR sequences from patients with or without of helminth co-infection clustered with HIV-1 subtype C with two distinct subclusters (C and C’). The enhancer element was found to have three copies of 10-base pair binding sites for NF-κBs which is an evidence for predominance of triple NF-κB sites (94%) in HIV-1C isolates irrespective of helminths co-infection and subclusters. Moreover, irrespective of helminth co-infection and C/C’ subclusters high sequences similarity in LTR was observed. There was no significant difference in plasma HIV RNA level between HIV-1 C and C’ subclusters. Conclusions Despite the small sample size, the predominance of triple NF-κB binding sites and high sequence similarities in LTR region irrespective of helminths infection suggest the natural occurrence of the three NF-κB binding sites in HIV-1C isolates without the influence of secondary infection. Thus, the higher HIV-1C viraemia in helminth co-infected individuals is more likely a result of immune activation rather than LTR sequence variation. Moreover, the lack of significant difference in plasma HIV RNA level

  13. The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits.

    PubMed

    Lusis, Aldons J; Seldin, Marcus M; Allayee, Hooman; Bennett, Brian J; Civelek, Mete; Davis, Richard C; Eskin, Eleazar; Farber, Charles R; Hui, Simon; Mehrabian, Margarete; Norheim, Frode; Pan, Calvin; Parks, Brian; Rau, Christoph D; Smith, Desmond J; Vallim, Thomas; Wang, Yibin; Wang, Jessica

    2016-06-01

    The Hybrid Mouse Diversity Panel (HMDP) is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits. While not nearly as powerful for mapping genetic loci contributing to the traits as human genome-wide association studies, it has some important advantages. First, environmental factors can be controlled. Second, relevant tissues are accessible for global molecular phenotyping. Finally, because inbred strains are renewable, results from separate studies can be integrated. Thus far, the HMDP has been studied for traits relevant to obesity, diabetes, atherosclerosis, osteoporosis, heart failure, immune regulation, fatty liver disease, and host-gut microbiota interactions. High-throughput technologies have been used to examine the genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes of the mice under various environmental conditions. All of the published data are available and can be readily used to formulate hypotheses about genes, pathways and interactions. PMID:27099397

  14. Developing genetic tools to exploit Chaetomium thermophilum for biochemical analyses of eukaryotic macromolecular assemblies

    PubMed Central

    Kellner, Nikola; Schwarz, Johannes; Sturm, Miriam; Fernandez-Martinez, Javier; Griesel, Sabine; Zhang, Wenzhu; Chait, Brian T.; Rout, Michael P.; Kück, Ulrich; Hurt, Ed

    2016-01-01

    We describe a method to genetically manipulate Chaetomium thermophilum, a eukaryotic thermophile, along with various biochemical applications. The transformation method depends on a thermostable endogenous selection marker operating at high temperatures combined with chromosomal integration of target genes. Our technique allows exploiting eukaryotic thermophiles as source for purifying thermostable native macromolecular complexes with an emphasis on the nuclear pore complex, holding great potential for applications in basic science and biotechnology. PMID:26864114

  15. Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia

    PubMed Central

    Khaw, Yam Sim; Chan, Yoke Fun; Jafar, Faizatul Lela; Othman, Norlijah; Chee, Hui Yee

    2016-01-01

    Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5′ and 3′ non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63–81% among themselves and 63–96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection. PMID:27199901

  16. The relationship between schizophrenia and rheumatoid arthritis revisited: Genetic and epidemiological analyses

    PubMed Central

    Breen, Gerome; Farmer, Anne; McGuffin, Peter; Lewis, Cathryn M

    2015-01-01

    Epidemiological studies are inconsistent on the relationship between schizophrenia (SCZ) and rheumatoid arthritis (RA). Several studies have shown that SCZ has a protective effect on RA, with RA occurring less frequently in SCZ cases than would be expected by chance, whilst other studies have failed to replicate this. We sought to test the hypothesis that this effect is due to a protective effect of SCZ risk alleles on RA onset. We first reviewed the literature on the comorbidity of RA and SCZ and performed a meta‐analysis. We then used polygenic risk scoring in an RA case control study in order to investigate the contribution of SCZ risk alleles to RA risk. Meta‐analysis across studies over the past half‐century showed that prevalence of RA in SCZ cases was significantly reduced (OR = 0.48, 95% CI: 0.34–0.67, p  < 0.0001). The relationship between SCZ genetic risk and RA status was weak. Polygenic risk of SCZ explained a small (0.1%) and non‐significant (p = 0.085) proportion of variance in RA case control status. This relationship was nominally positive, with RA cases carrying more SCZ risk alleles than controls. The current findings do not support the assertion that the relationship between RA and SCZ is explained by genetic factors, which appear to have little or no effect. The protective effect of SCZ on RA may be due to environmental factors, such as an anti‐inflammatory effect of anti‐psychotic medication or merely due to confounding limitations in study designs. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc. PMID:25656077

  17. Development of microsatellites for population genetic analyses of Tabanus nigrovittatus (Diptera: Tabanidae).

    PubMed

    Husseneder, Claudia; Delatte, Jennifer R; Krumholt, Jeremy; Foil, Lane D

    2014-01-01

    The greenhead horse fly, Tabanus nigrovittatus Macquart (Diptera: Tabanidae), is frequently found in coastal marshes of the Eastern United States. The females are autogenous (i.e., able to develop eggs without a bloodmeal),but they become a considerable pest to both humans and animals when they pursue a source of blood protein to produce additional eggs. In this study, we identified microsatellite markers to provide first insight into the population genetic structure of this notorious pest species. Because no prior genomic information was available for T. nigrovittatus, we used direct shotgun pyrosequencing technology to characterize microsatellite loci. Approximately 10% of the 105,634 short sequence reads generated from random genome sampling contained microsatellites with at least four repeats ofdi-, tri-, tetra-, penta-, and hexamers. Primers were designed for 36 different microsatellite loci with di-, tri-, and tetramer repeat units. After optimization, 20 primer pairs yielded consistent PCR products and were validated for population genetic application in six populations in Western Louisiana Ten loci were polymorphic with 2-9 alleles per locus and an average observed heterozygosity of 0.20 across populations. The horse fly populations from different trap sites (distance 50-144 km) or years of collection (2010 vs 2011) were genetically distinct from each other (FST = 0.05-0.39) and genetically diverse (gene diversity: 0.24-0.37) but considerably inbred (FIS: 0.22-0.47), with high mean relatedness among individuals (r = 0.27), suggesting the capture of a high percentage of sisters at the same trap location who were progeny of incest. PMID:24605460

  18. Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia.

    PubMed

    Khaw, Yam Sim; Chan, Yoke Fun; Jafar, Faizatul Lela; Othman, Norlijah; Chee, Hui Yee

    2016-01-01

    Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5' and 3' non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63-81% among themselves and 63-96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection. PMID:27199901

  19. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.

    PubMed

    Thompson, Paul M; Stein, Jason L; Medland, Sarah E; Hibar, Derrek P; Vasquez, Alejandro Arias; Renteria, Miguel E; Toro, Roberto; Jahanshad, Neda; Schumann, Gunter; Franke, Barbara; Wright, Margaret J; Martin, Nicholas G; Agartz, Ingrid; Alda, Martin; Alhusaini, Saud; Almasy, Laura; Almeida, Jorge; Alpert, Kathryn; Andreasen, Nancy C; Andreassen, Ole A; Apostolova, Liana G; Appel, Katja; Armstrong, Nicola J; Aribisala, Benjamin; Bastin, Mark E; Bauer, Michael; Bearden, Carrie E; Bergmann, Orjan; Binder, Elisabeth B; Blangero, John; Bockholt, Henry J; Bøen, Erlend; Bois, Catherine; Boomsma, Dorret I; Booth, Tom; Bowman, Ian J; Bralten, Janita; Brouwer, Rachel M; Brunner, Han G; Brohawn, David G; Buckner, Randy L; Buitelaar, Jan; Bulayeva, Kazima; Bustillo, Juan R; Calhoun, Vince D; Cannon, Dara M; Cantor, Rita M; Carless, Melanie A; Caseras, Xavier; Cavalleri, Gianpiero L; Chakravarty, M Mallar; Chang, Kiki D; Ching, Christopher R K; Christoforou, Andrea; Cichon, Sven; Clark, Vincent P; Conrod, Patricia; Coppola, Giovanni; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Deary, Ian J; de Geus, Eco J C; den Braber, Anouk; Delvecchio, Giuseppe; Depondt, Chantal; de Haan, Lieuwe; de Zubicaray, Greig I; Dima, Danai; Dimitrova, Rali; Djurovic, Srdjan; Dong, Hongwei; Donohoe, Gary; Duggirala, Ravindranath; Dyer, Thomas D; Ehrlich, Stefan; Ekman, Carl Johan; Elvsåshagen, Torbjørn; Emsell, Louise; Erk, Susanne; Espeseth, Thomas; Fagerness, Jesen; Fears, Scott; Fedko, Iryna; Fernández, Guillén; Fisher, Simon E; Foroud, Tatiana; Fox, Peter T; Francks, Clyde; Frangou, Sophia; Frey, Eva Maria; Frodl, Thomas; Frouin, Vincent; Garavan, Hugh; Giddaluru, Sudheer; Glahn, David C; Godlewska, Beata; Goldstein, Rita Z; Gollub, Randy L; Grabe, Hans J; Grimm, Oliver; Gruber, Oliver; Guadalupe, Tulio; Gur, Raquel E; Gur, Ruben C; Göring, Harald H H; Hagenaars, Saskia; Hajek, Tomas; Hall, Geoffrey B; Hall, Jeremy; Hardy, John; Hartman, Catharina A; Hass, Johanna; Hatton, Sean N; Haukvik, Unn K; Hegenscheid, Katrin; Heinz, Andreas; Hickie, Ian B; Ho, Beng-Choon; Hoehn, David; Hoekstra, Pieter J; Hollinshead, Marisa; Holmes, Avram J; Homuth, Georg; Hoogman, Martine; Hong, L Elliot; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Hwang, Kristy S; Jack, Clifford R; Jenkinson, Mark; Johnston, Caroline; Jönsson, Erik G; Kahn, René S; Kasperaviciute, Dalia; Kelly, Sinead; Kim, Sungeun; Kochunov, Peter; Koenders, Laura; Krämer, Bernd; Kwok, John B J; Lagopoulos, Jim; Laje, Gonzalo; Landen, Mikael; Landman, Bennett A; Lauriello, John; Lawrie, Stephen M; Lee, Phil H; Le Hellard, Stephanie; Lemaître, Herve; Leonardo, Cassandra D; Li, Chiang-Shan; Liberg, Benny; Liewald, David C; Liu, Xinmin; Lopez, Lorna M; Loth, Eva; Lourdusamy, Anbarasu; Luciano, Michelle; Macciardi, Fabio; Machielsen, Marise W J; Macqueen, Glenda M; Malt, Ulrik F; Mandl, René; Manoach, Dara S; Martinot, Jean-Luc; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mattingsdal, Morten; Meyer-Lindenberg, Andreas; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Milaneschi, Yuri; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Moses, Eric K; Mueller, Bryon A; Muñoz Maniega, Susana; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Mwangi, Benson; Nauck, Matthias; Nho, Kwangsik; Nichols, Thomas E; Nilsson, Lars-Göran; Nugent, Allison C; Nyberg, Lars; Olvera, Rene L; Oosterlaan, Jaap; Ophoff, Roel A; Pandolfo, Massimo; Papalampropoulou-Tsiridou, Melina; Papmeyer, Martina; Paus, Tomas; Pausova, Zdenka; Pearlson, Godfrey D; Penninx, Brenda W; Peterson, Charles P; Pfennig, Andrea; Phillips, Mary; Pike, G Bruce; Poline, Jean-Baptiste; Potkin, Steven G; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rietschel, Marcella; Rijpkema, Mark; Risacher, Shannon L; Roffman, Joshua L; Roiz-Santiañez, Roberto; Romanczuk-Seiferth, Nina; Rose, Emma J; Royle, Natalie A; Rujescu, Dan; Ryten, Mina; Sachdev, Perminder S; Salami, Alireza; Satterthwaite, Theodore D; Savitz, Jonathan; Saykin, Andrew J; Scanlon, Cathy; Schmaal, Lianne; Schnack, Hugo G; Schork, Andrew J; Schulz, S Charles; Schür, Remmelt; Seidman, Larry; Shen, Li; Shoemaker, Jody M; Simmons, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soares, Jair C; Sponheim, Scott R; Sprooten, Emma; Starr, John M; Steen, Vidar M; Strakowski, Stephen; Strike, Lachlan; Sussmann, Jessika; Sämann, Philipp G; Teumer, Alexander; Toga, Arthur W; Tordesillas-Gutierrez, Diana; Trabzuni, Daniah; Trost, Sarah; Turner, Jessica; Van den Heuvel, Martijn

    2014-06-01

    The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. PMID:24399358

  20. Pronounced genetic differentiation and recent secondary contact in the mangrove tree Lumnitzera racemosa revealed by population genomic analyses

    PubMed Central

    Li, Jianfang; Yang, Yuchen; Chen, Qipian; Fang, Lu; He, Ziwen; Guo, Wuxia; Qiao, Sitan; Wang, Zhengzhen; Guo, Miaomiao; Zhong, Cairong; Zhou, Renchao; Shi, Suhua

    2016-01-01

    Systematically investigating the impacts of Pleistocene sea-level fluctuations on mangrove plants may provide a better understanding of their demographic history and useful information for their conservation. Therefore, we conducted population genomic analyses of 88 nuclear genes to explore the population dynamics of a mangrove tree Lumnitzera racemosa across the Indo-West Pacific region. Our results revealed pronounced genetic differentiation in this species between the populations from the Indian Ocean and the Pacific Ocean, which may be attributable to the long-term isolation between the western and eastern coasts of the Malay Peninsula during sea-level drops in the Pleistocene glacial periods. The mixing of haplotypes from the two highly divergent groups was identified in a Cambodian population at almost all 88 nuclear genes, suggesting genetic admixture of the two lineages at the boundary region. Similar genetic admixture was also found in other populations from Southeast Asia based on the Bayesian clustering analysis of six nuclear genes, which suggests extensive and recent secondary contact of the two divergent lineages in Southeast Asia. Computer simulations indicated substantial migration from the Indian Ocean towards the South China Sea, which likely results in the genetic admixture in Southeast Asia. PMID:27380895

  1. Pronounced genetic differentiation and recent secondary contact in the mangrove tree Lumnitzera racemosa revealed by population genomic analyses.

    PubMed

    Li, Jianfang; Yang, Yuchen; Chen, Qipian; Fang, Lu; He, Ziwen; Guo, Wuxia; Qiao, Sitan; Wang, Zhengzhen; Guo, Miaomiao; Zhong, Cairong; Zhou, Renchao; Shi, Suhua

    2016-01-01

    Systematically investigating the impacts of Pleistocene sea-level fluctuations on mangrove plants may provide a better understanding of their demographic history and useful information for their conservation. Therefore, we conducted population genomic analyses of 88 nuclear genes to explore the population dynamics of a mangrove tree Lumnitzera racemosa across the Indo-West Pacific region. Our results revealed pronounced genetic differentiation in this species between the populations from the Indian Ocean and the Pacific Ocean, which may be attributable to the long-term isolation between the western and eastern coasts of the Malay Peninsula during sea-level drops in the Pleistocene glacial periods. The mixing of haplotypes from the two highly divergent groups was identified in a Cambodian population at almost all 88 nuclear genes, suggesting genetic admixture of the two lineages at the boundary region. Similar genetic admixture was also found in other populations from Southeast Asia based on the Bayesian clustering analysis of six nuclear genes, which suggests extensive and recent secondary contact of the two divergent lineages in Southeast Asia. Computer simulations indicated substantial migration from the Indian Ocean towards the South China Sea, which likely results in the genetic admixture in Southeast Asia. PMID:27380895

  2. Mathematical Analysis of the Effects of HIV-Malaria Co-infection on Workplace Productivity.

    PubMed

    Seidu, Baba; Makinde, Oluwole D; Seini, Ibrahim Y

    2015-06-01

    In this paper, a nonlinear dynamical system is proposed and qualitatively analyzed to study the dynamics and effects of HIV-malaria co-infection in the workplace. Basic reproduction numbers of sub-models are derived and are shown to have LAS disease-free equilibria when their respective basic reproduction numbers are less than unity. Conditions for existence of endemic equilibria of sub-models are also derived. Unlike the HIV-only model, the malaria-only model is shown to exhibit a backward bifurcation under certain conditions. Conditions for optimal control of the co-infection are derived using the Pontryagin's maximum principle. Numerical experimentation on the resulting optimality system is performed. Using the incremental cost-effectiveness ratio, it is observed that combining preventative measures for both diseases is the best strategy for optimal control of HIV-malaria co-infection at the workplace. PMID:25980477

  3. Seroprevalence of HIV and hepatitis C co-infection among blood donors in Kathmandu Valley, Nepal.

    PubMed

    Karki, Surendra; Ghimire, Prakash; Tiwari, Bishnu Raj; Shrestha, Ashish Chandra; Gautam, Avhishekh; Rajkarnikar, Manita

    2009-01-01

    We assessed the seroprevalence of human immunodeficiency virus (HIV) in different categories of blood donors and the hepatitis C virus (HCV) co-infection rate. A total of 33,255 blood samples were screened for HIV using a third generation ELISA test at the Central Blood Transfusion Service, Nepal Red Cross Society, Kathmandu from December 2006 to September 2007. The seroprevalence of HIV was 0.19% (95% CI= 0.15-0.25) and co-infection with HCV was found in 10.8% (95% CI= 4.4-20.9). There were no significant differences in HIV seroprevalence among the different categories of age, sex, type of donation and time of donation. The study revealed a relatively lower seroprevalence of HIV among blood donors in Kathmandu Valley than reported earlier but a higher HCV co-infection rate. The similar seroprevalence between first time and repeat donors suggests the need for more improved donor education and counselling. PMID:19323036

  4. Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B.

    PubMed

    Liu, Yanling; Xiong, Yujiao; Huang, Wenxiang; Jia, Bei

    2014-01-01

    We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy. PMID:24884719

  5. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection.

    PubMed

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-02-12

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  6. Low Prevalence of Liver Disease but Regional Differences in HBV Treatment Characteristics Mark HIV/HBV Co-Infection in a South African HIV Clinical Trial

    PubMed Central

    Ive, Prudence; MacLeod, William; Mkumla, Nompumelelo; Orrell, Catherine; Jentsch, Ute; Wallis, Carole L.; Stevens, Wendy; Wood, Robin; Sanne, Ian; Bhattacharya, Debika

    2013-01-01

    Background Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA ‘Safeguard the household study’ in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation. Methods 812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline. Results Forty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3–4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007). Conclusion One third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations. PMID:24324573

  7. Selection of Genetic Markers for Association Analyses, Using Linkage Disequilibrium and Haplotypes

    PubMed Central

    Meng, Zhaoling; Zaykin, Dmitri V.; Xu, Chun-Fang; Wagner, Michael; Ehm, Margaret G.

    2003-01-01

    The genotyping of closely spaced single-nucleotide polymorphism (SNP) markers frequently yields highly correlated data, owing to extensive linkage disequilibrium (LD) between markers. The extent of LD varies widely across the genome and drives the number of frequent haplotypes observed in small regions. Several studies have illustrated the possibility that LD or haplotype data could be used to select a subset of SNPs that optimize the information retained in a genomic region while reducing the genotyping effort and simplifying the analysis. We propose a method based on the spectral decomposition of the matrices of pairwise LD between markers, and we select markers on the basis of their contributions to the total genetic variation. We also modify Clayton’s “haplotype tagging SNP” selection method, which utilizes haplotype information. For both methods, we propose sliding window–based algorithms that allow the methods to be applied to large chromosomal regions. Our procedures require genotype information about a small number of individuals for an initial set of SNPs and selection of an optimum subset of SNPs that could be efficiently genotyped on larger numbers of samples while retaining most of the genetic variation in samples. We identify suitable parameter combinations for the procedures, and we show that a sample size of 50–100 individuals achieves consistent results in studies of simulated data sets in linkage equilibrium and LD. When applied to experimental data sets, both procedures were similarly effective at reducing the genotyping requirement while maintaining the genetic information content throughout the regions. We also show that haplotype-association results that Hosking et al. obtained near CYP2D6 were almost identical before and after marker selection. PMID:12796855

  8. Population Genetic Analyses of the Fungal Pathogen Colletotrichum fructicola on Tea-Oil Trees in China.

    PubMed

    Li, He; Zhou, Guo-Ying; Liu, Jun-Ang; Xu, Jianping

    2016-01-01

    The filamentous fungus Colletotrichum fructicola is found in all five continents and is capable of causing severe diseases in a number of economically important plants such as avocado, fig, cocoa, pear, and tea-oil trees. However, almost nothing is known about its patterns of genetic variation and epidemiology on any of its host plant species. Here we analyzed 167 isolates of C. fructicola obtained from the leaves of tea-oil tree Camellia oleifera at 15 plantations in seven Chinese provinces. Multilocus sequence typing was conducted for all isolates based on DNA sequences at fragments of four genes: the internal transcribed spacers of the nuclear ribosomal RNA gene cluster (539 bp), calmodulin (633 bp), glutamine synthetase (711 bp), and glyceraldehyde-3-phosphate dehydrogenase (190 bp), yielding 3.52%, 0.63%, 8.44%, and 7.89% of single nucleotide polymorphic sites and resulting in 15, 5, 12 and 11 alleles respectively at the four gene fragments in the total sample. The combined allelic information from all four loci identified 53 multilocus genotypes with the most frequent represented by 21 isolates distributed in eight tea-oil plantations in three provinces, consistent with long-distance clonal dispersal. However, despite evidence for clonal dispersal, statistically significant genetic differentiation among geographic populations was detected. In addition, while no evidence of recombination was found within any of the four gene fragments, signatures of recombination were found among the four gene fragments in most geographic populations, consistent with sexual mating of this species in nature. Our study provides the first insights into the population genetics and epidemiology of the important plant fungal pathogen C. fructicola. PMID:27299731

  9. Population Genetic Analyses of the Fungal Pathogen Colletotrichum fructicola on Tea-Oil Trees in China

    PubMed Central

    Li, He; Zhou, Guo-Ying; Liu, Jun-Ang; Xu, Jianping

    2016-01-01

    The filamentous fungus Colletotrichum fructicola is found in all five continents and is capable of causing severe diseases in a number of economically important plants such as avocado, fig, cocoa, pear, and tea-oil trees. However, almost nothing is known about its patterns of genetic variation and epidemiology on any of its host plant species. Here we analyzed 167 isolates of C. fructicola obtained from the leaves of tea-oil tree Camellia oleifera at 15 plantations in seven Chinese provinces. Multilocus sequence typing was conducted for all isolates based on DNA sequences at fragments of four genes: the internal transcribed spacers of the nuclear ribosomal RNA gene cluster (539 bp), calmodulin (633 bp), glutamine synthetase (711 bp), and glyceraldehyde-3-phosphate dehydrogenase (190 bp), yielding 3.52%, 0.63%, 8.44%, and 7.89% of single nucleotide polymorphic sites and resulting in 15, 5, 12 and 11 alleles respectively at the four gene fragments in the total sample. The combined allelic information from all four loci identified 53 multilocus genotypes with the most frequent represented by 21 isolates distributed in eight tea-oil plantations in three provinces, consistent with long-distance clonal dispersal. However, despite evidence for clonal dispersal, statistically significant genetic differentiation among geographic populations was detected. In addition, while no evidence of recombination was found within any of the four gene fragments, signatures of recombination were found among the four gene fragments in most geographic populations, consistent with sexual mating of this species in nature. Our study provides the first insights into the population genetics and epidemiology of the important plant fungal pathogen C. fructicola. PMID:27299731

  10. Genetic analyses of atypical Toxoplasma gondii strains reveals a fourth clonal lineage in North America

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we examined an expanded set of strains using sequenced-based phylogenetic and population analyses to re-evaluate the population structure of T. gondii in North America. Our findings reveal that strains previous defined by atypical RFLP patterns fall into two discrete groups. In one case, these...

  11. Integrative analyses of genetic variation in enzyme activities of primary carbohydrate metabolism reveal distinct modes of regulation in Arabidopsis thaliana

    PubMed Central

    Keurentjes, Joost JB; Sulpice, Ronan; Gibon, Yves; Steinhauser, Marie-Caroline; Fu, Jingyuan; Koornneef, Maarten; Stitt, Mark; Vreugdenhil, Dick

    2008-01-01

    Background Plant primary carbohydrate metabolism is complex and flexible, and is regulated at many levels. Changes of transcript levels do not always lead to changes in enzyme activities, and these do not always affect metabolite levels and fluxes. To analyze interactions between these three levels of function, we have performed parallel genetic analyses of 15 enzyme activities involved in primary carbohydrate metabolism, transcript levels for their encoding structural genes, and a set of relevant metabolites. Quantitative analyses of each trait were performed in the Arabidopsis thaliana Ler × Cvi recombinant inbred line (RIL) population and subjected to correlation and quantitative trait locus (QTL) analysis. Results Traits affecting primary metabolism were often correlated, possibly due to developmental control affecting multiple genes, enzymes, or metabolites. Moreover, the activity QTLs of several enzymes co-localized with the expression QTLs (eQTLs) of their structural genes, or with metabolite accumulation QTLs of their substrates or products. In addition, many trait-specific QTLs were identified, revealing that there is also specific regulation of individual metabolic traits. Regulation of enzyme activities often occurred through multiple loci, involving both cis- and trans-acting transcriptional or post-transcriptional control of structural genes, as well as independently of the structural genes. Conclusion Future studies of the regulatory processes in primary carbohydrate metabolism will benefit from an integrative genetic analysis of gene transcription, enzyme activity, and metabolite content. The multiparallel QTL analyses of the various interconnected transducers of biological information flow, described here for the first time, can assist in determining the causes and consequences of genetic regulation at different levels of complex biological systems. PMID:18710526

  12. Climate Extremes Promote Fatal Co-Infections during Canine Distemper Epidemics in African Lions

    PubMed Central

    Munson, Linda; Terio, Karen A.; Kock, Richard; Mlengeya, Titus; Roelke, Melody E.; Dubovi, Edward; Summers, Brian; Sinclair, Anthony R. E.; Packer, Craig

    2008-01-01

    Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality. A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five “silent” CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer). As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may

  13. Culture proven Salmonella typhi co-infection in a child with Dengue fever: a case report.

    PubMed

    Srinivasaraghavan, Rangan; Narayanan, Parameswaran; Kanimozhi, Thandapani

    2015-09-01

    Infectious diseases are one of the major causes of morbidity and mortality in developing countries. Sometimes concurrent infections with multiple infectious agents may occur in one patient, which make the diagnosis and management a challenging task. The authors here present a case of co-infection of typhoid fever with dengue fever in a ten-year-old child and discuss the pertinent issues. The authors emphasize that the risk factors predicting the presence of such co-infections, if developed, will be immensely useful in areas where dengue outbreak occurs in the background of high transmission of endemic infections. PMID:26409747

  14. Clear genetic distinctiveness between human- and pig-derived Trichuris based on analyses of mitochondrial datasets.

    PubMed

    Liu, Guo-Hua; Gasser, Robin B; Su, Ang; Nejsum, Peter; Peng, Lifei; Lin, Rui-Qing; Li, Ming-Wei; Xu, Min-Jun; Zhu, Xing-Quan

    2012-01-01

    The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions. PMID:22363831

  15. Clear Genetic Distinctiveness between Human- and Pig-Derived Trichuris Based on Analyses of Mitochondrial Datasets

    PubMed Central

    Liu, Guo-Hua; Gasser, Robin B.; Su, Ang; Nejsum, Peter; Peng, Lifei; Lin, Rui-Qing; Li, Ming-Wei; Xu, Min-Jun; Zhu, Xing-Quan

    2012-01-01

    The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions. PMID:22363831

  16. Genetic analyses of Xianbei populations about 1,500-1,800 years old.

    PubMed

    Yu, C C; Zhao, Y B; Zhou, H

    2014-03-01

    To understand the profile of genetic structure of Xianbei and trace its impacts on the formation and development of the minorities from northern China, we analyzed the sequences of the hypervariable segment I (HVS-I, 16.035-16.398) in mtDNA control region of 17 Tuoba Xianbei remains from Shangdu Dongdajing cemetery (Inner Mongolia). Its haplotype diversity and nucleotide diversity were 0.971 ± 0.032 and 0.0184 ± 0.010, respectively, and the haplogroup status presented 29.5% C, 23.5% D4, 17.6% D5, 17.6% A, 5.9% B and 5.9% G. When the data from Qilang Mountain Tuoba remains and other relevant populations were considered, we found that Dongdajing Tuoba Xianbei presented the closest genetic affinity to Qilang Mountain Tuoba Xianbei. Tuoba Xianbei and Murong Xianbei showed a significant differentiation in the maternal lineages. Tuoba Xianbei may contribute to the gene pool of some northern minorities, and it may mix with Xiongnu in northern China. PMID:25438556

  17. Genetic analyses of Xianbei populations about 1,500-1,800 years old.

    PubMed

    Yu, C C; Zhao, Y B; Zhou, H

    2014-03-01

    To understand the profile of genetic structure of Xianbei and trace its impacts on the formation and development of the minorities from northern China, we analyzed the sequences of the hypervariable segment I (HVS-I, 16.035-16.398) in mtDNA control region of 17 Tuoba Xianbei remains from Shangdu Dongdajing cemetery (Inner Mongolia). Its haplotype diversity and nucleotide diversity were 0.971 ± 0.032 and 0.0184 ± 0.010, respectively, and the haplogroup status presented 29.5% C, 23.5% D4, 17.6% D5, 17.6% A, 5.9% B and 5.9% G. When the data from Qilang Mountain Tuoba remains and other relevant populations were considered, we found that Dongdajing Tuoba Xianbei presented the closest genetic affinity to Qilang Mountain Tuoba Xianbei. Tuoba Xianbei and Murong Xianbei showed a significant differentiation in the maternal lineages. Tuoba Xianbei may contribute to the gene pool of some northern minorities, and it may mix with Xiongnu in northern China. PMID:25508087

  18. Genetic analyses of endoreduplication in Zea mays endosperm: evidence of sporophytic and zygotic maternal control.

    PubMed Central

    Dilkes, Brian P; Dante, Ricardo A; Coelho, Cintia; Larkins, Brian A

    2002-01-01

    Flow cytometry was used to assess the variability of endoreduplication in endosperms of maize inbred lines. Little variation was found between midwestern dent types, and high levels of endoreduplication were observed in popcorns. Endoreduplication is different between inbred lines by 13-18 days after pollination, and flow cytometric analysis of ploidy level was feasible until 20 DAP. To study the genetic regulation of endoreduplication, four inbreds were crossed to B73 and developing endosperms from both parental, reciprocal F(1), and backcross generations were subjected to flow cytometric analysis. Three measurements of endoreduplication were calculated from these data and analyzed as quantitative genetic traits. Multiple models of trait inheritance were considered including triploid, diploid, sporophytic maternal, and maternal and paternal zygotic nuclear inheritance. Maternal zygotic effects, often considered a form of parental imprinting, and maternal sporophytic effects were detected. To test the feasibility of introgressing a high endoreduplication phenotype into a midwestern dent inbred line, a backcross population was generated from B73 x Sg18. Parental and progeny endoreduplication levels were compared and heritabilities assessed. The heritabilities calculated from these data generally agree with the values calculated in the larger crossing experiments. PMID:11901131

  19. What risk assessments of genetically modified organisms can learn from institutional analyses of public health risks.

    PubMed

    Rajan, S Ravi; Letourneau, Deborah K

    2012-01-01

    The risks of genetically modified organisms (GMOs) are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT) as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large. PMID:23193357

  20. Genetic analyses, phenotypic adaptability and stability in sugarcane genotypes for commercial cultivation in Pernambuco.

    PubMed

    Dutra Filho, J A; Junior, T C; Simões Neto, D E

    2015-01-01

    In the present study, we assessed the agro-industrial performance of 22 sugarcane genotypes adaptable to edaphoclimatic conditions in production microregions in the State of Pernambuco, Brazil, and we recommended the commercial cultivation of select genotypes. The variables analyzed were as follows: sucrose percentage in cane juice, tonnage of saccharose per hectare (TPH), sugarcane tonnage per hectare (TCH), fiber, solid soluble contents, total recoverable sugar tonnage (ATR), and total recoverable sugar tonnage per hectare (ATR t/ha). A randomized block design with 4 repeats was used. Combined variance of the experiments, genetic parameter estimates, and environment stratification were analyzed. Phenotypic adaptability and stability were analyzed using the Annicchiarico and Wricke methods and analysis of variance. Genetic gain was estimated using the classic index and sum of ranks. Genotype selection was efficient for TPH, TCH, and ATR t/ha. Genotypes presented a great potential for improvement and a similar response pattern in Litoral Norte and Mata Sul microregions for TPH and TCH and Litoral Norte and Litoral Sul microregions for ATR t/ha. Genotypes SP78-4764, RB813804, and SP79-101 showed better productivity and phenotypic adaptability and stability, according to the Wricke and Annicchiarico methods. These genotypes can be recommended for cultivation in the sugarcane belt in the State of Pernambuco. PMID:26505357

  1. Genetic analyses of agronomic traits in Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.)

    PubMed Central

    Li, Chunhua; Kobayashi, Kiwa; Yoshida, Yasuko; Ohsawa, Ryo

    2012-01-01

    The consumption of products made from Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) has increased in recent years in Japan. Increased consumer demand has led to recognition of the need for early varieties of this crop with high and stable yields. In order to accomplish this, more information is needed on the genetic mechanisms affecting earliness and yield. We conducted genetic analysis of 3 agronomic traits (days to flowering, plant height and total seed weight per plant) to segregate F2 and F3 populations derived from a cross between Tartary buckwheat cultivars ‘Hokuriku No. 4’ and ‘Ishisoba’. Broad-sense heritability estimates for days to flowering, plant height and total seed weight were 0.70, 0.62 and 0.75, respectively, in F3 population. Narrow-sense heritability for total seed weight (0.51) was highest, followed by heritability for days to flowering (0.37), with heritability for plant height (0.26) lowest. Later flowering was associated with increased plant height and higher yields. From the F4 generation, we identified twelve candidate plants with earlier maturity and reduced plant height compared to ‘Hokuriku No. 4’, but almost the same total seed weight. These results suggest that hybridization breeding using the single seed descent (SSD) method is an effective approach for improving agronomic characteristics of Tartary buckwheat. PMID:23341743

  2. What Risk Assessments of Genetically Modified Organisms Can Learn from Institutional Analyses of Public Health Risks

    PubMed Central

    Rajan, S. Ravi; Letourneau, Deborah K.

    2012-01-01

    The risks of genetically modified organisms (GMOs) are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT) as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large. PMID:23193357

  3. Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics.

    PubMed

    Agrawal, Arpana; Edenberg, Howard J; Gelernter, Joel

    2016-09-01

    Meta-analyses of genome-wide association study data have begun to lead to promising new discoveries for behavioral and psychiatrically relevant phenotypes (e.g., schizophrenia, educational attainment). We outline how this methodology can similarly lead to novel discoveries in genomic studies of substance use disorders, and discuss challenges that will need to be overcome to accomplish this goal. We illustrate our approach with the work of the newly established Substance Use Disorders workgroup of the Psychiatric Genomics Consortium. PMID:27588522

  4. Direct radiocarbon dating and genetic analyses on the purported Neanderthal mandible from the Monti Lessini (Italy).

    PubMed

    Talamo, Sahra; Hajdinjak, Mateja; Mannino, Marcello A; Fasani, Leone; Welker, Frido; Martini, Fabio; Romagnoli, Francesca; Zorzin, Roberto; Meyer, Matthias; Hublin, Jean-Jacques

    2016-01-01

    Anatomically modern humans replaced Neanderthals in Europe around 40,000 years ago. The demise of the Neanderthals and the nature of the possible relationship with anatomically modern humans has captured our imagination and stimulated research for more than a century now. Recent chronological studies suggest a possible overlap between Neanderthals and anatomically modern humans of more than 5,000 years. Analyses of ancient genome sequences from both groups have shown that they interbred multiple times, including in Europe. A potential place of interbreeding is the notable Palaeolithic site of Riparo Mezzena in Northern Italy. In order to improve our understanding of prehistoric occupation at Mezzena, we analysed the human mandible and several cranial fragments from the site using radiocarbon dating, ancient DNA, ZooMS and isotope analyses. We also performed a more detailed investigation of the lithic assemblage of layer I. Surprisingly we found that the Riparo Mezzena mandible is not from a Neanderthal but belonged to an anatomically modern human. Furthermore, we found no evidence for the presence of Neanderthal remains among 11 of the 13 cranial and post-cranial fragments re-investigated in this study. PMID:27389305

  5. University Students' Knowledge Structures and Informal Reasoning on the Use of Genetically Modified Foods: Multidimensional Analyses

    NASA Astrophysics Data System (ADS)

    Wu, Ying-Tien

    2012-12-01

    This study aims to provide insights into the role of learners' knowledge structures about a socio-scientific issue (SSI) in their informal reasoning on the issue. A total of 42 non-science major university students' knowledge structures and informal reasoning were assessed with multidimensional analyses. With both qualitative and quantitative analyses, this study revealed that those students with more extended and better-organized knowledge structures, as well as those who more frequently used higher-order information processing modes, were more oriented towards achieving a higher-level informal reasoning quality. The regression analyses further showed that the "richness" of the students' knowledge structures explained 25 % of the variation in their rebuttal construction, an important indicator of reasoning quality, indicating the significance of the role of students' sophisticated knowledge structure in SSI reasoning. Besides, this study also provides some initial evidence for the significant role of the "core" concept within one's knowledge structure in one's SSI reasoning. The findings in this study suggest that, in SSI-based instruction, science instructors should try to identify students' core concepts within their prior knowledge regarding the SSI, and then they should try to guide students to construct and structure relevant concepts or ideas regarding the SSI based on their core concepts. Thus, students could obtain extended and well-organized knowledge structures, which would then help them achieve better learning transfer in dealing with SSIs.

  6. Biochemical, mechanical, and spectroscopic analyses of genetically engineered flax fibers producing bioplastic (poly-beta-hydroxybutyrate).

    PubMed

    Wróbel-Kwiatkowska, Magdalena; Skórkowska-Telichowska, Katarzyna; Dymińska, Lucyna; Maczka, Mirosław; Hanuza, Jerzy; Szopa, Jan

    2009-01-01

    The interest in biofibers has grown in recent years due to their expanding range of applications in fields as diverse as biomedical science and the automotive industry. Their low production costs, biodegradability, physical properties, and perceived eco-friendliness allow for their extensive use as composite components, a role in which they could replace petroleum-based synthetic polymers. We performed biochemical, mechanical, and structural analyses of flax stems and fibers derived from field-grown transgenic flax enriched with PHB (poly-beta-hydroxybutyrate). The analyses of the plant stems revealed an increase in the cellulose content and a decrease in the lignin and pectin contents relative to the control plants. However, the contents of the fibers' major components (cellulose, lignin, pectin) remain unchanged. An FT-IR study confirmed the results of the biochemical analyses of the flax fibers. However, the arrangement of the cellulose polymer in the transgenic fibers differed from that in the control, and a significant increase in the number of hydrogen bonds was detected. The mechanical properties of the transgenic flax stems were significantly improved, reflecting the cellulose content increase. However, the mechanical properties of the fibers did not change in comparison with the control, with the exception of the fibers from transgenic line M13. The generated transgenic flax plants, which produce both components of the flax/PHB composites (i.e., fibers and thermoplastic matrix in the same plant organ) are a source of an attractive and ecologically safe material for industry and medicine. PMID:19572280

  7. Direct radiocarbon dating and genetic analyses on the purported Neanderthal mandible from the Monti Lessini (Italy)

    PubMed Central

    Talamo, Sahra; Hajdinjak, Mateja; Mannino, Marcello A.; Fasani, Leone; Welker, Frido; Martini, Fabio; Romagnoli, Francesca; Zorzin, Roberto; Meyer, Matthias; Hublin, Jean-Jacques

    2016-01-01

    Anatomically modern humans replaced Neanderthals in Europe around 40,000 years ago. The demise of the Neanderthals and the nature of the possible relationship with anatomically modern humans has captured our imagination and stimulated research for more than a century now. Recent chronological studies suggest a possible overlap between Neanderthals and anatomically modern humans of more than 5,000 years. Analyses of ancient genome sequences from both groups have shown that they interbred multiple times, including in Europe. A potential place of interbreeding is the notable Palaeolithic site of Riparo Mezzena in Northern Italy. In order to improve our understanding of prehistoric occupation at Mezzena, we analysed the human mandible and several cranial fragments from the site using radiocarbon dating, ancient DNA, ZooMS and isotope analyses. We also performed a more detailed investigation of the lithic assemblage of layer I. Surprisingly we found that the Riparo Mezzena mandible is not from a Neanderthal but belonged to an anatomically modern human. Furthermore, we found no evidence for the presence of Neanderthal remains among 11 of the 13 cranial and post-cranial fragments re-investigated in this study. PMID:27389305

  8. Genetic Analyses Reveal a Role for Vitamin D Insufficiency in HCV-Associated Hepatocellular Carcinoma Development

    PubMed Central

    Lange, Christian M.; Miki, Daiki; Ochi, Hidenori; Nischalke, Hans-Dieter; Bojunga, Jörg; Bibert, Stéphanie; Morikawa, Kenichi; Gouttenoire, Jérôme; Cerny, Andreas; Dufour, Jean-François; Gorgievski-Hrisoho, Meri; Heim, Markus H.; Malinverni, Raffaele; Müllhaupt, Beat; Negro, Francesco; Semela, David; Kutalik, Zoltan; Müller, Tobias; Spengler, Ulrich; Berg, Thomas; Chayama, Kazuaki; Moradpour, Darius; Bochud, Pierre-Yves

    2013-01-01

    Background Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Methodology/Principal Findings Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3) serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657), GC (rs2282679), and DHCR7 (rs7944926, rs12785878) genotypes and 25(OH)D3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs) that are associated with reduced 25(OH)D3 serum levels were found to be associated with HCV-related HCC (P = 0.07 [OR = 1.13, 95% CI = 0.99–1.28] for CYP2R1, P = 0.007 [OR = 1.56, 95% CI = 1.12–2.15] for GC, P = 0.003 [OR = 1.42, 95% CI = 1.13–1.78] for DHCR7; ORs for risk genotypes). In contrast, no association between these genetic variations and liver fibrosis progression rate (P>0.2 for each SNP) or outcome of standard therapy with pegylated interferon-α and ribavirin (P>0.2 for each SNP) was observed, suggesting a specific influence of the genetic determinants of 25(OH)D3 serum levels on hepatocarcinogenesis. Conclusions/Significance Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis. PMID:23734184

  9. Application of cryopreservation to genetic analyses of a photosynthetic picoeukaryote community.

    PubMed

    Kawachi, Masanobu; Kataoka, Takafumi; Sato, Mayumi; Noël, Mary-Hélène; Kuwata, Akira; Demura, Mikihide; Yamaguchi, Haruyo

    2016-02-01

    Cryopreservation is useful for long-term maintenance of living strains in microbial culture collections. We applied this technique to environmental specimens from two monitoring sites at Sendai Bay, Japan and compared the microbial diversity of photosynthetic picoeukaryotes in samples before and after cryopreservation. Flow cytometry (FCM) showed no considerable differences between specimens. We used 2500 cells sorted with FCM for next-generation sequencing of 18S rRNA gene amplicons and after removing low-quality sequences obtained 10,088-37,454 reads. Cluster analysis and comparative correlation analysis of observed high-level operational taxonomic units indicated similarity between specimens before and after cryopreservation. The effects of cryopreservation on cells were assessed with representative culture strains, including fragile cryptophyte cells. We confirmed the usefulness of cryopreservation for genetic studies on environmental specimens, and found that small changes in FCM cytograms after cryopreservation may affect biodiversity estimation. PMID:26506442

  10. Cervical Cancer Genetic Susceptibility: A Systematic Review and Meta-Analyses of Recent Evidence

    PubMed Central

    Martínez-Nava, Gabriela A.; Fernández-Niño, Julián A.; Madrid-Marina, Vicente; Torres-Poveda, Kirvis

    2016-01-01

    Introduction Cervical cancer (CC) has one of the highest mortality rates among women worldwide. Several efforts have been made to identify the genetic susceptibility factors underlying CC development. However, only a few polymorphisms have shown consistency among studies. Materials and Methods We conducted a systematic review of all recent case-control studies focused on the evaluation of single nucleotide polymorphisms (SNPs) and CC risk, stringently following the “PRISMA” statement recommendations. The MEDLINE data base was used for the search. A total of 100 case-control studies were included in the meta-analysis. Polymorphisms that had more than two reports were meta-analyzed by fixed or random models according to the heterogeneity presented among studies. Results We found significant negative association between the dominant inheritance model of p21 rs1801270 polymorphism (C/A+A/A) and CC (pooled OR = 0.76; 95%CI: 0.63–0.91; p<0.01). We also found a negative association with the rs2048718 BRIP1 polymorphism dominant inheritance model (T/C+C/C) and CC (pooled OR = 0.83; 95%CI: 0.70–0.98; p = 0.03), as well as with the rs11079454 BRIP1 polymorphism recessive inheritance model and CC (pooled OR = 0.79; 95%CI: 0.63–0.99; p = 0.04). Interestingly, we observed a strong tendency of the meta-analyzed studies to be of Asiatic origin (67%). We also found a significant low representation of African populations (4%). Conclusions Our results provide evidence of the negative association of p21 rs1801270 polymorphism, as well as BRIP1 rs2048718 and rs11079454 polymorphisms, with CC risk. This study suggests the urgent need for more replication studies focused on GWAS identified CC susceptibility variants, in order to reveal the most informative genetic susceptibility markers for CC across different populations. PMID:27415837

  11. Pleiotropy and pathway analyses of genetic variants associated with both type 2 diabetes and prostate cancer

    PubMed Central

    Raynor, LA; Pankow, James S; Rasmussen-Torvik, Laura J; Tang, Weihong; Prizment, Anna; Couper, David J

    2013-01-01

    Aims: Epidemiological evidence shows that diabetes is associated with a reduced risk of prostate cancer. The objective of this study was to identify genes that may contribute to both type 2 diabetes and prostate cancer outcomes and the biological pathways these diseases may share. Methods: The Atherosclerosis Risk in Communities (ARIC) Study is a population-based prospective cohort study in four U.S. communities that included a baseline examination in 1987-89 and three follow-up exams at three year intervals. Participants were 45-64 years old at baseline. We conducted a genomewide association (GWA) study of incident type 2 diabetes in males, summarized variation across genetic loci into a polygenic risk score, and determined if that diabetes risk score was also associated with incident prostate cancer in the same study population. Secondarily we conducted a separate GWA study of prostate cancer, performed a pathway analysis of both type 2 diabetes and prostate cancer, and qualitatively determined if any of the biochemical pathways identified were shared between the two outcomes. Results: We found that the polygenic risk score for type 2 diabetes was not statistically significantly associated with prostate cancer. The pathway analysis also found no overlap between pathways associated with type 2 diabetes and prostate cancer. However, it did find that the growth hormone signaling pathway was statistically significantly associated with type 2 diabetes (p=0.0001). Conclusion: The inability of this study to find an association between type 2 diabetes polygenic risk scores with prostate cancer or biological pathways in common suggests that shared genetic variants may not contribute significantly to explaining shared etiology. PMID:23565322

  12. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

    PubMed

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel G; Fontana, Mark Alan; Meddens, S Fleur W; Linnér, Richard Karlsson; Rietveld, Cornelius A; Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Miller, Michael B; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davies, Gail; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Steptoe, Andrew; Terracciano, Antonio; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    2016-06-01

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association. PMID:27089181

  13. EDENetworks: a user-friendly software to build and analyse networks in biogeography, ecology and population genetics.

