Sample records for lactase persistence genetic

  1. Genetic diversity of lactase persistence in East African populations.

    PubMed

    Hassan, Hisham Y; van Erp, Anke; Jaeger, Martin; Tahir, Hanan; Oosting, Marije; Joosten, Leo A B; Netea, Mihai G

    2016-01-04

    The expression of lactase which digests lactose from milk in humans is generally lost after weaning, but selected mutations influencing the promoter of the lactase gene have spread into the human populations. This is considered a classical example of gene-culture co-evolution, and several studies suggested that the lactase gene has been under strong directional evolutionary selective pressure in the past 5000 to 10,000 years. In the present study we investigated the distribution of three gene variants leading to lactase persistence in 12 different East African populations as well as one European population. Our results show that with the exception of Copts and Nilotic populations who are fully lactose non-persistent, the majority of populations of East Africa show at least partly lactose persistence, with both ethnic and socio-economic aspects playing an important role in the distribution of genetic variants. In this study, the variants C/G-13907 and T/G-13915, which are the major variants among the nomadic Arabs in the Arabia and Beja of East Africa, showed remarkable frequencies in Sudanese populations, especially those of pastoralists, in line with the historical links and bidirectional migration of nomadic populations between Arabia and East Africa. The C/T-13910 variant, generally associated with European populations is uniquely present among the Fulani. These data indicate that a combination of socio-economic, ethnic and evolutionary factors converged to shape the genetic structure of lactase persistence in East African populations.

  2. Low prevalence of lactase persistence in Neolithic South-West Europe

    PubMed Central

    Plantinga, Theo S; Alonso, Santos; Izagirre, Neskuts; Hervella, Montserrat; Fregel, Rosa; van der Meer, Jos WM; Netea, Mihai G; de la Rúa, Concepcion

    2012-01-01

    The ability of humans to digest the milk component lactose after weaning requires persistent production of the lactose-converting enzyme lactase. Genetic variation in the promoter of the lactase gene (LCT) is known to be associated with lactase production and is therefore a genetic determinant for either lactase deficiency or lactase persistence during adulthood. Large differences in this genetic trait exist between populations in Africa and the Middle-East on the one hand, and European populations on the other; this is thought to be due to evolutionary pressures exerted by consumption of dairy products in Neolithic populations in Europe. In this study, we have investigated lactase persistence of 26 out of 46 individuals from Late Neolithic through analysis of ancient South-West European DNA samples, obtained from two burials in the Basque Country originating from 5000 to 4500 YBP. This investigation revealed that these populations had an average frequency of lactase persistence of 27%, much lower than in the modern Basque population, which is compatible with the concept that Neolithic and post-Neolithic evolutionary pressures by cattle domestication and consumption of dairy products led to high lactase persistence in Southern European populations. Given the heterogeneity in the frequency of the lactase persistence allele in ancient Europe, we suggest that in Southern Europe the selective advantage of lactose assimilation in adulthood most likely took place from standing population variation, after cattle domestication, at a post-Neolithic time when fresh milk consumption was already fully adopted as a consequence of a cultural influence. PMID:22234158

  3. Evolution of lactase persistence: an example of human niche construction

    PubMed Central

    Gerbault, Pascale; Liebert, Anke; Itan, Yuval; Powell, Adam; Currat, Mathias; Burger, Joachim; Swallow, Dallas M.; Thomas, Mark G.

    2011-01-01

    Niche construction is the process by which organisms construct important components of their local environment in ways that introduce novel selection pressures. Lactase persistence is one of the clearest examples of niche construction in humans. Lactase is the enzyme responsible for the digestion of the milk sugar lactose and its production decreases after the weaning phase in most mammals, including most humans. Some humans, however, continue to produce lactase throughout adulthood, a trait known as lactase persistence. In European populations, a single mutation (−13910*T) explains the distribution of the phenotype, whereas several mutations are associated with it in Africa and the Middle East. Current estimates for the age of lactase persistence-associated alleles bracket those for the origins of animal domestication and the culturally transmitted practice of dairying. We report new data on the distribution of −13910*T and summarize genetic studies on the diversity of lactase persistence worldwide. We review relevant archaeological data and describe three simulation studies that have shed light on the evolution of this trait in Europe. These studies illustrate how genetic and archaeological information can be integrated to bring new insights to the origins and spread of lactase persistence. Finally, we discuss possible improvements to these models. PMID:21320900

  4. Lactase non-persistence is directed by DNA variation-dependent epigenetic aging

    PubMed Central

    Labrie, Viviane; Buske, Orion J; Oh, Edward; Jeremian, Richie; Ptak, Carolyn; Gasiūnas, Giedrius; Maleckas, Almantas; Petereit, Rūta; Žvirbliene, Aida; Adamonis, Kęstutis; Kriukienė, Edita; Koncevičius, Karolis; Gordevičius, Juozas; Nair, Akhil; Zhang, Aiping; Ebrahimi, Sasha; Oh, Gabriel; Šikšnys, Virginijus; Kupčinskas, Limas; Brudno, Michael; Petronis, Arturas

    2016-01-01

    Inability to digest lactose due to lactase non-persistence is a common trait in adult mammals, with the exception of certain human populations that exhibit lactase persistence. It is not clear how the lactase gene can be dramatically downregulated with age in most individuals, but remains active in some. We performed a comprehensive epigenetic study of the human and mouse intestine using chromosome-wide DNA modification profiling and targeted bisulfite sequencing. Epigenetically-controlled regulatory elements were found to account for the differences in lactase mRNA levels between individuals, intestinal cell types and species. The importance of these regulatory elements in modulating lactase mRNA levels was confirmed by CRISPR-Cas9-induced deletions. Genetic factors contribute to epigenetic changes occurring with age at the regulatory elements, as lactase persistence- and non-persistence-DNA haplotypes demonstrated markedly different epigenetic aging. Thus, genetic factors facilitate a gradual accumulation of epigenetic changes with age to affect phenotypic outcome. PMID:27159559

  5. Lactase Non-persistence and Lactose Intolerance.

    PubMed

    Bayless, Theodore M; Brown, Elizabeth; Paige, David M

    2017-05-01

    To evaluate the clinical and nutritional significance of genetically determined lactase non-persistence and potential lactose and milk intolerance in 65-70% of the world's adult population. Milk consumption is decreasing in the USA and is the lowest in countries with a high prevalence of lactase non-persistence. The dairy industry and Minnesota investigators have made efforts to minimize the influence of lactose intolerance on milk consumption. Some lactose intolerant individuals, without co-existent irritable bowel syndrome, are able to consume a glass of milk with a meal with no or minor symptoms. The high frequency of lactase persistence in offspring of Northern European countries and in some nomadic African tribes is due to mutations in the promoter of the lactase gene in association with survival advantage of milk drinking. Educational and commercial efforts to improve calcium and Vitamin D intake have focused on urging consumption of tolerable amounts of milk with a meal, use of lowered lactose-content foods including hard cheeses, yogurt, and lactose-hydrolyzed milk products.

  6. The origins of lactase persistence in Europe.

    PubMed

    Itan, Yuval; Powell, Adam; Beaumont, Mark A; Burger, Joachim; Thomas, Mark G

    2009-08-01

    Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (-13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the--13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on--13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the--13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.

  7. The Origins of Lactase Persistence in Europe

    PubMed Central

    Itan, Yuval; Powell, Adam; Beaumont, Mark A.; Burger, Joachim; Thomas, Mark G.

    2009-01-