    PubMed

    Kivelä, Mikko; Arnaud-Haond, Sophie; Saramäki, Jari

    2015-01-01

    The recent application of graph-based network theory analysis to biogeography, community ecology and population genetics has created a need for user-friendly software, which would allow a wider accessibility to and adaptation of these methods. EDENetworks aims to fill this void by providing an easy-to-use interface for the whole analysis pipeline of ecological and evolutionary networks starting from matrices of species distributions, genotypes, bacterial OTUs or populations characterized genetically. The user can choose between several different ecological distance metrics, such as Bray-Curtis or Sorensen distance, or population genetic metrics such as FST or Goldstein distances, to turn the raw data into a distance/dissimilarity matrix. This matrix is then transformed into a network by manual or automatic thresholding based on percolation theory or by building the minimum spanning tree. The networks can be visualized along with auxiliary data and analysed with various metrics such as degree, clustering coefficient, assortativity and betweenness centrality. The statistical significance of the results can be estimated either by resampling the original biological data or by null models based on permutations of the data. PMID:24902875

  14. Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses.

    PubMed

    Mukherjee, Shubhabrata; Walter, Stefan; Kauwe, John S K; Saykin, Andrew J; Bennett, David A; Larson, Eric B; Crane, Paul K; Glymour, M Maria

    2015-12-01

    Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk. PMID:26079416

  15. Characterizing Genetic Diversity of Contemporary Pacific Chickens Using Mitochondrial DNA Analyses

    PubMed Central

    Dancause, Kelsey Needham; Vilar, Miguel G.; Steffy, Rlene; Lum, J. Koji

    2011-01-01

    Background Mitochondrial DNA (mtDNA) hypervariable region (HVR) sequences of prehistoric Polynesian chicken samples reflect dispersal of two haplogroups—D and E—by the settlers of the Pacific. The distribution of these chicken haplogroups has been used as an indicator of human movement. Recent analyses suggested similarities between prehistoric Pacific and South American chicken samples, perhaps reflecting prehistoric Polynesian introduction of the chicken into South America. These analyses have been heavily debated. The current distribution of the D and E lineages among contemporary chicken populations in the Western Pacific is unclear, but might ultimately help to inform debates about the movements of humans that carried them. Objectives We sought to characterize contemporary mtDNA diversity among chickens in two of the earliest settled archipelagoes of Remote Oceania, the Marianas and Vanuatu. Methods We generated HVR sequences for 43 chickens from four islands in Vanuatu, and for 5 chickens from Guam in the Marianas. Results Forty samples from Vanuatu and three from Guam were assigned to haplogroup D, supporting this as a Pacific chicken haplogroup that persists in the Western Pacific. Two haplogroup E lineages were observed in Guam and two in Vanuatu. Of the E lineages in Vanuatu, one was identical to prehistoric Vanuatu and Polynesian samples and the other differed by one polymorphism. Contrary to our expectations, we observed few globally distributed domesticate lineages not associated with Pacific chicken dispersal. This might suggest less European introgression of chickens into Vanuatu than expected. If so, the E lineages might represent lineages maintained from ancient Pacific chicken introductions. The Vanuatu sample might thus provide an opportunity to distinguish between maintained ancestral Pacific chicken lineages and replacement by global domesticates through genomic analyses, which could resolve questions of contemporary haplogroup E chicken

  16. Virulence Structure of Blumeria graminis f. sp. tritici and Its Genetic Diversity by ISSR and SRAP Profiling Analyses.

    PubMed

    Liu, Na; Liu, Z Lewis; Gong, Guoshu; Zhang, Min; Wang, Xu; Zhou, You; Qi, Xiaobo; Chen, Huabao; Yang, Jizhi; Luo, Peigao; Yang, Chunping

    2015-01-01

    Blumeria graminis f. sp. tritici, which causes wheat powdery mildew, is an obligate biotrophic pathogen that can easily genetically adapt to its host plant. Understanding the virulence structure of and genetic variations in this pathogen is essential for disease control and for breeding resistance to wheat powdery mildew. This study investigated 17 pathogenic populations in Sichuan, China and classified 109 isolates into two distinct groups based on pathogenicity analysis: high virulence (HV, 92 isolates) and low virulence (LV, 17 isolates). Populations from Yibin (Southern region), Xichang (Western region), and Meishan (Middle region) showed lower virulence frequencies than populations from other regions. Many of the previously known resistance genes did not confer resistance in this study. The resistance gene Pm21 displayed an immune response to pathogenic challenge with all populations in Sichuan, and Pm13, Pm5b, Pm2+6, and PmXBD maintained resistance. AMOVA revealed significantly higher levels of variation within populations and lower levels of variation among populations within regions. High levels of gene flow were detected among populations in the four regions. Closely related populations within each region were distinguished by cluster analyses using ISSR and SRAP alleles. Both ISSR and SRAP allele profiling analyses revealed high levels of genetic diversity among pathogenic populations in Sichuan. Although ISSR and SRAP profiling analysis showed similar resolutions, the SRAP alleles appeared to be more informative. We did not detect any significant association between these alleles and the virulence or pathogenicity of the pathogen. Our results suggest that ISSR and SRAP alleles are more efficient for the characterization of small or closely related populations versus distantly related populations. PMID:26098844

  17. Virulence Structure of Blumeria graminis f. sp. tritici and Its Genetic Diversity by ISSR and SRAP Profiling Analyses

    PubMed Central

    Liu, Na; Liu, Z. Lewis; Gong, Guoshu; Zhang, Min; Wang, Xu; Zhou, You; Qi, Xiaobo; Chen, Huabao; Yang, Jizhi; Luo, Peigao; Yang, Chunping

    2015-01-01

    Blumeria graminis f. sp. tritici, which causes wheat powdery mildew, is an obligate biotrophic pathogen that can easily genetically adapt to its host plant. Understanding the virulence structure of and genetic variations in this pathogen is essential for disease control and for breeding resistance to wheat powdery mildew. This study investigated 17 pathogenic populations in Sichuan, China and classified 109 isolates into two distinct groups based on pathogenicity analysis: high virulence (HV, 92 isolates) and low virulence (LV, 17 isolates). Populations from Yibin (Southern region), Xichang (Western region), and Meishan (Middle region) showed lower virulence frequencies than populations from other regions. Many of the previously known resistance genes did not confer resistance in this study. The resistance gene Pm21 displayed an immune response to pathogenic challenge with all populations in Sichuan, and Pm13, Pm5b, Pm2+6, and PmXBD maintained resistance. AMOVA revealed significantly higher levels of variation within populations and lower levels of variation among populations within regions. High levels of gene flow were detected among populations in the four regions. Closely related populations within each region were distinguished by cluster analyses using ISSR and SRAP alleles. Both ISSR and SRAP allele profiling analyses revealed high levels of genetic diversity among pathogenic populations in Sichuan. Although ISSR and SRAP profiling analysis showed similar resolutions, the SRAP alleles appeared to be more informative. We did not detect any significant association between these alleles and the virulence or pathogenicity of the pathogen. Our results suggest that ISSR and SRAP alleles are more efficient for the characterization of small or closely related populations versus distantly related populations. PMID:26098844

  18. Molecular genetic analyses of historical lake sediments from the East African Rift Valley

    NASA Astrophysics Data System (ADS)

    Epp, L. S.; Stoof, K.; Trauth, M. H.; Tiedemann, R.

    2009-04-01

    Ancient DNA research, especially that of environmental samples, has to date focussed mainly on samples obtained from colder regions, owing to better DNA preservation. We explored the potential of using ancient DNA from sediments and sediment cores of shallow lakes in Kenya. These lakes, located in the eastern branch of the East African Rift Valley, are in close proximity, yet display strikingly different hydrological and geological features. Present day lakes range in alkalinity from pH 11 (Lake Elmenteita) to pH 8 (Lake Naivasha), and in depth from less than one meter to 15 meters. Historically they have undergone a number of drastic changes in lake level and environmental conditions, both on geological timescales and during the last centuries. Within this setting we employed molecular genetic methods to study DNA from recent and historic lake sediments, focussing on rotifers and diatoms. We analyzed population and species succession in the alkaline-saline crater lake Sonachi since the beginning of the 19th century, as well as distributions in recent and historic sediments of other lakes of the East African Rift System. To specifically detect diatoms, we developed a protocol using taxon-specific polymerase chain reactions and separation of products by denaturing high performance liquid chromatography (DHPLC). Employing this protocol we retrieved "ancient" DNA from a number of taxonomically diverse organisms, but found diatoms only in sediments younger than approximately 90 years. Using higly specific reactions for rotifers of the genus Brachionus, we tracked species and population succession in Lake Sonachi during the last 200 years. Populations were dominated by a single mitochondrial haplotype for a period of 150 years, and two putatively intraspecific turnovers in dominance occurred. They were both correlated to major environmental changes documented by profound visible changes in sediment composition of the core: the deposition of a volcanic ash and a

  19. Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism.

    PubMed

    Pilorge, M; Fassier, C; Le Corronc, H; Potey, A; Bai, J; De Gois, S; Delaby, E; Assouline, B; Guinchat, V; Devillard, F; Delorme, R; Nygren, G; Råstam, M; Meier, J C; Otani, S; Cheval, H; James, V M; Topf, M; Dear, T N; Gillberg, C; Leboyer, M; Giros, B; Gautron, S; Hazan, J; Harvey, R J; Legendre, P; Betancur, C

    2016-07-01

    Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the α2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR α2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2(Δex8-9)). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2(Δex8)(-)(9) protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and markedly reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell-surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon-branching defects, rescued by injection of wild type but not GLRA2(Δex8-9) or R153Q transcripts, providing further evidence for their loss-of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive

  20. Integrating Genetic, Transcriptional, and Functional Analyses to Identify Five Novel Genes for Atrial Fibrillation

    PubMed Central

    Sinner, Moritz F.; Tucker, Nathan R.; Lunetta, Kathryn L.; Ozaki, Kouichi; Smith, J. Gustav; Trompet, Stella; Bis, Joshua C.; Lin, Honghuang; Chung, Mina K.; Nielsen, Jonas B.; Lubitz, Steven A.; Krijthe, Bouwe P.; Magnani, Jared W.; Ye, Jiangchuan; Gollob, Michael H.; Tsunoda, Tatsuhiko; Müller-Nurasyid, Martina; Lichtner, Peter; Peters, Annette; Dolmatova, Elena; Kubo, Michiaki; Smith, Jonathan D.; Psaty, Bruce M.; Smith, Nicholas L.; Jukema, J. Wouter; Chasman, Daniel I.; Albert, Christine M.; Ebana, Yusuke; Furukawa, Tetsushi; MacFarlane, Peter; Harris, Tamara B.; Darbar, Dawood; Dörr, Marcus; Holst, Anders G.; Svendsen, Jesper H.; Hofman, Albert; Uitterlinden, Andre G.; Gudnason, Vilmundur; Isobe, Mitsuaki; Malik, Rainer; Dichgans, Martin; Rosand, Jonathan; Van Wagoner, David R.; Benjamin, Emelia J.; Milan, David J.; Melander, Olle; Heckbert, Susan R.; Ford, Ian; Liu, Yongmei; Barnard, John; Olesen, Morten S.; Stricker, Bruno H.C.; Tanaka, Toshihiro; Kääb, Stefan; Ellinor, Patrick T.

    2014-01-01

    Background Atrial fibrillation (AF) affects over 30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. Methods & Results To identify new AF-related genes, we utilized a multifaceted approach, combining large-scale genotyping in two ethnically distinct populations, cis-eQTL mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501, RR=1.18, 95%CI 1.13 – 1.23, p=6.5×10−16), GJA1 (rs13216675, RR=1.10, 95%CI 1.06 – 1.14, p=2.2×10−8), TBX5 (rs10507248, RR=1.12, 95%CI 1.08 – 1.16, p=5.7×10−11), and CAND2 (rs4642101, RR=1.10, 95%CI 1.06 – 1.14, p=9.8×10−9). In Japanese, novel loci were identified near NEURL (rs6584555, RR=1.32, 95%CI 1.26–1.39, p=2.0×10−25) and CUX2 (rs6490029, RR=1.12, 95%CI 1.08–1.16, p=3.9×10−9). The top SNPs or their proxies were identified as cis-eQTLs for the genes CAND2 (p=2.6×10−19), GJA1 (p=2.66×10−6), and TBX5 (p=1.36×10−05). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). Conclusions We have identified five novel loci for AF. Our results further expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation. PMID:25124494

  1. Parallelization and optimization of genetic analyses in isolation by distance web service

    PubMed Central

    Turner, Julia L; Kelley, Scott T; Otto, James S; Valafar, Faramarz; Bohonak, Andrew J

    2009-01-01

    Background The Isolation by Distance Web Service (IBDWS) is a user-friendly web interface for analyzing patterns of isolation by distance in population genetic data. IBDWS enables researchers to perform a variety of statistical tests such as Mantel tests and reduced major axis regression (RMA), and returns vector based graphs. The more than 60 citations since 2005 confirm the popularity and utility of this website. Despite its usefulness, the data sets with over 65 populations can take hours or days to complete due to the computational intensity of the statistical tests. This is especially troublesome for web-based software analysis, since users tend to expect real-time results on the order of seconds, or at most, minutes. Moreover, as genetic data continue to increase and diversify, so does the demand for more processing power. In order to increase the speed and efficiency of IBDWS, we first determined which aspects of the code were most time consuming and whether they might be amenable to improvements by parallelization or algorithmic optimization. Results Runtime tests uncovered two areas of IBDWS that consumed significant amounts of time: randomizations within the Mantel test and the RMA calculations. We found that these sections of code could be restructured and parallelized to improve efficiency. The code was first optimized by combining two similar randomization routines, implementing a Fisher-Yates shuffling algorithm, and then parallelizing those routines. Tests of the parallelization and Fisher-Yates algorithmic improvements were performed on a variety of data sets ranging from 10 to 150 populations. All tested algorithms showed runtime reductions and a very close fit to the predicted speedups based on time-complexity calculations. In the case of 150 populations with 10,000 randomizations, data were analyzed 23 times faster. Conclusion Since the implementation of the new algorithms in late 2007, datasets have continued to increase substantially in size

  2. DNA extraction from paraffin embedded material for genetic and epigenetic analyses.

    PubMed

    Pikor, Larissa A; Enfield, Katey S S; Cameron, Heryet; Lam, Wan L

    2011-01-01

    Disease development and progression are characterized by frequent genetic and epigenetic aberrations including chromosomal rearrangements, copy number gains and losses and DNA methylation. Advances in high-throughput, genome-wide profiling technologies, such as microarrays, have significantly improved our ability to identify and detect these specific alterations. However as technology continues to improve, a limiting factor remains sample quality and availability. Furthermore, follow-up clinical information and disease outcome are often collected years after the initial specimen collection. Specimens, typically formalin-fixed and paraffin embedded (FFPE), are stored in hospital archives for years to decades. DNA can be efficiently and effectively recovered from paraffin-embedded specimens if the appropriate method of extraction is applied. High quality DNA extracted from properly preserved and stored specimens can support quantitative assays for comparisons of normal and diseased tissues and generation of genetic and epigenetic signatures (1). To extract DNA from paraffin-embedded samples, tissue cores or microdissected tissue are subjected to xylene treatment, which dissolves the paraffin from the tissue, and then rehydrated using a series of ethanol washes. Proteins and harmful enzymes such as nucleases are subsequently digested by proteinase K. The addition of lysis buffer, which contains denaturing agents such as sodium dodecyl sulfate (SDS), facilitates digestion (2). Nucleic acids are purified from the tissue lysate using buffer-saturated phenol and high speed centrifugation which generates a biphasic solution. DNA and RNA remain in the upper aqueous phase, while proteins, lipids and polysaccharides are sequestered in the inter- and organic-phases respectively. Retention of the aqueous phase and repeated phenol extractions generates a clean sample. Following phenol extractions, RNase A is added to eliminate contaminating RNA. Additional phenol extractions

  3. Transcriptome analyses based on genetic screens for Pax3 myogenic targets in the mouse embryo

    PubMed Central

    2010-01-01

    Background Pax3 is a key upstream regulator of the onset of myogenesis, controlling progenitor cell survival and behaviour as well as entry into the myogenic programme. It functions in the dermomyotome of the somite from which skeletal muscle derives and in progenitor cell populations that migrate from the somite such as those of the limbs. Few Pax3 target genes have been identified. Identifying genes that lie genetically downstream of Pax3 is therefore an important endeavour in elucidating the myogenic gene regulatory network. Results We have undertaken a screen in the mouse embryo which employs a Pax3GFP allele that permits isolation of Pax3 expressing cells by flow cytometry and a Pax3PAX3-FKHR allele that encodes PAX3-FKHR in which the DNA binding domain of Pax3 is fused to the strong transcriptional activation domain of FKHR. This constitutes a gain of function allele that rescues the Pax3 mutant phenotype. Microarray comparisons were carried out between Pax3GFP/+ and Pax3GFP/PAX3-FKHR preparations from the hypaxial dermomyotome of somites at E9.5 and forelimb buds at E10.5. A further transcriptome comparison between Pax3-GFP positive and negative cells identified sequences specific to myogenic progenitors in the forelimb buds. Potential Pax3 targets, based on changes in transcript levels on the gain of function genetic background, were validated by analysis on loss or partial loss of function Pax3 mutant backgrounds. Sequences that are up- or down-regulated in the presence of PAX3-FKHR are classified as somite only, somite and limb or limb only. The latter should not contain sequences from Pax3 positive neural crest cells which do not invade the limbs. Verification by whole mount in situ hybridisation distinguishes myogenic markers. Presentation of potential Pax3 target genes focuses on signalling pathways and on transcriptional regulation. Conclusions Pax3 orchestrates many of the signalling pathways implicated in the activation or repression of myogenesis

  4. Blood-borne viral co-infections among human immunodeficiency virus-infected inmates.

    PubMed

    Pontali, Emanuele; Bobbio, Nicoletta; Zaccardi, Marilena; Urciuoli, Renato

    2016-06-13

    Purpose - The purpose of this paper is to evaluate the prevalence of HBV and/or HCV co-infection among HIV-infected inmates entering the correctional facility. Design/methodology/approach - Prospective collection of data of HIV-infected inmates entered the institution over a ten-year period. Findings - During study period 365 consecutive different inmates were evaluated. HCV co-infection was observed in more than 80 per cent of the tested HIV-infected inmates, past HBV infection in 71.6 per cent and active HBV co-infection was detected in 7.1 per cent; triple coinfection (HIV, HCV and HBs-Ag positivity) was present in 6 per cent of the total. Originality/value - This study confirms high prevalence of co-infections among HIV-infected inmates. Testing for HBV and HCV in all HIV-infected inmates at entry in any correctional system is recommended to identify those in need of specific care and/or preventing interventions. PMID:27219906

  5. Relative reproductive success of co-infecting parasite genotypes under intensified within-host competition.

    PubMed

    Seppälä, Otto; Louhi, Katja-Riikka; Karvonen, Anssi; Rellstab, Christian; Jokela, Jukka

    2015-12-01

    In nature, host individuals are commonly simultaneously infected with more than one genotype of the same parasite species. These co-infecting parasites often interact, which can affect their fitness and shape host-parasite ecology and evolution. Many of such interactions take place through competition for limited host resources. Therefore, variation in ecological factors modifying the host resource level could be important in determining the intensity of competition and the outcome of co-infections. We tested this hypothesis by measuring the relative reproductive success of co-infecting genotypes of the trematode parasite Diplostomum pseudospathaceum in its snail host Lymnaea stagnalis while experimentally manipulating snail resource level using contrasting feeding treatments (ad libitum food supply, no food). We found that food deprivation constrained the overall parasite within-host reproduction as the release of parasite transmission stages (cercariae) was reduced. This indicates intensified competition among the parasite genotypes. The genotypic composition of the released cercariae, however, was not affected by the feeding treatments. This suggests that in this system, the relative reproductive success of co-infecting parasite genotypes, which is an important component determining their fitness, is robust to variation in ecological factors modifying the strength of resource competition. PMID:26296607

  6. Hemophagocytic lymphohistiocytosis secondary to Epstein Barr virus and Leishmania co-infection in a toddler

    PubMed Central

    Domínguez-Pinilla, N; Baro-Fernández, M; González-Granado, LI

    2015-01-01

    This is the report of an EBV + Leishmanial co-infection. The patient developed hemophagocytic syndrome (HLH) and was treated with the standard HLH-2004 protocol. However, PCR in bone marrow discovered this secondary cause for HLH. In endemic countries, visceral leishmaniasis should be considered in the differential diagnosis even in EBV-related HLH, as chemotherapy toxicity may be avoided. PMID:25511219

  7. Experimental co-infection of chickens and turkeys with avian influenza and newcastle disease viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are the two most important viruses affecting poultry worldwide. Co-infections of poultry with AIV and NDV are a problem from both the clinical point of view and the diagnosis of these viruses. The goal of this study was to examine the i...

  8. In vitro model of mycobacteria and HIV-1 co-infection for drug discovery.

    PubMed

    Vijayakumar, Sudhamathi; Finney John, Sarah; Nusbaum, Rebecca J; Ferguson, Monique R; Cirillo, Jeffrey D; Olaleye, Omonike; Endsley, Janice J

    2013-12-01

    Tuberculosis (TB) has become a global health threat in the wake of the Human Immunodeficiency Virus (HIV) pandemic and is the leading cause of death in people with HIV/AIDS. Treatment of patients with Mycobacterium tuberculosis (Mtb)/HIV co-infection is complicated by drug interactions and toxicity that present huge challenges for clinical intervention. Discovery efforts to identify novel compounds with increased effectiveness and decreased drug-drug interactions against Mtb, HIV-1, or both, would be greatly aided by the use of a co-infection model for screening drug libraries. Currently, inhibitors of Mtb are screened independently in mycobacterial cell cultures or target based biochemical screens and less often in macrophages or peripheral blood leukocytes. Similarly, HIV-1 drugs are screened in vitro independently from anti-mycobacterial compounds. Here, we describe an in vitro model where primary human peripheral blood mononuclear cells or monocyte-derived macrophages are infected with Mycobacterium bovis BCG and HIV-1, and used to evaluate drug toxicity and activity in a co-infection setting. Our results with standard compounds (e.g. Azidothymidine, Rifampicin) demonstrate the utility of this in vitro model to evaluate drug effectiveness relevant to cellular toxicity, HIV-1 replication, and intracellular mycobacterial growth, through the use of ELISA, bacterial enumeration, and multi-variate flow cytometry. This model and associated assays have great value in accelerating the discovery of compounds for use in Mtb/HIV-1 co-infected patients. PMID:24388652

  9. Infection-related hemolysis and susceptibility to Gram-negative bacterial co-infection

    PubMed Central

    Orf, Katharine; Cunnington, Aubrey J.

    2015-01-01

    Increased susceptibility to co-infection with enteric Gram-negative bacteria, particularly non-typhoidal Salmonella, is reported in malaria and Oroya fever (Bartonella bacilliformis infection), and can lead to increased mortality. Accumulating epidemiological evidence indicates a causal association with risk of bacterial co-infection, rather than just co-incidence of common risk factors. Both malaria and Oroya fever are characterized by hemolysis, and observations in humans and animal models suggest that hemolysis causes the susceptibility to bacterial co-infection. Evidence from animal models implicates hemolysis in the impairment of a variety of host defense mechanisms, including macrophage dysfunction, neutrophil dysfunction, and impairment of adaptive immune responses. One mechanism supported by evidence from animal models and human data, is the induction of heme oxygenase-1 in bone marrow, which impairs the ability of developing neutrophils to mount a competent oxidative burst. As a result, dysfunctional neutrophils become a new niche for replication of intracellular bacteria. Here we critically appraise and summarize the key evidence for mechanisms which may contribute to these very specific combinations of co-infections, and propose interventions to ameliorate this risk. PMID:26175727

  10. Imbalanced Oxidative Stress Causes Chlamydial Persistence during Non-Productive Human Herpes Virus Co-Infection

    PubMed Central

    Prusty, Bhupesh K.; Böhme, Linda; Bergmann, Birgit; Siegl, Christine; Krause, Eva; Mehlitz, Adrian; Rudel, Thomas

    2012-01-01

    Both human herpes viruses and Chlamydia are highly prevalent in the human population and are detected together in different human disorders. Here, we demonstrate that co-infection with human herpes virus 6 (HHV6) interferes with the developmental cycle of C. trachomatis and induces persistence. Induction of chlamydial persistence by HHV6 is independent of productive virus infection, but requires the interaction and uptake of the virus by the host cell. On the other hand, viral uptake is strongly promoted under co-infection conditions. Host cell glutathione reductase activity was suppressed by HHV6 causing NADPH accumulation, decreased formation of reduced glutathione and increased oxidative stress. Prevention of oxidative stress restored infectivity of Chlamydia after HHV6-induced persistence. We show that co-infection with Herpes simplex virus 1 or human Cytomegalovirus also induces chlamydial persistence by a similar mechanism suggesting that Chlamydia -human herpes virus co-infections are evolutionary shaped interactions with a thus far unrecognized broad significance. PMID:23077614

  11. Infection-related hemolysis and susceptibility to Gram-negative bacterial co-infection.

    PubMed

    Orf, Katharine; Cunnington, Aubrey J

    2015-01-01

    Increased susceptibility to co-infection with enteric Gram-negative bacteria, particularly non-typhoidal Salmonella, is reported in malaria and Oroya fever (Bartonella bacilliformis infection), and can lead to increased mortality. Accumulating epidemiological evidence indicates a causal association with risk of bacterial co-infection, rather than just co-incidence of common risk factors. Both malaria and Oroya fever are characterized by hemolysis, and observations in humans and animal models suggest that hemolysis causes the susceptibility to bacterial co-infection. Evidence from animal models implicates hemolysis in the impairment of a variety of host defense mechanisms, including macrophage dysfunction, neutrophil dysfunction, and impairment of adaptive immune responses. One mechanism supported by evidence from animal models and human data, is the induction of heme oxygenase-1 in bone marrow, which impairs the ability of developing neutrophils to mount a competent oxidative burst. As a result, dysfunctional neutrophils become a new niche for replication of intracellular bacteria. Here we critically appraise and summarize the key evidence for mechanisms which may contribute to these very specific combinations of co-infections, and propose interventions to ameliorate this risk. PMID:26175727

  12. Co-infection of dengue fever and hepatitis A in a Russian traveler.

    PubMed

    Volchkova, Elena; Umbetova, Karina; Belaia, Olga; Sviridova, Maria; Dmitrieva, Ludmila; Arutyunova, Daria; Chernishov, Dmitriy; Karan, Ludmila

    2016-01-01

    We report a hepatitis A (HAV) and dengue virus (DENV) co-infection in Russian man who had been traveling to Dominican Republic. At admission to the hospital hemorrhagic and jaundice symptoms were observed in patient. PCR tests of blood serum and urine revealed RNA dengue virus type 3, HAV RNA, anti-HAV-IgM. PMID:27516967

  13. Genetic analyses in a variant of Mayer-Rokitansky-Kuster-Hauser syndrome (MURCS association).

    PubMed

    Hofstetter, Gerda; Concin, Nicole; Marth, Christian; Rinne, Tuula; Erdel, Martin; Janecke, Andreas

    2008-01-01

    Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by the congenital absence of uterus and upper part of the vagina as a result of Mullerian duct agenesis. The combination of MRKH syndrome with renal anomalies and cervicothoracic dysplasia is known as MURCS association (Mullerian aplasia, Renal anomalies, and Cervicothoracic Somite dysplasia). The etiology remains poorly understood. We delineate this disease by reporting on a 16-year-old patient showing the cardinal features of MURCS association accompanied by a persistent left superior vena cava and atrial septal defect, orofacial clefting, and mild reduction deformities of the left hand. Fluorescence in situ hybridization did not show major deletions or duplications of the DiGeorge/VCFS (velocardiofacial syndrome) region at chromosome 22q11.1 as well as the TBX5/TBX3 region at 12q24.1. In addition, sequencing of the TP63L (p63) gene, residing at 3q27, remained normal in the presented patient. Thus, we provide further evidence for the genetic heterogeneity of MURCS association. PMID:18726671

  14. Genetic differentiation of the Cabo Verde archipelago population analysed by STR polymorphisms.

    PubMed

    Fernandes, A T; Velosa, R; Jesus, J; Carracedo, A; Brehm, A

    2003-07-01

    Allele frequencies for 17 STR loci were analyzed in a sample of unrelated males from the Cabo Verde Archipelago. The samples were gathered in such a way that the origin of the subjects was perfectly identified, and they could be included in one of the leeward or windward groups of islands. This study reveals that there are significant differences between both groups of islands, and between Cabo Verdeans and other populations from sub-Sahara Africa including the Guineans, the most probable source population for Cabo Verdeans. This study confirms mtDNA data and, together with HLA and Y chromosome data already published, shows that the Cabo Verde population is sub-structured and atypical, diverging substantially from mainland sub-Saharan populations. Overall these differences are most probably due to admixture between sub-Saharan slaves brought into the islands and other settlers of European origin. In the absence of a clear indication of a different ethnic composition of the first sub-Saharan settlers of Cabo Verde, the differentiation exhibited in both groups of islands can be most probably be attributed to genetic drift. PMID:12914568

  15. Comparison of morphological and genetic analyses reveals cryptic divergence and morphological plasticity in Stylophora (Cnidaria, Scleractinia)

    NASA Astrophysics Data System (ADS)

    Stefani, Fabrizio; Benzoni, F.; Yang, S.-Y.; Pichon, M.; Galli, P.; Chen, C. A.

    2011-12-01

    A combined morphological and genetic study of the coral genus Stylophora investigated species boundaries in the Gulf of Aden, Yemen. Two mitochondrial regions, including the hypervariable IGS9 spacer and the control region, and a fragment of rDNA were used for phylogenetic analysis. Results were compared by multivariate analysis on the basis of branch morphology and corallite morphometry. Two species were clearly discriminated by both approaches. The first species was characterised by small corallites and a low morphological variability and was ascribed to a new geographical record of Stylophora madagascarensis on the basis of its phylogenetic distinction and its morphological similarity to the type material. The second species was characterised by larger corallite size and greater morphological variability and was ascribed to Stylophora pistillata. The analysis was extended to the intrageneric level for other S. pistillata populations from the Red Sea and the Pacific Ocean. Strong internal divergence was evident in the genus Sty lophora. S. pistillata populations were split into two highly divergent Red Sea/Gulf of Aden and western Pacific lineages with significant morphological overlap, which suggests they represent two distinct cryptic species. The combined use of morphological and molecular approaches, so far proved to be a powerful tool for the re-delineation of species boundaries in corals, provided novel evidence of cryptic divergence in this group of marine metazoans.

  16. Evaluation of the botanical origin of black cohosh products by genetic and chemical analyses.

    PubMed

    Masada-Atsumi, Sayaka; Kumeta, Yukie; Takahashi, Yutaka; Hakamatsuka, Takashi; Goda, Yukihiro

    2014-01-01

    Despite the increasing sales of black cohosh (the dried rhizome and root of Cimicifuga racemosa L.) in the world herbal market, these products have continuous adulteration issues. The botanical authenticity of the black cohosh products is the first important step for ensuring their quality, safety and efficacy. In this study, we genetically identified the botanical sources of 10 black cohosh products and 5 Cimicifuga Rhizome crude drugs of Japanese Pharmacopoeia grade, and analyzed the metabolic profiling of 25 black cohosh products using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Consequently, we found that C. dahurica and possibly C. foetida are misused as sources of the black cohosh products and in some cases, the extracts of black cohosh were adulterated with the plant materials of C. dahurica. We demonstrated that these three species can be distinguished by three marker compounds in a specific mass range. These results must be helpful in establishing regulations for the safe use of the black cohosh products. PMID:24583864

  17. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder

    PubMed Central

    Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Fagerness, Jesen A.; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Cardona Silgado, Julio C.; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M.J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosário, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Valencia Duarte, Ana V.; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Walkup, John; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G.M.; Yao, Yin; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Rouleau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson; Stewart, S. Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

    2014-01-01

    Obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS) are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. Here, we report a combined genome-wide association study (GWAS) of TS and OCD in 2723 cases (1310 with OCD, 834 with TS, 579 with OCD plus TS/chronic tics (CT)), 5667 ancestry-matched controls, and 290 OCD parent-child trios. Although no individual single nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels, i.e. expression quantitative loci (eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10−4), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, TS had a smaller, non-significant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and TS/CT were included in the analysis (p=0.01). Previous work has shown that TS and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of TS and OCD. Furthermore, OCD with co-occurring TS/CT may have different underlying genetic susceptibility compared to OCD alone. PMID:25158072

  18. Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co-infection

    PubMed Central

    Vriend, Henrike J; Bogaards, Johannes A; van Bergen, Jan E A M; Brink, Antoinette A T P; van den Broek, Ingrid V F; Hoebe, Christian J P A; King, Audrey J; van der Sande, Marianne A B; Wolffs, Petra F G; de Melker, Hester E

    2015-01-01

    We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16–29 years-old) participating in two consecutive rounds of a chlamydia screening implementation trial, swabs were polymerase chain reaction tested to detect chlamydia and 14 carcinogenic HPV genotypes. HPV type-specific incidence and persistence rates were stratified for chlamydia positivity at follow-up. Associations were assessed by multilevel logistic regression analyses with correction for sexual risk factors. HPV type-specific incidence ranged from 1.4% to 8.9% and persistence from 22.7% to 59.4% after a median follow-up of 11 months (interquartile range: 11–12). Differences in 1-year HPV persistence rates between chlamydia -infected and noninfected women were less distinct than differences in HPV incidence rates (pooled adjusted odds ratios of 1.17 [95% CI: 0.69–1.96] and 1.84 [95% CI: 1.36–2.47], respectively). The effect of chlamydia co-infection on HPV-infection risk did not significantly differ by HPV genotype. In conclusion, infection with chlamydia increases the risk of infection by carcinogenic HPV types and may enhance persistence of some HPV types. Although these findings could reflect residual confounding through unobserved risk factors, our results do give reason to explore more fully the association between chlamydia and HPV type-specific acquisition and persistence. PMID:26194784

  19. Co-infection and disease severity of Ohio Maize dwarf mosaic virus and Maize chlorotic dwarf virus strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two major maize viruses have been reported in the United States: Maize dwarf mosaic virus (MDMV) and Maize chlorotic dwarf virus (MCDV). These viruses co-occur in regions where maize is grown such that co-infections are likely. Co-infection of different strains of MCDV is also observed frequently...

  20. Human Infections with Spirometra decipiens Plerocercoids Identified by Morphologic and Genetic Analyses in Korea.

    PubMed

    Jeon, Hyeong-Kyu; Park, Hansol; Lee, Dongmin; Choe, Seongjun; Kim, Kyu-Heon; Huh, Sun; Sohn, Woon-Mok; Chai, Jong-Yil; Eom, Keeseon S

    2015-06-01

    Tapeworms of the genus Spirometra are pseudophyllidean cestodes endemic in Korea. At present, it is unclear which Spirometra species are responsible for causing human infections, and little information is available on the epidemiological profiles of Spirometra species infecting humans in Korea. Between 1979 and 2009, a total of 50 spargana from human patients and 2 adult specimens obtained from experimentally infected carnivorous animals were analyzed according to genetic and taxonomic criteria and classified as Spirometra erinaceieuropaei or Spirometra decipiens depending on the morphology. Morphologically, S. erinaceieuropaei and S. decipiens are different in that the spirally coiled uterus in S. erinaceieuropaei has 5-7 complete coils, while in S. decipiens it has only 4.5 coils. In addition, there is a 9.3% (146/1,566) sequence different between S. erinaceieuropaei and S. decipiens in the cox1 gene. Partial cox1 sequences (390 bp) from 35 Korean isolates showed 99.4% (388/390) similarity with the reference sequence of S. erinaceieuropaei from Korea (G1724; GenBank KJ599680) and an additional 15 Korean isolates revealed 99.2% (387/390) similarity with the reference sequences of S. decipiens from Korea (G1657; GenBank KJ599679). Based on morphologic and molecular databases, the estimated population ratio of S. erinaceieuropaei to S. decipiens was 35: 15. Our results indicate that both S. erinaceieuropaei and S. decipiens found in Korea infect humans, with S. erinaceieuropaei being 2 times more prevalent than S. decipiens. This study is the first to report human sparganosis caused by S. decipiens in humans in Korea. PMID:26174823

  1. Malaria endemicity and co-infection with tissue-dwelling parasites in Sub-Saharan Africa: a review.

    PubMed

    Onkoba, Nyamongo W; Chimbari, Moses J; Mukaratirwa, Samson

    2015-01-01

    Mechanisms and outcomes of host-parasite interactions during malaria co-infections with gastrointestinal helminths are reasonably understood. In contrast, very little is known about such mechanisms in cases of malaria co-infections with tissue-dwelling parasites. This is lack of knowledge is exacerbated by misdiagnosis, lack of pathognomonic clinical signs and the chronic nature of tissue-dwelling helminthic infections. A good understanding of the implications of tissue-dwelling parasitic co-infections with malaria will contribute towards the improvement of the control and management of such co-infections in endemic areas. This review summarises and discusses current information available and gaps in research on malaria co-infection with gastro-intestinal helminths and tissue-dwelling parasites with emphasis on helminthic infections, in terms of the effects of migrating larval stages and intra and extracellular localisations of protozoan parasites and helminths in organs, tissues, and vascular and lymphatic circulations. PMID:26377900

  2. Genome-wide association analyses of genetic, phenotypic, and environmental risks in the age-related eye disease study

    PubMed Central

    Ryu, Euijung; Fridley, Brooke L.; Tosakulwong, Nirubol; Bailey, Kent R.

    2010-01-01

    Purpose To present genome-wide association analyses of genotypic and environmental risks on age-related macular degeneration (AMD) using 593 subjects from the age-related eye disease study (AREDS), after adjusting for population stratification and including questionable controls. Methods Single nucleotide polymorphism (SNP) associations with AMD for the non-Hispanic white population were investigated using a log-additive model after adjusting for population stratification. Replication of possible SNP-disease association was performed by genotyping an independent group of 444 AMD case and 300 control subjects. Logistic regression models were used to assess interaction effects between smoking and SNPs associated with AMD. Independent genetic risk effects among the disease-associated SNPs were also investigated using multiple logistic regression models. Results Population stratification was observed among the individuals having a self-reported race of non-Hispanic white. Risk allele frequencies at established AMD loci demonstrated that questionable control subjects were similar to control subjects in the AREDS, suggesting that they could be used as true controls in the analyses. Genetic loci (complement factor H [CFH], complement factor B [CFB], the age-related maculopathy susceptibility 2 locus containing the hypothetical gene [LOC387715]/the high-temperature requirement A-1 [HTRA1], and complement component 3 [C3]) that were already known to be associated with AMD were identified. An additional 26 novel SNPs potentially associated with AMD were identified, but none were definitely replicated in a second independent group of subjects. Smoking did not interact with known AMD loci, but was associated with late AMD. Statistically independent genetic signals were observed within the Pleckstrin homology domain-containing family A member 1 (PLEKHA1) region near LOC387715/HTRA1 and within a haplotype spanning exon 19 of the C3 gene. Conclusions Population stratification

  3. Genetic analyses of the human eye colours using a novel objective method for eye colour classification.

    PubMed

    Andersen, Jeppe D; Johansen, Peter; Harder, Stine; Christoffersen, Susanne R; Delgado, Mikaela C; Henriksen, Sarah T; Nielsen, Mette M; Sørensen, Erik; Ullum, Henrik; Hansen, Thomas; Dahl, Anders L; Paulsen, Rasmus R; Børsting, Claus; Morling, Niels

    2013-09-01

    In this study, we present a new objective method for measuring the eye colour on a continuous scale that allows researchers to associate genetic markers with different shades of eye colour. With the use of the custom designed software Digital Iris Analysis Tool (DIAT), the iris was automatically identified and extracted from high resolution digital images. DIAT was made user friendly with a graphical user interface. The software counted the number of blue and brown pixels in the iris image and calculated a Pixel Index of the Eye (PIE-score) that described the eye colour quantitatively. The PIE-score ranged from -1 to 1 (brown to blue). The software eliminated the need for user based interpretation and qualitative eye colour categories. In 94% (570) of 605 analyzed eye images, the iris region was successfully extracted and a PIE-score was calculated. A very high correlation between the PIE-score and the human perception of eye colour was observed. The correlations between the PIE-scores and the six IrisPlex SNPs (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, TYR rs1393350, SLC45A2 rs16891982 and IRF4 rs12203592) were analyzed in 570 individuals. Significant differences (p<10(-6)) in the PIE-scores of the individuals typed as HERC2 rs12913832 G (PIE=0.99) and rs12913832 GA (PIE=-0.71) or A (PIE=-0.87) were observed. We adjusted for the effect of HERC2 rs12913832 and showed that the quantitative PIE-scores were significantly associated with SNPs with minor effects (OCA2 rs1800407, SLC24A4 rs12896399 and TYR rs1393350) on the eye colour. We evaluated the two published prediction models for eye colour (IrisPlex [1] and Snipper[2]) and compared the predictions with the PIE-scores. We found good concordance with the prediction from individuals typed as HERC2 rs12913832 G. However, both methods had difficulties in categorizing individuals typed as HERC2 rs12913832 GA because of the large variation in eye colour in HERC2 rs12913832 GA individuals. With the use of

  4. The Salmonella typhimurium mar locus: molecular and genetic analyses and assessment of its role in virulence.

    PubMed Central

    Sulavik, M C; Dazer, M; Miller, P F

    1997-01-01

    The marRAB operon is a regulatory locus that controls multiple drug resistance in Escherichia coli. marA encodes a positive regulator of the antibiotic resistance response, acting by altering the expression of unlinked genes. marR encodes a repressor of marRAB transcription and controls the production of MarA in response to environmental signals. A molecular and genetic study of the homologous operon in Salmonella typhimurium was undertaken, and the role of marA in virulence in a murine model was assessed. Expression of E. coli marA (marAEC) present on a multicopy plasmid in S. typhimurium resulted in a multiple antibiotic resistance (Mar) phenotype, suggesting that a similar regulon exists in this organism. A genomic plasmid library containing S. typhimurium chromosomal sequences was introduced into an E. coli strain that was deleted for the mar locus and contained a single-copy marR'-'lacZ translational fusion. Plasmid clones that contained both S. typhimurium marR (marRSt) and marA (marASt) genes were identified as those that were capable of repressing expression of the fusion and which resulted in a Mar phenotype. The predicted amino acid sequences of MarRSt, MarASt, and MarBSt were 91, 86, and 42% identical, respectively, to the same genes from E. coli, while the operator/promoter region of the operon was 86% identical to the same 98-nucleotide-upstream region in E. coli. The marRAB transcriptional start sites for both organisms were determined by primer extension, and a marRABSt transcript of approximately 1.1 kb was identified by Northern blot analysis. Its accumulation was shown to be inducible by sodium salicylate. Open reading frames flanking the marRAB operon were also conserved. An S. typhimurium marA disruption strain was constructed by an allelic exchange method and compared to the wild-type strain for virulence in a murine BALB/c infection model. No effect on virulence was noted. The endogenous S. typhimurium plasmid that is associated with virulence

  5. Immunologic and genetic analyses of VmpA of a neurotropic strain of Borrelia turicatae.

    PubMed Central

    Cadavid, D; Pennington, P M; Kerentseva, T A; Bergström, S; Barbour, A G

    1997-01-01

    In mice infected with serotype A but not serotype B of the relapsing fever spirochete Borrelia turicatae, early invasion of the brain occurs. Serotypes A and B are further distinguished by the abundant surface protein they produce: VmpA and VmpB, respectively. Western blotting with monoclonal antibodies, one-dimensional peptide mapping, and partial amino acid sequencing demonstrated regions of the VmpA protein that differed from VmpB. Oligonucleotide primers based on the partial amino acid sequences of unique regions were used to amplify a portion of the VmpA gene (vmpA) by PCR, and the product was used as a probe in Southern blot and Northern blot analyses. These experiments showed that (i) expression of the vmpA sequence was determined at the level of transcription and (ii) the vmpA sequence was in two locations in serotype A and one location in serotype B. The vmpA gene at the expression-linked locus of serotype A was cloned and sequenced. An open reading frame would encode a polypeptide of 214 amino acids. The polypeptide expressed by Escherichia coli was bound by VmA-specific but not VmpB-specific antibody. Primer extension analysis identified a consensus sigma70-type promoter for vmpA at the expression locus. Phylogenetic analysis revealed that VmpA is homologous to small Vmp (Vsp) proteins of B. hermsii and to OspC proteins of B. burgdorferi. These findings indicate that a function of the Vsp-OspC family of proteins of Borrelia spp. may be differential localization in organs, including the brain, during infection. PMID:9234797

  6. Molecular Genetic Analyses of Mating Pheromones Reveal Intervariety Mating or Hybridization in Cryptococcus neoformans

    PubMed Central

    Chaturvedi, Vishnu; Fan, Jinjiang; Stein, Birgit; Behr, Melissa J.; Samsonoff, William A.; Wickes, Brian L.; Chaturvedi, Sudha

    2002-01-01

    The sexual mating of the pathogenic yeast Cryptococcus neoformans is important for pathogenesis studies because the fungal virulence is linked to the α mating type (MATα). We characterized C. neoformans mating pheromones (MFα 1 and MFa1) from 122 strains to understand intervariety hybridization or mating and intervariety virulence. MFα 1 in three C. neoformans varieties showed (a) specific nucleotide polymorphisms, (b) different copy numbers and chromosomal localizations, and (c) unique deduced amino acids in two geographic populations of C. neoformans var. gattii. MFα 1 of different varieties cross-hybridized in Southern hybridizations. Their phylogenetic analyses showed purifying selection (neutral evolution). These observations suggested that MATα strains from any of the three C. neoformans varieties could mate or hybridize in nature with MATa strains of C. neoformans var. neoformans. A few serotype A/D diploid strains provided evidence for mating or hybridization, while a majority of A/D strains tested positive for haploid MFα 1 identical to that of C. neoformans var. grubii. MFα 1 sequence and copy numbers in diploids were identical to those of C. neoformans var. grubii, while their MFa1 sequences were identical to those of C. neoformans var. neoformans; thus, these strains were hybrids. The mice survival curves and histological lesions revealed A/D diploids to be highly pathogenic, with pathogenicity levels similar to that of the C. neoformans var. grubii type strain and unlike the low pathogenicity levels of C. neoformans var. neoformans strains. In contrast to MFα 1 in three varieties, MFa1 amplicons and hybridization signals could be obtained only from two C. neoformans var. neoformans reference strains and eight A/D diploids. This suggested that a yet undiscovered MFa pheromone(s) in C. neoformans var. gattii and C. neoformans var. grubii is unrelated to, highly divergent from, or rarer than that in C. neoformans var. neoformans. These

  7. Minding the gap: Frequency of indels in mtDNA control region sequence data and influence on population genetic analyses

    USGS Publications Warehouse

    Pearce, J.M.

    2006-01-01

    Insertions and deletions (indels) result in sequences of various lengths when homologous gene regions are compared among individuals or species. Although indels are typically phylogenetically informative, occurrence and incorporation of these characters as gaps in intraspecific population genetic data sets are rarely discussed. Moreover, the impact of gaps on estimates of fixation indices, such as FST, has not been reviewed. Here, I summarize the occurrence and population genetic signal of indels among 60 published studies that involved alignments of multiple sequences from the mitochondrial DNA (mtDNA) control region of vertebrate taxa. Among 30 studies observing indels, an average of 12% of both variable and parsimony-informative sites were composed of these sites. There was no consistent trend between levels of population differentiation and the number of gap characters in a data block. Across all studies, the average influence on estimates of ??ST was small, explaining only an additional 1.8% of among population variance (range 0.0-8.0%). Studies most likely to observe an increase in ??ST with the inclusion of gap characters were those with < 20 variable sites, but a near equal number of studies with few variable sites did not show an increase. In contrast to studies at interspecific levels, the influence of indels for intraspecific population genetic analyses of control region DNA appears small, dependent upon total number of variable sites in the data block, and related to species-specific characteristics and the spatial distribution of mtDNA lineages that contain indels. ?? 2006 Blackwell Publishing Ltd.

  8. Genetic analyses of the major and minor locus groups of bacterial wilt resistance in tobacco using a diallel cross design.

    PubMed

    Qian, Y L; Chen, J; Dong, J J; Wu, Z C; Liu, Y H; Xue, B Y; Shao, F W; Sun, X Y

    2016-01-01

    Tobacco germplasm samples with various levels of resistance to bacterial wilt were selected to construct F1 combinations of parental inbred lines and orthogonal diallel crosses using samples collected in 2009 (15 germplasms), 2010 (15 germplasms), and 2011 (16 germplasms). A total of 1/2P (P + 1) experimental materials were used for analysis. Based on the analyses of major and minor locus groups, genetic effects on the incidence rate and index of bacterial wilt in tobacco were investigated on the 15th and 25th day during the early stage. Significant effects were observed in major locus groups, but not in minor locus groups. Specifically, adjacent major locus groups (J1 = 13,056 and J1 = 13,055; J1 = 14,080 and J1 = 14,079) were detected in both the first and second analyses with considerable effects. Based on the additive effects of minor locus groups on the rate and index of bacterial wilt, the effects on the incidence rates of Yunyan 85, DB101, and RG11 as well as the effects on the disease index of the latter two germplasms reached the maximum. This was consistent with the disease resistance indicators of these tobacco varieties in the field (corresponding broad heritability >20%). Genetic homozygous dominant loci (+ +) increased the rate of bacterial wilt (susceptible), whereas homozygous recessive loci (- -) reduced the index of bacterial wilt (resistant) with considerable additive effects and low dominant effects, suggesting that the inheritance of the bacterial wilt rate and index in tobacco mainly relies on additive inheritance. PMID:26909932

  9. Genetic variation over space and time: Analyses of extinct and remnant lake trout populations in the Upper Great Lakes

    USGS Publications Warehouse

    Guinand, B.; Scribner, K.T.; Page, K.S.; Burnham-Curtis, M. K.

    2003-01-01

    Lake trout (Salvelinus namaycush) in the upper Laurentian Great Lakes of North America experienced striking reductions in abundance and distribution during the mid–twentieth century. Complete collapse of populations was documented for Lake Michigan, and a few remnant populations remained only in lakes Huron and Superior. Using DNA obtained from historical scale collections, we analysed patterns of genetic diversity at five microsatellite loci from archived historical samples representing 15 populations (range 1940–1959) and from three contemporary remnant populations across lakes Huron and Superior (total n = 893). Demographic declines in abundance and the extirpation of native lake trout populations during the past 40 years have resulted in the loss of genetic diversity between lakes owing to extirpation of Lake Michigan populations and a temporal trend for reduction in allelic richness in the populations of lakes Superior and Huron. Naturally reproducing populations in Lake Superior, which had been considered to be remnants of historical populations, and which were believed to be responsible for the resurgence of lake trout numbers and distribution, have probably been affected by hatchery supplementation.

  10. The role of host genetic factors in respiratory tract infectious diseases: systematic review, meta-analyses and field synopsis

    PubMed Central

    Patarčić, Inga; Gelemanović, Andrea; Kirin, Mirna; Kolčić, Ivana; Theodoratou, Evropi; Baillie, Kenneth J.; de Jong, Menno D.; Rudan, Igor; Campbell, Harry; Polašek, Ozren

    2015-01-01

    Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of studies on tuberculosis, influenza, respiratory syncytial virus, SARS-Coronavirus and pneumonia. One single-nucleotide polymorphism from IL4 gene was significant for pooled respiratory infections (rs2070874; 1.66 [1.29–2.14]). We also detected an association of TLR2 gene with tuberculosis (rs5743708; 3.19 [2.03–5.02]). Subset analyses identified CCL2 as an additional risk factor for tuberculosis (rs1024611; OR = 0.79 [0.72–0.88]). The IL4-TLR2-CCL2 axis could be a highly interesting target for translation towards clinical use. However, this conclusion is based on low credibility of evidence - almost 95% of all identified studies had strong risk of bias or confounding. Future studies must build upon larger-scale collaborations, but also strictly adhere to the highest evidence-based principles in study design, in order to reduce research waste and provide clinically translatable evidence. PMID:26524966

  11. P. vivax Malaria and Dengue Fever Co-infection: A Cross-Sectional Study in the Brazilian Amazon

    PubMed Central

    Magalhães, Belisa M. L.; Siqueira, André M.; Alexandre, Márcia A. A.; Souza, Marcela S.; Gimaque, João B.; Bastos, Michele S.; Figueiredo, Regina M. P.; Melo, Gisely C.; Lacerda, Marcus V. G.; Mourão, Maria P. G.

    2014-01-01

    Background Malaria and dengue are the most prevalent vector-borne diseases worldwide and represent major public health problems. Both are endemic in tropical regions, propitiating co-infection. Only few co-infection cases have been reported around the world, with insufficient data so far to enhance the understanding of the effects of co-infection in the clinical presentation and severity. Methodology/Principal Findings A cross-sectional study was conducted (2009 to 2011) in hospitalized patients with acute febrile syndrome in the Brazilian Amazon. All patients were submitted to thick blood smear and PCR for Plasmodium sp. detection, ELISA, PCR and NS1 tests for dengue, viral hepatitis, HIV and leptospirosis. In total, 1,578 patients were recruited. Among them, 176 (11.1%) presented P. vivax malaria mono-infection, 584 (37%) dengue fever mono-infection, and 44 (2.8%) were co-infected. Co-infected patients had a higher chance of presenting severe disease (vs. dengue mono-infected), deep bleeding (vs. P. vivax mono-infected), hepatomegaly, and jaundice (vs. dengue mono-infected). Conclusions/Significance In endemic areas for dengue and malaria, jaundice (in dengue patients) and spontaneous bleeding (in malaria patients) should raise the suspicion of co-infection. Besides, whenever co-infection is confirmed, we recommend careful monitoring for bleeding and hepatic complications, which may result in a higher chance of severity, despite of the fact that no increased fatality rate was seen in this group. PMID:25340346

  12. Fatal leptospirosis and chikungunya co-infection: Do not forget leptospirosis during chikungunya outbreaks.

    PubMed

    Nhan, Tu-Xuan; Bonnieux, Eric; Rovery, Clarisse; De Pina, Jean-Jacques; Musso, Didier

    2016-01-01

    In endemic areas, leptospirosis can be missed by erroneous clinical or laboratory diagnosis of arboviroses or co-infections with arboviruses and an increase in mortality due to leptospirosis has already been reported during arboviruses outbreaks. During the French Polynesian chikungunya virus outbreak in 2014-2015, two leptospirosis and chikungunya co-infections were reported, one of which was fatal. Diagnosis of leptospiroses was delayed in the context of chikungunya outbreak. In the context of arbovirus outbreak, the risk of misdiagnosis of leptospirosis is maximum and clinicians should initiate early antibiotic therapy if leptospirosis is suspected. A delayed diagnosis of leptospirosis can be responsible for fatal outcome. Leptospirosis should be considered even if dengue or chikungunya virus infections are confirmed by reference molecular testing. PMID:27413690

  13. An 11-year-old boy with Plasmodium falciparum malaria and dengue co-infection.

    PubMed

    Issaranggoon na ayuthaya, Satja; Wangjirapan, Anchalee; Oberdorfer, Peninnah

    2014-01-01

    Malaria and dengue fever are major mosquito-borne public health problems in tropical countries. The authors report a malaria and dengue co-infection in an 11-year-old boy who presented with sustained fever for 10 days. The physical examination revealed a flushed face, injected conjunctivae and left submandibular lymphadenopathy. His peripheral blood smear showed few ring-form trophozoites of Plasmodium falciparum. His blood tests were positive for dengue NS-1 antigen and IgM antibody, and negative for IgG antibody. After the initiation of antimalarial treatment with artesunate and mefloquine, his clinical condition gradually improved. However, he still had low-grade fever that persisted for 6 days. Finally, he recovered well without fluid leakage, shock or severe bleeding. This case report emphasises that early recognition and concomitant treatment of malaria and dengue co-infection in endemic areas can improve clinical outcome and prevent serious complications. PMID:24692379

  14. Systematic permutation testing in GWAS pathway analyses: identification of genetic networks in dilated cardiomyopathy and ulcerative colitis

    PubMed Central

    2014-01-01

    Background Genome wide association studies (GWAS) are applied to identify genetic loci, which are associated with complex traits and human diseases. Analogous to the evolution of gene expression analyses, pathway analyses have emerged as important tools to uncover functional networks of genome-wide association data. Usually, pathway analyses combine statistical methods with a priori available biological knowledge. To determine significance thresholds for associated pathways, correction for multiple testing and over-representation permutation testing is applied. Results We systematically investigated the impact of three different permutation test approaches for over-representation analysis to detect false positive pathway candidates and evaluate them on genome-wide association data of Dilated Cardiomyopathy (DCM) and Ulcerative Colitis (UC). Our results provide evidence that the gold standard - permuting the case–control status – effectively improves specificity of GWAS pathway analysis. Although permutation of SNPs does not maintain linkage disequilibrium (LD), these permutations represent an alternative for GWAS data when case–control permutations are not possible. Gene permutations, however, did not add significantly to the specificity. Finally, we provide estimates on the required number of permutations for the investigated approaches. Conclusions To discover potential false positive functional pathway candidates and to support the results from standard statistical tests such as the Hypergeometric test, permutation tests of case control data should be carried out. The most reasonable alternative was case–control permutation, if this is not possible, SNP permutations may be carried out. Our study also demonstrates that significance values converge rapidly with an increasing number of permutations. By applying the described statistical framework we were able to discover axon guidance, focal adhesion and calcium signaling as important DCM-related pathways

  15. Co-Infection by Chytrid Fungus and Ranaviruses in Wild and Harvested Frogs in the Tropical Andes.

    PubMed

    Warne, Robin W; LaBumbard, Brandon; LaGrange, Seth; Vredenburg, Vance T; Catenazzi, Alessandro

    2016-01-01

    While global amphibian declines are associated with the spread of Batrachochytrium dendrobatidis (Bd), undetected concurrent co-infection by other pathogens may be little recognized threats to amphibians. Emerging viruses in the genus Ranavirus (Rv) also cause die-offs of amphibians and other ectotherms, but the extent of their distribution globally, or how co-infections with Bd impact amphibians are poorly understood. We provide the first report of Bd and Rv co-infection in South America, and the first report of Rv infections in the amphibian biodiversity hotspot of the Peruvian Andes, where Bd is associated with extinctions. Using these data, we tested the hypothesis that Bd or Rv parasites facilitate co-infection, as assessed by parasite abundance or infection intensity within individual adult frogs. Co-infection occurred in 30% of stream-dwelling frogs; 65% were infected by Bd and 40% by Rv. Among terrestrial, direct-developing Pristimantis frogs 40% were infected by Bd, 35% by Rv, and 20% co-infected. In Telmatobius frogs harvested for the live-trade 49% were co-infected, 92% were infected by Bd, and 53% by Rv. Median Bd and Rv loads were similar in both wild (Bd = 101.2 Ze, Rv = 102.3 viral copies) and harvested frogs (Bd = 103.1 Ze, Rv = 102.7 viral copies). While neither parasite abundance nor infection intensity were associated with co-infection patterns in adults, these data did not include the most susceptible larval and metamorphic life stages. These findings suggest Rv distribution is global and that co-infection among these parasites may be common. These results raise conservation concerns, but greater testing is necessary to determine if parasite interactions increase amphibian vulnerability to secondary infections across differing life stages, and constitute a previously undetected threat to declining populations. Greater surveillance of parasite interactions may increase our capacity to contain and mitigate the impacts of these and other wildlife

  16. Hepatitis C in human immunodeficiency virus co-infected individuals: Is this still a “special population”?

    PubMed Central

    Karageorgopoulos, Drosos E; Allen, Joanna; Bhagani, Sanjay

    2015-01-01

    A substantial proportion of individuals with chronic hepatitis C virus (HCV) are co-infected with human immunodeficiency virus (HIV). Co-infected individuals are traditionally considered as one of the “special populations” amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals (DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the “special population” designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users. PMID:26244068

  17. Co-Infection by Chytrid Fungus and Ranaviruses in Wild and Harvested Frogs in the Tropical Andes

    PubMed Central

    Warne, Robin W.; LaBumbard, Brandon; LaGrange, Seth; Vredenburg, Vance T.; Catenazzi, Alessandro

    2016-01-01

    While global amphibian declines are associated with the spread of Batrachochytrium dendrobatidis (Bd), undetected concurrent co-infection by other pathogens may be little recognized threats to amphibians. Emerging viruses in the genus Ranavirus (Rv) also cause die-offs of amphibians and other ectotherms, but the extent of their distribution globally, or how co-infections with Bd impact amphibians are poorly understood. We provide the first report of Bd and Rv co-infection in South America, and the first report of Rv infections in the amphibian biodiversity hotspot of the Peruvian Andes, where Bd is associated with extinctions. Using these data, we tested the hypothesis that Bd or Rv parasites facilitate co-infection, as assessed by parasite abundance or infection intensity within individual adult frogs. Co-infection occurred in 30% of stream-dwelling frogs; 65% were infected by Bd and 40% by Rv. Among terrestrial, direct-developing Pristimantis frogs 40% were infected by Bd, 35% by Rv, and 20% co-infected. In Telmatobius frogs harvested for the live-trade 49% were co-infected, 92% were infected by Bd, and 53% by Rv. Median Bd and Rv loads were similar in both wild (Bd = 101.2 Ze, Rv = 102.3 viral copies) and harvested frogs (Bd = 103.1 Ze, Rv = 102.7 viral copies). While neither parasite abundance nor infection intensity were associated with co-infection patterns in adults, these data did not include the most susceptible larval and metamorphic life stages. These findings suggest Rv distribution is global and that co-infection among these parasites may be common. These results raise conservation concerns, but greater testing is necessary to determine if parasite interactions increase amphibian vulnerability to secondary infections across differing life stages, and constitute a previously undetected threat to declining populations. Greater surveillance of parasite interactions may increase our capacity to contain and mitigate the impacts of these and other wildlife

  18. Microsporidian parasites feminise hosts without paramyxean co-infection: support for convergent evolution of parasitic feminisation.

    PubMed

    Ironside, Joseph Edward; Alexander, Jenna

    2015-05-01

    Feminisation of amphipod crustaceans is associated with the presence of at least three microsporidian parasites and one paramyxean parasite, suggesting that the ability to feminise has evolved multiple times in parasites of amphipods. Co-infection by a paramyxean with one of the putative microsporidian feminisers, Dictyocoela duebenum, has inspired the alternative hypothesis that all feminisation of amphipods is caused by paramyxea and that all microsporidian associations with feminisation are due to co-infection with paramyxea (Short et al., 2012). In a population of the amphipod Gammarus duebeni, breeding experiments demonstrate that the microsporidia D. duebenum and Nosema granulosis are associated with feminisation in the absence of paramyxea. Co-infection of the two microsporidia is no more frequent than expected at random and each parasite is associated with feminisation in the absence of the other. These findings support the original hypothesis that the ability to feminise amphipods has evolved in microsporidia on multiple occasions. Additionally, the occurrence of a non-feminising strain of D. duebenum in Gammarus pulex suggests that different strains vary in their feminising ability, even within microsporidian species. The presence or absence of feminising ability in a particular microsporidian strain should not therefore be generalised to the species as a whole. PMID:25747725

  19. Survival Rates of Human Immunodeficiency Virus and Tuberculosis Co-Infected Patients

    PubMed Central

    Roshanaei, Ghodratollah; Sabouri Ghannad, Masoud; Saatchi, Mohammad; Khazaei, Salman; Mirzaei, Mohammad

    2014-01-01

    Background: At present, limited clinical data is available regarding survival rates of patients co-infected with human immunodeficiency virus (HIV)/tuberculosis (TB) in developing countries. Objectives: The present study aimed to evaluate the effect of HIV infection on the survival chances of active TB adults who disclosed their symptoms of TB in this part of Iran. Patients and Methods: The records and data of 807 patients only infected with TB and 21 co-infected patients with HIV/TB, who were admitted to primary health care units in Iran, were evaluated. Their survival time was analyzed using the Kaplan-Meier Estimator, Log-rank test and SPSS version 16. Results: Cox regression analysis showed that co-infection with HIV significantly affects the survival rate of TB patients so that the rate of death was 20.7 (8.1-53) times more than TB infected patients alone. Also, married patients with tuberculosis were 2.7 times more at risk of death than single subjects. We also confirmed that in HIV/TB positive patients, married individuals were more prone to death than single subjects (P value < 0.001). Conclusions: Our results denote the need to progress diagnostic and preventive measures in this part of Iran. PMID:25371800

  20. HIV-Mycobacterium tuberculosis co-infection: a 'danger-couple model' of disease pathogenesis.

    PubMed

    Shankar, Esaki M; Vignesh, Ramachandran; Ellegård, Rada; Barathan, Muttiah; Chong, Yee K; Bador, M Kahar; Rukumani, Devi V; Sabet, Negar S; Kamarulzaman, Adeeba; Velu, Vijayakumar; Larsson, Marie

    2014-03-01

    Tuberculosis (TB) and human immunodeficiency virus (HIV) infection interfere and impact the pathogenesis phenomena of each other. Owing to atypical clinical presentations and diagnostic complications, HIV/TB co-infection continues to be a menace for healthcare providers. Although the increased access to highly active antiretroviral therapy (HAART) has led to a reduction in HIV-associated opportunistic infections and mortality, the concurrent management of HIV/TB co-infection remains a challenge owing to adverse effects, complex drug interactions, overlapping toxicities and tuberculosis -associated immune reconstitution inflammatory syndrome. Several hypotheses have been put forward for the exacerbation of tuberculosis by HIV and vice versa supported by immunological studies. Discussion on the mechanisms produced by infectious cofactors with impact on disease pathology could shed light on how to design potential interventions that could decelerate disease progression. With no vaccine for HIV and lack of an effective vaccine for tuberculosis, it is essential to design strategies against HIV-TB co-infection. PMID:24214523

  1. Within guild co-infections influence parasite community membership: a longitudinal study in African Buffalo.

    PubMed

    Henrichs, Brian; Oosthuizen, Marinda C; Troskie, Milana; Gorsich, Erin; Gondhalekar, Carmen; Beechler, Brianna R; Ezenwa, Vanessa O; Jolles, Anna E

    2016-07-01

    Experimental studies in laboratory settings have demonstrated a critical role of parasite interactions in shaping parasite communities. The sum of these interactions can produce diverse effects on individual hosts as well as influence disease emergence and persistence at the population level. A predictive framework for the effects of parasite interactions in the wild remains elusive, largely because of limited longitudinal or experimental data on parasite communities of free-ranging hosts. This 4-year study followed a community of haemoparasites in free-ranging African buffalo (Syncerus caffer). We detected infection by 11 haemoparasite species using PCR-based diagnostic techniques, and analyzed drivers of infection patterns using generalized linear mixed models to understand the role of host characteristics and season on infection likelihood. We tested for (i) effects of co-infection by other haemoparasites (within guild) and (ii) effects of parasites infecting different tissue types (across guild). We found that within guild co-infections were the strongest predictors of haemoparasite infections in the buffalo; but that seasonal and host characteristics also had important effects. In contrast, the evidence for across-guild effects of parasites utilizing different tissue on haemoparasite infection was weak. These results provide a nuanced view of the role of co-infections in determining haemoparasite infection patterns in free living mammalian hosts. Our findings suggest a role for interactions among parasites infecting a single tissue type in determining infection patterns. PMID:27084785

  2. Cutaneous Co-infected Cytomegalovirus and Herpes Simplex Virus Perigenital Ulcers in Human Immunodeficiency Virus Patients.

    PubMed

    Schoenfeld, Jason; Cannon, Sarah; Cam, Kristin; Keller, Matthew

    2013-10-01

    There is uncertainty regarding the pathogenic nature of cytomegalovirus in cutaneous lesions co-infected with herpes simplex virus. It is widely believed that herpes simplex virus is the main pathogenic factor in such lesions and that cytomegalovirus plays little if any role. There are, however, isolated case reports that describe cytomegalovirus as an important driving pathogen in such lesions. The authors present two human immunodeficiency virus patients who have cytomegalovirus and herpes simplex virus co-infected perigenital ulcers, one of whom improved on valacyclovir, while the other, who was already on valacyclovir for chronic herpes simplex virus suppression, showed no improvement with a single dose of cidofovir. He only showed rapid improvement when treated with valganciclovir. The latter patient underscores the viewpoint that at least in some cases, cytomegalovirus may be an important driving force behind the formation of such lesions. The authors therefore recommend that clinicians be aware of the possible pathogenic role of cytomegalovirus in these ulcers, and, in nonhealing ulcers, use anti-cytomegalovirus agents to prevent the onset of systemic disease. These results warrant further study of the pathogenesis of cytomegalovirus in co-infected herpes simplex virus ulcers. PMID:24155993

  3. Implications of co-infection of Leptomonas in visceral leishmaniasis in India.

    PubMed

    Selvapandiyan, Angamuthu; Ahuja, Kavita; Puri, Niti; Krishnan, Anuja

    2015-12-01

    Protozoan parasites Leishmania donovani (family: Trypanosomatidae) cause fatal visceral leishmaniasis (VL) and the infection relapses in apparently cured population as post kala-azar dermal leishmaniasis (PKDL) in the Indian subcontinent. In recent years co-infection of another Trypanosomatid parasite Leptomonas with L. donovani during VL/PKDL in this region has become prominent. The observation of clinically lesser-known insect parasite, Leptomonas in leishmaniasis is intriguing to researchers. The presence of Leishmania look alike Leptomonas in the cultures of clinical isolates of Leishmania has been worrisome to those, who prefer to work with pure Leishmania cultures for drug and vaccine development or immune response studies. The exact implications of such a co-habitation, which might lead to a delay in the diagnostics of VL and elevate mortality, need a thorough investigation. Also whether Leptomonas is involved in leishmaniasis manifestation needs to be ascertained. Thus we are currently witnessing a new paradigm of a parasitic co-infection in VL/PKDL cases in India and this review outlines various opportunities for further research in understanding such emerging co-infection. PMID:26492813

  4. Genetics

    MedlinePlus

    Homozygous; Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  5. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  6. Phenotypic and Genetic Analyses of the Varroa Sensitive Hygienic Trait in Russian Honey Bee (Hymenoptera: Apidae) Colonies

    PubMed Central

    Kirrane, Maria J.; de Guzman, Lilia I.; Holloway, Beth; Frake, Amanda M.; Rinderer, Thomas E.; Whelan, Pádraig M.

    2015-01-01

    Varroa destructor continues to threaten colonies of European honey bees. General hygiene, and more specific Varroa Sensitive Hygiene (VSH), provide resistance towards the Varroa mite in a number of stocks. In this study, 32 Russian (RHB) and 14 Italian honey bee colonies were assessed for the VSH trait using two different assays. Firstly, colonies were assessed using the standard VSH behavioural assay of the change in infestation of a highly infested donor comb after a one-week exposure. Secondly, the same colonies were assessed using an “actual brood removal assay” that measured the removal of brood in a section created within the donor combs as a potential alternative measure of hygiene towards Varroa-infested brood. All colonies were then analysed for the recently discovered VSH quantitative trait locus (QTL) to determine whether the genetic mechanisms were similar across different stocks. Based on the two assays, RHB colonies were consistently more hygienic toward Varroa-infested brood than Italian honey bee colonies. The actual number of brood cells removed in the defined section was negatively correlated with the Varroa infestations of the colonies (r2 = 0.25). Only two (percentages of brood removed and reproductive foundress Varroa) out of nine phenotypic parameters showed significant associations with genotype distributions. However, the allele associated with each parameter was the opposite of that determined by VSH mapping. In this study, RHB colonies showed high levels of hygienic behaviour towards Varroa -infested brood. The genetic mechanisms are similar to those of the VSH stock, though the opposite allele associates in RHB, indicating a stable recombination event before the selection of the VSH stock. The measurement of brood removal is a simple, reliable alternative method of measuring hygienic behaviour towards Varroa mites, at least in RHB stock. PMID:25909856

  7. Phenotypic and genetic analyses of the varroa sensitive hygienic trait in Russian honey bee (hymenoptera: apidae) colonies.

    PubMed

    Kirrane, Maria J; de Guzman, Lilia I; Holloway, Beth; Frake, Amanda M; Rinderer, Thomas E; Whelan, Pádraig M

    2014-01-01

    Varroa destructor continues to threaten colonies of European honey bees. General hygiene, and more specific Varroa Sensitive Hygiene (VSH), provide resistance towards the Varroa mite in a number of stocks. In this study, 32 Russian (RHB) and 14 Italian honey bee colonies were assessed for the VSH trait using two different assays. Firstly, colonies were assessed using the standard VSH behavioural assay of the change in infestation of a highly infested donor comb after a one-week exposure. Secondly, the same colonies were assessed using an "actual brood removal assay" that measured the removal of brood in a section created within the donor combs as a potential alternative measure of hygiene towards Varroa-infested brood. All colonies were then analysed for the recently discovered VSH quantitative trait locus (QTL) to determine whether the genetic mechanisms were similar across different stocks. Based on the two assays, RHB colonies were consistently more hygienic toward Varroa-infested brood than Italian honey bee colonies. The actual number of brood cells removed in the defined section was negatively correlated with the Varroa infestations of the colonies (r2 = 0.25). Only two (percentages of brood removed and reproductive foundress Varroa) out of nine phenotypic parameters showed significant associations with genotype distributions. However, the allele associated with each parameter was the opposite of that determined by VSH mapping. In this study, RHB colonies showed high levels of hygienic behaviour towards Varroa -infested brood. The genetic mechanisms are similar to those of the VSH stock, though the opposite allele associates in RHB, indicating a stable recombination event before the selection of the VSH stock. The measurement of brood removal is a simple, reliable alternative method of measuring hygienic behaviour towards Varroa mites, at least in RHB stock. PMID:25909856

  8. Co-infection of Ticks: The Rule Rather Than the Exception

    PubMed Central

    Moutailler, Sara; Valiente Moro, Claire; Vaumourin, Elise; Michelet, Lorraine; Tran, Florence Hélène; Devillers, Elodie; Cosson, Jean-François; Gasqui, Patrick; Van, Van Tran; Mavingui, Patrick; Vourc’h, Gwenaël; Vayssier-Taussat, Muriel

    2016-01-01

    Introduction Ticks are the most common arthropod vectors of both human and animal diseases in Europe, and the Ixodes ricinus tick species is able to transmit a large number of bacteria, viruses and parasites. Ticks may also be co-infected with several pathogens, with a subsequent high likelihood of co-transmission to humans or animals. However few data exist regarding co-infection prevalences, and these studies only focus on certain well-known pathogens. In addition to pathogens, ticks also carry symbionts that may play important roles in tick biology, and could interfere with pathogen maintenance and transmission. In this study we evaluated the prevalence of 38 pathogens and four symbionts and their co-infection levels as well as possible interactions between pathogens, or between pathogens and symbionts. Methodology/principal findings A total of 267 Ixodes ricinus female specimens were collected in the French Ardennes and analyzed by high-throughput real-time PCR for the presence of 37 pathogens (bacteria and parasites), by rRT-PCR to detect the presence of Tick-Borne encephalitis virus (TBEV) and by nested PCR to detect four symbionts. Possible multipartite interactions between pathogens, or between pathogens and symbionts were statistically evaluated. Among the infected ticks, 45% were co-infected, and carried up to five different pathogens. When adding symbiont prevalences, all ticks were infected by at least one microorganism, and up to eight microorganisms were identified in the same tick. When considering possible interactions between pathogens, the results suggested a strong association between Borrelia garinii and B. afzelii, whereas there were no significant interactions between symbionts and pathogens. Conclusion/significance Our study reveals high pathogen co-infection rates in ticks, raising questions about possible co-transmission of these agents to humans or animals, and their consequences to human and animal health. We also demonstrated high

  9. TB-HIV co-infection among pregnant women in Karnataka, South India: A case series.

    PubMed

    Suresh, Shastri; Sharath, Burugina N; Anita, Shet; Lalitha, Ravindra; Prasad, Tripathy J; Rewari, Bharat B

    2016-01-01

    Tuberculosis (TB) is a significant contributor to mortality in HIV-infected patients. Concurrent TB infection is also a significant contributing factor to maternal mortality in human immunodeficiency virus (HIV)-infected pregnant women. Studies addressing the outcomes of TB and HIV co-infection among pregnant women are generally infrequent. Although limited, the records maintained by the Revised National Tuberculosis Control Programme (RNTCP) and the National AIDS Control Programme (NACP) in Karnataka State, Southern India provide information about the numbers of pregnant women who are co-infected with TB and HIV and their pregnancy outcomes. We reviewed the data and conducted this study to understand how TB-HIV co-infection influences the outcomes of pregnancy in this setting. We sought to determine the incidence and treatment and delivery outcomes of TB-HIV co-infected pregnant women in programmatic settings in Karnataka State in southern India. The study participants were all the HIV-infected pregnant women who were screened for tuberculosis under the NACP from 2008 to 2012. For the purposes of this study, the program staff in the field gathered the data regarding on treatment and delivery outcomes of pregnant women. A total of seventeen pregnant women with TB-HIV co-infection were identified among 3,165,729 pregnant women (for an incidence of 5.4 per million pregnancies). The median age of these pregnant women was 24 years, and majority were primiparous women with WHO HIV stage III disease and were on a stavudine-based ART regimen. The maternal mortality rates were 18% before delivery and 24% after delivery. The abortion rate was 24%, and the neonatal mortality rate was 10%. The anti-tuberculosis treatment and anti-retroviral treatment outcome mortality rates were 30% and 53%, respectively. Although the incidence of TB among the HIV-infected pregnant women was marginally less than that among the non-HIV-infected women, the delivery outcomes were relatively

  10. Quality of life among tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health care patients in three districts in South Africa

    PubMed Central

    2012-01-01

    Introduction TB and HIV co-morbidity amount to a massive burden on healthcare systems in many countries. This study investigates health related quality of life among tuberculosis (TB), TB retreatment and TB-HIV co-infected public primary health care patients in three districts in South Africa. Methods A cross sectional study was conducted among 4900 TB patients who were in the first month of anti-TB treatment in primary public health care clinics in three districts in South Africa. Quality of life was assessed using the social functioning (SF)-12 Health Survey through face to face interviews. Associations of physical health (Physical health Component Summary = PCS) and mental health (Mental health Component Summary = MCS) were identified using logistic regression analyses. Results The overall physical and mental health scores were 42.5 and 40.7, respectively. Emotional role, general health and bodily pain had the lowest sub-scale scores, while energy and fatigue and mental health had the highest domain scores. Independent Kruskal–Wallis tests found significant positive effects of being TB-HIV co-infected on the domains of mental health functioning, emotional role, energy and fatigue, social function and physical role, while significant negative effects were observed on general health, bodily pain and physical function. In multivariable analysis higher educational, lower psychological distress, having fewer chronic conditions and being HIV negative were significantly positively associated with PCS, and low poverty, low psychological distress and being HIV positive were positively significantly associated with MCS. Conclusion TB and HIV weaken patients’ physical functioning and impair their quality of life. It is imperative that TB control programmes at public health clinics design strategies to improve the quality of health of TB and HIV co-infected patients. PMID:22742511

  11. Combining case-control and case-trio data from the same population in genetic association analyses: overview of approaches and illustration with a candidate gene study.

    PubMed

    Infante-Rivard, Claire; Mirea, Lucia; Bull, Shelley B

    2009-09-01

    In genetic association studies, investigators compare allele or genotype frequencies in unrelated case and control subjects or examine preferential allele transmissions from parents to affected offspring. In many genetic case-control studies, the collection of DNA material extends to relatives such as parents of cases. Thus, case-control and case-parent trio association analyses are possible. Whereas the goal of collecting genetic information from family members in a study initially designed as a case-control study is to enrich the genetic analysis, increase power, or address concern about population structure bias, methods of combining genetic data from unrelated case and control subjects with genetic trio data from the same study population are not well known. A number of hybrid approaches have been developed that utilize such data together. In this paper, the authors describe key features of genetic case-control and case-parent trio studies and review commonly used methods of genetic analysis for case-parent trio designs. In addition, they provide a pragmatic review of statistical methods and available software for existing hybrid approaches that combine various components of case-control and genetic trio data. The application of all methods is illustrated using a candidate gene study of childhood leukemia that included case-control subjects and their parents. PMID:19635737

  12. Structural and genetic analyses reveal the protein SepF as a new membrane anchor for the Z ring

    PubMed Central

    Duman, Ramona; Ishikawa, Shu; Celik, Ilkay; Strahl, Henrik; Ogasawara, Naotake; Troc, Paulina; Löwe, Jan; Hamoen, Leendert W.

    2013-01-01

    A key step in bacterial cell division is the polymerization of the tubulin homolog FtsZ at midcell. FtsZ polymers are anchored to the cell membrane by FtsA and are required for the assembly of all other cell division proteins. In Gram-positive and cyanobacteria, FtsZ filaments are aligned by the protein SepF, which in vitro polymerizes into large rings that bundle FtsZ filaments. Here we describe the crystal structure of the only globular domain of SepF, located within the C-terminal region. Two-hybrid data revealed that this domain comprises the FtsZ binding site, and EM analyses showed that it is sufficient for ring formation, which is explained by the filaments in the crystals of SepF. Site-directed mutagenesis, gel filtration, and analytical ultracentrifugation indicated that dimers form the basic units of SepF filaments. High-resolution structured illumination microscopy suggested that SepF is membrane associated, and it turned out that purified SepF not only binds to lipid membranes, but also recruits FtsZ. Further genetic and biochemical analyses showed that an amphipathic helix at the N terminus functions as the membrane-binding domain, making SepF a unique membrane anchor for the FtsZ ring. This clarifies why Bacillus subtilis grows without FtsA or the putative membrane anchor EzrA and why bacteria lacking FtsA contain SepF homologs. Both FtsA and SepF use an amphipathic helix for membrane binding. These helices prefer positively curved membranes due to relaxed lipid density; therefore this type of membrane anchor may assist in keeping the Z ring positioned at the strongly curved leading edge of the developing septum. PMID:24218584

  13. Symptomatic co-infection with Babesia microti and Borrelia burgdorferi in patient after international exposure; a challenging case in Poland.

    PubMed

    Jabłońska, Joanna; Żarnowska-Prymek, Hanna; Stańczak, Joanna; Kozłowska, Joanna; Wiercińska-Drapało, Alicja

    2016-06-01

    The report presents a well-documented case of symptomatic co-infection of Babesia microti and Borrelia burgdorferi in a Polish immunocompetent patient after travelling to Canada and the USA. PMID:27294655

  14. Genome-wide association analyses reveal complex genetic architecture underlying natural variation for flowering time in canola.

    PubMed

    Raman, H; Raman, R; Coombes, N; Song, J; Prangnell, R; Bandaranayake, C; Tahira, R; Sundaramoorthi, V; Killian, A; Meng, J; Dennis, E S; Balasubramanian, S

    2016-06-01

    Optimum flowering time is the key to maximize canola production in order to meet global demand of vegetable oil, biodiesel and canola-meal. We reveal extensive variation in flowering time across diverse genotypes of canola under field, glasshouse and controlled environmental conditions. We conduct a genome-wide association study and identify 69 single nucleotide polymorphism (SNP) markers associated with flowering time, which are repeatedly detected across experiments. Several associated SNPs occur in clusters across the canola genome; seven of them were detected within 20 Kb regions of a priori candidate genes; FLOWERING LOCUS T, FRUITFUL, FLOWERING LOCUS C, CONSTANS, FRIGIDA, PHYTOCHROME B and an additional five SNPs were localized within 14 Kb of a previously identified quantitative trait loci for flowering time. Expression analyses showed that among FLC paralogs, BnFLC.A2 accounts for ~23% of natural variation in diverse accessions. Genome-wide association analysis for FLC expression levels mapped not only BnFLC.C2 but also other loci that contribute to variation in FLC expression. In addition to revealing the complex genetic architecture of flowering time variation, we demonstrate that the identified SNPs can be modelled to predict flowering time in diverse canola germplasm accurately and hence are suitable for genomic selection of adaptative traits in canola improvement programmes. PMID:26428711

  15. Quantitative Proteomic and Genetic Analyses of the Schizophrenia Susceptibility Factor Dysbindin Identify Novel Roles of the BLOC-1 Complex

    PubMed Central

    Gokhale, Avanti; Larimore, Jennifer; Werner, Erica; So, Lomon; De Luca, Andres Moreno; Lese-Martin, Christa; Lupashin, Vladimir V.; Smith, Yoland; Faundez, Victor

    2012-01-01

    The Biogenesis of Lysosome-Related Organelles Complex 1 (BLOC-1) is a protein complex containing the schizophrenia susceptibility factor dysbindin, which is encoded by the gene DTNBP1. However, mechanisms engaged by dysbindin defining schizophrenia susceptibility pathways have not been quantitatively elucidated. Here, we discovered prevalent and novel cellular roles of the BLOC-1 complex in neuronal cells by performing large-scale Stable Isotopic Labeling of Cells in Culture quantitative proteomics (SILAC) combined with genetic analyses in dysbindin-null mice (Mus musculus) and the genome of schizophrenia patients. We identified 24 proteins that associate with the BLOC-1 complex many of which were altered in content/distribution in cells or tissues deficient in BLOC-1. New findings include BLOC-1 interactions with the COG complex, a Golgi apparatus tether, and antioxidant enzymes peroxiredoxins 1-2. Importantly, loci encoding eight of the 24 proteins are affected by genomic copy number variation in schizophrenia patients. Thus, our quantitative proteomic studies expand the functional repertoire of the BLOC-1 complex and provide insight into putative molecular pathways of schizophrenia susceptibility. PMID:22423091

  16. Using detection dogs and genetic analyses of scat to expand knowledge and assist felid conservation in Misiones, Argentina.

    PubMed

    DeMatteo, Karen E; Rinas, Miguel A; Argüelles, Carina F; Holman, Bernardo E; Di Bitetti, Mario S; Davenport, Barbara; Parker, Patricia G; Eggert, Lori S

    2014-11-01

    Many carnivores require large ranges to meet their ecological and energetic needs; however, anthropogenic changes threaten species and their habitats. Camera traps have been used to effectively collect data on carnivores in a variety of habitat types; however, a single survey effort is typically limited to species that have similar body size, habitat use and movement patterns, and individual identification of animals is not always possible. We evaluated whether scat detection dogs could effectively survey for 4 wide-ranging felids that vary in these characteristics: jaguars (Panthera onca), pumas (Puma concolor), ocelots (Leopardus pardalis) and oncillas (Leopardus tigrinus). From June to October 2009 and May to August 2011, a detection dog-handler team detected 588 scats, from which 176 unique genotypes were detected. We assigned sex to 84.7% of the genotyped scats and identified 55 individuals multiple times. The effectiveness of these noninvasive techniques (detection dogs and genetic analyses of scat) not only opens the door for additional studies in areas that were previously difficult or impossible with standard survey techniques, but also provides conservationists with a set of tools that overcome some of the limitations associated with the use of camera traps alone. PMID:25236691

  17. Nematode–coccidia parasite co-infections in African buffalo: Epidemiology and associations with host condition and pregnancy

    PubMed Central

    Gorsich, Erin E.; Ezenwa, Vanessa O.; Jolles, Anna E.

    2014-01-01

    Co-infections are common in natural populations and interactions among co-infecting parasites can significantly alter the transmission and host fitness costs of infection. Because both exposure and susceptibility vary over time, predicting the consequences of parasite interactions on host fitness and disease dynamics may require detailed information on their effects across different environmental (season) and host demographic (age, sex) conditions. This study examines five years of seasonal health and co-infection patterns in African buffalo (Syncerus caffer). We use data on two groups of gastrointestinal parasites, coccidia and nematodes, to test the hypothesis that co-infection and season interact to influence (1) parasite prevalence and intensity and (2) three proxies for host fitness: host pregnancy, host body condition, and parasite aggregation. Our results suggest that season-dependent interactions between nematodes and coccidia affect the distribution of infections. Coccidia prevalence, coccidia intensity and nematode prevalence were sensitive to factors that influence host immunity and exposure (age, sex, and season) but nematode intensity was most strongly predicted by co-infection with coccidia and its interaction with season. The influence of co-infection on host body condition and parasite aggregation occurred in season-dependent manner. Co-infected buffalo in the early wet season were in worse condition, had a less aggregated distribution of nematode parasites, and lower nematode infection intensity than buffalo infected with nematodes alone. We did not detect an effect of infection or co-infection on host pregnancy. These results suggest that demographic and seasonal variation may mediate the effects of parasites, and their interactions, on the distribution and fitness costs of infection. PMID:25161911

  18. Co-infection with Plasmodium berghei and Trypanosoma brucei increases severity of malaria and trypanosomiasis in mice.

    PubMed

    Ademola, Isaiah Oluwafemi; Odeniran, Paul Olalekan

    2016-07-01

    Individuals in natural populations may be infected with multiple different parasites at a time. These parasites may interact with each other or act independently in the host, and this may result to varying outcomes on host health and survival. This study therefore aimed at investigating the health impact of co-infection of mice with Plasmodium berghei and Trypanosoma brucei. Forty Swiss albino mice (14-17g) were divided into four groups of ten. Mice in groups A and B received 10(6)P. berghei and groups B and C 10(5)T. brucei, while group D were uninfected. The co-infected mice had higher P. berghei and T. brucei parasitaemia, compared with the mono-infected mice. The co-infected mice had significantly (p<0.05) lower survival rate compared with the mono-infected mice. Co-infection of mice with P. berghei and T. brucei resulted in rapid P. berghei and T. brucei development and increased parasitaemia. The leukocyte numbers significantly (p<0.05) reduced on days 12 and 15 post infection among P. berghei infected mice, in the presence or absence of T. brucei. Anaemia and hypoglycaemia was more severe in the co-infected mice. Therefore, co-infection of mice with P. berghei and T. brucei may increase pathologic impact to the host by increasing parasitaemia. PMID:27021269

  19. Hepatitis B and C co-infection in HIV/AIDS population in the state of Michigan.

    PubMed

    Butt, Z A; Wilkins, M J; Hamilton, E; Todem, D; Gardiner, J C; Saeed, M

    2013-12-01

    A retrospective cohort study was conducted from 1 January 2006 to 31 December 2009 in Michigan to estimate the prevalence of HIV and hepatitis co-infection and identify associated factors. The prevalence of co-infection was 4.1% [95% confidence interval (CI) 3.8-4.5]. Multivariable logistic regression analysis revealed a significant association between co-infection and being male and: of Black race [odds ratio (OR) 2.0, 95% CI 1.2-3.6] and of Other race (OR 3.5, 95% CI 1.7-7.0) compared to Hispanic race. A significant association was found between co-infection and risk categories of blood products (OR 11.1, 95% CI 6.2-20.2), injecting drug user (IDU) (OR 3.6, 95% CI 2.7-4.8) and men who have sex with men/IDU (OR 3.4, 95% CI 2.4-4.9) in addition to two interactions; one between sex and current HIV status and the other between current HIV status and age at HIV diagnosis. Our results document the changing epidemiology of HIV-hepatitis co-infection which can guide preventive measures and interventions to reduce the prevalence of hepatitis co-infection. PMID:23481310

  20. Trypanosoma cruzi-Trypanosoma rangeli co-infection ameliorates negative effects of single trypanosome infections in experimentally infected Rhodnius prolixus.

    PubMed

    Peterson, Jennifer K; Graham, Andrea L; Elliott, Ryan J; Dobson, Andrew P; Triana Chávez, Omar

    2016-08-01

    Trypanosoma cruzi, causative agent of Chagas disease, co-infects its triatomine vector with its sister species Trypanosoma rangeli, which shares 60% of its antigens with T. cruzi. Additionally, T. rangeli has been observed to be pathogenic in some of its vector species. Although T. cruzi-T. rangeli co-infections are common, their effect on the vector has rarely been investigated. Therefore, we measured the fitness (survival and reproduction) of triatomine species Rhodnius prolixus infected with just T. cruzi, just T. rangeli, or both T. cruzi and T. rangeli. We found that survival (as estimated by survival probability and hazard ratios) was significantly different between treatments, with the T. cruzi treatment group having lower survival than the co-infected treatment. Reproduction and total fitness estimates in the T. cruzi and T. rangeli treatments were significantly lower than in the co-infected and control groups. The T. cruzi and T. rangeli treatment group fitness estimates were not significantly different from each other. Additionally, co-infected insects appeared to tolerate higher doses of parasites than insects with single-species infections. Our results suggest that T. cruzi-T. rangeli co-infection could ameliorate negative effects of single infections of either parasite on R. prolixus and potentially help it to tolerate higher parasite doses. PMID:27174360

  1. Direct and indirect costs of co-infection in the wild: Linking gastrointestinal parasite communities, host hematology, and immune function☆

    PubMed Central

    Budischak, Sarah A.; Jolles, Anna E.; Ezenwa, Vanessa O.

    2012-01-01

    Most animals are concurrently infected with multiple parasites, and interactions among these parasites may influence both disease dynamics and host fitness. However, the sublethal costs of parasite infections are difficult to measure and the effects of concomitant infections with multiple parasite species on individual physiology and fitness are poorly described for wild hosts. To understand the direct and indirect physiological costs of co-infection, we investigated the relationships among gastrointestinal parasite richness, species identity, and abundance and host hematological parameters, body condition, and investment in lymphocyte defenses. Using aggregate-scale parasite data from African buffalo (Syncerus caffer), we found few direct or indirect associations between infection and hematology in male hosts, and no significant associations were observed in female hosts or with respect to body condition in either sex. These results suggest that only strong physiological effects are detectable with aggregate-scale parasite data, and that hematological variables may be more sensitive to changes in condition than standard body fat condition indices. Analyses accounting for parasite species identity in female buffalo revealed that different parasites show distinct relationships with host hematology, body condition, and immune investment. However, four of six species-specific associations were obscured when parasites were considered in combination. Overall, fitness-related physiological mediators such as hematological indices may provide assessments of direct and indirect effects of parasite infection, particularly when parasite species identity and community composition are considered. PMID:24533308

  2. Genetic Structure and Preliminary Findings of Cryptic Diversity of the Malaysian Mahseer (Tor tambroides Valenciennes: Cyprinidae) Inferred from Mitochondrial DNA and Microsatellite Analyses

    PubMed Central

    Abdul Rahim, Khairul Adha

    2013-01-01

    This study examines the population genetic structure of Tor tambroides, an important freshwater fish species in Malaysia, using fifteen polymorphic microsatellite loci and sequencing of 464 base pairs of the mitochondrial cytochrome c oxidase I (COI) gene. A total of 152 mahseer samples were collected from eight populations throughout the Malaysia river system. Microsatellites results found high levels of intrapopulation variations, but mitochondrial COI results found high levels of interpopulations differentiation. The possible reasons for their discrepancies might be the varying influence of genetic drift on each marker or the small sample sizes used in most of the populations. The Kelantan population showed very low levels of genetic variations using both mitochondrial and microsatellite analyses. Phylogenetic analysis of the COI gene found a unique haplotype (ER8∗), possibly representing a cryptic lineage of T. douronensis, from the Endau-Rompin population. Nevertheless, the inclusion of nuclear microsatellite analyses could not fully resolve the genetic identity of haplotype ER8∗ in the present study. Overall, the findings showed a serious need for more comprehensive and larger scale samplings, especially in remote river systems, in combination with molecular analyses using multiple markers, in order to discover more cryptic lineages or undescribed “genetic species” of mahseer. PMID:24455674

  3. High Prevalence of HIV, HCV, HBV and Co-Infection and Associated Risk Factors among Injecting Drug Users in Yunnan Province, China

    PubMed Central

    Liu, Feng-Liang; Li, Hong; Jiang, Li; Zhu, Jia-Wu; Zheng, Yong-Tang

    2012-01-01

    Objective To estimate the prevalence of HIV, HCV, HBV and co-infection with 2 or 3 viruses and evaluate risk factors among injecting drug users (IDUs) in Yunnan province, China. Methods 2080 IDUs were recruited from 5 regions of Yunnan Province, China to detect the infection status of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Statistical analysis was performed to evaluate risk factors related to HIV, HCV and HBV infections. Results The infection rates among all participants were 25.5% for HIV, 77.7% for HCV, 19.2% for HBV, 15% for HIV/HCV, 0.3% for HIV/HBV, 7.8% for HCV/HBV and 7.1% for HIV/HCV/HBV. The prevalence of virus infection varied widely by region in Yunnan of China. Statistical analyses indicated that high prevalence of HIV and HCV among IDUs was positively associated with the duration of drug injection and sharing needles/syringes; besides, HCV infection was associated with the frequency of drug injection. Conclusions HIV, HCV, HBV infections and co-infections were still very prevalent among IDUs in Yunnan province because of drug use behaviors. PMID:22916185

  4. HIV-1 and herpes simplex virus type-2 genital shedding among co-infected women using self-collected swabs in Chiang Rai, Thailand.

    PubMed

    Forhan, S E; Dunne, E F; Sternberg, M R; Whitehead, S J; Leelawiwat, W; Thepamnuay, S; Chen, C; Evans-Strickfaden, Tt; McNicholl, J M; Markowitz, L E

    2012-08-01

    We analysed 528 genital self-collected swabs (SCS) from 67 HIV-1 and herpes simplex virus type-2 (HSV-2) co-infected women collected during the placebo month of a randomized crossover clinical trial of suppressive acyclovir in Chiang Rai, Thailand. In this first longitudinal study of HIV-1 and HSV-2 co-infected women using genital SCS specimens, we found frequent mucosal HIV-1 shedding. Overall, 372 (70%) swabs had detectable HIV-1 RNA with median HIV-1 viral load of 2.61 log(10) copies/swab. We found no statistically significant association between detectable HIV-1 RNA and HSV-2 DNA in the same SCS specimen (adjusted odds ratio [aOR] 1.40; 95% confidence intervals [CI], 0.78-2.60, P = 0.25). Only baseline HIV-1 plasma viral load was independently associated with genital HIV-1 RNA shedding (aOR, 7.6; 95% CI, 3.3-17.2, P < 0.0001). SCS may be useful for future HIV-1 and HSV-2 studies because this method allows for frequent genital sampling, and inclusion of genital sites other than the cervix. PMID:22930292

  5. Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study.

    PubMed

    Crotty, Matthew P; Meyers, Shelby; Hampton, Nicholas; Bledsoe, Stephanie; Ritchie, David J; Buller, Richard S; Storch, Gregory A; Micek, Scott T; Kollef, Marin H

    2015-12-01

    Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48  h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk. PMID:26683973

  6. Human Papillomavirus and Epstein-Barr virus co-infection in Cervical Carcinoma in Algerian women

    PubMed Central

    2013-01-01

    Background Despite the fact that the implication of human papillomavirus (HPV) in the carcinogenesis and prognosis of cervical cancer is well established, the impact of a co-infection with high risk HPV (HR-HPV) and Epstein-Barr virus (EBV) is still not fully understood. Methods Fifty eight randomly selected cases of squamous cell carcinomas (SCC) of the uterine cervix, 14 normal cervices specimens, 21 CIN-2/3 and 16 CIN-1 cases were examined for EBV and HPV infections. Detection of HR-HPV specific sequences was carried out by PCR amplification using consensus primers of Manos and by Digene Hybrid Capture. The presence of EBV was revealed by amplifying a 660 bp specific EBV sequence of BALF1. mRNA expression of LMP-1 in one hand and protein levels of BARF-1, LMP-1 and EBNA-1 in the other hand were assessed by RT-PCR and immunoblotting and/or immunohischemistry respectively. Results HR-HPV infection was found in patients with SCC (88%), low-grade (75%) and high grade (95%) lesions compared to only 14% of normal cervix cases. However, 69%, 12.5%, 38.1%, and 14% of SCC, CIN-1, CIN-2/3 and normal cervix tissues, respectively, were EBV infected. The highest co-infection (HR-HPV and EBV) was found in squamous cell carcinoma cases (67%). The latter cases showed 27% and 29% expression of EBV BARF-1 and LMP-1 oncogenes respectively. Conclusion The high rate of HR-HPV and EBV co-infection in SCC suggests that EBV infection is incriminated in cervical cancer progression. This could be taken into account as bad prognosis in this type of cancer. However, the mode of action in dual infection in cervical oncogenesis needs further investigation. PMID:24252325

  7. Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity

    PubMed Central

    Matar, Caline G.; Anthony, Neil R.; O’Flaherty, Brigid M.; Jacobs, Nathan T.; Priyamvada, Lalita; Engwerda, Christian R.; Speck, Samuel H.; Lamb, Tracey J.

    2015-01-01

    Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV) by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68) infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh) cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i) suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii) plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission. PMID:25996913

  8. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  9. Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity.

    PubMed

    Matar, Caline G; Anthony, Neil R; O'Flaherty, Brigid M; Jacobs, Nathan T; Priyamvada, Lalita; Engwerda, Christian R; Speck, Samuel H; Lamb, Tracey J

    2015-05-01

    Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV) by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68) infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh) cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i) suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii) plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission. PMID:25996913

  10. Parasite Co-Infections and Their Impact on Survival of Indigenous Cattle

    PubMed Central

    Thumbi, Samuel M.; Bronsvoort, Barend Mark de Clare; Poole, Elizabeth Jane; Kiara, Henry; Toye, Philip G.; Mbole-Kariuki, Mary Ndila; Conradie, Ilana; Jennings, Amy; Handel, Ian Graham; Coetzer, Jacobus Andries Wynand; Steyl, Johan C. A.; Hanotte, Olivier; Woolhouse, Mark E. J.

    2014-01-01

    In natural populations, individuals may be infected with multiple distinct pathogens at a time. These pathogens may act independently or interact with each other and the host through various mechanisms, with resultant varying outcomes on host health and survival. To study effects of pathogens and their interactions on host survival, we followed 548 zebu cattle during their first year of life, determining their infection and clinical status every 5 weeks. Using a combination of clinical signs observed before death, laboratory diagnostic test results, gross-lesions on post-mortem examination, histo-pathology results and survival analysis statistical techniques, cause-specific aetiology for each death case were determined, and effect of co-infections in observed mortality patterns. East Coast fever (ECF) caused by protozoan parasite Theileria parva and haemonchosis were the most important diseases associated with calf mortality, together accounting for over half (52%) of all deaths due to infectious diseases. Co-infection with Trypanosoma species increased the hazard for ECF death by 6 times (1.4–25; 95% CI). In addition, the hazard for ECF death was increased in the presence of Strongyle eggs, and this was burden dependent. An increase by 1000 Strongyle eggs per gram of faeces count was associated with a 1.5 times (1.4–1.6; 95% CI) increase in the hazard for ECF mortality. Deaths due to haemonchosis were burden dependent, with a 70% increase in hazard for death for every increase in strongyle eggs per gram count of 1000. These findings have important implications for disease control strategies, suggesting a need to consider co-infections in epidemiological studies as opposed to single-pathogen focus, and benefits of an integrated approach to helminths and East Coast fever disease control. PMID:24586220

  11. Parasite co-infections and their impact on survival of indigenous cattle.

    PubMed

    Thumbi, Samuel M; Bronsvoort, Barend Mark de Clare; Poole, Elizabeth Jane; Kiara, Henry; Toye, Philip G; Mbole-Kariuki, Mary Ndila; Conradie, Ilana; Jennings, Amy; Handel, Ian Graham; Coetzer, Jacobus Andries Wynand; Steyl, Johan C A; Hanotte, Olivier; Woolhouse, Mark E J

    2014-01-01

    In natural populations, individuals may be infected with multiple distinct pathogens at a time. These pathogens may act independently or interact with each other and the host through various mechanisms, with resultant varying outcomes on host health and survival. To study effects of pathogens and their interactions on host survival, we followed 548 zebu cattle during their first year of life, determining their infection and clinical status every 5 weeks. Using a combination of clinical signs observed before death, laboratory diagnostic test results, gross-lesions on post-mortem examination, histo-pathology results and survival analysis statistical techniques, cause-specific aetiology for each death case were determined, and effect of co-infections in observed mortality patterns. East Coast fever (ECF) caused by protozoan parasite Theileria parva and haemonchosis were the most important diseases associated with calf mortality, together accounting for over half (52%) of all deaths due to infectious diseases. Co-infection with Trypanosoma species increased the hazard for ECF death by 6 times (1.4-25; 95% CI). In addition, the hazard for ECF death was increased in the presence of Strongyle eggs, and this was burden dependent. An increase by 1000 Strongyle eggs per gram of faeces count was associated with a 1.5 times (1.4-1.6; 95% CI) increase in the hazard for ECF mortality. Deaths due to haemonchosis were burden dependent, with a 70% increase in hazard for death for every increase in strongyle eggs per gram count of 1000. These findings have important implications for disease control strategies, suggesting a need to consider co-infections in epidemiological studies as opposed to single-pathogen focus, and benefits of an integrated approach to helminths and East Coast fever disease control. PMID:24586220

  12. Combined Genotypic, Phylogenetic, and Epidemiologic Analyses of Mycobacterium tuberculosis Genetic Diversity in the Rhône Alpes Region, France

    PubMed Central

    Pichat, Catherine; Couvin, David; Carret, Gérard; Frédénucci, Isabelle; Jacomo, Véronique; Carricajo, Anne; Boisset, Sandrine; Dumitrescu, Oana; Flandrois, Jean-Pierre; Lina, Gérard; Rastogi, Nalin

    2016-01-01

    Background The present work relates to identification and a deep molecular characterization of circulating Mycobacterium tuberculosis complex (MTBC) strains in the Rhône-Alpes region, France from 2000 to 2010. It aimed to provide with a first snapshot of MTBC genetic diversity in conjunction with bacterial drug resistance, type of disease and available demographic and epidemiologic characteristics over an eleven-year period, in the south-east of France. Methods Mycobacterium tuberculosis complex (MTBC) strains isolated in the Rhône-Alpes region, France (n = 2257, 1 isolate per patient) between 2000 and 2010 were analyzed by spoligotyping. MIRU-VNTR typing was applied on n = 1698 strains (with full results available for 974 strains). The data obtained were compared with the SITVIT2 database, followed by detailed genotyping, phylogenetic, and epidemiologic analyses in correlation with anonymized data on available demographic, and epidemiologic characteristics, and location of disease (pulmonary or extrapulmonary TB). Results The most predominant spoligotyping clusters were SIT53/T1 (n = 346, 15.3%) > SIT50/H3 (n = 166, 7.35%) > SIT42/LAM9 (n = 125, 5.5%) > SIT1/Beijing (n = 72, 3.2%) > SIT47/H1 (n = 71, 3.1%). Evolutionary-recent strains belonging to the Principal Genetic Group (PGG) 2/3, or Euro-American lineages (T, LAM, Haarlem, X, S) were predominant and represented 1768 or 78.33% of all isolates. For strains having drug resistance information (n = 1119), any drug resistance accounted for 14.83% cases vs. 1.52% for multidrug resistance (MDR); and was significantly more associated with age group 21–40 years (p-value<0.001). Extra-pulmonary TB was more common among female patients while pulmonary TB predominated among men (p-value<0.001; OR = 2.16 95%CI [1.69; 2.77]). Also, BOV and CAS lineages were significantly well represented in patients affected by extra-pulmonary TB (p-value<0.001). The origin was known for 927/2257 patients: 376 (40.6%) being French

  13. Deworming helminth co-infected individuals for delaying HIV disease progression

    PubMed Central

    Walson, Judd L; Herrin, Bradley R; John-Stewart, Grace

    2009-01-01

    Background The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings where other infectious diseases, such as helminth infections, also are highly prevalent. There are biologically plausible reasons for possible effects of helminth infection in HIV-1-infected individuals, and findings from multiple studies suggest that helminth infection may adversely affect HIV-1 progression. Since initial publication of this review (Walson 2007), additional data from randomized controlled trials (RCTs) has become available. We sought to evaluate all currently available evidence to determine if treatment of helminth infection in HIV-1 co-infected individuals impacts HIV-1 progression. Objectives To determine if treating helminth infection in individuals with HIV-1 can reduce the progression of HIV-1 as determined by changes in CD4 count, viral load, or clinical disease progression. Search strategy In this 2008 update, we searched online for published and unpublished studies in The Cochrane Library, MEDLINE, EMBASE, CENTRAL, and AIDSEARCH. We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted authors of included studies. Selection criteria We searched for RCTs and quasi-RCTs that compared HIV-1 progression as measured by changes in CD4 count, viral load, or clinical disease progression in HIV-1 infected individuals receiving anti-helminthic therapy. Data collection and analysis Data regarding changes in CD4 count, HIV-1 RNA levels, and/or clinical staging after treatment of helminth co-infection were extracted from identified studies. Main results Of 7,019 abstracts identified (6,384 from original searches plus 635 from updated searches), 17 abstracts were identified as meeting criteria for potential inclusion (15 from previous review plus an additional two RCTs). After restricting inclusion to RCTs, a total of three studies were eligible for inclusion in this updated review. All three

  14. HCV co-infection in HIV positive population in British Columbia, Canada

    PubMed Central

    2010-01-01

    Background As HIV and hepatitis C (HCV) share some modes of transmission co-infection is not uncommon. This study used a population-based sample of HIV and HCV tested individuals to determine the prevalence of HIV/HCV co-infection, the sequence of virus diagnoses, and demographic and associated risk factors. Methods Positive cases of HIV were linked to the combined laboratory database (of negative and positive HCV antibody results) and HCV reported cases in British Columbia (BC). Results Of 4,598 HIV cases with personal identifiers, 3,219 (70%) were linked to the combined HCV database, 1,700 (53%) of these were anti-HCV positive. HCV was diagnosed first in 52% of co-infected cases (median time to HIV identification 3 1/2 years). HIV and HCV was diagnosed within a two week window in 26% of cases. Among individuals who were diagnosed with HIV infection at baseline, subsequent diagnoses of HCV infection was independently associated with: i) intravenous drug use (IDU) in males and females, Hazard Ratio (HR) = 6.64 (95% CI: 4.86-9.07) and 9.76 (95% CI: 5.76-16.54) respectively; ii) reported Aboriginal ethnicity in females HR = 2.09 (95% CI: 1.34-3.27) and iii) males not identified as men-who-have-sex-with-men (MSM), HR = 2.99 (95% CI: 2.09-4.27). Identification of HCV first compared to HIV first was independently associated with IDU in males and females OR = 2.83 (95% CI: 1.84-4.37) and 2.25 (95% CI: 1.15-4.39) respectively, but not Aboriginal ethnicity or MSM. HIV was identified first in 22%, with median time to HCV identification of 15 months; Conclusion The ability to link BC public health and laboratory HIV and HCV information provided a unique opportunity to explore demographic and risk factors associated with HIV/HCV co-infection. Over half of persons with HIV infection who were tested for HCV were anti-HCV positive; half of these had HCV diagnosed first with HIV identification a median 3.5 years later. This highlights the importance of public health follow-up and

  15. Genetic introgression and hybridization in Antillean freshwater turtles (Trachemys) revealed by coalescent analyses of mitochondrial and cloned nuclear markers.

    PubMed

    Parham, James F; Papenfuss, Theodore J; Dijk, Peter Paul van; Wilson, Byron S; Marte, Cristian; Schettino, Lourdes Rodriguez; Brian Simison, W

    2013-04-01

    Determining whether a conflict between gene trees and species trees represents incomplete lineage sorting (ILS) or hybridization involving native and/or invasive species has implications for reconstructing evolutionary relationships and guiding conservation decisions. Among vertebrates, turtles represent an exceptional case for exploring these issues because of the propensity for even distantly related lineages to hybridize. In this study we investigate a group of freshwater turtles (Trachemys) from a part of its range (the Greater Antilles) where it is purported to have undergone reticulation events from both natural and anthropogenic processes. We sequenced mtDNA for 83 samples, sequenced three nuDNA markers for 45 samples, and cloned 29 polymorphic sequences, to identify species boundaries, hybridization, and intergrade zones for Antillean Trachemys and nearby mainland populations. Initial coalescent analyses of phased nuclear alleles (using (*)BEAST) recovered a Bayesian species tree that strongly conflicted with the mtDNA phylogeny and traditional taxonomy, and appeared to be confounded by hybridization. Therefore, we undertook exploratory phylogenetic analyses of mismatched alleles from the "coestimated" gene trees (Heled and Drummond, 2010) in order to identify potential hybrid origins. The geography, morphology, and sampling context of most samples with potential introgressed alleles suggest hybridization over ILS. We identify contact zones between different species on Jamaica (T. decussata × T. terrapen), on Hispaniola (T. decorata × T. stejnegeri), and in Central America (T. emolli × T. venusta). We are unable to determine whether the distribution of T. decussata on Jamaica is natural or the result of prehistoric introduction by Native Americans. This uncertainty means that the conservation status of the Jamaican T. decussata populations and contact zone with T. terrapen are unresolved. Human-mediated dispersal events were more conclusively implicated

  16. Meat Production in a Feedlot System of Zebu—Holstein Steers and Heifers with Dairy Genetics: Productive and Biological Analyses

    PubMed Central

    Menezes, Gustavo Chamon de Castro; Valadares Filho, Sebastião de Campos; Ruas, José Reinaldo Mendes; Detmann, Edenio; Menezes, Arismar de Castro; Zanett, Diego; Mariz, Lays Débora Silva; Rennó, Luciana Navajas; da Silva Junior, Jarbas Miguel

    2014-01-01

    The aim of this study was to evaluate the productive and biological efficiency of steers and heifers from dairy genetics in a feedlot system in terms of meat production. Twenty-four steers and 24 heifers at 10 monthes of age, (3/4) Zebu × (1/4) Holstein were utilized. They were distributed over four feedlot times, 30, 60, 90, and 120 days with four replications for each sex, and were slaughtered at the end of each period. The productive and biological analyses were performed through comparative slaughter to determine the body composition. Heifers presented with greater intakes (P < 0.05) of dry matter in grams per kg of body weight. Steers presented with a greater (P < 0.05) final empty body weight, carcass gain, cold carcass weight, and meat proportion in the carcass; however, heifers presented with a greater subcutaneous fat thickness (P < 0.05) and, consequently, a greater (P < 0.05) fat proportion in the carcass. We conclude that steers are more efficient in their productive performance than heifers in a feedlot. For the finishing carcass fat cover, heifers need 90 days in the feedlot. The net energy requirements for maintenance are 67 kcal/EBW0.75/d, and the net requirements of energy (NEg) and protein (NPg) for gain can be estimated by the following equations: NEg(Mcal/d) = 0.067 × EBW0.75 × EBG1.095 and NPg = 162 × EBG − 5.62 × RE for the two sexes. PMID:25574483

  17. Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse.

    PubMed

    Peña-Oliver, Yolanda; Carvalho, Fabiana M; Sanchez-Roige, Sandra; Quinlan, Erin B; Jia, Tianye; Walker-Tilley, Tom; Rulten, Stuart L; Pearl, Frances M G; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Büchel, Christian; Conrod, Patricia J; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Gowland, Penny; Paillere Martinot, Marie-Laure; Paus, Tomáš; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Schumann, Gunter; Stephens, David N

    2016-01-01

    Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking. PMID:27092175

  18. Genetic Analyses of the Internal Transcribed Spacer Sequences Suggest Introgression and Duplication in the Medicinal Mushroom Agaricus subrufescens.

    PubMed

    Chen, Jie; Moinard, Magalie; Xu, Jianping; Wang, Shouxian; Foulongne-Oriol, Marie; Zhao, Ruilin; Hyde, Kevin D; Callac, Philippe

    2016-01-01

    The internal transcribed spacer (ITS) region of the nuclear ribosomal RNA gene cluster is widely used in fungal taxonomy and phylogeographic studies. The medicinal and edible mushroom Agaricus subrufescens has a worldwide distribution with a high level of polymorphism in the ITS region. A previous analysis suggested notable ITS sequence heterogeneity within the wild French isolate CA487. The objective of this study was to investigate the pattern and potential mechanism of ITS sequence heterogeneity within this strain. Using PCR, cloning, and sequencing, we identified three types of ITS sequences, A, B, and C with a balanced distribution, which differed from each other at 13 polymorphic positions. The phylogenetic comparisons with samples from different continents revealed that the type C sequence was similar to those found in Oceanian and Asian specimens of A. subrufescens while types A and B sequences were close to those found in the Americas or in Europe. We further investigated the inheritance of these three ITS sequence types by analyzing their distribution among single-spore isolates from CA487. In this analysis, three co-dominant markers were used firstly to distinguish the homokaryotic offspring from the heterokaryotic offspring. The homokaryotic offspring were then analyzed for their ITS types. Our genetic analyses revealed that types A and B were two alleles segregating at one locus ITSI, while type C was not allelic with types A and B but was located at another unlinked locus ITSII. Furthermore, type C was present in only one of the two constitutive haploid nuclei (n) of the heterokaryotic (n+n) parent CA487. These data suggest that there was a relatively recent introduction of the type C sequence and a duplication of the ITS locus in this strain. Whether other genes were also transferred and duplicated and their impacts on genome structure and stability remain to be investigated. PMID:27228131

  19. Genetic Analyses of the Internal Transcribed Spacer Sequences Suggest Introgression and Duplication in the Medicinal Mushroom Agaricus subrufescens

    PubMed Central

    Chen, Jie; Moinard, Magalie; Xu, Jianping; Wang, Shouxian; Foulongne-Oriol, Marie; Zhao, Ruilin; Hyde, Kevin D.; Callac, Philippe

    2016-01-01

    The internal transcribed spacer (ITS) region of the nuclear ribosomal RNA gene cluster is widely used in fungal taxonomy and phylogeographic studies. The medicinal and edible mushroom Agaricus subrufescens has a worldwide distribution with a high level of polymorphism in the ITS region. A previous analysis suggested notable ITS sequence heterogeneity within the wild French isolate CA487. The objective of this study was to investigate the pattern and potential mechanism of ITS sequence heterogeneity within this strain. Using PCR, cloning, and sequencing, we identified three types of ITS sequences, A, B, and C with a balanced distribution, which differed from each other at 13 polymorphic positions. The phylogenetic comparisons with samples from different continents revealed that the type C sequence was similar to those found in Oceanian and Asian specimens of A. subrufescens while types A and B sequences were close to those found in the Americas or in Europe. We further investigated the inheritance of these three ITS sequence types by analyzing their distribution among single-spore isolates from CA487. In this analysis, three co-dominant markers were used firstly to distinguish the homokaryotic offspring from the heterokaryotic offspring. The homokaryotic offspring were then analyzed for their ITS types. Our genetic analyses revealed that types A and B were two alleles segregating at one locus ITSI, while type C was not allelic with types A and B but was located at another unlinked locus ITSII. Furthermore, type C was present in only one of the two constitutive haploid nuclei (n) of the heterokaryotic (n+n) parent CA487. These data suggest that there was a relatively recent introduction of the type C sequence and a duplication of the ITS locus in this strain. Whether other genes were also transferred and duplicated and their impacts on genome structure and stability remain to be investigated. PMID:27228131

  20. Genetic Analyses Reveal Functions for MAP2K3 and MAP2K6 in Mouse Testis Determination.

    PubMed

    Warr, Nick; Siggers, Pam; Carré, Gwenn-Aël; Wells, Sara; Greenfield, Andy

    2016-05-01

    Testis determination in mammals is initiated by expression of SRY in somatic cells of the embryonic gonad. Genetic analyses in the mouse have revealed a requirement for mitogen-activated protein kinase (MAPK) signaling in testis determination: targeted loss of the kinases MAP3K4 and p38 MAPK causes complete XY embryonic gonadal sex reversal. These kinases occupy positions at the top and bottom level, respectively, in the canonical three-tier MAPK-signaling cascade: MAP3K, MAP2K, MAPK. To date, no role in sex determination has been attributed to a MAP2K, although such a function is predicted to exist. Here, we report roles for the kinases MAP2K3 and MAP2K6 in testis determination. C57BL/6J (B6) embryos lacking MAP2K3 exhibited no significant abnormalities of testis development, whilst those lacking MAP2K6 exhibited a minor delay in testis determination. Compound mutants lacking three out of four functional alleles at the two loci also exhibited delayed testis determination and transient ovotestis formation as a consequence, suggestive of partially redundant roles for these kinases in testis determination. Early lethality of double-knockout embryos precludes analysis of sexual development. To reveal their roles in testis determination more clearly, we generated Map2k mutant B6 embryos using a weaker Sry allele (Sry(AKR)). Loss of Map2k3 on this highly sensitized background exacerbates ovotestis development, whilst loss of Map2k6 results in complete XY gonadal sex reversal associated with reduction of Sry expression at 11.25 days postcoitum. Our data suggest that MAP2K6 functions in mouse testis determination, via positive effects on Sry, and also indicate a minor role for MAP2K3. PMID:27009039

  1. Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse

    PubMed Central

    Peña-Oliver, Yolanda; Carvalho, Fabiana M.; Sanchez-Roige, Sandra; Quinlan, Erin B.; Jia, Tianye; Walker-Tilley, Tom; Rulten, Stuart L.; Pearl, Frances M. G.; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; Büchel, Christian; Conrod, Patricia J.; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Gowland, Penny; Paillere Martinot, Marie-Laure; Paus, Tomáš; Rietschel, Marcella; Robbins, Trevor W.; Smolka, Michael N.; Schumann, Gunter; Stephens, David N.

    2016-01-01

    Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking. PMID:27092175

  2. Detailed Phenotypic and Molecular Analyses of Genetically Modified Mice Generated by CRISPR-Cas9-Mediated Editing

    PubMed Central

    Parikh, Bijal A.; Beckman, Diana L.; Patel, Swapneel J.; White, J. Michael; Yokoyama, Wayne M.

    2015-01-01

    The bacterial CRISPR-Cas9 system has been adapted for use as a genome editing tool. While several recent reports have indicated that successful genome editing of mice can be achieved, detailed phenotypic and molecular analyses of the mutant animals are limited. Following pronuclear micro-injection of fertilized eggs with either wild-type Cas9 or the nickase mutant (D10A) and single or paired guide RNA (sgRNA) for targeting of the tyrosinase (Tyr) gene, we assessed genome editing in mice using rapid phenotypic readouts (eye and coat color). Mutant mice with insertions or deletions (indels) in Tyr were efficiently generated without detectable off-target cleavage events. Gene correction of a single nucleotide by homologous recombination (HR) could only occur when the sgRNA recognition sites in the donor DNA were modified. Gene repair did not occur if the donor DNA was not modified because Cas9 catalytic activity was completely inhibited. Our results indicate that allelic mosaicism can occur following -Cas9-mediated editing in mice and appears to correlate with sgRNA cleavage efficiency at the single-cell stage. We also show that larger than expected deletions may be overlooked based on the screening strategy employed. An unbiased analysis of all the deleted nucleotides in our experiments revealed that the highest frequencies of nucleotide deletions were clustered around the predicted Cas9 cleavage sites, with slightly broader distributions than expected. Finally, additional analysis of founder mice and their offspring indicate that their general health, fertility, and the transmission of genetic changes were not compromised. These results provide the foundation to interpret and predict the diverse outcomes following CRISPR-Cas9-mediated genome editing experiments in mice. PMID:25587897

  3. Genetic and phylogenetic analyses of influenza A H1N1pdm virus in Buenos Aires, Argentina.

    PubMed

    Barrero, P R; Viegas, M; Valinotto, L E; Mistchenko, A S

    2011-01-01

    An influenza pandemic caused by swine-origin influenza virus A/H1N1 (H1N1pdm) spread worldwide in 2009, with 12,080 confirmed cases and 626 deaths occurring in Argentina. A total of 330 H1N1pdm viruses were detected from May to August 2009, and phylogenetic and genetic analyses of 21 complete genome sequences from both mild and fatal cases were achieved with reference to concatenated whole genomes. In addition, the analysis of another 16 hemagglutinin (HA), neuraminidase (NA), and matrix (M) gene sequences of Argentinean isolates was performed. The microevolution timeline was assessed and resistance monitoring of an NA fragment from 228 samples throughout the 2009 pandemic peak was performed by sequencing and pyrosequencing. We also assessed the viral growth kinetics for samples with replacements at the genomic level or special clinical features. In this study, we found by Bayesian inference that the Argentinean complete genome sequences clustered with globally distributed clade 7 sequences. The HA sequences were related to samples from the northern hemisphere autumn-winter from September to December 2009. The NA of Argentinean sequences belonged to the New York group. The N-4 fragment as well as the hierarchical clustering of samples showed that a consensus sequence prevailed in time but also that different variants, including five H275Y oseltamivir-resistant strains, arose from May to August 2009. Fatal and oseltamivir-resistant isolates had impaired growth and a small plaque phenotype compared to oseltamivir-sensitive and consensus strains. Although these strains might not be fit enough to spread in the entire population, molecular surveillance proved to be essential to monitor resistance and viral dynamics in our country. PMID:21047959

  4. Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia.

    PubMed

    Weissenbacher-Lang, Christiane; Kureljušić, Branislav; Nedorost, Nora; Matula, Bettina; Schießl, Wolfgang; Stixenberger, Daniela; Weissenböck, Herbert

    2016-01-01

    Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2)) and bacterial (Bordetella bronchiseptica (B. b.), Mycoplasma hyopneumoniae (M. h.), and Pasteurella multocida (P. m.)) co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases. PMID:27428002

  5. Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia

    PubMed Central

    Weissenbacher-Lang, Christiane; Kureljušić, Branislav; Nedorost, Nora; Matula, Bettina; Schießl, Wolfgang; Stixenberger, Daniela; Weissenböck, Herbert

    2016-01-01

    Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2)) and bacterial (Bordetella bronchiseptica (B. b.), Mycoplasma hyopneumoniae (M. h.), and Pasteurella multocida (P. m.)) co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases. PMID:27428002

  6. Clinical and Laboratory Characteristics of Dengue-Orientia tsutsugamushi co-Infection from a Tertiary Care Center in South India

    PubMed Central

    Basheer, Aneesh; Iqbal, Nayyar; Mookkappan, Sudhagar; Anitha, Patricia; Nair, Shashikala; Kanungo, Reba; Kandasamy, Ravichandran

    2016-01-01

    Background Concurrent infection with multiple pathogens is common in tropics, posing diagnostic and treatment challenges. Although co-infections of dengue, malaria, leptospirosis and typhoid in various combinations have been described, data on dengue and scrub typhus co-infection is distinctly limited. Methodology This study was a retrospective analysis of dengue and scrub typhus co-infection diagnosed between January 2010 and July 2014 at a tertiary care center. Clinical and laboratory features of these cases were compared with age and gender-matched patients with isolated dengue fever and isolated scrub typhus. Positive test for dengue non-structural 1 (NS1) antigen was considered diagnostic of dengue whereas scrub typhus was diagnosed by IgM scrub antibodies demonstrated by ELISA. Results There were 6 cases of dengue-scrub co-infection during the review period which fitted clinical and laboratory profile with a mean age of 42.5 years. Fever, headache, and arthralgia were common. Normal hemoglobin, significant thrombocytopenia, transaminitis, and hypoalbuminemia were identified in these patients. Compared to patients with isolated dengue, those with co-infection had higher pulse rate, lower systolic blood pressure, normal leucocyte counts, higher levels of liver enzymes, greater prolongation of partial thromboplastin time (aPTT) and lower serum albumin. Co-infection was characterized by a lower nadir platelet count compared to scrub typhus, and lesser time to nadir platelet count and longer duration of hospital stay compared to either isolated dengue or scrub typhus. Conclusion Dengue-scrub typhus co-infection may be under-diagnosed in tropics, particularly confounded during dengue epidemics. Normal leukocyte counts, early drop in platelets and hypoalbuminemia in dengue patients could be clues to concurrent scrub typhus infection. Prompt recognition and treatment of scrub typhus in such cases may reduce unnecessary hospital stay and cost. PMID:27413521

  7. Co-Infection of Blacklegged Ticks with Babesia microti and Borrelia burgdorferi Is Higher than Expected and Acquired from Small Mammal Hosts

    PubMed Central

    Hersh, Michelle H.; Ostfeld, Richard S.; McHenry, Diana J.; Tibbetts, Michael; Brunner, Jesse L.; Killilea, Mary E.; LoGiudice, Kathleen; Schmidt, Kenneth A.; Keesing, Felicia

    2014-01-01

    Humans in the northeastern and midwestern United States are at increasing risk of acquiring tickborne diseases – not only Lyme disease, but also two emerging diseases, human granulocytic anaplasmosis and human babesiosis. Co-infection with two or more of these pathogens can increase the severity of health impacts. The risk of co-infection is intensified by the ecology of these three diseases because all three pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti) are transmitted by the same vector, blacklegged ticks (Ixodes scapularis), and are carried by many of the same reservoir hosts. The risk of exposure to multiple pathogens from a single tick bite and the sources of co-infected ticks are not well understood. In this study, we quantify the risk of co-infection by measuring infection prevalence in 4,368 questing nymphs throughout an endemic region for all three diseases (Dutchess County, NY) to determine if co-infections occur at frequencies other than predicted by independent assortment of pathogens. Further, we identify sources of co-infection by quantifying rates of co-infection on 3,275 larval ticks fed on known hosts. We find significant deviations of levels of co-infection in questing nymphs, most notably 83% more co-infection with Babesia microti and Borrelia burgdorferi than predicted by chance alone. Further, this pattern of increased co-infection was observed in larval ticks that fed on small mammal hosts, but not on meso-mammal, sciurid, or avian hosts. Co-infections involving A. phagocytophilum were less common, and fewer co-infections of A. phagocytophilum and B. microti than predicted by chance were observed in both questing nymphs and larvae fed on small mammals. Medical practitioners should be aware of the elevated risk of B. microti/B. burgdorferi co-infection. PMID:24940999

  8. Bivariate Genetic Analyses of Stuttering and Nonfluency in a Large Sample of 5-Year-Old Twins

    ERIC Educational Resources Information Center

    van Beijsterveldt, Catharina Eugenie Maria; Felsenfeld, Susan; Boomsma, Dorret Irene

    2010-01-01

    Purpose: Behavioral genetic studies of speech fluency have focused on participants who present with clinical stuttering. Knowledge about genetic influences on the development and regulation of normal speech fluency is limited. The primary aims of this study were to identify the heritability of stuttering and high nonfluency and to assess the…

  9. Towards Systems Genetic Analyses in Barley: Integration of Phenotypic, Expression and Genotype Data into GeneNetwork

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A typical genetical genomics experiment results in three separate data sets: genotype, gene expression, and higher-order phenotypic data. Used in concert, these data sets provide the opportunity to perform genetic analysis at a systems level. The predictive power of these experiments is largely d...

  10. Endemic infection reduces transmission potential of an epidemic parasite during co-infection

    PubMed Central

    Randall, J.; Cable, J.; Guschina, I. A.; Harwood, J. L.; Lello, J.

    2013-01-01

    Endemic, low-virulence parasitic infections are common in nature. Such infections may deplete host resources, which in turn could affect the reproduction of other parasites during co-infection. We aimed to determine whether the reproduction, and therefore transmission potential, of an epidemic parasite was limited by energy costs imposed on the host by an endemic infection. Total lipids, triacylglycerols (TAG) and polar lipids were measured in cockroaches (Blattella germanica) that were fed ad libitum, starved or infected with an endemic parasite, Gregarina blattarum. Reproductive output of an epidemic parasite, Steinernema carpocapsae, was then assessed by counting the number of infective stages emerging from these three host groups. We found both starvation and gregarine infection reduced cockroach lipids, mainly through depletion of TAG. Further, both starvation and G. blattarum infection resulted in reduced emergence of nematode transmission stages. This is, to our knowledge, the first study to demonstrate directly that host resource depletion caused by endemic infection could affect epidemic disease transmission. In view of the ubiquity of endemic infections in nature, future studies of epidemic transmission should take greater account of endemic co-infections. PMID:23966641

  11. Outcomes of co-infection by two potyviruses: implications for the evolution of manipulative strategies.

    PubMed

    Salvaudon, Lucie; De Moraes, Consuelo M; Mescher, Mark C

    2013-04-01

    Recent studies have documented effects of plant viruses on host plants that appear to enhance transmission by insect vectors. But, almost no empirical work has explored the implications of such apparent manipulation for interactions among co-infecting pathogens. We examined single and mixed infections of two potyviruses, watermelon mosaic virus (WMV) and zucchini yellow mosaic virus (ZYMV), that frequently co-occur in cucurbitaceae populations and share the same aphid vectors. We found that ZYMV isolates replicated at similar rates in single and mixed infections, whereas WMV strains accumulated to significantly lower levels in the presence of ZYMV. Furthermore, ZYMV induced changes in leaf colour and volatile emissions that enhanced aphid (Aphis gossypii) recruitment to infected plants. By contrast, WMV did not elicit strong effects on plant-aphid interactions. Nevertheless, WMV was still readily transmitted from mixed infections, despite fairing poorly in in-plant competition. These findings suggest that pathogen effects on host-vector interactions may well influence competition among co-infecting pathogens. For example, if non-manipulative pathogens benefit from the increased vector traffic elicited by manipulative competitors, their costs of competition may be mitigated to some extent. Conversely, the benefits of manipulation may be limited by free-rider effects in systems where there is strong competition among pathogens for host resources and/or access to vectors. PMID:23407835

  12. Chemokines responses to Plasmodium falciparum malaria and co-infections among rural Cameroonians.

    PubMed

    Che, Jane Nchangnwi; Nmorsi, Onyebiguwa Patrick Goddey; Nkot, Baleguel Pierre; Isaac, Clement; Okonkwo, Browne Chukwudi

    2015-04-01

    Malaria remains the major cause of disease morbidity and mortality in sub-Saharan Africa with complex immune responses associated with disease outcomes. Symptoms associated with severe malaria have generally shown chemokine upregulation but little is known of responses to uncomplicated malaria. Eight villages in central Cameroon of 1045 volunteers were screened. Among these, malaria-positive individuals with some healthy controls were selected for chemokine analysis using Enzyme-Linked Immunosorbent Assay (ELISA) kits. Depressed serum levels of CXCL5 and raised CCL28 were observed in malarial positives when compared with healthy controls. The mean concentration of CXCL11 was higher in symptomatic than asymptomatic group, while CCL28 was lower in symptomatic individuals. Lower chemokine levels were associated with symptoms of uncomplicated malaria except for CXCL11 which was upregulated among fever-positive group. The mean CXCL5 level was higher in malaria sole infection than co-infections with HIV and Loa loa. Also, there was a raised mean level of malaria+HIV co-infection for CXCL9. This study hypothesises a situation where depressed chemokines in the face of clinical presentations could indicate an attempt by the immune system in preventing a progression process from uncomplicated to complicated outcomes with CXCL11 being identified as possible biomarker for malarial fever. PMID:25462711

  13. Plasmodium vivax and Mansonella ozzardi co-infection in north-western Argentina.

    PubMed

    Dantur Juri, María J; Veggiani Aybar, Cecilia A; Ortega, Eugenia S; Galante, Guillermina B; Zaidenberg, Mario O

    2013-01-01

    A case of co-infection with Plasmodium vivax and Mansonella ozzardi was detected in a blood sample from a person who had shown symptoms of malaria and lived in a city that was close to the Argentina/Bolivia border. The case was detected during a random revision of thick and thin smears from patients diagnosed with malaria from various towns and cities located in north-western Argentina between 1983 and 2001. Trophozoites of P. vivax were observed in the thin blood smear along with M. ozzardi microfilaria (larval form), which presented a long, slender, pointed anucleate tail and the absence of the sheath. This last characteristic is shared with Mansonella perstans, Mansonella streptocerca and Onchocerca volvulus. More rigorously controlled studies to detect other co-infection cases in the area as well as the possibility of importation from Bolivia into Argentina are currently ongoing. The relationship between the malaria parasite and microfilaria, the potential effect of malaria treatment on the development of M. ozzardi, and the possible impact of this microfilaria on the immunity of a person against P. vivax are all still unknown. This contribution constitutes a point of focus for future studies involving the interaction between the parasites and the potential risk that humans are exposed to. PMID:23866313

  14. Endemic infection reduces transmission potential of an epidemic parasite during co-infection.

    PubMed

    Randall, J; Cable, J; Guschina, I A; Harwood, J L; Lello, J

    2013-10-22

    Endemic, low-virulence parasitic infections are common in nature. Such infections may deplete host resources, which in turn could affect the reproduction of other parasites during co-infection. We aimed to determine whether the reproduction, and therefore transmission potential, of an epidemic parasite was limited by energy costs imposed on the host by an endemic infection. Total lipids, triacylglycerols (TAG) and polar lipids were measured in cockroaches (Blattella germanica) that were fed ad libitum, starved or infected with an endemic parasite, Gregarina blattarum. Reproductive output of an epidemic parasite, Steinernema carpocapsae, was then assessed by counting the number of infective stages emerging from these three host groups. We found both starvation and gregarine infection reduced cockroach lipids, mainly through depletion of TAG. Further, both starvation and G. blattarum infection resulted in reduced emergence of nematode transmission stages. This is, to our knowledge, the first study to demonstrate directly that host resource depletion caused by endemic infection could affect epidemic disease transmission. In view of the ubiquity of endemic infections in nature, future studies of epidemic transmission should take greater account of endemic co-infections. PMID:23966641

  15. Tuberculosis and HIV co-infection, California, USA, 1993–2008.

    PubMed

    Metcalfe, John Z; Porco, Travis C; Westenhouse, Janice; Damesyn, Mark; Facer, Matt; Hill, Julia; Xia, Qiang; Watt, James P; Hopewell, Philip C; Flood, Jennifer

    2013-03-01

    To understand the epidemiology of tuberculosis (TB) and HIV co-infection in California, we cross-matched incident TB cases reported to state surveillance systems during 1993–2008 with cases in the state HIV/AIDS registry. Of 57,527 TB case-patients, 3,904 (7%) had known HIV infection. TB rates for persons with HIV declined from 437 to 126 cases/100,000 persons during 1993–2008; rates were highest for Hispanics (225/100,000) and Blacks (148/100,000). Patients co-infected with TB–HIV during 2001–2008 were significantly more likely than those infected before highly active antiretroviral therapy became available to be foreign born, Hispanic, or Asian/Pacific Islander and to have pyrazinamide-monoresistant TB. Death rates decreased after highly active antiretroviral therapy became available but remained twice that for TB patients without HIV infection and higher for women. In California, HIV-associated TB has concentrated among persons from low- and middle-income countries who often acquire HIV infection in the peri-immigration period. PMID:23745218

  16. Streptococcal co-infection augments Candida pathogenicity by amplifying the mucosal inflammatory response

    PubMed Central

    Xu, H; Sobue, T; Thompson, A; Xie, Z; Poon, K; Ricker, A; Cervantes, J; Diaz, P I; Dongari-Bagtzoglou, A

    2013-01-01

    Summary Mitis-group streptococci are ubiquitous oral commensals that can promote polybacterial biofilm virulence. Using a novel murine oral mucosal co-infection model we sought to determine for the first time whether these organisms promote the virulence of C. albicans mucosal biofilms in oropharyngeal infection and explored mechanisms of pathogenic synergy. We found that Streptococcus oralis colonization of the oral and gastrointestinal tract was augmented in the presence of C. albicans. S. oralis and C. albicans co-infection significantly augmented the frequency and size of oral thrush lesions. Importantly, S. oralis promoted deep organ dissemination of C. albicans. Whole mouse genome tongue microarray analysis showed that when compared with animals infected with one organism, the doubly infected animals had genes in the major categories of neutrophilic response/chemotaxis/inflammation significantly upregulated, indicative of an exaggerated inflammatory response. This response was dependent on TLR2 signalling since oral lesions, transcription of pro-inflammatory genes and neutrophil infiltration, were attenuated in TLR2−/− animals. Furthermore, S. oralis activated neutrophils in a TLR2-dependent manner in vitro. In summary, this study identifies a previously unrecognized pathogenic synergy between oral commensal bacteriaand C. albicans. This is the first report of the ability of mucosal commensal bacteria to modify the virulence of an opportunistic fungal pathogen. PMID:24079976

  17. Tuberculosis and HIV Co-infection, California, USA, 1993–2008

    PubMed Central

    Porco, Travis C.; Westenhouse, Janice; Damesyn, Mark; Facer, Matt; Hill, Julia; Xia, Qiang; Watt, James P.; Hopewell, Philip C.; Flood, Jennifer

    2013-01-01

    To understand the epidemiology of tuberculosis (TB) and HIV co-infection in California, we cross-matched incident TB cases reported to state surveillance systems during 1993–2008 with cases in the state HIV/AIDS registry. Of 57,527 TB case-patients, 3,904 (7%) had known HIV infection. TB rates for persons with HIV declined from 437 to 126 cases/100,000 persons during 1993–2008; rates were highest for Hispanics (225/100,000) and Blacks (148/100,000). Patients co-infected with TB–HIV during 2001–2008 were significantly more likely than those infected before highly active antiretroviral therapy became available to be foreign born, Hispanic, or Asian/Pacific Islander and to have pyrazinamide-monoresistant TB. Death rates decreased after highly active antiretroviral therapy became available but remained twice that for TB patients without HIV infection and higher for women. In California, HIV-associated TB has concentrated among persons from low and middle income countries who often acquire HIV infection in the peri-immigration period. PMID:23745218

  18. Co-infections determine patterns of mortality in a population exposed to parasite infection

    PubMed Central

    Woolhouse, Mark E. J.; Thumbi, Samuel M.; Jennings, Amy; Chase-Topping, Margo; Callaby, Rebecca; Kiara, Henry; Oosthuizen, Marinda C.; Mbole-Kariuki, Mary N.; Conradie, Ilana; Handel, Ian G.; Poole, E. Jane; Njiiri, Evalyne; Collins, Nicola E.; Murray, Gemma; Tapio, Miika; Auguet, Olga Tosas; Weir, Willie; Morrison, W. Ivan; Kruuk, Loeske E. B.; Bronsvoort, B. Mark de C.; Hanotte, Olivier; Coetzer, Koos; Toye, Philip G.

    2015-01-01

    Many individual hosts are infected with multiple parasite species, and this may increase or decrease the pathogenicity of the infections. This phenomenon is termed heterologous reactivity and is potentially an important determinant of both patterns of morbidity and mortality and of the impact of disease control measures at the population level. Using infections with Theileria parva (a tick-borne protozoan, related to Plasmodium) in indigenous African cattle [where it causes East Coast fever (ECF)] as a model system, we obtain the first quantitative estimate of the effects of heterologous reactivity for any parasitic disease. In individual calves, concurrent co-infection with less pathogenic species of Theileria resulted in an 89% reduction in mortality associated with T. parva infection. Across our study population, this corresponds to a net reduction in mortality due to ECF of greater than 40%. Using a mathematical model, we demonstrate that this degree of heterologous protection provides a unifying explanation for apparently disparate epidemiological patterns: variable disease-induced mortality rates, age-mortality profiles, weak correlations between the incidence of infection and disease (known as endemic stability), and poor efficacy of interventions that reduce exposure to multiple parasite species. These findings can be generalized to many other infectious diseases, including human malaria, and illustrate how co-infections can play a key role in determining population-level patterns of morbidity and mortality due to parasite infections. PMID:26601143

  19. Co-infections determine patterns of mortality in a population exposed to parasite infection.

    PubMed

    Woolhouse, Mark E J; Thumbi, Samuel M; Jennings, Amy; Chase-Topping, Margo; Callaby, Rebecca; Kiara, Henry; Oosthuizen, Marinda C; Mbole-Kariuki, Mary N; Conradie, Ilana; Handel, Ian G; Poole, E Jane; Njiiri, Evalyne; Collins, Nicola E; Murray, Gemma; Tapio, Miika; Auguet, Olga Tosas; Weir, Willie; Morrison, W Ivan; Kruuk, Loeske E B; Bronsvoort, B Mark de C; Hanotte, Olivier; Coetzer, Koos; Toye, Philip G

    2015-03-01

    Many individual hosts are infected with multiple parasite species, and this may increase or decrease the pathogenicity of the infections. This phenomenon is termed heterologous reactivity and is potentially an important determinant of both patterns of morbidity and mortality and of the impact of disease control measures at the population level. Using infections with Theileria parva (a tick-borne protozoan, related to Plasmodium) in indigenous African cattle [where it causes East Coast fever (ECF)] as a model system, we obtain the first quantitative estimate of the effects of heterologous reactivity for any parasitic disease. In individual calves, concurrent co-infection with less pathogenic species of Theileria resulted in an 89% reduction in mortality associated with T. parva infection. Across our study population, this corresponds to a net reduction in mortality due to ECF of greater than 40%. Using a mathematical model, we demonstrate that this degree of heterologous protection provides a unifying explanation for apparently disparate epidemiological patterns: variable disease-induced mortality rates, age-mortality profiles, weak correlations between the incidence of infection and disease (known as endemic stability), and poor efficacy of interventions that reduce exposure to multiple parasite species. These findings can be generalized to many other infectious diseases, including human malaria, and illustrate how co-infections can play a key role in determining population-level patterns of morbidity and mortality due to parasite infections. PMID:26601143

  20. Plasmodium vivax and Mansonella ozzardi co-infection in north-western Argentina

    PubMed Central

    2013-01-01

    A case of co-infection with Plasmodium vivax and Mansonella ozzardi was detected in a blood sample from a person who had shown symptoms of malaria and lived in a city that was close to the Argentina/Bolivia border. The case was detected during a random revision of thick and thin smears from patients diagnosed with malaria from various towns and cities located in north-western Argentina between 1983 and 2001. Trophozoites of P. vivax were observed in the thin blood smear along with M. ozzardi microfilaria (larval form), which presented a long, slender, pointed anucleate tail and the absence of the sheath. This last characteristic is shared with Mansonella perstans, Mansonella streptocerca and Onchocerca volvulus. More rigorously controlled studies to detect other co-infection cases in the area as well as the possibility of importation from Bolivia into Argentina are currently ongoing. The relationship between the malaria parasite and microfilaria, the potential effect of malaria treatment on the development of M. ozzardi, and the possible impact of this microfilaria on the immunity of a person against P. vivax are all still unknown. This contribution constitutes a point of focus for future studies involving the interaction between the parasites and the potential risk that humans are exposed to. PMID:23866313

  1. Treatment of helminth co-infection in HIV-1 infected individuals in resource-limited settings

    PubMed Central

    Walson, Judd L; John-Stewart, Grace

    2012-01-01

    Background The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings. These areas often also have high prevalence of other infectious diseases, such as helminth infections. It is important to determine if helminth infection affects the progression of HIV-1 in these co-infected individuals. There are biologically plausible reasons for possible effects of helminth infection in HIV-1 infected individuals and findings from some observational studies suggest that helminth infection may adversely affect HIV-1 progression. We sought to evaluate the available evidence from published and unpublished studies to determine if treatment of helminth infection in HIV-1 co-infected individuals impacts HIV-1 progression. Objectives Our objective was to determine if treating helminth infection in individuals with HIV-1 can reduce the progression of HIV-1 as determined by changes in CD4 count, viral load, or clinical disease progression (including mortality). Search strategy We searched online for published and unpublished studies in The Cochrane Library (Issue 3, 2006), MEDLINE (November 2006), EMBASE (November 2006), CENTRAL (July 2006), AIDSEARCH (August 2006). We also searched databases listing conference abstracts, scanned reference lists of articles, and contacted authors of included studies. Selection criteria We searched for randomized and quasi-randomized controlled trials that compared HIV-1 progression as measured by changes in CD4 count, viral load, or clinical disease progression in HIV-1 infected individuals receiving anti-helminth therapy. Observational studies with relevant data were also included. Data collection and analysis Data regarding changes in CD4 count, HIV-1 RNA levels, clinical staging and/or mortality after treatment of helminth co-infection were extracted from the reports of the studies. Main results Of 6,384 abstracts identified, 15 met criteria for potential inclusion, of which five were eligible for inclusion. In

  2. Phylogeographic Analyses of Submesophotic Snappers Etelis coruscans and Etelis “marshi” (Family Lutjanidae) Reveal Concordant Genetic Structure across the Hawaiian Archipelago

    PubMed Central

    Andrews, Kimberly R.; Moriwake, Virginia N.; Wilcox, Christie; Grau, E. Gordon; Kelley, Christopher; Pyle, Richard L.; Bowen, Brian W.

    2014-01-01

    The Hawaiian Archipelago has become a natural laboratory for understanding genetic connectivity in marine organisms as a result of the large number of population genetics studies that have been conducted across this island chain for a wide taxonomic range of organisms. However, population genetic studies have been conducted for only two species occurring in the mesophotic or submesophotic zones (30+m) in this archipelago. To gain a greater understanding of genetic connectivity in these deepwater habitats, we investigated the genetic structure of two submesophotic fish species (occurring ∼200–360 m) in this archipelago. We surveyed 16 locations across the archipelago for submesophotic snappers Etelis coruscans (N = 787) and E. “marshi” (formerly E. carbunculus; N = 770) with 436–490 bp of mtDNA cytochrome b and 10–11 microsatellite loci. Phylogeographic analyses reveal no geographic structuring of mtDNA lineages and recent coalescence times that are typical of shallow reef fauna. Population genetic analyses reveal no overall structure across most of the archipelago, a pattern also typical of dispersive shallow fishes. However some sites in the mid-archipelago (Raita Bank to French Frigate Shoals) had significant population differentiation. This pattern of no structure between ends of the Hawaiian range, and significant structure in the middle, was previously observed in a submesophotic snapper (Pristipomoides filamentosus) and a submesophotic grouper (Hyporthodus quernus). Three of these four species also have elevated genetic diversity in the mid-archipelago. Biophysical larval dispersal models from previous studies indicate that this elevated diversity may result from larval supplement from Johnston Atoll, ∼800 km southwest of Hawaii. In this case the boundaries of stocks for fishery management cannot be defined simply in terms of geography, and fishery management in Hawaii may need to incorporate external larval supply into management plans

  3. Analysis of HLA association among North Indian HIV-positive individuals co-infected with Mycobacterium tuberculosis

    PubMed Central

    Saikia, Biman; Wanchu, Ajay; Mahakur, Sobhana; Bind, Mahendra; Sarkar, Krishnakali; Minz, Ranjana W

    2015-01-01

    Background: Genetic variation in HLA genes influence the immune response and may thus contribute to differential development of tuberculosis (TB) in HIV-infected individuals. The study was designed to determine whether HLA polymorphisms influence the development of Mycobacterium tuberculosis infection in HIV-infected individuals. Materials and Methods: Fifty HIV-positive individuals without TB (HIV+TB−), 50 HIV patients co-infected with TB (HIV+TB+) and 50 control subjects (HIV-TB-) were analyzed for HLA Class I and II polymorphisms. Results: In HLA Class II, frequency of occurrence of DRB1*13 (OR 3.165, CI 1.176–8.518, P value 0.019), DRB5 (OR 2.253, CI 1.011–5.019, P value 0.045) and DQB1*06 (OR 2.705, CI 1.197–6.113, P value 0.016) were increased in HIV+TB+compared to HIV+TB−. HLA DQB1*02 (OR 0.436, CI 0.185–1.029, P value 0.05) on the other hand conferred a protective role. In HLA Class I, frequency of B*15 (OR 2.705, CI 1.040–7.036, P value 0.038) was increased, whereas B*51 (OR 0.148, CI 0.031–0.706, P value 0.007) was decreased in HIV+TB+group compared to HIV+TB−. These differences however were not significant when compared with healthy controls. Conclusion: HLA polymorphisms independently did not account for the susceptibility to either of the disease mostly, although they seem to play a role once the infection(s) has established in a particular individual. Further studies are needed on a larger sample size to confirm these observations. PMID:26628757

  4. Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages

    PubMed Central

    Andersson, Anna-Maria; Andersson, Blanka; Lorell, Christoffer; Raffetseder, Johanna; Larsson, Marie; Blomgran, Robert

    2016-01-01

    To survive and replicate in macrophages Mycobacterium tuberculosis (Mtb) has developed strategies to subvert host defence mechanisms, including autophagy. Autophagy induction has the potential to clear Mtb, but little is known about its effect during controlled tuberculosis and HIV co-infection. Mammalian target of rapamycin complex1 (mTORC1) inhibitors were used to induce autophagy in human macrophages pre-infected with HIV-1BaL and infected with a low dose of Mtb (co-infected), or single Mtb infected (single infected). The controlled Mtb infection was disrupted upon mTOR inhibition resulting in increased Mtb replication in a dose-dependent manner which was more pronounced during co-infection. The increased Mtb replication could be explained by the marked reduction in phagosome acidification upon mTOR inhibition. Autophagy stimulation targeting mTORC1 clearly induced a basal autophagy with flux that was unlinked to the subcellular environment of the Mtb vacuoles, which showed a concurrent suppression in acidification and maturation/flux. Overall our findings indicate that mTOR inhibition during Mtb or HIV/Mtb co-infection interferes with phagosomal maturation, thereby supporting mycobacterial growth during low-dose and controlled infection. Therefore pharmacological induction of autophagy through targeting of the canonical mTORC1-pathway should be handled with caution during controlled tuberculosis, since this could have serious consequences for patients with HIV/Mtb co-infection. PMID:27302320

  5. Immunological alterations and associated diseases in mandrills (Mandrillus sphinx) naturally co-infected with SIV and STLV.

    PubMed

    Souquière, Sandrine; Makuwa, Maria; Sallé, Bettina; Lepelletier, Yves; Mortreux, Franck; Hermine, Olivier; Kazanji, Mirdad

    2014-04-01

    Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates. PMID:24725945

  6. Factors associated with HIV and syphilis co-infection among men who have sex with men in seven Chinese cities

    PubMed Central

    Das, Aritra; Li, Jianjun; Zhong, Fei; Ouyang, Lin; Mahapatra, Tanmay; Tang, Weiming; Fu, Gengfeng; Zhao, Jinkou; Detels, Roger

    2014-01-01

    HIV-syphilis co-infection is often cited as a major reason behind recent resurgence in syphilis prevalence among men who have sex with men (MSM) in China. Most published literatures explore factors associated with either HIV or syphilis, but not their co-infection. We analyzed data from a cross-sectional survey on MSM in seven Chinese cities. Snowball sampling was used to recruit participants for the survey. Socio-demographic and behavioral predictors for HIV-syphilis mono/co-infection were examined using ordinal logistic regression. Factor scores were used to summarize; 1) HIV related knowledge, and 2) access to HIV preventive services. Prevalence of HIV, syphilis, and their co-infection, among 2936 self-identified MSM, were 7.7%, 14.3%, and 2.6%, respectively. In the adjusted analysis, the significant positive correlates of poorer diagnoses (co-infection vs mono- & no infection or co- & mono-infection vs no infection) were −30 to 39 years and ≥40 years age, education up to senior high school, unprotected anal intercourse (UAI), recent STD symptoms, incorrect knowledge about routes of transmission, and access to preventive or counselling/testing services for HIV. For effective control of this dual epidemic, integrated HIV and syphilis surveillance and targeted intervention strategies for Chinese MSM are need of the hour. PMID:24737881

  7. Proteomics approach to understand reduced clearance of mycobacteria and high viral titers during HIV-mycobacteria co-infection.

    PubMed

    Ganji, Rakesh; Dhali, Snigdha; Rizvi, Arshad; Sankati, Swetha; Vemula, Mani Harika; Mahajan, Gaurang; Rapole, Srikanth; Banerjee, Sharmistha

    2016-03-01

    Environmental mycobacteria, highly prevalent in natural and artificial (including chlorinated municipal water) niches, are emerging as new threat to human health, especially to HIV-infected population. These seemingly harmless non-pathogenic mycobacteria, which are otherwise cleared, establish as opportunistic infections adding to HIV-associated complications. Although immune-evading strategies of pathogenic mycobacteria are known, the mechanisms underlying the early events by which opportunistic mycobacteria establish infection in macrophages and influencing HIV infection are unclear. Proteomics of phagosome-enriched fractions from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) mono-infected and HIV-M. bovis BCG co-infected THP-1 cells by LC-MALDI-MS/MS revealed differential distribution of 260 proteins. Validation of the proteomics data showed that HIV co-infection helped the survival of non-pathogenic mycobacteria by obstructing phagosome maturation, promoting lipid biogenesis and increasing intracellular ATP equivalents. In turn, mycobacterial co-infection up-regulated purinergic receptors in macrophages that are known to support HIV entry, explaining increased viral titers during co-infection. The mutualism was reconfirmed using clinically relevant opportunistic mycobacteria, Mycobacterium avium, Mycobacterium kansasii and Mycobacterium phlei that exhibited increased survival during co-infection, together with increase in HIV titers. Additionally, the catalogued proteins in the study provide new leads that will significantly add to the understanding of the biology of opportunistic mycobacteria and HIV coalition. PMID:26332641

  8. Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study.

    PubMed

    Li, Changwei; He, Jiang; Chen, Jing; Zhao, Jinying; Gu, Dongfeng; Hixson, James E; Rao, Dabeeru C; Jaquish, Cashell E; Gu, Charles C; Chen, Jichun; Huang, Jianfeng; Chen, Shufeng; Kelly, Tanika N

    2016-08-01

    We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10(-4)) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP (P=3.13×10(-9)). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90×10(-12)) and LOC105369882 rs11104632 (P=4.51×10(-8)) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11×10(-22)) and mean arterial pressure (P=2.86×10(-15)). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10(-7)), C2orf80 (P<1.00×10(-12)), EPHA6 (P=2.88×10(-7)), SCOC-AS1 (P=4.35×10(-14)), SCOC (P=6.46×10(-11)), CLGN (P=3.68×10(-13)), MGAT4D (P=4.73×10(-11)), ARHGAP42 (P≤1.00×10(-12)), CASP4 (P=1.31×10(-8)), and LINC01478 (P=6.75×10(-10)) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium. PMID:27271309

  9. Prevalence of emerging porcine parvoviruses and their co-infections with porcine circovirus type 2 in China.

    PubMed

    Sun, Jianhui; Huang, Liping; Wei, Yanwu; Wang, Yiping; Chen, Dongjie; Du, Wenjuan; Wu, Hongli; Liu, Changming

    2015-05-01

    A total of 450 samples from domestic pigs in China were tested for porcine parvoviruses (PPVs) and co-infections with porcine circovirus type 2 (PCV2), and their complete capsid genes were sequenced. The prevalence of PPV1, PPV2, PPV3, PPV4, and PCV2 was 5.56 %, 39.56 %, 45.11 %, 21.56 %, and 47.33 %, respectively, and co-infection with PCV2 occurred in 4 % (PPV1), 22.44 % (PPV2), 24 % (PPV3), and 12 % (PPV4) of the samples. Phylogenetic analysis revealed two main lineages for each virus, and residues that differentiated these viruses were identified. The co-infections of emerging PPVs and PCV2 were prevalent, indicating their cooperative roles in porcine circovirus-associated diseases. PMID:25742931

  10. Genome-Wide Association Meta-Analyses to Identify Common Genetic Variants Associated with Hallux Valgus in Caucasian and African Americans

    PubMed Central

    Hsu, Yi-Hsiang; Liu, Youfang; Hannan, Marian T.; Maixner, William; Smith, Shad B.; Diatchenko, Luda; Golightly, Yvonne M.; Menz, Hylton B.; Kraus, Virginia B.; Doherty, Michael; Wilson, A.G.; Jordan, Joanne M.

    2016-01-01

    Objective Hallux valgus (HV) affects ~36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated with HV. Methods HV was assessed in 3 Caucasian cohorts (n=2,263, n=915, and n=1,231 participants, respectively). In each cohort, a GWAS was conducted using 2.5M imputed single nucleotide polymorphisms (SNPs). Mixed-effect regression with the additive genetic model adjusted for age, sex, weight and within-family correlations was used for both sex-specific and combined analyses. To combine GWAS results across cohorts, fixed-effect inverse-variance meta-analyses were used. Following meta-analyses, top-associated findings were also examined in an African American cohort (n=327). Results The proportion of HV variance explained by genome-wide genotyped SNPs was 50% in men and 48% in women. A higher proportion of genetic determinants of HV was sex-specific. The most significantly associated SNP in men was rs9675316 located on chr17q23-a24 near the AXIN2 gene (p=5.46×10−7); the most significantly associated SNP in women was rs7996797 located on chr13q14.1-q14.2 near the ESD gene (p=7.21×10−7). Genome-wide significant SNP-by-sex interaction was found for SNP rs1563374 located on chr11p15.1 near the MRGPRX3 gene (interaction p-value =4.1×10−9). The association signals diminished when combining men and women. Conclusion Findings suggest that the potential pathophysiological mechanisms of HV are complex and strongly underlined by sex-specific interactions. The identified genetic variants imply contribution of biological pathways observed in osteoarthritis as well as new pathways, influencing skeletal development and inflammation. PMID:26337638

  11. Synergistic pathogenic effects of co-infection of subgroup J avian leukosis virus and reticuloendotheliosis virus in broiler chickens.

    PubMed

    Dong, Xuan; Zhao, Peng; Chang, Shuang; Ju, Sidi; Li, Yang; Meng, Fanfeng; Sun, Peng; Cui, Zhizhong

    2015-01-01

    To study interactions between avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) and the effects of co-infection on pathogenicity of these viruses, 1-day-old broiler chicks were infected with ALV-J, REV or both ALV-J and REV. The results indicated that co-infection of ALV-J and REV induced more growth retardation and higher mortality rate than ALV-J or REV single infection (P < 0.05). Chickens co-infected with ALV-J and REV also showed more severe immunosuppression than those with a single infection. This was manifested by significantly lower bursa of Fabricius and thymus to body weight ratios and lower antibody responses to Newcastle disease virus and H9-avian influenza virus (P < 0.05). Perihepatitis and pericarditis related to severe infection with Escherichia coli were found in many of the dead birds. E. coli was isolated from each case of perihepatitis and pericarditis. The mortality associated with E. coli infection in the co-infection groups was significantly higher than in the other groups (P < 0.05). Among 516 tested E. coli isolates from 58 dead birds, 12 serotypes of the O-antigen were identified in two experiments. Different serotypes of E. coli strains were even isolated from the same organ of the same bird. Diversification of O-serotypes suggested that perihepatitis and pericarditis associated with E. coli infection was the most frequent secondary infection following the immunosuppression induced by ALV-J and REV co-infection. These results suggested that the co-infection of ALV-J and REV caused more serious synergistic pathogenic effects, growth retardation, immunosuppression, and secondary E. coli infection in broiler chickens. PMID:25484188

  12. Prognostic significance of the intervals between the initiation of antiretroviral therapy and anti-tuberculosis treatment in HIV-tuberculosis co-infected patients: Results from the TREAT Asia HIV Observational Database

    PubMed Central

    Han, Sang Hoon; Zhou, Jialun; Lee, Man Po; Zhao, Hongxin; Chen, Yi-Ming Arthur; Kumarasamy, Nagalingeswaran; Pujari, Sanjay; Lee, Christopher; Faridah Syed Omar, Sharifah; Ditangco, Rossana; Phanuphak, Nittaya; Kiertiburanakul, Sasisopin; Chaiwarith, Romanee; Merati, Tuti Parwati; Yunihastuti, Evy; Tanuma, Junko; Saphonn, Vonthanak; Sohn, Annette H.; Choi, Jun Yong

    2013-01-01

    Objectives We evaluated the effect of time intervals between the initiation of antiretroviral therapy (ART) and tuberculosis (TB) treatment on clinical outcomes in HIV-TB co-infected patients in an Asian regional cohort. Methods Adult HIV-TB co-infected patients in an observational HIV cohort database who had a known date of ART initiation and history of TB treatment were eligible for study inclusion. The time intervals between the initiation of ART and TB treatment were categorized as follows: TB diagnosed while on ART, early ART (<90 days after TB treatment), delayed ART (>90 days after TB treatment), and ART not started. Outcomes were assessed using survival analyses. Results A total of 768 HIV-TB co-infected patients were included in this study. Median CD4 T-cell count at TB diagnosis was 100 (IQR 40–208) cells/µL. The treatment outcomes between early ART and delayed ART initiation were not significantly different. Kaplan-Meier analysis indicated that mortality was highest for those diagnosed with TB while on ART (3.77 deaths per 100 person-years), and the prognoses of other groups were not different (in deaths per 100 person-years: 2.12 early ART, 1.46 delayed ART, and 2.94 ART not started). In a multivariate model, the interval between ART initiation and TB therapy did not significantly impact all-cause mortality. Conclusions The negative impact of delayed ART in patients co-infected with TB was not observed in this observational cohort of moderately to severely immunosuppressed patients. The broader impact of earlier ART in actual clinical practice should be monitored more closely. PMID:23980589

  13. HIV and Syphilis Co-Infection Increasing among Men Who Have Sex with Men in China: A Systematic Review and Meta-Analysis

    PubMed Central

    Chow, Eric P. F.; Wilson, David P.; Zhang, Lei

    2011-01-01

    Background This study aims to estimate the magnitude and changing trends of HIV, syphilis and HIV-syphilis co-infections among men who have sex with men (MSM) in China during 2003–2008 through a systematic review of published literature. Methodology/Principal Findings Chinese and English literatures were searched for studies reporting HIV and syphilis prevalence among MSM from 2003 to 2008. The prevalence estimates were summarized and analysed by meta-analyses. Meta-regression was used to identify the potential factors that are associated with high heterogeneities in meta-analysis. Seventy-one eligible articles were selected in this review (17 in English and 54 in Chinese). Nationally, HIV prevalence among MSM increased from 1.3% during 2003–2004 to 2.4% during 2005–2006 and to 4.7% during 2007–2008. Syphilis prevalence increased from 6.8% during 2003–2004 to 10.4% during 2005–2006 and to 13.5% during 2007–2008. HIV-syphilis co-infection increased from 1.4% during 2005–2006 to 2.7% during 2007–2008. Study locations and study period are the two major contributors of heterogeneities of both HIV and syphilis prevalence among Chinese MSM. Conclusions/Significance There have been significant increases in HIV and syphilis prevalence among MSM in China. Scale-up of HIV and syphilis screening and implementation of effective public health intervention programs should target MSM to prevent further spread of HIV and syphilis infection. PMID:21857952

  14. Molecular Identification of Falciparum Malaria and Human Tuberculosis Co-Infections in Mummies from the Fayum Depression (Lower Egypt)

    PubMed Central

    Bianucci, Raffaella; Welte, Beatrix; Nerlich, Andreas G.; Kun, Jürgen F. J.; Pusch, Carsten M.

    2013-01-01

    Due to the presence of the lake Quarun and to the particular nature of its irrigation system, it has been speculated that the Fayum, a large depression 80 kilometers south- west of modern Cairo, was exposed to the hazards of malaria in historic times. Similarly, it has been speculated that, in the same area, also human tuberculosis might have been far more widespread in the antiquity than in its recent past. If these hypotheses were confirmed, it would imply that frequent cases of co-infection between the two pathogens might have occurred in ancient populations. To substantiate those speculations, molecular analyses were carried out on sixteen mummified heads recovered from the necropolis of Abusir el Meleq (Fayum) dating from the 3rd Intermediate Period (1064- 656 BC) to the Roman Period (30 BC- 300 AD). Soft tissue biopsies were used for DNA extractions and PCR amplifications using well-suited protocols. A partial 196-bp fragment of Plasmodium falciparum apical membrane antigen 1 gene and a 123-bp fragment of the Mycobacterium tuberculosis complex insertion sequence IS6110 were amplified and sequenced in six and five of the sixteen specimens, respectively. A 100% concordance rates between our sequences and those of P. falciparum and M. tuberculosis complex ones were obtained. Lastly, concomitant PCR amplification of P. falciparum and M. tuberculosis complex DNA specific fragments was obtained in four mummies, three of which are 14 C dated to the Late and Graeco-Roman Periods. Our data confirm that the hydrography of Fayum was extremely conducive to the spread of malaria. They also support the notion that the agricultural boom and dense crowding occurred in this region, especially under the Ptolemies, highly increased the probability for the manifestation and spread of tuberculosis. Here we extend back-wards to ca. 800 BC new evidence for malaria tropica and human tuberculosis co-occurrence in ancient Lower Egypt. PMID:23565222

  15. Molecular identification of falciparum malaria and human tuberculosis co-infections in mummies from the Fayum depression (Lower Egypt).

    PubMed

    Lalremruata, Albert; Ball, Markus; Bianucci, Raffaella; Welte, Beatrix; Nerlich, Andreas G; Kun, Jürgen F J; Pusch, Carsten M

    2013-01-01

    Due to the presence of the lake Quarun and to the particular nature of its irrigation system, it has been speculated that the Fayum, a large depression 80 kilometers south-west of modern Cairo, was exposed to the hazards of malaria in historic times. Similarly, it has been speculated that, in the same area, also human tuberculosis might have been far more widespread in the antiquity than in its recent past. If these hypotheses were confirmed, it would imply that frequent cases of co-infection between the two pathogens might have occurred in ancient populations. To substantiate those speculations, molecular analyses were carried out on sixteen mummified heads recovered from the necropolis of Abusir el Meleq (Fayum) dating from the 3(rd) Intermediate Period (1064-656 BC) to the Roman Period (30 BC-300 AD). Soft tissue biopsies were used for DNA extractions and PCR amplifications using well-suited protocols. A partial 196-bp fragment of Plasmodium falciparum apical membrane antigen 1 gene and a 123-bp fragment of the Mycobacterium tuberculosis complex insertion sequence IS6110 were amplified and sequenced in six and five of the sixteen specimens, respectively. A 100% concordance rates between our sequences and those of P. falciparum and M. tuberculosis complex ones were obtained. Lastly, concomitant PCR amplification of P. falciparum and M. tuberculosis complex DNA specific fragments was obtained in four mummies, three of which are (14)C dated to the Late and Graeco-Roman Periods. Our data confirm that the hydrography of Fayum was extremely conducive to the spread of malaria. They also support the notion that the agricultural boom and dense crowding occurred in this region, especially under the Ptolemies, highly increased the probability for the manifestation and spread of tuberculosis. Here we extend back-wards to ca. 800 BC new evidence for malaria tropica and human tuberculosis co-occurrence in ancient Lower Egypt. PMID:23565222

  16. Challenges and perspectives for improved management of HIV/Mycobacterium tuberculosis co-infection.

    PubMed

    Sester, M; Giehl, C; McNerney, R; Kampmann, B; Walzl, G; Cuchí, P; Wingfield, C; Lange, C; Migliori, G B; Kritski, A L; Meyerhans, A

    2010-12-01

    HIV and Mycobacterium tuberculosis (MTB) are two widespread and highly successful microbes whose synergy in pathogenesis has created a significant threat for human health globally. In acknowledgement of this fact, the European Union (EU) has funded a multinational support action, the European Network for global cooperation in the field of AIDS and TB (EUCO-Net), that brings together experts from Europe and those regions that bear the highest burden of HIV/MTB co-infection. Here, we summarise the main outcome of the EUCO-Net project derived from an expert group meeting that took place in Stellenbosch (South Africa) (AIDS/TB Workshop on Research Challenges and Opportunities for Future Collaboration) and the subsequent discussions, and propose priority areas for research and concerted actions that will have impact on future EU calls. PMID:21119204

  17. Review: HIV-Plasmodium Co-infection: Malaria in AIDS patients.

    PubMed

    Qadir, Muhammad Imran; Maqbool, Faheem; Maqbool, Ayesha; Ali, Muhammad

    2015-09-01

    Malaria and HIV are amongst the two main diseases worldwide and creating troubles of our time. Together, they grounds extra than four million deaths a year. Malaria causes around about for more than a million deaths each year, of which over 80-90 % come about in tropical Africa, somewhere malaria is the primary source of mortality in children below six years of age. Sideways as of adolescent, children, pregnant women are surrounded by the largest part exaggerated by the disease. In the wide geographical extend beyond in event and the follow-on co-infection, the interface flanked as a result of the two diseases visibly has foremost communal strength results. Thus both are dangerous for health at the same time. PMID:26408902

  18. [Current opportunities for treatment of chronic hepatitis C in patients with HIV co-infection].

    PubMed

    Inglot, Małgorzata; Szymczak, Aleksandra; Gasiorowski, Jacek

    2008-01-01

    Liver diseases, mainly chronic viral hepatitis, recently have become the main cause of hospitalization and death in individuals with HIV infection. As HCV infection is predominant condition in this group of patients, treatment of hepatitis C is extremely important in halting hepatic injury. Large clinical trials (APRICOT, RIBAVIC, ACTG 5071) showed satisfactory efficacy and safety of therapy with pegylated interferon alpha and ribavirin. Other trials, searching ways to improve efficacy of chronic hepatitis C treatment in HIV co-infected individuals, are still running. Management possibilities include higher doses of ribavirin and, prolonged course of treatment. The article summarizes current state of knowledge in the field of chronic hepatitis C treatment in HIV/HCV-coinfected individuals. PMID:18807485

  19. The Impact of HIV Co-Infection on the Genomic Response to Sepsis

    PubMed Central

    Huson, Michaëla A. M.; Scicluna, Brendon P.; van Vught, Lonneke A.; Wiewel, Maryse A.; Hoogendijk, Arie J.; Cremer, Olaf L.; Bonten, Marc J. M.; Schultz, Marcus J.; Franitza, Marek; Toliat, Mohammad R.; Nürnberg, Peter; Grobusch, Martin P.; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. PMID:26871709

  20. Prevalence and Correlates of Helminth Co-infection in Kenyan HIV-1 Infected Adults

    PubMed Central

    Walson, Judd L.; Stewart, Barclay T.; Sangaré, Laura; Mbogo, Loice W.; Otieno, Phelgona A.; Piper, Benjamin K. S.; Richardson, Barbra A.; John-Stewart, Grace

    2010-01-01

    Background Deworming HIV-1 infected individuals may delay HIV-1 disease progression. It is important to determine the prevalence and correlates of HIV-1/helminth co-infection in helminth-endemic areas. Methods HIV-1 infected individuals (CD4>250 cells/ul) were screened for helminth infection at ten sites in Kenya. Prevalence and correlates of helminth infection were determined. A subset of individuals with soil-transmitted helminth infection was re-evaluated 12 weeks following albendazole therapy. Results Of 1,541 HIV-1 seropositive individuals screened, 298 (19.3%) had detectable helminth infections. Among individuals with helminth infection, hookworm species were the most prevalent (56.3%), followed by Ascaris lumbricoides (17.1%), Trichuris trichiura (8.7%), Schistosoma mansoni (7.1%), and Stongyloides stercoralis (1.3%). Infection with multiple species occurred in 9.4% of infections. After CD4 count was controlled for, rural residence (RR 1.40, 95% CI: 1.08–1.81), having no education (RR 1.57, 95% CI: 1.07–2.30), and higher CD4 count (RR 1.36, 95% CI: 1.07–1.73) remained independently associated with risk of helminth infection. Twelve weeks following treatment with albendazole, 32% of helminth-infected individuals had detectable helminths on examination. Residence, education, and CD4 count were not associated with persistent helminth infection. Conclusions Among HIV-1 seropositive adults with CD4 counts above 250 cells/mm3 in Kenya, traditional risk factors for helminth infection, including rural residence and lack of education, were associated with co-infection, while lower CD4 counts were not. Trial Registration ClinicalTrials.gov NCT00130910 PMID:20361031

  1. Systemic Cytokine and Interferon Responsiveness Patterns in HIV and HCV Mono and Co-Infections

    PubMed Central

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael

    2014-01-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV+/HCV+), HCV mono-infected (HIV−/HCV+), HIV mono-infected (HIV+/HCV−) female patients and HIV- and HCV-uninfected women (HIV−/HCV−) who had enrolled in the Women's Interagency HIV Study (WIHS). HIV+/HCV+ women had higher plasma levels of pro-inflammatory cytokines as well as caspase-1 compared with other groups. Both HIV+/HCV+ and HIV+/HCV− women had significantly higher sCD14 levels compared with other groups. Peripheral blood mononuclear cells from HCV mono-infected patients had reduced levels of phosphorylation of STAT1 compared with other groups as well as lower basal levels of expression of the IFN-stimulated genes, OAS1, ISG15, and USP18 (UBP43). Basal expression of USP18, a functional antagonist of ISG15, as well as USP18/ISG15 ratios were increased in the HIV+/HCV+ group compared with HIV−/HCV+ and HIV+/HCV− groups. A more pronounced systemic inflammatory profile as well as increased expression ratios of USP18 to ISG15 may contribute to the more rapid progression of liver disease in HIV+/HCV+ individuals. PMID:24955730

  2. Systemic cytokine and interferon responsiveness Patterns in HIV and HCV mono and co-infections.

    PubMed

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-11-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV(+)/HCV(+)), HCV mono-infected (HIV(-)/HCV(+)), HIV mono-infected (HIV(+)/HCV(-)) female patients and HIV- and HCV-uninfected women (HIV(-)/HCV(-)) who had enrolled in the Women's Interagency HIV Study (WIHS). HIV(+)/HCV(+) women had higher plasma levels of pro-inflammatory cytokines as well as caspase-1 compared with other groups. Both HIV(+)/HCV(+) and HIV(+)/HCV(-) women had significantly higher sCD14 levels compared with other groups. Peripheral blood mononuclear cells from HCV mono-infected patients had reduced levels of phosphorylation of STAT1 compared with other groups as well as lower basal levels of expression of the IFN-stimulated genes, OAS1, ISG15, and USP18 (UBP43). Basal expression of USP18, a functional antagonist of ISG15, as well as USP18/ISG15 ratios were increased in the HIV(+)/HCV(+) group compared with HIV(-)/HCV(+) and HIV(+)/HCV(-) groups. A more pronounced systemic inflammatory profile as well as increased expression ratios of USP18 to ISG15 may contribute to the more rapid progression of liver disease in HIV(+)/HCV(+) individuals. PMID:24955730

  3. Parasite co-infection and interaction as drivers of host heterogeneity.

    PubMed

    Cattadori, I M; Boag, B; Hudson, P J

    2008-03-01

    We examined the hypothesis that the interaction between concomitant infecting parasites modifies host susceptibility, parasite intensity and the pattern of parasite distribution within the host population. We used a 26 year time series of three common parasites in a natural population of rabbits: two gastrointestinal nematodes (Trichostrongylus retortaeformis and Graphidium strigosum) and the immunosuppressive myxoma virus. The frequency distribution of nematodes in the host population and the relationship between host age and nematode intensity were explored in rabbits with either single or dual nematode infections and rabbits infected with the nematodes and myxoma virus. The aggregation of T. retortaeformis and G. strigosum among the rabbits varied with the nature of the co-infection both in male and female hosts. The two nematodes exhibited different age-intensity profiles: G. strigosum intensity increased exponentially with host age while T. retortaeformis intensity exhibited a convex shape. The presence of a secondary infection did not change the age-intensity profile for G. strigosum but for T. retortaeformis co-infection (either both nematodes or myxoma-nematodes) resulted in significantly greater intensities in adult hosts. Results suggest that multi-species infections contributed to aggregation of parasites in the host population and to seasonal variation in intensity, but also enhanced differences in parasitism between sexes. This effect was apparent for T. retortaeformis, which appears to elicit a strong acquired immune response but not for G. strigosum which does not produce any evident immune reaction. We concluded that concomitant infections mediated by host immunity are important in modifying host susceptibility and influencing heterogeneity amongst individual hosts. PMID:17936286

  4. Clinical and laboratory characteristics of ocular syphilis, co-infection, and therapy response

    PubMed Central

    Sahin, Ozlem; Ziaei, Alireza

    2016-01-01

    Purpose To describe the clinical presentation of patients diagnosed with presumed latent ocular syphilis and congenital ocular syphilis at tertiary referral center in Turkey, and to compare the clinical findings with patients described in other studies, specifically focusing on demographics and co-infections. Methods This is a retrospective study reviewing the medical records of patients diagnosed with ocular inflammation between January 2012 and June 2014 at a tertiary referral center in Turkey. Ocular syphilis was diagnosed on the basis of non-treponemal and treponemal antibody tests, and cerebrospinal fluid analysis. All the patients diagnosed with ocular syphilis were tested for human immunodeficiency virus (HIV), Toxoplasma gondii, rubella, cytomegalovirus, and herpes. Results A total of 1,115 patients were evaluated between January 2012 and June 2014, and 12 patients (1.07%) were diagnosed with ocular syphilis based on the inclusion criteria. None of the patients were seropositive for HIV. Two patients were seropositive for T. gondii-specific IgG. Clinical presentations include non-necrotizing anterior scleritis, non-necrotizing sclerokeratitis, anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis, and optic neuritis. All of the patients showed clinical improvement in the level of ocular inflammation with intravenous penicillin 24 million U/day for 10 days. Three patients received additional oral methotrexate as an adjunctive therapy. Two cases received low-dose trimethoprim–sulfamethoxazole. Conclusion Ocular syphilis is an uncommon cause of ocular inflammation in HIV-negative patients. Central retinochoroiditis is the most common ocular manifestation, and it is the most common cause of visual impairment. Ocular syphilis might present associated with co-infections such as T. gondii in developing countries. Oral methotrexate might be beneficial as an adjunctive therapy for ocular syphilis in resolving the residual intraocular inflammation

  5. The Impact of HIV Co-Infection on the Genomic Response to Sepsis.

    PubMed

    Huson, Michaëla A M; Scicluna, Brendon P; van Vught, Lonneke A; Wiewel, Maryse A; Hoogendijk, Arie J; Cremer, Olaf L; Bonten, Marc J M; Schultz, Marcus J; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Grobusch, Martin P; van der Poll, Tom

    2016-01-01

    HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. PMID:26871709

  6. Spatial Genetic Analyses Reveal Cryptic Population Structure and Migration Patterns in a Continuously Harvested Grey Wolf (Canis lupus) Population in North-Eastern Europe

    PubMed Central

    Hindrikson, Maris; Remm, Jaanus; Männil, Peep; Ozolins, Janis; Tammeleht, Egle; Saarma, Urmas

    2013-01-01

    Spatial genetics is a relatively new field in wildlife and conservation biology that is becoming an essential tool for unravelling the complexities of animal population processes, and for designing effective strategies for conservation and management. Conceptual and methodological developments in this field are therefore critical. Here we present two novel methodological approaches that further the analytical possibilities of STRUCTURE and DResD. Using these approaches we analyse structure and migrations in a grey wolf (Canislupus) population in north-eastern Europe. We genotyped 16 microsatellite loci in 166 individuals sampled from the wolf population in Estonia and Latvia that has been under strong and continuous hunting pressure for decades. Our analysis demonstrated that this relatively small wolf population is represented by four genetic groups. We also used a novel methodological approach that uses linear interpolation to statistically test the spatial separation of genetic groups. The new method, which is capable of using program STRUCTURE output, can be applied widely in population genetics to reveal both core areas and areas of low significance for genetic groups. We also used a recently developed spatially explicit individual-based method DResD, and applied it for the first time to microsatellite data, revealing a migration corridor and barriers, and several contact zones. PMID:24069446

  7. Genetic Structure of Mycobacterium avium subsp. paratuberculosis Population in Cattle Herds in Quebec as Revealed by Using a Combination of Multilocus Genomic Analyses

    PubMed Central

    Sohal, Jagdip Singh; Arsenault, Julie; Labrecque, Olivia; Fairbrother, Julie-Hélène; Roy, Jean-Philippe; Fecteau, Gilles

    2014-01-01

    Mycobacterium avium subsp. paratuberculosis is the etiological agent of paratuberculosis, a granulomatous enteritis affecting a wide range of domestic and wild ruminants worldwide. A variety of molecular typing tools are used to distinguish M. avium subsp. paratuberculosis strains, contributing to a better understanding of M. avium subsp. paratuberculosis epidemiology. In the present study, PCR-based typing methods, including mycobacterial interspersed repetitive units/variable-number tandem repeats (MIRU-VNTR) and small sequence repeats (SSR) in addition to IS1311 PCR-restriction enzyme analysis (PCR-REA), were used to investigate the genetic heterogeneity of 200 M. avium subsp. paratuberculosis strains from dairy herds located in the province of Quebec, Canada. The majority of strains were of the “cattle type,” or type II, although 3 strains were of the “bison type.” A total of 38 genotypes, including a novel one, were identified using a combination of 17 genetic markers, which generated a Simpson's index of genetic diversity of 0.876. Additional analyses revealed no differences in genetic diversity between environmental and individual strains. Of note, a spatial and spatiotemporal cluster was evidenced regarding the distribution of one of the most common genotypes. The population had an overall homogeneous genetic structure, although a few strains stemmed out of the consensus cluster, including the bison-type strains. The genetic structure of M. avium subsp. paratuberculosis populations within most herds suggested intraherd dissemination and microevolution, although evidence of interherd contamination was also revealed. The level of genetic diversity obtained by combining MIRU-VNTR and SSR markers shows a promising avenue for molecular epidemiology investigations of M. avium subsp. paratuberculosis transmission patterns. PMID:24829229

  8. RNA Expression and Post-Transcriptional Editing Analyses of Cucumber Plastids Reveals Genetic Differences Associated with Chilling Tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tolerance to chilling injury in cucumber (Cucumis sativus L.) is associated with three plastomic single nucleotide polymorphisms (ptSNPs) at bp positions 4,813, 56,561, and 126,349 that are co-inherited. An understanding of the genetic expression of these ptSNPs as a response to chilling is critical...

  9. Virulence structure of Blumeria graminis f.sp. tritici and its genetic diversity by ISSR and SRAP profiling analyses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blumeria graminis f. sp. tritici is an obligate biotrophic pathogen causing wheat powdery mildew that has a great genetic flexibility and variations in relationship to its host plant. Application of disease resistant cultivars is an essential disease management measurement. Due to its rapid adaptati...

  10. Angus sattle at high altitude: Genetic relationships and initial genome-wide association analyses of pulmonary arterial pressure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Records from yearling Angus (n = 10,647) cattle from elevation 2,340 m were used in genetic analysis of pulmonary arterial pressure (PAP). Bulls were developed within a grain-supplemented performance test, whereas heifers and steers were grazed. The BovineSNP50 Beadchip was used to genotype a subset...

  11. Melon (Cucumis melo L.) Diversity Analyses Provide Strategies for Germplasm Curation, Genetic Improvement and Evidentiary Support of Domestication Patterns

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genetic diversity of melon market types (Cucumis melo L., 2n = 2x = 24) in China, an important secondary center of diversity, has not been examined. Therefore, reference accessions (India, Africa, Crete/Greece, Japan, Europe, USA, and Spain) and 68 Chinese cultigens (fresh market non-netted thi...

  12. Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

    PubMed Central

    Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

    2012-01-01

    Background Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. Methods Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. Results Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. Conclusions AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays

  13. Characterization of a new megabirnavirus that confers hypovirulence with the aid of a co-infecting partitivirus to the host fungus, Rosellinia necatrix.

    PubMed

    Sasaki, Atsuko; Nakamura, Hitoshi; Suzuki, Nobuhiro; Kanematsu, Satoko

    2016-07-01

    A new virus termed Rosellinia necatrix megabirnavirus 2 (RnMBV2) was molecularly and biologically characterized. RnMBV2 was originally harbored in isolate W8 of R. necatrix co-infected with the previously reported virus Rosellinia necatrix partitivirus 1 (RnPV1). RnMBV2 has molecular features similar and different from precedent megabirnaviruses, Rosellinia necatrix megabirnavirus 1 (RnMBV1) and Sclerotinia sclerotiorum megabirnavirus 1 (SsMBV1). The two genomic segments of RnMBV2 (9.0-kbp dsRNA1 and 8.0-kbp dsRNA2) each possess two open reading frames (ORF1 and 2 on dsRNA1 and ORF3 and 4 on dsRNA2), with a well conserved 5'-long untranslated region (UTR) of 1.7-1.8kb between the segments, and relatively short 3'-UTR. The RnMBV2 dsRNA1-coded capsid protein (CP) and RNA-dependent RNA polymerase (RdRp) show higher sequence identity to those of SsMBV1 than to those of RnMBV1, whereas the RnMBV2 ORF3-coded protein is more closely related to the counterpart of RnMBV1. No significant amino acid sequence similarity was detected among ORF4-coded sequences of the three megabirnaviruses. Virion transfection and co-culturing allowed for single and double infection of mycelial incompatible isolates W37 and W97 by RnMBV2 and/or RnPV1. Their comparative analyses showed RnMBV2 to be able to confer hypovirulence with the aid of a co-infecting RnPV1, while the individual viruses exhibited asymptomatic infections. Interestingly, RnPV1 accumulation appeared to be increased in co-infected fungal strain with two segments of RnMBV2 relative to singly infected fungal strains. Furthermore, the dispensability of RnMBV2 dsRNA2 was demonstrated to be similar to that of the other two megabirnaviruses. PMID:26718720

  14. Phylogeographic analyses of the southern leopard frog: the impact of geography and climate on the distribution of genetic lineages vs. subspecies.

    PubMed

    Newman, Catherine E; Rissler, Leslie J

    2011-12-01

    The southeastern United States is a major phylogeographic break hotspot for amphibians, but the processes underlying this hotspot remain to be explicitly tested. We test the correlation of genetic lineages with subspecies breaks in the southeastern United States and the association of such breaks with climate, using Rana sphenocephala as a case study, and place our results in the broader context of the Alabama-Appalachian suture zone (AL-Appalachian SZ). We use genetic and ecological methods to (i) determine whether genetic lineages are coincident with the AL-Appalachian SZ or the subspecies and (ii) test the correlation of major climatic breaks with genetic structure and morphological variation in R. sphenocephala. Bayesian phylogenetic analyses of the ND1 mtDNA gene and microsatellite cluster analyses revealed two distinct lineages with over 4% sequence divergence. The geographic distributions of the two lineages are concordant with the AL-Appalachian SZ but do not correspond to the ranges of the subspecies based on morphology. Mantel tests revealed that isolation by distance and historical barriers to gene flow, rather than climate, are the major drivers of genetic divergence at neutral loci. Examination of climate breaks across the Southeast revealed a pattern incongruent with suture zone hotspots, suggesting that phylogenetic structure has been driven primarily by historical factors, such as isolation, the Appalachian Mountains and the Apalachicola/Chattahoochee/Flint River Basin. However, climate breaks are consistent with the geographic distribution of the subspecies of R. sphenocephala, suggesting that environmental pressures may be driving divergence in morphological traits that outpaces molecular evolution. PMID:22066968

  15. Combined analyses of kinship and FST suggest potential drivers of chaotic genetic patchiness in high gene-flow populations

    PubMed Central

    Iacchei, Matthew; Ben-Horin, Tal; Selkoe, Kimberly A; Bird, Christopher E; García-Rodríguez, Francisco J; Toonen, Robert J

    2013-01-01

    We combine kinship estimates with traditional F-statistics to explain contemporary drivers of population genetic differentiation despite high gene flow. We investigate range-wide population genetic structure of the California spiny (or red rock) lobster (Panulirus interruptus) and find slight, but significant global population differentiation in mtDNA (ΦST = 0.006, P = 0.001; Dest_Chao = 0.025) and seven nuclear microsatellites (FST = 0.004, P < 0.001; Dest_Chao = 0.03), despite the species’ 240- to 330-day pelagic larval duration. Significant population structure does not correlate with distance between sampling locations, and pairwise FST between adjacent sites often exceeds that among geographically distant locations. This result would typically be interpreted as unexplainable, chaotic genetic patchiness. However, kinship levels differ significantly among sites (pseudo-F16,988 = 1.39, P = 0.001), and ten of 17 sample sites have significantly greater numbers of kin than expected by chance (P < 0.05). Moreover, a higher proportion of kin within sites strongly correlates with greater genetic differentiation among sites (Dest_Chao, R2 = 0.66, P < 0.005). Sites with elevated mean kinship were geographically proximate to regions of high upwelling intensity (R2 = 0.41, P = 0.0009). These results indicate that P. interruptus does not maintain a single homogenous population, despite extreme dispersal potential. Instead, these lobsters appear to either have substantial localized recruitment or maintain planktonic larval cohesiveness whereby siblings more likely settle together than disperse across sites. More broadly, our results contribute to a growing number of studies showing that low FST and high family structure across populations can coexist, illuminating the foundations of cryptic genetic patterns and the nature of marine dispersal. PMID:23802550

  16. Combined analyses of kinship and FST suggest potential drivers of chaotic genetic patchiness in high gene-flow populations.

    PubMed

    Iacchei, Matthew; Ben-Horin, Tal; Selkoe, Kimberly A; Bird, Christopher E; García-Rodríguez, Francisco J; Toonen, Robert J

    2013-07-01

    We combine kinship estimates with traditional F-statistics to explain contemporary drivers of population genetic differentiation despite high gene flow. We investigate range-wide population genetic structure of the California spiny (or red rock) lobster (Panulirus interruptus) and find slight, but significant global population differentiation in mtDNA (ΦST = 0.006, P = 0.001; D(est_Chao) = 0.025) and seven nuclear microsatellites (F(ST) = 0.004, P < 0.001; D(est_Chao) = 0.03), despite the species' 240- to 330-day pelagic larval duration. Significant population structure does not correlate with distance between sampling locations, and pairwise FST between adjacent sites often exceeds that among geographically distant locations. This result would typically be interpreted as unexplainable, chaotic genetic patchiness. However, kinship levels differ significantly among sites (pseudo-F(16,988) = 1.39, P = 0.001), and ten of 17 sample sites have significantly greater numbers of kin than expected by chance (P < 0.05). Moreover, a higher proportion of kin within sites strongly correlates with greater genetic differentiation among sites (D(est_Chao), R(2) = 0.66, P < 0.005). Sites with elevated mean kinship were geographically proximate to regions of high upwelling intensity (R(2) = 0.41, P = 0.0009). These results indicate that P. interruptus does not maintain a single homogenous population, despite extreme dispersal potential. Instead, these lobsters appear to either have substantial localized recruitment or maintain planktonic larval cohesiveness whereby siblings more likely settle together than disperse across sites. More broadly, our results contribute to a growing number of studies showing that low F(ST) and high family structure across populations can coexist, illuminating the foundations of cryptic genetic patterns and the nature of marine dispersal. PMID:23802550

  17. A Case Report of Plasmodium Vivax, Plasmodium Falciparum and Dengue Co-Infection in a 6 Months Pregnancy

    PubMed Central

    Pande, A; Guharoy, D

    2013-01-01

    India being a tropical country, parasitic infections especially with Plasmodium species are very common in this region. The present case report is that of Plasmodium vivax, Plasmodium falciparum and dengue co-infection in a 6 months pregnant lady who was timely diagnosed and appropriately treated followed by a complete recovery along with feto-maternal well-being. PMID:24349838

  18. The relative importance of host characteristics and co-infection in generating variation in Heligmosomoides polygyrus fecundity.

    PubMed

    Luong, L T; Perkins, S E; Grear, D A; Rizzoli, A; Hudson, P J

    2010-05-01

    We examined the relative importance of intrinsic host factors and microparasite co-infection in generating variation in Heligmosomoides polygyrus fecundity, a parameter that serves as a proxy for infectiousness. We undertook extensive trapping of Apodemus flavicollis, the yellow-necked mouse in the woodlands of the Italian Alps and recorded eggs in utero from the dominant nematode species H. polygyrus, and tested for the presence of five microparasite infections. The results showed that sex and breeding status interact, such that males in breeding condition harboured more fecund nematodes than other hosts; in particular, worms from breeding males had, on average, 52% more eggs in utero than worms from non-breeding males. In contrast, we found a weak relationship between intensity and body mass, and no relationship between intensity and sex or intensity and breeding condition. We did not find any evidence to support the hypothesis that co-infection with microparasites contributed to variation in worm fecundity in this system. The age-intensity profiles for mice singly-infected with H. polygyrus and those co-infected with the nematode and at least one microparasite were both convex and not statistically different from each other. We concluded that intrinsic differences between hosts, specifically with regard to sex and breeding condition, contribute relatively more to the variation in worm fecundity than parasite co-infection status. PMID:20109249

  19. Clinical care versus ethical obligations: HIV-1 and -2 co-infection with hepatitis B in a pregnant Jehovah's Witness.

    PubMed

    Quinn, K J; McCarty, E J; Dinsmore, W M; Quah, S P

    2012-07-01

    Co-infection with HIV-1 and -2 is rare, even in west Africa. We present the case of a 38-year-old pregnant Jehovah's Witness presenting late in pregnancy with triple infection with HIV-1, HIV-2 and hepatitis B virus. There was a successful outcome in averting vertical transmission despite objections to management based on religious and cultural beliefs. PMID:22844019

  20. Antagonism between two intestinal parasites in humans: the importance of co-infection for infection risk and recovery dynamics

    PubMed Central

    Blackwell, Aaron D.; Martin, Melanie; Kaplan, Hillard; Gurven, Michael

    2013-01-01

    Co-infection may affect transmission and recovery from infection, but remains an understudied element of disease ecology, particularly with regard to antagonism between parasites sharing a host. Helminth and giardia infections are often endemic in the same populations and both occupy the small intestine; yet few studies have examined interactions between these parasites. We report on helminth–giardia co-infections in a panel study of forager–horticulturalists in the Bolivian lowlands. Parasites were identified in faecal samples from 3275 participants, collected during 5235 medical exams over 6 years. Longitudinal co-infection patterns were examined using logistic mixed and multi-state Markov models. The most prevalent infections were hookworm (56%), Giardia lamblia (30%) and Ascaris lumbricoides (15%). Cross-sectionally, hookworm and A. lumbricoides were negatively associated with G. lamblia (OR = 0.60; OR = 0.65, respectively). Longitudinally, giardia infection was less likely in helminth-infected individuals (HR: 0.46). Infection with helminths was also less likely for individuals infected with giardia (HR: 0.71). Finally, treatment with mebendazole reduced subsequent hookworm infections, but resulted in a marginal increase in the odds of G. lamblia infection. Our results provide evidence for an antagonistic relationship between helminths and giardia, and suggest that co-infection should be considered in disease transmission models and treatment decisions. PMID:23986108

  1. Co-infection of mallards with low virulence Newcastle disease virus and low pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Waterfowl are considered the natural reservoirs of low pathogenic avian influenza viruses (LPAIV) and low virulence Newcastle disease viruses (loNDV). The objective of this study was to investigate the effect of co-infections with loNDV and LPAIV on the infectivity and excretion of these viruses in ...

  2. Experimental co-infection studies with avian influenza viruses and Newcastle Disease viruses in chickens, turkeys and domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Co-infections of poultry with Newcastle Disease viruses (NDVs) and Avian Influenza viruses (AIVs) present a problem both from the clinical point of view and the diagnosis of these viruses. Little has been done to understand the interactions between these two viruses when infecting poultry. Exposur...

  3. Nitrite reductase is critical for Pseudomonas aeruginosa survival during co-infection with the oral commensal Streptococcus parasanguinis.

    PubMed

    Scoffield, Jessica A; Wu, Hui

    2016-02-01

    Pseudomonas aeruginosa is the major aetiological agent of chronic pulmonary infections in cystic fibrosis (CF) patients. However, recent evidence suggests that the polymicrobial community of the CF lung may also harbour oral streptococci, and colonization by these micro-organisms may have a negative impact on P. aeruginosa within the CF lung. Our previous studies demonstrated that nitrite abundance plays an important role in P. aeruginosa survival during co-infection with oral streptococci. Nitrite reductase is a key enzyme involved in nitrite metabolism. Therefore, the objective of this study was to examine the role nitrite reductase (gene nirS) plays in P. aeruginosa survival during co-infection with an oral streptococcus, Streptococcus parasanguinis. Inactivation of nirS in both the chronic CF isolate FRD1 and acute wound isolate PAO1 reduced the survival rate of P. aeruginosa when co-cultured with S. parasanguinis. Growth of both mutants was restored when co-cultured with S. parasanguinis that was defective for H2O2 production. Furthermore, the nitrite reductase mutant was unable to kill Drosophila melanogaster during co-infection with S. parasanguinis. Taken together, these results suggest that nitrite reductase plays an important role for survival of P. aeruginosa during co-infection with S. parasanguinis. PMID:26673783

  4. Prevalence, Features and Risk Factors for Malaria Co-Infections amongst Visceral Leishmaniasis Patients from Amudat Hospital, Uganda

    PubMed Central

    Adams, Emily R.; Mens, Pètra F.; Sentongo, Elizabeth; Mbulamberi, Dawson B.; Straetemans, Masja; Schallig, Henk D. F. H.; Chappuis, Francois

    2012-01-01

    Background and methodology Due to geographic overlap of malaria and visceral leishmaniasis (VL), co-infections may exist but have been poorly investigated. To describe prevalence, features and risk factors for VL-malaria co-infections, a case-control analysis was conducted on data collected at Amudat Hospital, Uganda (2000–2006) by Médecins sans Frontières. Cases were identified as patients with laboratory-confirmed VL and malaria at hospital admission or during hospitalization; controls were VL patients with negative malaria smears. A logistic regression analysis was performed to study the association between patients' characteristics and the occurrence of the co-infection. Results Of 2414 patients with confirmed VL, 450 (19%) were positively diagnosed with concomitant malaria. Most co-infected patients were males, residing in Kenya (69%). While young age was identified by multivariate analysis as a risk factor for concurrent VL and malaria, particularly the age groups 0–4 (odds ratio (OR): 2.44; 95% confidence interval (CI): 1.52–3.92) and 5–9 years (OR: 2.23, 95% CI: 1.45-3-45), mild (OR: 0.53; 95% CI: 0.32–0.88) and moderate (OR: 0.45; 95% CI: 0.27–0.77) anemia negatively correlated with the co-morbidity. VL patients harboring skin infections were nearly three times less likely to have the co-infection (OR: 0.35; 95% CI: 0.17–0.72), as highlighted by the multivariate model. Anorexia was slightly more frequent among co-infected patients (OR: 1.71; 95% CI: 0.96–3.03). The in-hospital case-fatality rate did not significantly differ between cases and controls, being 2.7% and 3.1% respectively (OR: 0.87; 95% CI: 0.46–1.63). Conclusions Concurrent malaria represents a common condition among young VL patients living in the Pokot region of Kenya and Uganda. Although these co-morbidities did not result in a poorer prognosis, possibly due to early detection of malaria, a positive trend towards more severe symptoms was identified, indicating that

  5. Field synopsis and meta-analyses of genetic epidemiological evidence for Kashin-Beck disease, an endemic osteoarthropathy in China.

    PubMed

    Yang, Lei; Zhao, Guang-Hui; Liu, Huan; Wang, Xi; Guo, Xiong; Lammi, Mikko J

    2016-10-01

    Kashin-Beck disease (KBD) is a chronic degenerative osteoarthropathy with unclear etiology. To provide current evidence supporting a genetic predisposition for KBD, we conducted a systematic review and meta-analysis of published literature on the genetic epidemiology of KBD. The PubMed, China National Knowledge Infrastructure and Wan Fang Data were searched up to August 2015 for articles published in English and Chinese. Genome-wide and exome sequencing, linkage, and case-control association studies for any genetic variants associated with KBD were included. Meta-analysis was performed for all single nucleotide polymorphisms (SNPs) that were evaluated in two or more studies. The effect size was summarized as odds ratios (ORs) with 95 % confidence intervals (CIs) by fixed and random effects models. A total of 24 articles were systematically reviewed. Eleven short tandem repeats on chromosomes 2, 11 and 12, 34 SNPs in 12 genes, as well as copy number variant 452 were identified as KBD susceptibility factors in individual studies. The meta-analysis of the GPX1 rs1050450, DIO2 rs225014, TrxR2 rs5748469 and HLA-DRB1 rs7745040 failed to reveal any associations with KBD. However, the meta-analysis of HLA-DRB1 rs9275295 allele A was associated with KBD (OR = 1.737, 95 % CI: 1.002-3.012). In addition, seven haplotypes in GPX1, GPX4, HLA-DRB1 and GDF5 genes also showed significant associations with KBD. In conclusions, our study could identify a number of genetic markers associated with KBD. However, the evidence does not currently support a strong association between the specific variants and KBD because of the limited number of studies, and in the future, more rigorous studies are needed to confirm KBD's links with these variants. PMID:27256326

  6. Analyses of genetic structure of Tibeto-Burman populations reveals sex-biased admixture in southern Tibeto-Burmans.

    PubMed

    Wen, Bo; Xie, Xuanhua; Gao, Song; Li, Hui; Shi, Hong; Song, Xiufeng; Qian, Tingzhi; Xiao, Chunjie; Jin, Jianzhong; Su, Bing; Lu, Daru; Chakraborty, Ranajit; Jin, Li

    2004-05-01

    An unequal contribution of male and female lineages from parental populations to admixed ones is not uncommon in the American continents, as a consequence of directional gene flow from European men into African and Hispanic Americans in the past several centuries. However, little is known about sex-biased admixture in East Asia, where substantial migrations are recorded. Tibeto-Burman (TB) populations were historically derived from ancient tribes of northwestern China and subsequently moved to the south, where they admixed with the southern natives during the past 2600 years. They are currently extensively distributed in China and Southeast Asia. In this study, we analyze the variations of 965 Y chromosomes and 754 mtDNAs in >20 TB populations from China. By examining the haplotype group distributions of Y-chromosome and mtDNA markers and their principal components, we show that the genetic structure of the extant southern Tibeto-Burman (STB) populations were primarily formed by two parental groups: northern immigrants and native southerners. Furthermore, the admixture has a bias between male and female lineages, with a stronger influence of northern immigrants on the male lineages (approximately 62%) and with the southern natives contributing more extensively to the female lineages (approximately 56%) in the extant STBs. This is the first genetic evidence revealing sex-biased admixture in STB populations, which has genetic, historical, and anthropological implications. PMID:15042512

  7. Population and forensic genetic analyses of mitochondrial DNA control region variation from six major provinces in the Korean population.

    PubMed

    Hong, Seung Beom; Kim, Ki Cheol; Kim, Wook

    2015-07-01

    We generated complete mitochondrial DNA (mtDNA) control region sequences from 704 unrelated individuals residing in six major provinces in Korea. In addition to our earlier survey of the distribution of mtDNA haplogroup variation, a total of 560 different haplotypes characterized by 271 polymorphic sites were identified, of which 473 haplotypes were unique. The gene diversity and random match probability were 0.9989 and 0.0025, respectively. According to the pairwise comparison of the 704 control region sequences, the mean number of pairwise differences between individuals was 13.47±6.06. Based on the result of mtDNA control region sequences, pairwise FST genetic distances revealed genetic homogeneity of the Korean provinces on a peninsular level, except in samples from Jeju Island. This result indicates there may be a need to formulate a local mtDNA database for Jeju Island, to avoid bias in forensic parameter estimates caused by genetic heterogeneity of the population. Thus, the present data may help not only in personal identification but also in determining maternal lineages to provide an expanded and reliable Korean mtDNA database. These data will be available on the EMPOP database via accession number EMP00661. PMID:25900647

  8. Niche Divergence versus Neutral Processes: Combined Environmental and Genetic Analyses Identify Contrasting Patterns of Differentiation in Recently Diverged Pine Species

    PubMed Central

    Moreno-Letelier, Alejandra; Ortíz-Medrano, Alejandra; Piñero, Daniel

    2013-01-01

    Background and Aims Solving relationships of recently diverged taxa, poses a challenge due to shared polymorphism and weak reproductive barriers. Multiple lines of evidence are needed to identify independently evolving lineages. This is especially true of long-lived species with large effective population sizes, and slow rates of lineage sorting. North American pines are an interesting group to test this multiple approach. Our aim is to combine cytoplasmic genetic markers with environmental information to clarify species boundaries and relationships of the species complex of Pinus flexilis, Pinus ayacahuite, and Pinus strobiformis. Methods Mitochondrial and chloroplast sequences were combined with previously obtained microsatellite data and contrasted with environmental information to reconstruct phylogenetic relationships of the species complex. Ecological niche models were compared to test if ecological divergence is significant among species. Key Results and Conclusion Separately, both genetic and ecological evidence support a clear differentiation of all three species but with different topology, but also reveal an ancestral contact zone between P. strobiformis and P. ayacahuite. The marked ecological differentiation of P. flexilis suggests that ecological speciation has occurred in this lineage, but this is not reflected in neutral markers. The inclusion of environmental traits in phylogenetic reconstruction improved the resolution of internal branches. We suggest that combining environmental and genetic information would be useful for species delimitation and phylogenetic studies in other recently diverged species complexes. PMID:24205167

  9. Joint genetic and network analyses identify loci associated with root growth under NaCl stress in Arabidopsis thaliana.

    PubMed

    Kobayashi, Yuriko; Sadhukhan, Ayan; Tazib, Tanveer; Nakano, Yuki; Kusunoki, Kazutaka; Kamara, Mohamed; Chaffai, Radhouane; Iuchi, Satoshi; Sahoo, Lingaraj; Kobayashi, Masatomo; Hoekenga, Owen A; Koyama, Hiroyuki

    2016-04-01

    Plants have evolved a series of tolerance mechanisms to saline stress, which perturbs physiological processes throughout the plant. To identify genetic mechanisms associated with salinity tolerance, we performed linkage analysis and genome-wide association study (GWAS) on maintenance of root growth of Arabidopsis thaliana in hydroponic culture with weak and severe NaCl toxicity. The top 200 single-nucleotide polymorphisms (SNPs) determined by GWAS could cumulatively explain approximately 70% of the variation observed at each stress level. The most significant SNPs were linked to the genes of ATP-binding cassette B10 and vacuolar proton ATPase A2. Several known salinity tolerance genes such as potassium channel KAT1 and calcium sensor SOS3 were also linked to SNPs in the top 200. In parallel, we constructed a gene co-expression network to independently verify that particular groups of genes work together to a common purpose. We identify molecular mechanisms to confer salt tolerance from both predictable and novel physiological sources and validate the utility of combined genetic and network analysis. Additionally, our study indicates that the genetic architecture of salt tolerance is responsive to the severity of stress. These gene datasets are a significant information resource for a following exploration of gene function. PMID:26667381

  10. Towards systems genetic analyses in barley: Integration of phenotypic, expression and genotype data into GeneNetwork

    PubMed Central

    Druka, Arnis; Druka, Ilze; Centeno, Arthur G; Li, Hongqiang; Sun, Zhaohui; Thomas, William TB; Bonar, Nicola; Steffenson, Brian J; Ullrich, Steven E; Kleinhofs, Andris; Wise, Roger P; Close, Timothy J; Potokina, Elena; Luo, Zewei; Wagner, Carola; Schweizer, Günther F; Marshall, David F; Kearsey, Michael J; Williams, Robert W; Waugh, Robbie

    2008-01-01

    Background A typical genetical genomics experiment results in four separate data sets; genotype, gene expression, higher-order phenotypic data and metadata that describe the protocols, processing and the array platform. Used in concert, these data sets provide the opportunity to perform genetic analysis at a systems level. Their predictive power is largely determined by the gene expression dataset where tens of millions of data points can be generated using currently available mRNA profiling technologies. Such large, multidimensional data sets often have value beyond that extracted during their initial analysis and interpretation, particularly if conducted on widely distributed reference genetic materials. Besides quality and scale, access to the data is of primary importance as accessibility potentially allows the extraction of considerable added value from the same primary dataset by the wider research community. Although the number of genetical genomics experiments in different plant species is rapidly increasing, none to date has been presented in a form that allows quick and efficient on-line testing for possible associations between genes, loci and traits of interest by an entire research community. Description Using a reference population of 150 recombinant doubled haploid barley lines we generated novel phenotypic, mRNA abundance and SNP-based genotyping data sets, added them to a considerable volume of legacy trait data and entered them into the GeneNetwork . GeneNetwork is a unified on-line analytical environment that enables the user to test genetic hypotheses about how component traits, such as mRNA abundance, may interact to condition more complex biological phenotypes (higher-order traits). Here we describe these barley data sets and demonstrate some of the functionalities GeneNetwork provides as an easily accessible and integrated analytical environment for exploring them. Conclusion By integrating barley genotypic, phenotypic and mRNA abundance data

  11. Frequency of Hepatitis B and C Co-Infection in Chronic Liver Disease Patients in Calabar, Cross River State, Nigeria.

    PubMed

    Kooffreh-Ada, M; Okpokam, D C; Okaormhe, Z A; Nna, V U

    2016-01-01

    Hepatitis B (HBsAg) and C (HCV) virus are becoming a significant causative factors in the aetiology of chronic liver disease (CLD) worldwide. However, the information on the frequency of HBsAg and HCV virus co-infection in CLD is sparsely reported in Nigeria. In this study, we assessed the frequency of HBsAg and HCV co-infection in CLD. One hundred and eleven subjects aged 19 - 76 years, comprising of 76 CLD patients and 35 apparently healthy subjects without CLD were tested for both HBsAg and HCV virus antibodies using ELISA test kits. Out of the 111 subjects recruited for this study, 76 (68.5%) were CLD patients tested positive for HBsAg and 35 (31.5%) tested negative for HBsAg and served as control. Out of the 76 CLD patients that tested positive for HBsAg, 34 (44.7%) of them also tested positive for HCV, thus, having co-infection with HBV. Incidence of co-infection was highest in those aged 36 - 45 years, and greater in males than females. Among the control group, 4 (11.4%) of the subjects (3 males and 1 female) tested positive for HCV, while 31 (88.6%) subjects (20 males and 11 females) tested negative. This work has shown that the co-infection with HBV and HCV among chronic liver disease patients and the incidence of HCV is high in our locality. Also, some of the supposed apparently healthy subjects in this study tested positive for HCV, hence the need for improving the awareness of this virus. It is therefore necessary to give immunization and test for HBsAg and HCV in both rural and urban areas. PMID:27574763

  12. Porcine epidemic diarrhea virus (PEDV) co-infection induced chlamydial persistence/stress does not require viral replication

    PubMed Central

    Schoborg, Robert V.; Borel, Nicole

    2014-01-01

    Chlamydiae may exist at the site of infection in an alternative replicative form, called the aberrant body (AB). ABs are produced during a viable but non-infectious developmental state termed “persistence” or “chlamydial stress.” As persistent/stressed chlamydiae: (i) may contribute to chronic inflammation observed in diseases like trachoma; and (ii) are more resistant to current anti-chlamydial drugs of choice, it is critical to better understand this developmental stage. We previously demonstrated that porcine epidemic diarrhea virus (PEDV) co-infection induced Chlamydia pecorum persistence/stress in culture. One critical characteristic of persistence/stress is that the chlamydiae remain viable and can reenter the normal developmental cycle when the stressor is removed. Thus, we hypothesized that PEDV-induced persistence would be reversible if viral replication was inhibited. Therefore, we performed time course experiments in which Vero cells were C. pecorum/PEDV infected in the presence of cycloheximide (CHX), which inhibits viral but not chlamydial protein synthesis. CHX-exposure inhibited PEDV replication, but did not inhibit induction of C. pecorum persistence at 24 h post-PEDV infection, as indicated by AB formation and reduced production of infectious EBs. Interestingly, production of infectious EBs resumed when CHX-exposed, co-infected cells were incubated 48–72 h post-PEDV co-infection. These data demonstrate that PEDV co-infection-induced chlamydial persistence/stress is reversible and suggest that this induction (i) does not require viral replication in host cells; and (ii) does not require de novo host or viral protein synthesis. These data also suggest that viral binding and/or entry may be required for this effect. Because the PEDV host cell receptor (CD13 or aminopeptidase N) stimulates cellular signaling pathways in the absence of PEDV infection, we suspect that PEDV co-infection might alter CD13 function and induce the chlamydiae to

  13. Parasite co-infections show synergistic and antagonistic interactions on growth performance of East African zebu cattle under one year.

    PubMed

    Thumbi, S M; de C Bronsvoort, B M; Poole, E J; Kiara, H; Toye, P; Ndila, M; Conradie, I; Jennings, A; Handel, I G; Coetzer, J A W; Hanotte, O; Woolhouse, M E J

    2013-12-01

    The co-occurrence of different pathogen species and their simultaneous infection of hosts are common, and may affect host health outcomes. Co-infecting pathogens may interact synergistically (harming the host more) or antagonistically (harming the host less) compared with single infections. Here we have tested associations of infections and their co-infections with variation in growth rate using a subset of 455 animals of the Infectious Diseases of East Africa Livestock (IDEAL) cohort study surviving to one year. Data on live body weight, infections with helminth parasites and haemoparasites were collected every 5 weeks during the first year of life. Growth of zebu cattle during the first year of life was best described by a linear growth function. A large variation in daily weight gain with a range of 0·03-0·34 kg, and a mean of 0·135 kg (0·124, 0·146; 95% CI) was observed. After controlling for other significant covariates in mixed effects statistical models, the results revealed synergistic interactions (lower growth rates) with Theileria parva and Anaplasma marginale co-infections, and antagonistic interactions (relatively higher growth rates) with T. parva and Theileria mutans co-infections, compared with infections with T. parva only. Additionally, helminth infections can have a strong negative effect on the growth rates but this is burden-dependent, accounting for up to 30% decrease in growth rate in heavily infected animals. These findings present evidence of pathogen-pathogen interactions affecting host growth, and we discuss possible mechanisms that may explain observed directions of interactions as well as possible modifications to disease control strategies when co-infections are present. PMID:24001119

  14. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  15. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  16. New fluorescence markers to distinguish co-infecting Trypanosoma brucei strains in experimental multiple infections.

    PubMed

    Balmer, Oliver; Tostado, Cristóbal

    2006-01-01

    Multiple-genotype infections are increasingly recognized as important factors in disease evolution, parasite transmission dynamics, and the evolution of drug resistance. However, the distinction of co-infecting parasite genotypes and the tracking of their dynamics have been difficult with traditional methods based on various genotyping techniques, leaving most questions unaddressed. Here we report new fluorescence markers of various colours that are inserted into the genome of Trypanosoma brucei to phenotypically label live parasites of all life cycle stages. If different parasite strains are labelled with different colours they can be easily distinguished from each other in experimental studies. A total of 10 T. brucei strains were successfully transfected with different fluorescence markers and were monitored in culture, tsetse flies and mice, to demonstrate stability of marker expression. The use of fluorescence activated cell sorting (FACS) allowed rapid and accurate identification of parasite strains labelled with different markers. Cell counts by FACS were virtually identical to counts by traditional microscopy (n=75, Spearman's rho: 0.91, p<0.0001) but were considerably faster and had a significantly lower sampling error (66% lower, d.f.=73, t=-17.1, p<0.0001). Co-infecting strains transfected with fluorescence genes of different colour were easily distinguished by eye and their relative and absolute densities were reliably counted by FACS in experimental multiple infections in mice. Since the FACS can simultaneously determine the population sizes of differently labelled T. brucei strains or subspecies it allows detailed and efficient tracking of multiple-genotype infections within a single host or vector individual, enabling more powerful studies on parasite dynamics. In addition, it also provides a simple way to separate genotypes after experimental mixed infections, to measure responses of the single strains to an applied treatment, thus eliminating the

  17. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  18. University Students' Knowledge Structures and Informal Reasoning on the Use of Genetically Modified Foods: Multidimensional Analyses

    ERIC Educational Resources Information Center

    Wu, Ying-Tien

    2013-01-01

    This study aims to provide insights into the role of learners' knowledge structures about a socio-scientific issue (SSI) in their informal reasoning on the issue. A total of 42 non-science major university students' knowledge structures and informal reasoning were assessed with multidimensional analyses. With both qualitative and…

  19. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

    PubMed

    Liu, Jimmy Z; van Sommeren, Suzanne; Huang, Hailiang; Ng, Siew C; Alberts, Rudi; Takahashi, Atsushi; Ripke, Stephan; Lee, James C; Jostins, Luke; Shah, Tejas; Abedian, Shifteh; Cheon, Jae Hee; Cho, Judy; Daryani, Naser E; Franke, Lude; Fuyuno, Yuta; Hart, Ailsa; Juyal, Ramesh C; Juyal, Garima; Kim, Won Ho; Morris, Andrew P; Poustchi, Hossein; Newman, William G; Midha, Vandana; Orchard, Timothy R; Vahedi, Homayon; Sood, Ajit; Sung, Joseph J Y; Malekzadeh, Reza; Westra, Harm-Jan; Yamazaki, Keiko; Yang, Suk-Kyun; Barrett, Jeffrey C; Franke, Andre; Alizadeh, Behrooz Z; Parkes, Miles; B K, Thelma; Daly, Mark J; Kubo, Michiaki; Anderson, Carl A; Weersma, Rinse K

    2015-09-01

    Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations. PMID:26192919

  20. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.

    PubMed

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M; McLaughlin, Russell L; Diekstra, Frank P; Pulit, Sara L; van der Spek, Rick A A; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H P; Koppers, Max; Blokhuis, Anna M; Sproviero, William; Jones, Ashley R; Kenna, Kevin P; van Eijk, Kristel R; Harschnitz, Oliver; Schellevis, Raymond D; Brands, William J; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E; Shaw, Pamela J; Hardy, John; Orrell, Richard W; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A; Staats, Kim A; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Basak, A Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A M; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M; van der Kooi, Anneke J; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E; Smith, Bradley N; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P; Fifita, Jennifer A; Nicholson, Garth A; Rowe, Dominic B; Pamphlett, Roger; Kiernan, Matthew C; Grosskreutz, Julian; Witte, Otto W; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A; Leigh, P Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C; Weishaupt, Jochen H; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H; Brown, Robert H; Glass, Jonathan D; Landers, John E; Hardiman, Orla; Andersen, Peter M; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R; Visscher, Peter M; de Bakker, Paul I W; van Es, Michael A; Pasterkamp, R Jeroen; Lewis, Cathryn M; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan H

    2016-09-01

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk. PMID:27455348

  1. Cryptic clonal lineages and genetic diversity in the loach Misgurnus anguillicaudatus (Teleostei: Cobitidae) inferred from nuclear and mitochondrial DNA analyses.

    PubMed

    Morishima, Kagayaki; Nakamura-Shiokawa, Yuka; Bando, Etsuko; Li, Ya-Juan; Boroń, Alicja; Khan, Md Mukhlesur Rahman; Arai, Katsutoshi

    2008-02-01

    In the loach Misgurnus anguillicaudatus, the asexual lineage, which produces unreduced clonal diploid eggs, has been identified. Among 833 specimens collected from 54 localities in Japan and two localities in China, 82 candidates of other lineage(s) of cryptic clones were screened by examining RFLP (restriction fragment length polymorphism)-PCR haplotypes in the control region of mtDNA. This analysis was performed because triploid loaches arise from the accidental incorporation of the sperm nucleus into unreduced diploid eggs of a clone. The categorization of members belonging to three newly identified lineages (clones 2-4) and the previously identified clonal lineage (clone 1) was verified by evaluating the genetic identity between two or more individuals from each clonal lineage based on RAPD (random amplified polymorphic DNA)-PCR and multilocus DNA fingerprints. We detected 75 haplotypes by observing the nucleotide status at variable sites from the control region of mtDNA. Phylogenic trees constructed from such sequences showed two highly diversified clades, A and B, that were beyond the level common for interspecific genetic differentiation. That result suggests that M. anguillicaudatus in Japan is not a single species entity. Two clone-specific mtDNA sequences were included in clade A, and the loaches with such sequences may be the maternal origin of the clones. PMID:17578669

  2. [Genetic and cytological analyses of the male sterility mutation induced in a sorghum tissue culture with streptomycin].

    PubMed

    El'konin, L A; Tsvetova, M I

    2008-05-01

    Treatment of sorghum callus cultures with 500-1000 mg/l streptomycin led to a high regeneration frequency of plants with complete or partial male sterility (MS), up to 100% of all green regenerants. The induced MS mutation (ms-str) was preserved in the F1 and BC1 progenies and was genetically unstable: many families produced semisterile and fertile revertants, whose progenies again contained semisterile and sterile mutants. The ms-str mutation was maintained through eight generations via selection and self-pollination of semisterile plants. The mutation was inherited as a recessive nuclear mutation in tester crosses of sterile plants segregated in the progenies of fertile and semisterile revertants and was expressed only in single cases in a test cross for ms-str transfer through pollen of hybrids with restored male fertility. Recessive nuclear mutations determining a low plant height (dwarfness) and the lack of waxy bloom on the stem and leaves (bloomless) were found in male-sterile plants with the ms-str mutation. Cytological analysis of sterile plants reveal multiple alterations of various pollen development stages and tapetal cells: cytomyxis, defects of chromosome conjugation, distorted cytokinesis in meiotic division II, a lack of tetrad separation, a defective formation of the microspore coat, generation of microspores with two to four nuclei, and the formation of micronuclei and large vacuoles in tapetal cells. A possible transfer of the induced cytoplasmic MS mutation into the nuclear genome and the causes of the high genetic instability are discussed. PMID:18672800

  3. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

    PubMed Central

    Huang, Hailiang; Ng, Siew C; Alberts, Rudi; Takahashi, Atsushi; Ripke, Stephan; Lee, James C; Jostins, Luke; Shah, Tejas; Abedian, Shifteh; Cheon, Jae Hee; Cho, Judy; Dayani, Naser E; Franke, Lude; Fuyuno, Yuta; Hart, Ailsa; Juyal, Ramesh C; Juyal, Garima; Kim, Won Ho; Morris, Andrew P; Poustchi, Hossein; Newman, William G; Midha, Vandana; Orchard, Timothy R; Vahedi, Homayon; Sood, Ajit; Sung, Joseph Y; Malekzadeh, Reza; Westra, Harm-Jan; Yamazaki, Keiko; Yang, Suk-Kyun; Barrett, Jeffrey C; Alizadeh, Behrooz Z; Parkes, Miles; BK, Thelma; Daly, Mark J; Kubo, Michiaki; Anderson, Carl A; Weersma, Rinse K

    2016-01-01

    Ulcerative colitis and Crohn’s disease are the two main forms of inflammatory bowel disease (IBD). Here, we report the first trans-ethnic association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East-Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of IBD risk loci, the direction and magnitude of effect is consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by a combination of differences in allele frequencies (NOD2), effect sizes (TNFSF15, ATG16L1) or a combination of both (IL23R, IRGM). Our results provide biological insights into the pathogenesis of IBD, and demonstrate the utility of trans-ethnic association studies for mapping complex disease loci and understanding genetic architecture across diverse populations. PMID:26192919

  4. Molecular and classical genetic analyses of his-3 mutants of Neurospora crassa. I. Tests for allelic complementation and specific revertibility.

    PubMed

    Overton, L K; Dubins, J S; de Serres, F J

    1989-10-01

    A collection of 81 his-3 mutants of Neurospora crassa was analyzed in assays for allelic complementation and specific revertibility. In these studies, the linearity of the complementation map of the his-3 cistron (Webber, 1965) was confirmed and mutants were classified as complementing with non-polarized or polarized complementation patterns, or non-complementing. In the assays for spontaneous or induced revertibility, 89% (71/80) of the mutants reverted either spontaneously or after treatment with the chemical mutagens N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, 2-methoxy-6-chloro-9-(3-[ethyl-2-chloroethyl]aminopropylamino) acridine dihydrochloride, nitrous acid or hydroxylamine. The frequency of revertible mutants among the non-polarized complementing mutants was 96% (45/47), and 79% (15/19) for the polarized complementing and 79% (11/14) for the non-complementing mutants. The results of these classical genetic assays for allelic complementation and specific revertibility suggest a correlation between complementation pattern and presumptive genetic alterations at the molecular level among his-3 mutants similar to that found with ad-3B mutants induced by nitrous acid (Malling and de Serres, 1967), ethyl methanesulfonate (Malling and de Serres, 1968), or ultraviolet (Kilbey et al., 1971). PMID:2529437

  5. Genetic influences on political ideologies: twin analyses of 19 measures of political ideologies from five democracies and genome-wide findings from three populations.

    PubMed

    Hatemi, Peter K; Medland, Sarah E; Klemmensen, Robert; Oskarsson, Sven; Littvay, Levente; Dawes, Christopher T; Verhulst, Brad; McDermott, Rose; Nørgaard, Asbjørn Sonne; Klofstad, Casey A; Christensen, Kaare; Johannesson, Magnus; Magnusson, Patrik K E; Eaves, Lindon J; Martin, Nicholas G

    2014-05-01

    Almost 40 years ago, evidence from large studies of adult twins and their relatives suggested that between 30 and 60% of the variance in social and political attitudes could be explained by genetic influences. However, these findings have not been widely accepted or incorporated into the dominant paradigms that explain the etiology of political ideology. This has been attributed in part to measurement and sample limitations, as well the relative absence of molecular genetic studies. Here we present results from original analyses of a combined sample of over 12,000 twins pairs, ascertained from nine different studies conducted in five democracies, sampled over the course of four decades. We provide evidence that genetic factors play a role in the formation of political ideology, regardless of how ideology is measured, the era, or the population sampled. The only exception is a question that explicitly uses the phrase "Left-Right". We then present results from one of the first genome-wide association studies on political ideology using data from three samples: a 1990 Australian sample involving 6,894 individuals from 3,516 families; a 2008 Australian sample of 1,160 related individuals from 635 families and a 2010 Swedish sample involving 3,334 individuals from 2,607 families. No polymorphisms reached genome-wide significance in the meta-analysis. The combined evidence suggests that political ideology constitutes a fundamental aspect of one's genetically informed psychological disposition, but as Fisher proposed long ago, genetic influences on complex traits will be composed of thousands of markers of very small effects and it will require extremely large samples to have enough power in order to identify specific polymorphisms related to complex social traits. PMID:24569950

  6. Genetic Influences on Political Ideologies: Twin Analyses of 19 Measures of Political Ideologies from Five Democracies and Genome-Wide Findings from Three Populations

    PubMed Central

    Hatemi, Peter K.; Medland, Sarah E.; Klemmensen, Robert; Oskarrson, Sven; Littvay, Levente; Dawes, Chris; Verhulst, Brad; McDermott, Rose; Nørgaard, Asbjørn Sonne; Klofstad, Casey; Christensen, Kaare; Johannesson, Magnus; Magnusson, Patrik K.E.; Eaves, Lindon J.; Martin, Nicholas G.

    2014-01-01

    Almost forty years ago, evidence from large studies of adult twins and their relatives suggested that between 30-60% of the variance in social and political attitudes could be explained by genetic influences. However, these findings have not been widely accepted or incorporated into the dominant paradigms that explain the etiology of political ideology. This has been attributed in part to measurement and sample limitations, as well the relative absence of molecular genetic studies. Here we present results from original analyses of a combined sample of over 12,000 twins pairs, ascertained from nine different studies conducted in five democracies, sampled over the course of four decades. We provide evidence that genetic factors play a role in the formation of political ideology, regardless of how ideology is measured, the era, or the population sampled. The only exception is a question that explicitly uses the phrase “Left-Right”. We then present results from one of the first genome-wide association studies on political ideology using data from three samples: a 1990 Australian sample involving 6,894 individuals from 3,516 families; a 2008 Australian sample of 1,160 related individuals from 635 families and a 2010 Swedish sample involving 3,334 individuals from 2,607 families. No polymorphisms reached genome-wide significance in the meta-analysis. The combined evidence suggests that political ideology constitutes a fundamental aspect of one’s genetically informed psychological disposition, but as Fisher proposed long ago, genetic influences on complex traits will be composed of thousands of markers of very small effects and it will require extremely large samples to have enough power in order to identify specific polymorphisms related to complex social traits. PMID:24569950

  7. Acute Confusional State: A Manifestation of Toxoplasma and CMV Co-infection in HIV Patient

    PubMed Central

    Jehangir, Waqas; Sareen, Romil; Sen, Shuvendu; Raoof, Nazar; Yousif, Abdalla

    2014-01-01

    Context: When dealing with a patient with HIV that presents with an altered mental status, there are various infections and disease etiologies a physician has to rule out that may play a role in complicating the inherent complex nature of HIV. Toxoplasma gondii (T. gondii) and cytomegalovirus (CMV) affect a large part of the world's population and lead to a varied and broad symptomatology depending upon the severity of HIV, the CD4 count and how early the infection is diagnosed. Case Report: We report an HIV+ patient in his early 50s and with a low CD4 count that presented with severe lethargy and confusion. Imaging studies that were performed after stabilizing the patient revealed a ring-enhancing lesion in the brain and after further testing, a diagnosis of reactivated T. gondii with co-infection with CMV was made. Patients infected with T. gondii that are already immune-compromised deteriorate rapidly and the disease diagnosis poses several challenges. Conclusion: Clinicians have to be extremely careful about making a prompt diagnosis and initiate treatment without delay before the infection takes a deadly toll on the patient. Since our patient was not on the required prophylactic medication to prevent infection with T. gondii, it was imperative to start treatment in a timely manner and to monitor the patient for any further decline in functioning. PMID:25489570

  8. Gene Expression Profiling of Tuberculous Meningitis Co-infected with HIV

    PubMed Central

    Kumar, Ghantasala S. Sameer; Venugopal, Abhilash K.; Kashyap, Manoj Kumar; Raju, Rajesh; Marimuthu, Arivusudar; Palapetta, Shyam Mohan; Subbanayya, Yashwanth; Goel, Renu; Chawla, Ankit; Dikshit, Jyoti Bajpai; Tata, Pramila; Harsha, H. C.; Maharudraiah, Jagadeesha; Ramachandra, Y. L.; Satishchandra, Parthasarathy; Prasad, T. S. Keshava; Pandey, Akhilesh; Mahadevan, Anita; Shankar, S. K.

    2015-01-01

    Tuberculous meningitis (TBM) is a fatal form of Mycobacterium tuberculosis infection of the central nervous system (CNS). The similarities in the clinical and radiological findings in TBM cases with or without HIV make the diagnosis very challenging. Identification of genes, which are differentially expressed in brain tissues of HIV positive and HIV negative TBM patients, would enable better understanding of the molecular aspects of the infection and would also serve as an initial platform to evaluate potential biomarkers. Here, we report the identification of 796 differentially regulated genes in brain tissues of TBM patients co-infected with HIV using oligonucleotide DNA microarrays. We also performed immunohistochemical validation and confirmed the abundance of four gene products-glial fibrillary acidic protein (GFAP), serpin peptidase inhibitor, clade A member 3 (SERPINA3), thymidine phosphorylase (TYMP/ECGF1) and heat shock 70 kDa protein 8 (HSPA8). Our study paves the way for understanding the mechanism of TBM in HIV positive patients and for further validation of potential disease biomarkers. PMID:27053842

  9. Molecular characterization of two evolutionarily distinct endornaviruses co-infecting common bean (Phaseolus vulgaris).

    PubMed

    Okada, Ryo; Yong, Chee Keat; Valverde, Rodrigo A; Sabanadzovic, Sead; Aoki, Nanako; Hotate, Shunsuke; Kiyota, Eri; Moriyama, Hiromitsu; Fukuhara, Toshiyuki

    2013-01-01

    Two high-molecular-mass dsRNAs of approximately 14 and 15 kbp were isolated from the common bean (Phaseolus vulgaris) cultivar Black Turtle Soup. These dsRNAs did not appear to cause obvious disease symptoms, and were transmitted through seeds at nearly 100% efficiency. Sequence information indicates that they are the genomes of distinct endornavirus species, for which the names Phaseolus vulgaris endornavirus 1 (PvEV-1) and Phaseolus vulgaris endornavirus 2 (PvEV-2) are proposed. The PvEV-1 genome consists of 13,908 bp and potentially encodes a single polyprotein of 4496 aa, while that of PvEV-2 consists of 14 820 bp and potentially encodes a single ORF of 4851 aa. PvEV-1 is more similar to Oryza sativa endornavirus, while PvEV-2 is more similar to bell pepper endornavirus. Both viruses have a site-specific nick near the 5' region of the coding strand, which is a common property of the endornaviruses. Their polyproteins contain domains of RNA helicase, UDP-glycosyltransferase and RNA-dependent RNA polymerase, which are conserved in other endornaviruses. However, a viral methyltransferase domain was found in the N-terminal region of PvEV-2, but was absent in PvEV-1. Results of cell-fractionation studies suggested that their subcellular localizations were different. Most endornavirus-infected bean cultivars tested were co-infected with both viruses. PMID:23015743

  10. [Aseptic purulent meningitis in two patients co-infected by HTLV-1 and Strongyloides stercoralis].

    PubMed

    Foucan, L; Genevier, I; Lamaury, I; Strobel, M

    1997-01-01

    Occurrence of anguilluliasis always progresses to hyperinfestation or disseminated anguilluliasis with severe clinical manifestations in carriers of HTLV-1. This prognosis is further illustrated by two new cases of non-septic purulent meningitis observed in two male patients from Guadalope. Ages were 61 and 64 years. In both cases examination of cerebrospinal fluid (CSF) demonstrated pleiocytosis with more than 3000 cells (mostly polynuclear neutrophils) per mm3, protein content greater than 3 g/l, and low sugar level. No soluble germs or antigens were found in the CSF. In both patients Strongyloides stercoralis larvae were detected in stools but not in CSF. Meningitis responded to antibiotic treatment but follow-up tests showed the persistence of larvae in stools despite treatment using thiabendazole. While similar cases of meningitis have been reported in carriers of HTLV-1, the underlying mechanism is still unclear. Co-infection with Strongyloides stercoralis appears to be a predisposing factor. This association may warrant preventive anti-parasitic treatment in patients infected by HTLV-1. PMID:9513154

  11. Tuberculosis and pulmonary candidiasis co-infection present in a previously healthy patient

    PubMed Central

    Jiménez Borré, Gustavo; Gómez Camargo, Doris; Chalavé Jiménez, Neylor; Bellido Rodríguez, Javier; Cuadrado Cano, Bernarda; Navarro Gómez, Shirley

    2016-01-01

    Background: The coexistance among fungal pathogens and tuberculosis pulmonary is a clinical condition that generally occurs in immunosuppressive patients, however, immunocompetent patients may have this condition less frequently. Objective: We report the case of an immunocompetent patient diagnosed with coinfection Mycobacterium tuberculosis and Candida albicans. Case Description: A female patient, who is a 22-years old, with fever and a new onset of hemoptysis. Clinical findings and diagnosis: Diminished vesicular breath sounds in the apical region and basal crackling rales in the left lung base were found in the physical examination. Microbiological tests include: chest radiography and CAT scan pictograms in high resolution, Ziehl-Neelsen stain, growth medium for fungus and mycobacteria through Sabouraudís agar method with D-glucose. Medical examinations showed Candida albicans fungus and Mycobacterium tuberculosis present in the patient. Treatment and Outcome: Patient was treated with anti-tuberculosis and anti-fungal medications, which produced good responses. Clinical relevance: Pulmonary tuberculosis and fungal co-infection are not common in immunocompetent patients. However, we can suspect that there is a presence of these diseases by detecting new onset of hemoptysis in patients. PMID:27546933

  12. Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals

    PubMed Central

    Achkar, Jacqueline M.; Cortes, Laetitia; Croteau, Pascal; Yanofsky, Corey; Mentinova, Marija; Rajotte, Isabelle; Schirm, Michael; Zhou, Yiyong; Junqueira-Kipnis, Ana Paula; Kasprowicz, Victoria O.; Larsen, Michelle; Allard, René; Hunter, Joanna; Paramithiotis, Eustache

    2015-01-01

    Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV−) and co-infected (HIV+) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV− individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV+ individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV− TB, 0.95 for HIV+ TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB. PMID:26501113

  13. Host Protein Biomarkers Identify Active Tuberculosis in HIV Uninfected and Co-infected Individuals.

    PubMed

    Achkar, Jacqueline M; Cortes, Laetitia; Croteau, Pascal; Yanofsky, Corey; Mentinova, Marija; Rajotte, Isabelle; Schirm, Michael; Zhou, Yiyong; Junqueira-Kipnis, Ana Paula; Kasprowicz, Victoria O; Larsen, Michelle; Allard, René; Hunter, Joanna; Paramithiotis, Eustache

    2015-09-01

    Biomarkers for active tuberculosis (TB) are urgently needed to improve rapid TB diagnosis. The objective of this study was to identify serum protein expression changes associated with TB but not latent Mycobacterium tuberculosis infection (LTBI), uninfected states, or respiratory diseases other than TB (ORD). Serum samples from 209 HIV uninfected (HIV(-)) and co-infected (HIV(+)) individuals were studied. In the discovery phase samples were analyzed via liquid chromatography and mass spectrometry, and in the verification phase biologically independent samples were analyzed via a multiplex multiple reaction monitoring mass spectrometry (MRM-MS) assay. Compared to LTBI and ORD, host proteins were significantly differentially expressed in TB, and involved in the immune response, tissue repair, and lipid metabolism. Biomarker panels whose composition differed according to HIV status, and consisted of 8 host proteins in HIV(-) individuals (CD14, SEPP1, SELL, TNXB, LUM, PEPD, QSOX1, COMP, APOC1), or 10 host proteins in HIV(+) individuals (CD14, SEPP1, PGLYRP2, PFN1, VASN, CPN2, TAGLN2, IGFBP6), respectively, distinguished TB from ORD with excellent accuracy (AUC = 0.96 for HIV(-) TB, 0.95 for HIV(+) TB). These results warrant validation in larger studies but provide promise that host protein biomarkers could be the basis for a rapid, blood-based test for TB. PMID:26501113

  14. Tuberculous Otitis with Proteus mirabilis Co-Infection: An Unsuspected Presentation Encountered in Clinical Practice

    PubMed Central

    Sardar, Moumita; Jadhav, Savita Vivek; Vyawahare, Chanda; Misra, Rabindranath

    2014-01-01

    Tuberculosis, a contagious bacterial disease which is caused by Mycobacterium tuberculosis, primarily involves the lungs.Though Pulmonary tuberculosis (PTB) is the commonest clinical presentation, there is a need for alertness towards uncommon presentations which involve other organs. Tuberculous otitis media (TOM) is one such rare presentation seen in paediatric practice. It is characterized by painless otorrhoea which fails to respond to the routine antibacterial treatment. TOM usually occurs secondary to PTB. Here is a case of tuberculous otitis media with Proteus mirabilis co-infection, with no evidence of PTB. In the sample of ear discharge obtained from the patient, acid fast bacilli were demonstrated on direct microscopy after Ziehl-Neelsen staining. Culture done on Lowenstein-Jensen medium demonstrated slow-growing Mycobacterium. Bacteriological culture and identification helped in isolating Proteus mirabilis. PCR, followed by Line- Probe Assay for early identification and susceptibility testing to primary drugs, was done. Further, patient tested negative for the Mantoux test. Patient was enrolled in National Tuberculosis programme- RNTCP. This case emphasizes on one of the less common presentations of a common disease. A high clinical suspicion and laboratory confirmation are required for appropriate patient management. PMID:24995225

  15. High number of diarrhoeal co-infections in travellers to Benin, West Africa

    PubMed Central

    2014-01-01

    Background Travellers’ diarrhoea (TD) is the most frequent health problem among travellers to the tropics. Using routine techniques, the aetiology mostly remains unresolved, whereas modern molecular methods enable reducing the number of equivocal cases considerably. While many studies address the aetiology of TD in Asian, Central American and North African tourist resorts, only few focus on Western Africa. Methods Stool samples from 45 travellers travelling in Benin, West Africa, were analyzed by a new multiplex qPCR assay for Salmonella, Yersinia, Campylobacter, Vibrio cholerae, Shigella or enteroinvasive (EIEC), enterohaemorrhagic (EHEC), enterotoxigenic (ETEC), enteroaggregative (EAEC), and enteropathogenic Escherichia coli (EPEC). Results All 18 pre-travel samples proved negative for bacterial pathogens. Of the 39/45 (87%) travellers having had TD, EPEC was detected in post-travel samples in 30 (77%) cases, EAEC in 23 (59%), ETEC in 22 (56%), Shigella or EIEC in 7 (18%), EHEC in two (5%), and Salmonella in one (3%). In 31(79%) of the TD cases two or more bacterial pathogens were identified. Two (8%) samples remained negative: both patients had taken antimicrobials for TD. Conclusions EPEC, EAEC and ETEC were the most common findings. 79% of the cases had a co-infection. As modern diagnostics reveals in most patients a multitude of pathogens, the role of each pathogen should be re-evaluated. PMID:24521079

  16. Epidemiology of human immunodeficiency virus-visceral leishmaniasis-co-infection.

    PubMed

    Naufal Spir, Patrícia Rodrigues; Zampieri D'Andrea, Lourdes Aparecida; Fonseca, Elivelton Silva; Prestes-Carneiro, Luiz Euribel

    2016-04-01

    In Brazil, the rates of mother-to-child-transmission (MTCT) of human immunodeficiency virus (HIV) decreased from 20% to 1-2% in some regions. However, the country contains 90% of individuals infected with visceral leishmaniasis (VL) in Latin America, and the west region of São Paulo state faces an alarming expansion of the disease. We describe the epidemiological aspects of the expanding infection of VL and a case report of an HIV-VL-co-infected child from the west region of São Paulo state. The patient was an AIDS-C3 with low levels of CD4, high viral load, severe diarrhea, oral and perineal candidiasis, severe thrombocytopenia, and protein-caloric malnourishment. She evolved with sepsis, renal and cardiac failure. An rK rapid diagnosis test, indirect fluorescent antibody test (IFAT), and bone marrow aspirate were performed for VL. Her symptoms improved significantly after liposomal amphotericin B administration. From the 45 municipalities that compose the Regional Health Department of Presidente Prudente, Lutzomyia longipalpis vectors were found in 58% of them. VL infected dogs were found in 33% of those municipalities, infected dogs and humans were found in 29%, 20% are starting and 33% of the municipalities are preparing VL investigation. It is likely, in this patient, that VL advanced the clinical progression of the HIV disease and the development of AIDS severity. Supported by favorable conditions, the region becomes a new frontier of VL in Brazil. PMID:23834783

  17. HTLV-1 and HIV-1 co-infection: A case report and review of the literature

    PubMed Central

    Isache, Carmen; Sands, Michael; Guzman, Nilmarie; Figueroa, Danisha

    2016-01-01

    HTLV type 1 and 2 are both involved in actively spreading epidemics, affecting over 15 million people worldwide. HTLV-1 has been described as the more clinically significant one, being associated with diseases such as adult T-cell leukemia and tropical spastic paraparesis. We report here a case of tropical spastic paraparesis in an HIV-positive patient who did not report any history of travel or residence in an HTLV endemic area. A 57 year old African-American male was admitted to the hospital due to bilateral upper and lower extremity weakness associated with stiffness. He had recently been diagnosed with HIV. His physical examination showed mild to moderate decreased motor strength, in both upper extremities and marked loss in both lower extremities. This was associated with hyperreflexia and clonus. Sensory function was intact. He looked cachectic and had several psoriatic plaques on both lower and upper extremities. Laboratory work-up showed a CD4 count decreased to 94 cells/mm3 and a HIV viral load of 273,000 copies/mL. Based on serum positivity for HTLV type 1 and the patient's clinical presentation suggestive of upper and lower motor neuron dysfunction, the diagnosis of tropical spastic paraparesis was made. HTLV and HIV share the same routes of transmission and the same tropism for T-lymphocytes. Co-infection occurs probably more frequently than we are aware, since testing for HTLV is not routinely performed in outpatient HIV clinics. PMID:27144124

  18. Co-infection with Multiple Respiratory Pathogens Contributes to Increased Mortality Rates in Algerian Poultry Flocks.

    PubMed

    Sid, Hicham; Benachour, Karine; Rautenschlein, Silke

    2015-09-01

    Respiratory infections are a common cause for increased mortality rates in poultry worldwide. To improve intervention strategies, circulating pathogens have to be identified and further characterized. Because of the lack of diagnostic tools, it was not known what pathogens contribute to the high mortality rates in association with respiratory disease in Algeria. Our objective was to determine if primary pathogens including Mycoplasma gallisepticum (MG), Mycoplasma synoviae (MS), avian influenza virus (AIV), infectious bronchitis virus (IBV), and avian metapneumovirus (aMPV), known to be present in neighboring countries, can also be detected in Algerian chicken and turkey flocks. Results demonstrate the circulation of the investigated pathogens in Algerian poultry flocks as multi-infections. Phylogenetic characterization of the Algerian IBV strains confirmed the circulation of nephropathogenic viruses that are different from the strains isolated in neighboring countries. This could suggest the existence of a new IBV genotype in North Africa. Additionally, we detected for the first time an aMPV subtype B field strain and avian influenza virus. Interestingly, all viral pathogens were present in co-infections with MG, which could exacerbate clinical disease. Additional pathogens may be present and should be investigated in the future. Our results suggest that multiple respiratory infections may be responsible for high mortality in Algerian poultry flocks and very probably also in other regions of the world, which demonstrates the need for the establishment of more comprehensive control strategies. PMID:26478165

  19. Co-infection of Scedosporium apiospermum and Mycobacterium chelonae in an immunocompetent host.

    PubMed

    Kim, Ji Seok; Choi, Misoo; Nam, Chan Hee; Kim, Jee Young; Hong, Seung Phil; Kim, Myung Hwa; Park, Byung Cheol

    2014-10-01

    A 75-year-old man presented with multiple, scaly, erythematous, grouped papules, nodules and plaques with tenderness ranging from the right forearm to hand dorsum and the right lower leg for 2-3 months. Five months prior to presentation, the patient had received an antibiotic skin test on his right forearm. Lesions appeared approximately 2-3 months after the antibiotic skin test, slowly progressing without clinical improvement. Culture for fungus on the right forearm revealed growth of Scedosporium apiospermum. The tissue acid-fast bacilli (AFB) culture for the right forearm and right leg revealed growth of non-tuberculous mycobacteria which was Mycobacterium chelonae, and subsequent tissue polymerase chain reaction of both sites reported positive signs of M. chelonae. On diastase periodic acid-Schiff stain of the biopsy specimen of the right forearm, fungal hyphae were found while rod-shaped bacilli could be seen in AFB stain for the biopsy specimen of the right leg. The patient was treated with oral clarithromycin and ciprofloxacin along with an oral antifungal agent for 13 weeks. After the treatment, the lesions subsided and left a scar. We report a rare case of co-infection of S. apiospermum and M. chelonae in an immunocompetent host. PMID:25228156

  20. Detection of Different Bovine Papillomavirus Types and Co-infection in Bloodstream of Cattle.

    PubMed

    Santos, E U D; Silva, M A R; Pontes, N E; Coutinho, L C A; Paiva, S S L; Castro, R S; Freitas, A C

    2016-02-01

    Bovine papillomavirus (BPV) is a diverse group of double-stranded DNA oncogenic viruses. BPVs are classically described as epitheliotropic, however, they have been detected in body fluids, such as blood and semen. The presence of BPV in these sites can have implications for the dissemination of BPV. The aim of this study was to verify the prevalence of BPV types in cattle blood. A total of 57 blood samples were analyzed by PCR using BPV type-specific primers to BPVs 1-6 and 8-10, and subsequent sequencing. Sequencing quality was determined using Staden package with Phred 20. Similarity analysis was performed with BioEdit and BLAST programs to assess the identity with known BPV types. Statistical analysis was performed by Fisher's exact test. The results showed seven different types of BPVs in the blood, with the exception of BPV 5 and 9. This is the first study that demonstrates BPVs 3, 6, 8 and 10 DNA in cattle blood. BPVs 1 and 2 were the viral types most frequent in blood, while BPVs 4 and 10 were the least frequent types. All the samples showed co-infection by at least two BPV types. These data suggest that several BPV types may infect blood cells at the same time and demonstrate the possibility that the BPV infection in non-epithelial tissue can occur without restriction to one or two viral types. These results can contribute to future studies aimed at the control and prevention of papillomaviruses. PMID:24889887

  1. JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region.

    PubMed

    Cayres-Vallinoto, Izaura Maria Vieira; Vallinoto, Antonio Carlos Rosário; Pena, Giselle Priscila Dos Anjos; Azevedo, Vânia Nakauth; Machado, Luiz Fernando Almeida; Ishak, Marluísa de Oliveira Guimarães; Ishak, Ricardo

    2016-01-01

    JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215bp) and IG (610bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4(+)/TCD8(+) lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups. PMID:27266589

  2. Multivariate analyses of Erzgebirge granite and rhyolite composition: Implications for classification of granites and their genetic relations

    USGS Publications Warehouse

    Forster, H.-J.; Davis, J.C.; Tischendorf, G.; Seltmann, R.

    1999-01-01

    High-precision major, minor and trace element analyses for 44 elements have been made of 329 Late Variscan granitic and rhyolitic rocks from the Erzgebirge metallogenic province of Germany. The intrusive histories of some of these granites are not completely understood and exposures of rock are not adequate to resolve relationships between what apparently are different plutons. Therefore, it is necessary to turn to chemical analyses to decipher the evolution of the plutons and their relationships. A new classification of Erzgebirge plutons into five major groups of granites, based on petrologic interpretations of geochemical and mineralogical relationships (low-F biotite granites; low-F two-mica granites; high-F, high-P2O5 Li-mica granites; high-F, low-P2O5 Li-mica granites; high-F, low-P2O5 biotite granites) was tested by multivariate techniques. Canonical analyses of major elements, minor elements, trace elements and ratio variables all distinguish the groups with differing amounts of success. Univariate ANOVA's, in combination with forward-stepwise and backward-elimination canonical analyses, were used to select ten variables which were most effective in distinguishing groups. In a biplot, groups form distinct clusters roughly arranged along a quadratic path. Within groups, individual plutons tend to be arranged in patterns possibly reflecting granitic evolution. Canonical functions were used to classify samples of rhyolites of unknown association into the five groups. Another canonical analysis was based on ten elements traditionally used in petrology and which were important in the new classification of granites. Their biplot pattern is similar to that from statistically chosen variables but less effective at distinguishing the five groups of granites. This study shows that multivariate statistical techniques can provide significant insight into problems of granitic petrogenesis and may be superior to conventional procedures for petrological interpretation.

  3. Comparison of genetic-algorithm and emissivity-ratio analyses of image data from OMEGA implosion cores.

    PubMed

    Nagayama, T; Mancini, R C; Florido, R; Tommasini, R; Koch, J A; Delettrez, J A; Regan, S P; Smalyuk, V A; Welser-Sherrill, L A; Golovkin, I E

    2008-10-01

    Detailed analysis of x-ray narrow-band images from argon-doped deuterium-filled inertial confinement fusion implosion experiments yields information about the temperature spatial structure in the core at the collapse of the implosion. We discuss the analysis of direct-drive implosion experiments at OMEGA, in which multiple narrow-band images were recorded with a multimonochromatic x-ray imaging instrument. The temperature spatial structure is investigated by using the sensitivity of the Ly beta/He beta line emissivity ratio to the temperature. Three analysis methods that consider the argon He beta and Ly beta image data are discussed and the results compared. The methods are based on a ratio of image intensities, ratio of Abel-inverted emissivities, and a search and reconstruction technique driven by a Pareto genetic algorithm. PMID:19044576

  4. Population genetic analyses of the Powerplex(®) Fusion kit in a cosmopolitan sample of Chubut Province (Patagonia Argentina).

    PubMed

    Parolin, María Laura; Real, Luciano E; Martinazzo, Liza B; Basso, Néstor G

    2015-11-01

    Allele frequencies and forensic parameters for 22 autosomal STR loci and DYS391 locus included in the PowerPlex(®) Fusion System kit were estimated in a sample of 770 unrelated individuals from Chubut Province, southern Patagonia. No significant deviations from Hardy-Weinberg equilibrium were observed after Bonferroni's correction. The combined power of discrimination and the combined probability of exclusion were >0.999999 and 0.999984, respectively. Comparisons with other worldwide populations were performed. The MDS obtained show a close biological relation between Chubut and Chile. The estimated interethnic admixture supports a high Native American contribution (46%) in the population sample of Chubut. These results enlarge the Argentine databases of autosomal STR and would provide a valuable contribution for identification tests and population genetic studies. PMID:26275612

  5. Comparison of genetic-algorithm and emissivity-ratio analyses of image data from OMEGA implosion cores

    SciTech Connect

    Nagayama, T.; Mancini, R. C.; Florido, R.; Tommasini, R.; Koch, J. A.; Delettrez, J. A.; Regan, S. P.; Smalyuk, V. A.; Welser-Sherrill, L. A.; Golovkin, I. E.

    2008-10-15

    Detailed analysis of x-ray narrow-band images from argon-doped deuterium-filled inertial confinement fusion implosion experiments yields information about the temperature spatial structure in the core at the collapse of the implosion. We discuss the analysis of direct-drive implosion experiments at OMEGA, in which multiple narrow-band images were recorded with a multimonochromatic x-ray imaging instrument. The temperature spatial structure is investigated by using the sensitivity of the Ly{beta}/He{beta} line emissivity ratio to the temperature. Three analysis methods that consider the argon He{beta} and Ly{beta} image data are discussed and the results compared. The methods are based on a ratio of image intensities, ratio of Abel-inverted emissivities, and a search and reconstruction technique driven by a Pareto genetic algorithm.

  6. Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

    PubMed Central

    Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas

    2012-01-01

    Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768

  7. Phylogenetic and molecular analyses of human parainfluenza type 3 virus in Buenos Aires, Argentina, between 2009 and 2013: The emergence of new genetic lineages.

    PubMed

    Goya, Stephanie; Mistchenko, Alicia Susana; Viegas, Mariana

    2016-04-01

    Despite that human parainfluenza type 3 viruses (HPIV3) are one of the leading causes of acute lower respiratory tract infections in children under five, there is no licensed vaccine and there is limited current information on the molecular characteristics of regional and global circulating strains. The aim of this study was to describe the molecular characterization of HPIV3 circulating in Buenos Aires. We performed a genetic and phylogenetic analysis of the HN glycoprotein gene. Between 2009 and 2013, 124 HPIV3-positive samples taken from hospitalized pediatric patients were analyzed. Four new genetic lineages were described. Among them, C1c and C3d lineages showed local circulation patterns, whereas C3e and C3f comprised sequences from very distant countries. Despite the diversity of the described genotypes, C3a and C3d predominated over the others, the latter was present during the first years of the study and it was progressively replaced by C3a. Molecular analyses showed 28 non-synonymous substitutions; of these, 13 were located in potentially predicted B-cell epitopes. Taken together, the emergence of genetic lineages and the information of the molecular characteristics of HN protein may contribute to the general knowledge of HPIV3 molecular epidemiology for future vaccine development and antiviral therapies. PMID:26780643

  8. A complete genetic linkage map and QTL analyses for bast fibre quality traits, yield and yield components in jute (Corchorus olitorius L.).

    PubMed

    Topdar, N; Kundu, A; Sinha, M K; Sarkar, D; Das, M; Banerjee, S; Kar, C S; Satya, P; Balyan, H S; Mahapatra, B S; Gupta, P K

    2013-01-01

    We report the first complete microsatellite genetic map of jute (Corchorus olitorius L.; 2n = 2x = 14) using an F6 recombinant inbred population. Of the 403 microsatellite markers screened, 82 were mapped on the seven linkage groups (LGs) that covered a total genetic distance of 799.9 cM, with an average marker interval of 10.7 cM. LG5 had the longest and LG7 the shortest genetic lengths, whereas LG1 had the maximum and LG7 the minimum number of markers. Segregation distortion of microsatellite loci was high (61%), with the majority of them (76%) skewed towards the female parent. Genomewide non-parametric single-marker analysis in combination with multiple quantitative trait loci (QTL)-models (MQM) mapping detected 26 definitive QTLs for bast fibre quality, yield and yield-related traits. These were unevenly distributed on six LGs, as colocalized clusters, at genomic sectors marked by 15 microsatellite loci. LG1 was the QTL-richest map sector, with the densest colocalized clusters of QTLs governing fibre yield, yield-related traits and tensile strength. Expectedly, favorable QTLs were derived from the desirable parents, except for nearly all of those of fibre fineness, which might be due to the creation of new gene combinations. Our results will be a good starting point for further genome analyses in jute. PMID:23821949

  9. Mining microsatellites in the peach genome: development of new long-core SSR markers for genetic analyses in five Prunus species.

    PubMed

    Dettori, Maria Teresa; Micali, Sabrina; Giovinazzi, Jessica; Scalabrin, Simone; Verde, Ignazio; Cipriani, Guido

    2015-01-01

    A wide inventory of molecular markers is nowadays available for individual fingerprinting. Microsatellites, or simple sequence repeats (SSRs), play a relevant role due to their relatively ease of use, their abundance in the plant genomes, and their co-dominant nature, together with the availability of primer sequences in many important agricultural crops. Microsatellites with long-core motifs are more easily scored and were adopted long ago in human genetics but they were developed only in few crops, and Prunus species are not among them. In the present work the peach whole-genome sequence was used to select 216 SSRs containing long-core motifs with tri-, tetra- and penta-nucleotide repeats. Microsatellite primer pairs were designed and tested for polymorphism in the five diploid Prunus species of economic relevance (almond, apricot, Japanese plum, peach and sweet cherry). A set of 26 microsatellite markers covering all the eight chromosomes, was also selected and used in the molecular characterization, population genetics and structure analyses of a representative sample of the five diploid Prunus species, assessing their transportability and effectiveness. The combined probability of identity between two random individuals for the whole set of 26 SSRs was quite low, ranging from 2.30 × 10(-7) in peach to 9.48 × 10(-10) in almond, confirming the usefulness of the proposed set for fingerprinting analyses in Prunus species. PMID:26185739

  10. Regression and Data Mining Methods for Analyses of Multiple Rare Variants in the Genetic Analysis Workshop 17 Mini-Exome Data

    PubMed Central

    Bailey-Wilson, Joan E.; Brennan, Jennifer S.; Bull, Shelley B; Culverhouse, Robert; Kim, Yoonhee; Jiang, Yuan; Jung, Jeesun; Li, Qing; Lamina, Claudia; Liu, Ying; Mägi, Reedik; Niu, Yue S.; Simpson, Claire L.; Wang, Libo; Yilmaz, Yildiz E.; Zhang, Heping; Zhang, Zhaogong

    2012-01-01

    Group 14 of Genetic Analysis Workshop 17 examined several issues related to analysis of complex traits using DNA sequence data. These issues included novel methods for analyzing rare genetic variants in an aggregated manner (often termed collapsing rare variants), evaluation of various study designs to increase power to detect effects of rare variants, and the use of machine learning approaches to model highly complex heterogeneous traits. Various published and novel methods for analyzing traits with extreme locus and allelic heterogeneity were applied to the simulated quantitative and disease phenotypes. Overall, we conclude that power is (as expected) dependent on locus-specific heritability or contribution to disease risk, large samples will be required to detect rare causal variants with small effect sizes, extreme phenotype sampling designs may increase power for smaller laboratory costs, methods that allow joint analysis of multiple variants per gene or pathway are more powerful in general than analyses of individual rare variants, population-specific analyses can be optimal when different subpopulations harbor private causal mutations, and machine learning methods may be useful for selecting subsets of predictors for follow-up in the presence of extreme locus heterogeneity and large numbers of potential predictors. PMID:22128066

  11. Integration of genotoxicity and population genetic analyses in kangaroo rats (Dipodomys merriami) exposed to radionuclide contamination at the Nevada Test Site, USA

    USGS Publications Warehouse

    Theodorakis, Christopher W.; Bickham, John W.; Lamb, Trip; Medica, Philip A.; Lyne, T. Barrett

    2001-01-01

    We examined effects of radionuclide exposure at two atomic blast sites on kangaroo rats (Dipodomys merriami) at the Nevada Test Site, Nevada, USA, using genotoxicity and population genetic analyses. We assessed chromosome damage by micronucleus and flow cytometric assays and genetic variation by randomly amplified polymorphic DNA (RAPD) and mitochondrial DNA (mtDNA) analyses. The RAPD analysis showed no population structure, but mtDNA exhibited differentiation among and within populations. Genotoxicity effects were not observed when all individuals were analyzed. However, individuals with mtDNA haplotypes unique to the contaminated sites had greater chromosomal damage than contaminated-site individuals with haplotypes shared with reference sites. When interpopulation comparisons used individuals with unique haplotypes, one contaminated site had greater levels of chromosome damage than one or both of the reference sites. We hypothesize that shared-haplotype individuals are potential migrants and that unique-haplotype individuals are potential long-term residents. A parsimony approach was used to estimate the minimum number of migration events necessary to explain the haplotype distributions on a phylogenetic tree. The observed predominance of migration events into the contaminated sites supported our migration hypothesis. We conclude the atomic blast sites are ecological sinks and that immigration masks the genotoxic effects of radiation on the resident populations.

  12. Genetic polymorphism analyses of a novel panel of 19 X-STR loci in the Chinese Uygur ethnic minority* #

    PubMed Central

    Guo, Yu-xin; Chen, Jian-gang; Wang, Yan; Yan, Jiang-wei; Chen, Jing; Yao, Tian-hua; Zhang, Li-ping; Yang, Guang; Meng, Hao-tian; Zhang, Yu-dang; Mei, Ting; Liu, Yao-shun; Dong, Qian; Zhu, Bo-feng

    2016-01-01

    The population genetic data and forensic parameters of 19 X-chromosome short tandem repeat (X-STR) loci in Chinese Uygur ethnic minority are presented. These loci were detected in a sample of 233 (94 males and 139 females) unrelated healthy individuals. We observed 238 alleles at the 19 X-STR loci, with the corresponding gene frequencies spanning the range from 0.0021 to 0.5644. After Bonferroni correction (P>0.0026), there were no significant deviations from Hardy-Weinberg equilibrium. The cumulative power of discrimination in females and males, and the probability of exclusion of the 19 X-STR loci were 0.999 999 999 999 999 999 998 091, 0.999 999 999 999 966, and 0.999 999 986 35, respectively. The cumulative mean exclusion chance was 0.999 999 992 849 in deficiency cases, 0.999 999 999 999 628 in normal trios, and 0.999 999 998 722 in duo cases. The high value of the forensic parameters mentioned above revealed that the novel panel of 19 loci had important values for forensic applications in the Uygur group. PMID:27143264

  13. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus

    PubMed Central

    Graham, Deborah S Cunninghame; Pinder, Christopher L; Tombleson, Philip; Behrens, Timothy W; Martín, Javier; Fairfax, Benjamin P; Knight, Julian C; Chen, Lingyan; Replogle, Joseph; Syvänen, Ann-Christine; Rönnblom, Lars; Graham, Robert R; Wither, Joan E; Rioux, John D; Alarcón-Riquelme, Marta E; Vyse, Timothy J

    2015-01-01

    Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry: a new GWAS, meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including 10 novel associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n=16) of transcription factors among SLE susceptibility genes. This supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE. PMID:26502338

  14. Genetic analyses of sulfonamide resistance and its dissemination in gram-negative bacteria illustrate new aspects of R plasmid evolution.

    PubMed Central

    Rådström, P; Swedberg, G; Sköld, O

    1991-01-01

    In contrast to what has been observed for many other antibiotic resistance mechanisms, there are only two known genes encoding plasmid-borne sulfonamide resistance. Both genes, sulI and sulII, encode a drug-resistant dihydropteroate synthase enzyme. In members of the family Enterobacteriaceae isolated from several worldwide sources, plasmid-mediated resistance to sulfonamides could be identified by colony hybridization as being encoded by sulI, sulII, or both. The sulI gene was in all cases found to be located in the newly defined, mobile genetic element, recently named an integron, which has been shown to contain a site-specific recombination system for the integration of various antibiotic resistance genes. The sulII gene was almost exclusively found as part of a variable resistance region on small, nonconjugative plasmids. Colony hybridization to an intragenic probe, restriction enzyme digestion, and nucleotide sequence analysis of small plasmids indicated that the sulII gene and contiguous sequences represent an independently occurring region disseminated in the bacterial population. The sulII resistance region was bordered by direct repeats, which in some plasmids were totally or partially deleted. The prevalence of sulI and sulII could thus be accounted for by their stable integration in transposons and in plasmids that are widely disseminated among gram-negative bacteria. Images PMID:1952855

  15. COMPARATIVE GENOMIC AND POPULATION GENETIC ANALYSES INDICATE HIGHLY POROUS GENOMES AND HIGH LEVELS OF GENE FLOW BETWEEN DIVERGENT HELIANTHUS SPECIES

    PubMed Central

    Kane, Nolan C.; King, Matthew G.; Barker, Michael S.; Raduski, Andrew; Karrenberg, Sophie; Yatabe, Yoko; Knapp, Steven J.; Rieseberg, Loren H.

    2009-01-01

    While speciation can be found in the presence of gene flow, it is not clear what impact this gene flow has on genome- and range-wide patterns of differentiation. Here we examine gene flow across the entire range of the common sunflower, H. annuus, its historically allopatric sister species H. argophyllus and a more distantly related, sympatric relative H. petiolaris. Analysis of genotypes at 26 microsatellite loci in 1015 individuals from across the range of the three species showed substantial introgression between geographically proximal populations of H. annuus and H. petiolaris, limited introgression between H. annuus and H. argophyllus, and essentially no gene flow between the allopatric pair, H. argophyllus and H. petiolaris. Analysis of sequence divergence levels among the three species in 1420 orthologs identified from EST databases identified a subset of loci showing extremely low divergence between H. annuus and H. petiolaris and extremely high divergence between the sister species H. annuus and H. argophyllus, consistent with introgression between H. annuus and H. petiolaris at these loci. Thus, at many loci, the allopatric sister species are more genetically divergent than the more distantly related sympatric species, which have exchanged genes across much of the genome while remaining morphologically and ecologically distinct. PMID:19473382

  16. Genetic polymorphism analyses of a novel panel of 19 X-STR loci in the Chinese Uygur ethnic minority.

    PubMed

    Guo, Yu-Xin; Chen, Jian-Gang; Wang, Yan; Yan, Jiang-Wei; Chen, Jing; Yao, Tian-Hua; Zhang, Li-Ping; Yang, Guang; Meng, Hao-Tian; Zhang, Yu-Dang; Mei, Ting; Liu, Yao-Shun; Dong, Qian; Zhu, Bo-Feng

    2016-05-01

    The population genetic data and forensic parameters of 19 X-chromosome short tandem repeat (X-STR) loci in Chinese Uygur ethnic minority are presented. These loci were detected in a sample of 233 (94 males and 139 females) unrelated healthy individuals. We observed 238 alleles at the 19 X-STR loci, with the corresponding gene frequencies spanning the range from 0.0021 to 0.5644. After Bonferroni correction (P>0.0026), there were no significant deviations from Hardy-Weinberg equilibrium. The cumulative power of discrimination in females and males, and the probability of exclusion of the 19 X-STR loci were 0.999 999 999 999 999 999 998 091, 0.999 999 999 999 966, and 0.999 999 986 35, respectively. The cumulative mean exclusion chance was 0.999 999 992 849 in deficiency cases, 0.999 999 999 999 628 in normal trios, and 0.999 999 998 722 in duo cases. The high value of the forensic parameters mentioned above revealed that the novel panel of 19 loci had important values for forensic applications in the Uygur group. PMID:27143264

  17. International collaborative study of the endogenous reference gene LAT52 used for qualitative and quantitative analyses of genetically modified tomato.

    PubMed

    Yang, Litao; Zhang, Haibo; Guo, Jinchao; Pan, Liangwen; Zhang, Dabing

    2008-05-28

    One tomato ( Lycopersicon esculentum) gene, LAT52, has been proved to be a suitable endogenous reference gene for genetically modified (GM) tomato detection in a previous study. Herein are reported the results of a collaborative ring trial for international validation of the LAT52 gene as endogenous reference gene and its analytical systems; 14 GMO detection laboratories from 8 countries were invited, and results were finally received from 13. These data confirmed the species specificity by testing 10 plant genomic DNAs, less allelic variation and stable single copy number of the LAT52 gene, among 12 different tomato cultivars. Furthermore, the limit of detection of LAT52 qualitative PCR was proved to be 0.1%, which corresponded to 11 copies of haploid tomato genomic DNA, and the limit of quantification for the quantitative PCR system was about 10 copies of haploid tomato genomic DNA with acceptable PCR efficiency and linearity. Additionally, the bias between the test and true values of 8 blind samples ranged from 1.94 to 10.64%. All of these validated results indicated that the LAT52 gene is suitable for use as an endogenous reference gene for the identification and quantification of GM tomato and its derivates. PMID:18442244

  18. Morphological and genetic analyses reveal a cryptic species complex in the echinoid Echinocardium cordatum and rule out a stabilizing selection explanation.

    PubMed

    Egea, E; David, B; Choné, T; Laurin, B; Féral, J P; Chenuil, A

    2016-01-01

    Preliminary analyses revealed the presence of at least five mitochondrial clades within the widespread sea urchin Echinocardium cordatum (Spatangoida). In this study, we analyzed the genetic (two mitochondrial and two nuclear sequence loci) and morphological characteristics (20 indices) from worldwide samples of this taxon to establish the species limits, morphological diversity and differentiation. Co-occurring spatangoid species were also analyzed with mitochondrial DNA. The nuclear sequences confirm that mitochondrial lineages correspond to true genetic entities and reveal that two clades (named A and B1) hybridize in their sympatry area, although a more closely related pair of clades (B1 and B2), whose distributions widely overlap, does not display hybridization. The morphology of all E. cordatum clade pairs was significantly differentiated, but no morphological diagnostic character was evidenced. By contrast, other spatangoid species pairs that diverged more recently than the E. cordatum clades display clear diagnostic characters. Morphological diversity thus appears responsible for the absence of diagnostic characters, ruling out stabilizing selection, a classical explanation for cryptic species. Alternative classical explanations are (i) environmental plasticity or (ii) a high diversity of genes determining morphology, maintained by varying environmental conditions. We suggest a new hypothesis that the observed morphological diversity is selectively neutral and reflects high effective population sizes in the E. cordatum complex. It is supported by the higher abundance of this taxon compared with other taxa, a trend for the genetic and morphological diversity to be correlated in Europe, and the higher genetic and morphological diversities found in clades of E cordatum (except B1) than in other spatangoid samples in Europe. However, the Pacific clades do not confirm these trends. PMID:26265259

  19. Provider and patient correlates of provider decisions to recommend HCV treatment to HIV co-infected patients.

    PubMed

    Wagner, Glenn; Osilla, Karen Chan; Garnett, Jeffrey; Ghosh-Dastidar, Bonnie; Bhatti, Laveeza; Witt, Mallory; Goetz, Matthew Bidwell

    2012-01-01

    Despite low uptake of hepatitis C virus (HCV) treatment among HIV co-infected patients, few studies have examined the factors that contribute to provider decisions to recommend treatment. Surveys of 173 co-infected patients and their primary care providers, as well as patient chart data, were collected at 3 HIV clinics in Los Angeles; 73% of the patients had any history of being recommended HCV treatment. Multivariate predictors of being offered treatment included being Caucasian, greater HCV knowledge, receiving depression treatment if depressed, and one's provider having a lower weekly patient load and more years working at the study site. These findings suggest that provider decisions to recommend HCV treatment are influenced by patient factors including race and psychosocial treatment readiness, as well as characteristics of their own practice and treatment philosophy. With changes to HCV treatment soon to emerge, further evaluation of factors influencing treatment decisions is needed to improve HCV treatment uptake. PMID:22564797

  20. Co-infection of the Siberian hamster (Phodopus sungorus) with a novel Helicobacter sp. and Campylobacter sp.

    PubMed

    Nagamine, Claude M; Shen, Zeli; Luong, Richard H; McKeon, Gabriel P; Ruby, Norman F; Fox, James G

    2015-05-01

    We report the isolation of a novel helicobacter isolated from the caecum of the Siberian hamster (Phodopus sungorus). Sequence analysis showed 97% sequence similarity to Helicobacter ganmani. In addition, we report the co-infection of these Siberian hamsters with a Campylobacter sp. and a second Helicobacter sp. with 99% sequence similarity to Helicobacter sp. flexispira taxon 8 (Helicobacter bilis), a species isolated previously from patients with bacteraemia. Gross necropsy and histopathology did not reveal any overt pathological lesions of the liver and gastrointestinal tract that could be attributed to the Helicobacter or Campylobacter spp. infections. This is the first helicobacter to be identified in the Siberian hamster and the first report of co-infection of Helicobacter spp. and Campylobacter sp. in asymptomatic Siberian hamsters. PMID:25752854

  1. Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015.

    PubMed

    Mercado, Marcela; Acosta-Reyes, Jorge; Parra, Edgar; Pardo, Lissethe; Rico, Angélica; Campo, Alfonso; Navarro, Edgar; Viasus, Diego

    2016-06-01

    We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease. PMID:27277216

  2. Co-infection of the Siberian hamster (Phodopus sungorus) with a novel Helicobacter sp. and Campylobacter sp.

    PubMed Central

    Shen, Zeli; Luong, Richard H.; McKeon, Gabriel P.; Ruby, Norman F.; Fox, James G.

    2015-01-01

    We report the isolation of a novel helicobacter isolated from the caecum of the Siberian hamster (Phodopus sungorus). Sequence analysis showed 97 % sequence similarity to Helicobacter ganmani. In addition, we report the co-infection of these Siberian hamsters with a Campylobacter sp. and a second Helicobacter sp. with 99 % sequence similarity to Helicobacter sp. flexispira taxon 8 (Helicobacter bilis), a species isolated previously from patients with bacteraemia. Gross necropsy and histopathology did not reveal any overt pathological lesions of the liver and gastrointestinal tract that could be attributed to the Helicobacter or Campylobacter spp. infections. This is the first helicobacter to be identified in the Siberian hamster and the first report of co-infection of Helicobacter spp. and Campylobacter sp. in asymptomatic Siberian hamsters. PMID:25752854

  3. Histoplasma capsulatum and Pneumocystis spp. co-infection in wild bats from Argentina, French Guyana, and Mexico

    PubMed Central

    2014-01-01

    Background Histoplasma capsulatum and Pneumocystis organisms cause host infections primarily affecting the lung tissue. H. capsulatum is endemic in the United States of America and Latin American countries. In special environments, H. capsulatum is commonly associated with bat and bird droppings. Pneumocystis-host specificity has been primarily studied in laboratory animals, and its ability to be harboured by wild animals remains as an important issue for understanding the spread of this pathogen in nature. Bats infected with H. capsulatum or Pneumocystis spp. have been found, with this mammal serving as a probable reservoir and disperser; however, the co-infection of bats with both of these microorganisms has never been explored. To evaluate the impact of H. capsulatum and Pneumocystis spp. infections in this flying mammal, 21 bat lungs from Argentina (AR), 13 from French Guyana (FG), and 88 from Mexico (MX) were screened using nested-PCR of the fragments, employing the Hcp100 locus for H. capsulatum and the mtLSUrRNA and mtSSUrRNA loci for Pneumocystis organisms. Results Of the 122 bats studied, 98 revealed H. capsulatum infections in which 55 of these bats exhibited this infection alone. In addition, 51 bats revealed Pneumocystis spp. infection of which eight bats exhibited a Pneumocystis infection alone. A total of 43 bats (eight from AR, one from FG, and 34 from MX) were found co-infected with both fungi, representing a co-infection rate of 35.2% (95% CI = 26.8-43.6%). Conclusion The data highlights the H. capsulatum and Pneumocystis spp.co-infection in bat population’s suggesting interplay with this wild host. PMID:24495513

  4. Fatal human eosinophilic meningo-encephalitis caused by CNS co-infection with Halicephalobus gingivalis and West Nile virus.

    PubMed

    Anwar, M A; Gokozan, H N; Ball, M K; Otero, J; McGwire, B S

    2015-10-01

    The saprophytic nematode Halicephalobus is a rare cause of fatal human meningo-encephalitis, and West Nile virus is neurotropic flavivirus implicated in a variety of clinical neurologic syndromes. Here we report a case of rapidly progressive CNS encephalopathy and death. Serologic, immuno-histochemical, histopathologic and nucleic acid studies demonstrate the presence of active Halicephalobus and West Nile virus in the CNS tissue. This is the first reported case of co-infection with these neurotropic pathogens. PMID:26050925

  5. Lower numbers of natural killer T cells in HIV-1 and Mycobacterium leprae co-infected patients

    PubMed Central

    Carvalho, Karina I; Bruno, Fernanda R; Snyder-Cappione, Jennifer E; Maeda, Solange M; Tomimori, Jane; Xavier, Marilia B; Haslett, Patrick A; Nixon, Douglas F; Kallas, Esper G

    2012-01-01

    Natural killer T (NKT) cells are a heterogeneous population of lymphocytes that recognize antigens presented by CD1d and have attracted attention because of their potential role linking innate and adaptive immune responses. Peripheral NKT cells display a memory-activated phenotype and can rapidly secrete large amounts of pro-inflammatory cytokines upon antigenic activation. In this study, we evaluated NKT cells in the context of patients co-infected with HIV-1 and Mycobacterium leprae. The volunteers were enrolled into four groups: 22 healthy controls, 23 HIV-1-infected patients, 20 patients with leprosy and 17 patients with leprosy and HIV-1-infection. Flow cytometry and ELISPOT assays were performed on peripheral blood mononuclear cells. We demonstrated that patients co-infected with HIV-1 and M. leprae have significantly lower NKT cell frequencies [median 0.022%, interquartile range (IQR): 0.007–0.051] in the peripheral blood when compared with healthy subjects (median 0.077%, IQR: 0.032–0.405, P < 0.01) or HIV-1 mono-infected patients (median 0.072%, IQR: 0.030–0.160, P < 0.05). Also, more NKT cells from co-infected patients secreted interferon-γ after stimulation with DimerX, when compared with leprosy mono-infected patients (P = 0.05). These results suggest that NKT cells are decreased in frequency in HIV-1 and M. leprae co-infected patients compared with HIV-1 mono-infected patients alone, but are at a more activated state. Innate immunity in human subjects is strongly influenced by their spectrum of chronic infections, and in HIV-1-infected subjects, a concurrent mycobacterial infection probably hyper-activates and lowers circulating NKT cell numbers. PMID:22269018

  6. Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas

    PubMed Central

    Davis-Yadley, Ashley H.; Lipka, Seth; Vardaros, Magdalene; Shen, Huafeng

    2016-01-01

    Background Limited knowledge exists about the effects chronic hepatitis C virus (HCV) infection has in the development of colorectal adenomas (CRA). Data regarding the association between chronic HIV infection and the development of CRA is scarce as well. We aim to determine if there is an association between the development of CRA and chronic infection with HCV and HCV/HIV co-infection. Methods From July 1, 2009 to March 31, 2011 a total of 2,051 patients that underwent colonoscopy were included in our study. The population was divided into 2 study groups: those patients who tested positive for HCV, and HCV/HIC; the control groups consisted of patients whose results were negative. Fisher’s exact χ2 test for categorical variables and t-test for continuous variables was used to analyze data between groups. Logistic regression was performed to obtain odds ratios (OR). Results CRA detection was higher in the HCV than in the control group (26.3% vs. 20.2%; P=1.02); Likewise, the incidence of CRA (25.5% vs. 20.8%; P=0.63) was higher in the co-infection group. However, in both of the study groups this difference was non-statistical. Conclusions A higher detection rate of CRP was seen in the HCV population; however, it failed to reach statistical significance. Whether co-infection with HIV/HCV increases the incidence of CRA and/or has a synergistic effect remains to be determined. The small sample population and the retrospective single institution nature of our study, as well as other confounders may have contributed to our negative results. However, our findings question whether HCV and HIV/HCV co-infected patients will benefit from screening colonoscopy at an earlier age. This issue merits further investigation with a large multi-center prospective study. PMID:27563452

  7. A multiplexed nucleic acid microsystem for point-of-care detection of HIV co-infection with MTB and PCP.

    PubMed

    Xu, Lingjia; Kong, Jilie

    2013-12-15

    Many individuals infected with the human immunodeficiency virus (HIV), especially children in African countries, die of co-infections with Mycobacterium tuberculosis (MTB) (coinfection rate: 50%) or Pneumocystis carinii pneumonia (PCP) (coinfection rate: 81%). The present proposal describes a rapid, portable, low-cost, multiplexed point-of-care diagnostic technique for simultaneously detecting HIV, MTB, and PCP. This technique incorporates a creative micro-device (hardware) and a loop-mediated isothermal amplification strategy (software). PMID:24209377

  8. CD4 lymphocyte dynamics in Tanzanian pulmonary tuberculosis patients with and without hiv co-infection

    PubMed Central

    2012-01-01

    Background The interaction of HIV and tuberculosis (TB) on CD4 levels over time is complex and has been divergently reported. Methods CD4 counts were assessed from time of diagnosis till the end of TB treatment in a cohort of pulmonary TB patients with and without HIV co-infection and compared with cross-sectional data on age- and sex-matched non-TB controls from the same area. Results Of 1,605 study participants, 1,250 were PTB patients and 355 were non-TB controls. At baseline, HIV was associated with 246 (95% CI: 203; 279) cells per μL lower CD4 counts. All PTB patients had 100 cells per μL lower CD4 counts than the healthy controls. The CD4 levels were largely unchanged during a five-month of TB treatment. HIV infected patients not receiving ART at any time and those already on ART at baseline had no increase in CD4 counts after 5 months of TB treatment, whereas those prescribed ART between baseline and 2 months, and between 2 and 5 months increased by 69 (22;117) and 110 (52; 168) CD4 cells per μL after 5 months. Conclusions The increase in circulating CD4 levels observed in PTB in patients is acquired after 2 months of treatment irrespective of HIV status. Initiation of ART is the strongest factor correlated with CD4 increase during TB treatment. Trial registration number Clinical trials.gov: NCT00311298 PMID:22436147

  9. Severity of bovine tuberculosis is associated with co-infection with common pathogens in wild boar.

    PubMed

    Risco, David; Serrano, Emmanuel; Fernández-Llario, Pedro; Cuesta, Jesús M; Gonçalves, Pilar; García-Jiménez, Waldo L; Martínez, Remigio; Cerrato, Rosario; Velarde, Roser; Gómez, Luis; Segalés, Joaquím; Hermoso de Mendoza, Javier

    2014-01-01

    Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under

  10. Incidence of tuberculosis and immunological profile of TB/HIV co-infected patients in Nigeria

    PubMed Central

    Musa, Baba Maiyaki; Musa, Babashani; Muhammed, Hamza; Ibrahim, Nashabaru; Musa, Abubakar Garbati

    2015-01-01

    BACKGROUND: We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HIV Treatment. We also modeled the relationship between incident TB and change in CD4 count over the follow-up period. METHODS: We analyzed the incidence of TB over 10 years from initiation of HIV treatment among 345 HIV treatment-naïve persons, who were enrolled in a cohort in Kano, Nigeria. We used Generalized Estimating Equation [GEE] to identify determinants of TB incidence and model the relationship between the occurrences of TB with change in CD4 count over the follow-up period. We created Kaplan-Meier curves stratified by anti-retroviral therapy (ART) treatment failure status to examine the effect of first line ART treatment failure on occurrence of TB. RESULT: During the 10-year period, 47(13.62%) had TB [incidence was 7.43 per (1,000) person year)]. It is associated with decreasing age (OR = 0.98), female gender (OR = 0.83), being on first line ART other than AZT (OR = 0.87), poor adherence (OR = 1.25), change in ART regimen (OR = 2.3) and ART treatment failure (OR = 1.51). Odds of TB occurrence was also associated with CD4 increment at 10 years (OR = 0.99). Those with TB/HIV co-infection tend to have statistically significant shorter time to failing first line ART regimen compared to those with HIV infection alone. CONCLUSION: There was high incidence of TB in the studied HIV cohort with a deleterious effect on the outcome of ART treatment. There is need for early TB screening and re-screening among all HIV patients. PMID:26229561

  11. Severity of Bovine Tuberculosis Is Associated with Co-Infection with Common Pathogens in Wild Boar

    PubMed Central

    Risco, David; Serrano, Emmanuel; Fernández-Llario, Pedro; Cuesta, Jesús M.; Gonçalves, Pilar; García-Jiménez, Waldo L.; Martínez, Remigio; Cerrato, Rosario; Velarde, Roser; Gómez, Luis; Segalés, Joaquím; Hermoso de Mendoza, Javier

    2014-01-01

    Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under

  12. HIV-Helicobacter pylori Co-Infection: Antibiotic Resistance, Prevalence, and Risk Factors

    PubMed Central

    Nkuize, Marcel; De Wit, Stéphane; Muls, Vinciane; Delforge, Marc; Miendje Deyi, Véronique Y.; Cadière, Guy B.; Buset, Michel

    2015-01-01

    Background Patients infected with human immunodeficiency virus (HIV) are living longer due to the availability of more potent treatments. However, prescription of antibiotics to treat or prevent infections in these patients may increase the likelihood of co-infection with antibiotic-resistant species. Aim To compare antimicrobial susceptibility of Helicobacter pylori (H. pylori) in HIV-positive and HIV-negative patients and assess risk-factors for resistance. Methods We prospectively collected data from consecutive HIV-positive and HIV-negative patients undergoing upper gastrointestinal endoscopy. Patients with H. pylori-positive gastric biopsies who had never received H. pylori treatment were included. Results Of the 353 patients included, 93 were HIV-positive and 260 HIV-negative. Among the HIV-positive patients, 56 (60%) had been infected for <10 years, the median CD4+ count was 493 cells/μl and median viral load was 61 copies/mL; 66 (71%) were receiving antiretroviral therapy. HIV-positive patients were more often male (p = 0.009), had a lower body mass index (p<0.0001), and had less frequently received antibiotics during the 12-months prior to the endoscopy (p<0.0001) than HIV-negative patients. HIV-positive patients were more likely to have H. pylori resistant to levofloxacin (p = 0.0004), metronidazole (p = 0.01), or multiple antibiotics (p = 0.006). HIV-positive Black Africans were more likely to have resistant strains than were HIV-negative Black Africans (p = 0.04). Ethnicity and HIV status were independent risk factors for H. pylori resistance in all patients and acquired immune deficiency syndrome (AIDS) and sex were risk factors in HIV-positive patients. Conclusions There was a higher prevalence of primary H. pylori-resistant strains in HIV-positive than in HIV-negative patients. AIDS and sex were predictors of H. pylori resistance in HIV-positive patients. PMID:26691198

  13. Outbreak of melioidosis and leptospirosis co-infection following a rescue operation.

    PubMed

    Sapian, M; Khair, M T; How, S H; Rajalingam, R; Sahhir, K; Norazah, A; Khebir, V; Jamalludin, A R

    2012-06-01

    We analyzed the epidemiological data of all people who were involved in the search and rescue operation in Lubuk Yu, a natural recreational forest with waterfall and stream. The hospital admission records of the cases who fulfilled the case definition and the environmental samples result taken at Lubuk Yu recreational area were studied. 153 people were exposed to this outbreak, 85 (55.5%) were professional rescuers from various government agencies and 68 (44.5%) were villagers. 21 fulfilled the case definition. Ten cases were confirmed melioidosis, six melioidosis alone and four coinfected with leptospirosis. There were eight deaths in this outbreak, seven were villagers and one professional rescuer. Overall case fatality was 70%. All confirmed melioidosis cases and seven who died had diabetes mellitus. The morbidity rate were higher among the villagers, 23.5% compared to professional rescuers, 5.9%. The case fatality rate were also higher in this group which was 100% compared to 33.3% in professional rescuers. The soil and water samples in Lubuk Yu recreational area were positive for leptospira and Burkholderia pseudomallei. The presence of co-infection and co-morbidities especially diabetes mellitus among the exposed led to the high mortality in this outbreak hence a high index of suspicion is important among the healthcare professionals in the management of melioidosis cases. To avoid similar incident in future, search and rescue operation should be only conducted by professional rescuers with appropriate personal protective equipment. A register of rescuers should be maintained for surveillance and follow up if necessary. PMID:23082420

  14. Studies on the molecular pathogenesis of extraskeletal myxoid chondrosarcoma-cytogenetic, molecular genetic, and cDNA microarray analyses.

    PubMed

    Sjögren, Helene; Meis-Kindblom, Jeanne M; Orndal, Charlotte; Bergh, Peter; Ptaszynski, Konrad; Aman, Pierre; Kindblom, Lars-Gunnar; Stenman, Göran

    2003-03-01

    Extraskeletal myxoid chondrosarcomas (EMCs) are characterized by recurrent chromosome translocations resulting in fusions of the nuclear receptor TEC to various NH(2)-terminal partners. Here we describe the phenotypic, cytogenetic, and molecular genetic characteristics of a series of 10 EMCs. Using spectral karyotyping and fluorescence in situ hybridization, clonal chromosome abnormalities were detected in all but one tumor. A t(9;22)(q22;q12) translocation was found in three cases; a del(22)(q12-13)in one case; and variant translocations, including t(9;17)(q22;q11-12), t(7;9;17)(q32;q22;q11), and t(9;15)(q22;q21), were detected in one case each. Recurrent, secondary abnormalities, including trisomy 1q, 7, 8, 12, and 19, were found in seven tumors. All tumors contained translocation-generated or cryptic gene fusions, including EWS-TEC (five cases, of which one was a novel fusion), TAF2N-TEC (four cases), and TCF12-TEC (one case). cDNA microarray analysis of the gene expression patterns of two EMCs and a myxoid liposarcoma reference tumor revealed a remarkably distinct and uniform expression profile in both EMCs despite the fact that they had different histologies and expressed different fusion transcripts. The most differentially expressed gene in both tumors was CHI3L1, which encodes a secreted glycoprotein (YKL-40) previously implicated in various pathological conditions of extracellular matrix degradation as well as in cancer. Our findings suggests that EMC exhibits a tumor-specific gene expression profile, including overexpression of several cancer-related genes as well as genes implicated in chondrogenesis and neural-neuroendocrine differentiation, thus distinguishing it from other soft tissue sarcomas. PMID:12598313

  15. Conservation of the 15-kilodalton lipoprotein among Treponema pallidum subspecies and strains and other pathogenic treponemes: genetic and antigenic analyses.

    PubMed Central

    Centurion-Lara, A; Arroll, T; Castillo, R; Shaffer, J M; Castro, C; Van Voorhis, W C; Lukehart, S A

    1997-01-01

    The 15-kDa lipoprotein of Treponema pallidum is a major immunogen during natural syphilis infection in humans and experimental infection in other hosts. The humoral and cellular immune responses to this molecule appear late in infection as resistance to reinfection is developing. One therefore might hypothesize that this antigen is important for protective immunity. This possibility is explored by using both genetic and antigenic approaches. Limited or no cross-protection has been demonstrated between the T. pallidum subspecies and strains or between Treponema species. We therefore hypothesized that if the 15-kDa antigen was of major importance in protective immunity, it might be a likely site of antigenic diversity. To explore this possibility, the sequences of the open reading frames of the 15-kDa gene have been determined for Treponema pallidum subsp. pallidum (Nichols and Bal-3 strains), T. pallidum subsp. pertenue (Gauthier strain), T. pallidum subsp. endemicum (Bosnia strain), Treponema paraluiscuniculi (Cuniculi A, H, and K strains), and a little-characterized simian isolate of Treponema sp. (Fribourg-Blanc strain). No significant differences in DNA sequences of the genes for the coding region of the 15-kDa antigen were found among the different species and subspecies studied. In addition, all organisms showed expression of the 15-kDa antigen as determined by monoclonal antibody staining. The role of the 15-kDa antigen in protection against homologous infection with T. pallidum subsp. pallidum Nichols was examined in rabbits immunized with a purified recombinant 15-kDa fusion protein. No alteration in chancre development was observed in immunized, compared to unimmunized, rabbits, and the antisera induced by the immunization failed to enhance phagocytosis of T. pallidum subsp. pallidum by macrophages in vitro. These results do not support a major role for this antigen in protection against syphilis infection. PMID:9119485

  16. Sex-biased natal dispersal and inbreeding avoidance in American black bears as revealed by spatial genetic analyses.

    PubMed

    Costello, Cecily M; Creel, Scott R; Kalinowski, Steven T; Vu, Ninh V; Quigley, Howard B

    2008-11-01

    We tested the hypothesis that sex-biased natal dispersal reduces close inbreeding in American black bears, a solitary species that exhibits nearly complete male dispersal and female philopatry. Using microsatellite DNA and spatial data from reproductively mature bears (>or= 4 years old), we examined the spatial genetic structure of two distinct populations in New Mexico from 1993 to 2000. As predicted, relatedness (r) and the frequency of close relationships (parent-offspring or full siblings) decreased with distance among female dyads, but little change was observed among male or opposite-sex dyads. Neighbouring females were more closely related than neighbouring males. The potential for inbreeding was low. Most opposite-sex pairs that lived sufficiently close to facilitate mating were unrelated, and few were close relatives. We found no evidence that bears actively avoided inbreeding in their selection of mates from this nearby pool, as mean r and relationship frequencies did not differ between potential and actual mating pairs (determined by parentage analysis). These basic patterns were apparent in both study areas despite a nearly two-fold difference in density. However, the sex bias in dispersal was less pronounced in the lower-density area, based on proportions of bears with male and female relatives residing nearby. This result suggests that male bears may respond to reduced competition by decreasing their rate or distance of dispersal. Evidence supports the hypothesis that inbreeding avoidance is achieved by means of male-biased dispersal but also indicates that competition (for mates or resources) modifies dispersal patterns. PMID:18828781

  17. New Players in the Same Old Game: Disturbance of Group 2 Innate Lymphoid Cells in HIV-1 and Mycobacterium leprae Co-infected Patients

    PubMed Central

    Papotto, Pedro Henrique; Maeda, Solange; Tomimori, Jane; Xavier, Marília Brasil; Rizzo, Luiz Vicente; Kallas, Esper Georges; Carvalho, Karina Inácio

    2015-01-01

    Abstract Leprosy control is achieved through a fine-tuning of TH1 and TH2 immune response pattern balance. Given the increasing epidemiological overlay of HIV and M. leprae infections, immune response in co-infected patients consists in an important contemporary issue. Here we describe for the first time the innate lymphoid cells compartment in peripheral blood of leprosy and HIV/M. leprae co-infected patients, and show that co-infection increases group 2 innate lymphoid whilst decreasing group 1 innate lymphoid cells frequencies and function. PMID:26335023

  18. The prevalence of Neospora caninum and co-infection with Toxoplasma gondii by PCR analysis in naturally occurring mammal populations.

    PubMed

    Hughes, J M; Williams, R H; Morley, E K; Cook, D A N; Terry, R S; Murphy, R G; Smith, J E; Hide, G

    2006-01-01

    Neospora caninum and Toxoplasma gondii are closely related intracellular protozoan parasites associated with bovine and ovine abortion respectively. Little is known about the extent of Neospora/Toxoplasma co-infection in naturally infected populations of animals. Using nested PCR techniques, based on primers from the Nc5 region of N. caninum and SAG1 for T. gondii, the prevalence of N. caninum and its co-infection with T. gondii were investigated in populations of Mus domesticus, Rattus norvegicus and aborted lambs (Ovis aries). A low frequency of infection with N. caninum was detected in the Mus domesticus (3%) and Rattus norvegicus (4.4%) populations. A relatively high frequency of infection with N. caninum was detected in the brains of aborted lambs (18.9%). There was no significant relationship between N. caninum and T. gondii co-infection. Investigation of the tissue distribution of Neospora, in aborted lambs, showed that Neospora could not be detected in tissues other than brain and this was in contrast to Toxoplasma where the parasite could be frequently detected in a range of tissues. PMID:16393351

  19. Prevalence of hepatitis B and C viral co-infections among HIV-1 infected individuals in Nairobi, Kenya

    PubMed Central

    2013-01-01

    Background Hepatitis B virus (HBV) and Hepatitis C virus (HCV) co-infections among HIV-1 infected individuals are growing worldwide health problems characterized by lack of effective vaccines, need for expensive treatment, chronicity of morbidity and associated mortality. Their prevalence and distribution patterns continue to vary across geographical locations with high prevalence being detected among high risk populations. To determine the prevalence of HBV and HCV among HIV-1 infected individuals, blood samples were collected from consenting study subjects visiting comprehensive HIV clinics in Nairobi during the period between October and December 2009. Methods Blood samples from volunteers were screened with ELISA tests for detecting HIV, HBV surface antigen (HBsAg) and anti-HCV antibodies. Results In a total of three (300) hundred infected individuals consisting of 129 (43%) males and 171 (57%) females 15.3% (46/300) were HIV-1 co-infected with either HBV or HCV or both, 10.3% (31/300) with HIV-1 and HCV and 6% (18/300) with HIV-1 and HBV infections. However, only three individuals (1%) were coinfected with the three viruses (HIV/HBV/HCV). Conclusion Though, low levels of co-infection with all three viruses were reported, there could be higher prevalence rates than reported here especially among high risk populations. PMID:24016453

  20. Tuberculin Skin-Test Reactions Are Unaffected by the Severity of Hyperendemic Intestinal Helminth Infections and Co-Infections

    PubMed Central

    Zevallos, Karine; Vergara, Katherine C.; Vergara, Antonio; Vidal, Carlos; Garcia, Hector H.; Evans, Carlton A.

    2010-01-01

    The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis antigens. Helminths suppress cell-mediated immunity, so we studied the effect of helminth infection and deworming on the TST in a randomized, double-blind, placebo-controlled study in an indigenous Amazon community (N = 195). Stool microscopy diagnosed helminths in 98% and co-infection with multiple species in 24% of study subjects. The TST was positive (≥ 10 mm) for 49%, and responses increased with age (P < 0.001), Bacille Calmette Guerin (BCG) vaccination (P = 0.01), and tuberculosis contact (P = 0.05). TST results had no association with helminth-egg concentrations, species, or co-infections (all P > 0.1). One month after deworming with albendazole (three daily 400-mg doses), helminths were reduced, but 63% remained infected with helminths. Albendazole did not cause a change in TST size (P = 0.8) or positivity (P = 0.9) relative to placebo. Thus, TST reactions were unaffected by albendazole therapy that partially cured intestinal helminth infections, and TST interpretation was unaffected by high-burden helminth infections and co-infection with multiple helminth species. PMID:20682875

  1. HIV/Tuberculosis Co-Infection among Patients Attending a Referral Chest Clinic in Nasarawa State, Nigeria

    NASA Astrophysics Data System (ADS)

    Umeh, E. U.; Ishaleku, D.; Iheukwumere, C. C.

    Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (TB) coinfection rate was investigated among patients referred to a chest clinic in Nasarawa State, Nigeria. Out of the 344 patients who presented with respiratory problems at the clinic, 44.8% had M. tuberculosis infection, 24.7% HIV infection and 12.8% HIV/tubercle bacilli co-infection. Coinfection rate in HIV infected persons (HIV+) was 51.8 and 28.6% in those with M. tuberculosis infection. The relative risk of HIV positive persons being coinfected was 1.075, while it was 0.401 for TB infected persons. The estimated Odds Ratio (OR) shows that the risk of co-infection was 2.68 times higher among HIV+ persons than among those with tuberculosis. The attributable risk was 45% and shows the extent to which co-infection could be attributed to HIV infection. A key socio-economic variable, eating in groups, was significantly correlated with coinfection (r = 0.107; p< 0.05). The results of this study may provide a useful policy guide in the formulation of HIV and tuberculosis control measures in Nigeria.

  2. Co-infection with the friend retrovirus and mouse scrapie does not alter prion disease pathogenesis in susceptible mice.

    PubMed

    Leblanc, Pascal; Hasenkrug, Kim; Ward, Anne; Myers, Lara; Messer, Ronald J; Alais, Sandrine; Timmes, Andrew; Priola, Suzette A; Priola, Sue

    2012-01-01

    Prion diseases are fatal, transmissible neurodegenerative diseases of the central nervous system. An abnormally protease-resistant and insoluble form (PrP(Sc)) of the normally soluble protease-sensitive host prion protein (PrP(C)) is the major component of the infectious prion. During the course of prion disease, PrP(Sc) accumulates primarily in the lymphoreticular and central nervous systems. Recent studies have shown that co-infection of prion-infected fibroblast cells with the Moloney murine leukemia virus (Mo-MuLV) strongly enhanced the release and spread of scrapie infectivity in cell culture, suggesting that retroviral coinfection might significantly influence prion spread and disease incubation times in vivo. We now show that another retrovirus, the murine leukemia virus Friend (F-MuLV), also enhanced the release and spread of scrapie infectivity in cell culture. However, peripheral co-infection of mice with both Friend virus and the mouse scrapie strain 22L did not alter scrapie disease incubation times, the levels of PrP(Sc) in the brain or spleen, or the distribution of pathological lesions in the brain. Thus, retroviral co-infection does not necessarily alter prion disease pathogenesis in vivo, most likely because of different cell-specific sites of replication for scrapie and F-MuLV. PMID:22295118

  3. Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection

    PubMed Central

    Cordero, Radames J. B.; Liedke, Susie Coutinho; de S. Araújo, Glauber R.; Martinez, Luis R.; Nimrichter, Leonardo; Frases, Susana; Peralta, Jose Mauro; Casadevall, Arturo; Rodrigues, Marcio L.; Nosanchuk, Joshua D.; Guimaraes, Allan J.

    2016-01-01

    Cryptococcus neoformans (Cn) and Histoplasma capsulatum (Hc) co-exist in the environment and occasionally co-infect individuals, which can lead to severe disease/lethal outcomes. We investigated specific interactions between Cn-Hc to determine the impact of synchronous infection in virulence and disease. Co-infected mice had significantly higher mortality than infection with either species or acapsular Cn-Hc. Coating of Hc with cryptococcal glycans (Cn-gly) resulted in higher pulmonary fungal burden in co-infected animals relative to control. Co-cultivation or addition of Cn-gly resulted in enhanced pellicle formation with a hybrid polysaccharide matrix with higher reactivity to GXM mAbs. Transfer and incorporation of Cn polysaccharide onto Hc surface was time and temperature dependent. Cn-gly transfer altered the zeta potential of Hc and was associated with increased resistance to phagocytosis and killing by macrophages. Mice infected with Hc and subsequently injected with purified Cn-gly died significantly more rapidly than Hc alone infected, establishing the precedent that virulence factors from one fungus can enhance the virulence of unrelated species. These findings suggest a new mechanism of microbial interaction involving the transfer of virulence traits that translates into enhanced lethality during mixed fungal infections and highlights the importance of studying heterogeneous microbial populations in the setting of infection. PMID:26908077

  4. Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection.

    PubMed

    Cordero, Radames J B; Liedke, Susie Coutinho; de S Araújo, Glauber R; Martinez, Luis R; Nimrichter, Leonardo; Frases, Susana; Peralta, Jose Mauro; Casadevall, Arturo; Rodrigues, Marcio L; Nosanchuk, Joshua D; Guimaraes, Allan J

    2016-01-01

    Cryptococcus neoformans (Cn) and Histoplasma capsulatum (Hc) co-exist in the environment and occasionally co-infect individuals, which can lead to severe disease/lethal outcomes. We investigated specific interactions between Cn-Hc to determine the impact of synchronous infection in virulence and disease. Co-infected mice had significantly higher mortality than infection with either species or acapsular Cn-Hc. Coating of Hc with cryptococcal glycans (Cn-gly) resulted in higher pulmonary fungal burden in co-infected animals relative to control. Co-cultivation or addition of Cn-gly resulted in enhanced pellicle formation with a hybrid polysaccharide matrix with higher reactivity to GXM mAbs. Transfer and incorporation of Cn polysaccharide onto Hc surface was time and temperature dependent. Cn-gly transfer altered the zeta potential of Hc and was associated with increased resistance to phagocytosis and killing by macrophages. Mice infected with Hc and subsequently injected with purified Cn-gly died significantly more rapidly than Hc alone infected, establishing the precedent that virulence factors from one fungus can enhance the virulence of unrelated species. These findings suggest a new mechanism of microbial interaction involving the transfer of virulence traits that translates into enhanced lethality during mixed fungal infections and highlights the importance of studying heterogeneous microbial populations in the setting of infection. PMID:26908077

  5. Evidence for Within-Host Genetic Recombination among the Human Pegiviral Strains in HIV Infected Subjects

    PubMed Central

    Wu, Haoming; Padhi, Abinash; Xu, Junqiang; Gong, Xiaoyan; Tien, Po

    2016-01-01

    The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV), the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co-circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female) were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV. PMID:27560699

  6. Evidence for Within-Host Genetic Recombination among the Human Pegiviral Strains in HIV Infected Subjects.

    PubMed

    Wu, Haoming; Padhi, Abinash; Xu, Junqiang; Gong, Xiaoyan; Tien, Po

    2016-01-01

    The non-pathogenic Human Pegivirus (HPgV, formerly GBV-C/HGV), the most prevalent RNA virus worldwide, is known to be associated with reduced morbidity and mortality in HIV-infected individuals. Although previous studies documented its ubiquity and important role in HIV-infected individuals, little is known about the underlying genetic mechanisms that maintain high genetic diversity of HPgV within the HIV-infected individuals. To assess the within-host genetic diversity of HPgV and forces that maintain such diversity within the co-infected hosts, we performed phylogenetic analyses taking into account 229 HPgV partial E1-E2 clonal sequences representing 15 male and 8 female co-infected HIV patients from Hubei province of central China. Our results revealed the presence of eleven strongly supported clades. While nine clades belonged to genotype 3, two clades belonged to genotype 2. Additionally, four clades that belonged to genotype 3 exhibited inter-clade recombination events. The presence of clonal sequences representing multiple clades within the HIV-infected individual provided the evidence of co-circulation of HPgV strains across the region. Of the 23 patients, six patients (i.e., five males and one female) were detected to have HPgV recombinant sequences. Our results also revealed that while male patients shared the viral strains with other patients, viral strains from the female patients had restricted dispersal. Taken together, the present study revealed that multiple infections with divergent HPgV viral strains may have caused within-host genetic recombination, predominantly in male patients, and therefore, could be the major driver in shaping genetic diversity of HPgV. PMID:27560699

  7. Genetic analyses involving microsatellite ETH10 genotypes on bovine chromosome 5 and performance trait measures in Angus- and Brahman-influenced cattle.

    PubMed

    DeAtley, K L; Rincon, G; Farber, C R; Medrano, J F; Luna-Nevarez, P; Enns, R M; VanLeeuwen, D M; Silver, G A; Thomas, M G

    2011-07-01

    ETH10 is a dinucleotide microsatellite within the promoter of signal transducer and activator of transcription 6 (STAT6) gene on bovine chromosome 5. ETH10 is included in the panel of genetic markers used in parentage testing procedures of cattle breed associations. Allelic sizes of ETH10 PCR amplicons range from 199 to 225 bp. Objectives of this study were to use microsatellite data from beef cattle breed associations to investigate genetic distance and population stratification among Angus- and Brahman-influenced cattle and to use ETH10 genotypes and growth and ultrasound carcass data to investigate their statistical relationships. Three series of genotype to phenotype association analyses were conducted with 1) Angus data (n=5,094), 2) Brangus data (3/8 Brahman × 5/8 Angus; n=2,296), and 3) multibreed data (n=4,426) of Angus and Brangus cattle. Thirteen alleles and 38 genotypes were observed, but frequencies varied among breed groups. Tests of genetic identity and distance among 6 breed composition groups increasing in Brahman influence from 0 to 75% revealed that as Brahman-influence increased to ≥50%, genetic distance from Angus ranged from 18.3 to 43.5%. This was accomplished with 10 microsatellite loci. A mixed effects model involving genotype as a fixed effect and sire as a random source of variation suggested that Angus cattle with the 217/219 genotype tended to have 2.1% heavier (P=0.07) 205-d BW than other genotypes. In Brangus cattle, allele combinations were classified as small (≤215 bp) or large (≥217 bp). Brangus cattle with the small/large genotype had 2.0% heavier (P<0.05) birth weight, yet cattle with the large/large genotype had approximately 5.1% greater (P<0.05) percentage of fat within LM and more LM per BW than cattle with small/large or small/small genotypes. Genotype-to-phenotype relationships were not detected in multibreed analyses. The ETH10 locus appears to be associated with growth and carcass traits in Angus and Brangus cattle

  8. Genetic Diversity of G3 Rotavirus Strains Circulating in Argentina during 1998–2012 Assessed by Full Genome Analyses

    PubMed Central

    Degiuseppe, Juan Ignacio; Parra, Gabriel Ignacio; Stupka, Juan Andrés

    2014-01-01

    Seasonal shifts in the predominant strains and the periodic emergence of new strains are epidemiological features of human rotaviruses. After the sporadic detection in two samples in 1998, G3P[8] strains reemerged as the predominant rotavirus during 2008–2009 in Argentina. Notably, in 2011 6.3% (37/587) of samples presented the G3P[6] genotypes, which coincided with the recent detection of G3P[6] and G2P[6] strains in South America and Europe. Analyses of the 11 gene segments of four G3P[8] and two G3P[6] strains revealed that G3P[8] strains detected a decade apart (1998 and 2009) presented minor differences, while the G3P[6] strains presented a complete different genomic constellation albeit showing a similar VP7 gene. This study provides insights in the dynamics and evolution of one of the genotypes with the wider range of hosts and inter-species transmission potential. PMID:25337915

  9. Genetic lineages of undifferentiated-type gastric carcinomas analysed by unsupervised clustering of genomic DNA microarray data

    PubMed Central

    2013-01-01

    Background It is suspected that early gastric carcinoma (GC) is a dormant variant that rarely progresses to advanced GC. We demonstrated that the dormant and aggressive variants of tubular adenocarcinomas (TUBs) of the stomach are characterized by loss of MYC and gain of TP53 and gain of MYC and/or loss of TP53, respectively. The aim of this study is to determine whether this is also the case in undifferentiated-type GCs (UGCs) of different genetic lineages: one with a layered structure (LS+), derived from early signet ring cell carcinomas (SIGs), and the other, mostly poorly differentiated adenocarcinomas, without LS but with a minor tubular component (TC), dedifferentiated from TUBs (LS−/TC+). Methods Using 29 surgically resected stomachs with 9 intramucosal and 20 invasive UGCs (11 LS+ and 9 LS−/TC+), 63 genomic DNA samples of mucosal and invasive parts and corresponding reference DNAs were prepared from formalin-fixed, paraffin-embedded tissues with laser microdissection, and were subjected to array-based comparative genomic hybridization (aCGH), using 60K microarrays, and subsequent unsupervised, hierarchical clustering. Of 979 cancer-related genes assessed, we selected genes with mean copy numbers significantly different between the two major clusters. Results Based on similarity in genomic copy-number profile, the 63 samples were classified into two major clusters. Clusters A and B, which were rich in LS+ UGC and LS−/TC+ UGC, respectively, were discriminated on the basis of 40 genes. The aggressive pattern was more frequently detected in LS−/TC+ UGCs, (20/26; 77%), than in LS+UGCs (17/37; 46%; P = 0.0195), whereas no dormant pattern was detected in any of the UGC samples. Conclusions In contrast to TUBs, copy number alterations of MYC and TP53 exhibited an aggressive pattern in LS+ SIG at early and advanced stages, indicating that early LS+ UGCs inevitably progress to an advanced GC. Cluster B (enriched in LS−/TC+) exhibited more

  10. Co-Infection Burden of Hepatitis C Virus and Human Immunodeficiency Virus among Injecting Heroin Users at the Kenyan Coast

    PubMed Central

    Mwatelah, Ruth S.; Lwembe, Raphael M.; Osman, Saida; Ogutu, Bernhards R.; Aman, Rashid; Kitawi, Rose C.; Wangai, Laura N.; Oloo, Florence A.; Kokwaro, Gilbert O.; Ochieng, Washingtone

    2015-01-01

    Background Injection drug use is steadily rising in Kenya. We assessed the prevalence of both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections among injecting heroin users (IHUs) at the Kenyan Coast. Methods A total of 186 IHUs (mean age, 33 years) from the Omari rehabilitation center program in Malindi were consented and screened for HIV-1 and HCV by serology and PCR and their CD4 T-cells enumerated by FACS. Results Prevalence of HIV-1 was 87.5%, that of HCV was 16.4%, co-infection was 17.9% and 18/152 (11.8%) were uninfected. Only 5.26% of the HIV-1 negative injectors were HCV positive. Co-infection was higher among injectors aged 30 to 40 years (20.7%) and among males (22.1%) than comparable groups. About 35% of the injectors were receiving antiretroviral treatment (ART). Co-infection was highest among injectors receiving D4T (75%) compared to those receiving AZT (21.6%) or TDF (10.5%) or those not on ART (10.5%). Mean CD4 T-cells were 404 (95% CI, 365 - 443) cells/mm3 overall, significantly lower for co-infected (mean, 146; 95% CI 114 – 179 cells/mm3) than HIV mono infected (mean, 437, 95% CI 386 – 487 cells/mm3, p<0.001) or uninfected (mean, 618, 95% CI 549 – 687 cells/mm3, p<0.001) injectors and lower for HIV mono-infected than uninfected injectors (p=0.002). By treatment arm, CD4 T-cells were lower for injectors receiving D4T (mean, 78; 95% CI, 0.4 – 156 cells/mm3) than TDF (mean 607, 95% CI, 196 – 1018 cells/mm3, p=0.005) or AZT (mean 474, 95% CI -377 – 571 cells/mm3, p=0.004). Conclusion Mono and dual infections with HIV-1 and HCV is high among IHUs in Malindi, but ART coverage is low. The co-infected IHUs have elevated risk of immunodeficiency due to significantly depressed CD4 T-cell numbers. Coinfection screening, treatment-as-prevention for both HIV and HCV and harm reduction should be scaled up to alleviate infection burden. PMID:26208212

  11. Genetic and functional analyses of PptA, a phospho-form transferase targeting type IV pili in Neisseria gonorrhoeae.

    PubMed

    Naessan, Cecilia L; Egge-Jacobsen, Wolfgang; Heiniger, Ryan W; Wolfgang, Matthew C; Aas, Finn Erik; Røhr, Asmund; Winther-Larsen, Hanne C; Koomey, Michael

    2008-01-01

    The PilE pilin subunit protein of Neisseria gonorrhoeae undergoes unique covalent modifications with phosphoethanolamine (PE) and phosphocholine (PC). The pilin phospho-form transferase A (PptA) protein, required for these modifications, shows sequence relatedness with and architectural similarities to lipopolysaccharide PE transferases. Here, we used regulated expression and mutagenesis as means to better define the relationships between PptA structure and function, as well as to probe the mechanisms by which other factors impact the system. We show here that pptA expression is coupled at the level of transcription to its distal gene, murF, in a division/cell wall gene operon and that PptA can act in a dose-dependent fashion in PilE phospho-form modification. Molecular modeling and site-directed mutagenesis provided the first direct evidence that PptA is a member of the alkaline phosphatase superfamily of metalloenzymes with similar metal-binding sites and conserved structural folds. Through phylogenetic analyses and sequence alignments, these conclusions were extended to include the lipopolysaccharide PE transferases, including members of the disparate Lpt6 subfamily, and the MdoB family of phosphoglycerol transferases. Each of these enzymes thus likely acts as a phospholipid head group transferase whose catalytic mechanism involves a trans-esterification step generating a protein-phospho-form ester intermediate. Coexpression of PptA with PilE in Pseudomonas aeruginosa resulted in high levels of PE modification but was not sufficient for PC modification. This and other findings show that PptA-associated PC modification is governed by as-yet-undefined ancillary factors unique to N. gonorrhoeae. PMID:17951381

  12. Complete chloroplast genome of the genus Cymbidium: lights into the species identification, phylogenetic implications and population genetic analyses

    PubMed Central

    2013-01-01

    Background Cymbidium orchids, including some 50 species, are the famous flowers, and they possess high commercial value in the floricultural industry. Furthermore, the values of different orchids are great differences. However, species identification is very difficult. To a certain degree, chloroplast DNA sequence data are a versatile tool for species identification and phylogenetic implications in plants. Different chloroplast loci have been utilized for evaluating phylogenetic relationships at each classification level among plant species, including at the interspecies and intraspecies levels. However, there is no evidence that a short sequence can distinguish all plant species from each other in order to infer phylogenetic relationships. Molecular markers derived from the complete chloroplast genome can provide effective tools for species identification and phylogenetic resolution. Results The complete nucleotide sequences of eight individuals from a total of five Cymbidium species’ chloroplast (cp) genomes were determined using Illumina sequencing technology of the total DNA via a combination of de novo and reference-guided assembly. The length of the Cymbidium cp genome is about 155 kb. The cp genomes contain 123 unique genes, and the IR regions contain 24 duplicates. Although the genomes, including genome structure, gene order and orientation, are similar to those of other orchids, they are not evolutionarily conservative. The cp genome of Cymbidium evolved moderately with more than 3% sequence divergence, which could provide enough information for phylogeny. Rapidly evolving chloroplast genome regions were identified and 11 new divergence hotspot regions were disclosed for further phylogenetic study and species identification in Orchidaceae. Conclusions Phylogenomic analyses were conducted using 10 complete chloroplast genomes from seven orchid species. These data accurately identified the individuals and established the phylogenetic relationships between

  13. Insight on trace element detoxification in the Black-tailed Godwit (Limosa limosa) through genetic, enzymatic and metallothionein analyses.

    PubMed

    Lucia, Magali; Bocher, Pierrick; Cosson, Richard P; Churlaud, Carine; Robin, Frédéric; Bustamante, Paco

    2012-04-15

    Trace element concentrations (Ag, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, Zn) were investigated in the liver, kidneys, muscle and feathers of 31 black-tailed godwits (Limosa limosa) accidentally killed during catches by mist net in the Pertuis Charentais, Atlantic coast of France. Analyses of carbon and nitrogen stable isotope ratios were carried out in liver, muscle and feathers in order to elucidate dietary patterns and to determine whether differences in diet explained the variation in elemental uptake. This study also aimed to have a preliminary assessment of sub-lethal effects triggered by trace elements through the investigation of gene expressions by quantitative real-time PCR, antioxidant enzyme activities (catalase, superoxide dismutase, glutathione peroxidase), and metallothionein (MT) levels. The results showed that Cr and Ni concentrations in tissues of adults were lower than in juveniles in part because adults may have eliminated these trace elements through moulting. Except for Cd and Ni, trace element concentrations were negatively correlated to the body mass of godwits. Ag, As, Hg and Se concentrations were positively linked with the trophic position of birds. The diet could be considered as a fundamental route of exposure for these elements demonstrating therefore the qualitative linkage between dietary habits of godwits and their contaminant concentrations. Our results strongly suggest that even though trace element concentrations were mostly below toxicity threshold level, the elevated concentrations of As, Ag, Cd, Cu, Fe and Se may however trigger sub-lethal effects. Trace elements appear to enhance expression of genes involved in oxidative stress defence, which indicates the production of reactive oxygen species. Moreover, birds with the highest concentrations appeared to have an increased mitochondrial metabolism suggesting that the fight against trace element toxicity requires additional energetic needs notably to produce detoxification

  14. Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent

    PubMed Central

    Guo, Yan; Warren Andersen, Shaneda; Shu, Xiao-Ou; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Garcia-Closas, Montserrat; Milne, Roger L.; Schmidt, Marjanka K.; Chang-Claude, Jenny; Dunning, Allison; Bojesen, Stig E.; Ahsan, Habibul; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Bogdanova, Natalia V.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Casey, Graham; Chenevix-Trench, Georgia; Couch, Fergus J.; Cross, Simon S.; Czene, Kamila; Dörk, Thilo; Dumont, Martine; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gammon, Marilie; Giles, Graham G.; Guénel, Pascal; Haiman, Christopher A.; Hamann, Ute; Hooning, Maartje J.; Hopper, John L.; Jakubowska, Anna; Jasmine, Farzana; Jenkins, Mark; John, Esther M.; Johnson, Nichola; Jones, Michael E.; Kabisch, Maria; Knight, Julia A.; Koppert, Linetta B.; Kosma, Veli-Matti; Kristensen, Vessela; Le Marchand, Loic; Lee, Eunjung; Li, Jingmei; Lindblom, Annika; Lubinski, Jan; Malone, Kathi E.; Mannermaa, Arto; Margolin, Sara; McLean, Catriona; Meindl, Alfons; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Olson, Janet E.; Perez, Jose I. A.; Perkins, Barbara; Phillips, Kelly-Anne; Pylkäs, Katri; Rudolph, Anja; Santella, Regina; Sawyer, Elinor J.; Schmutzler, Rita K.; Seynaeve, Caroline; Shah, Mitul; Shrubsole, Martha J.; Southey, Melissa C.; Swerdlow, Anthony J.; Toland, Amanda E.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Ursin, Giske; Van Der Luijt, Rob B.; Verhoef, Senno; Whittemore, Alice S.; Winqvist, Robert; Zhao, Hui; Zhao, Shilin; Hall, Per; Simard, Jacques; Kraft, Peter; Hunter, David; Easton, Douglas F.; Zheng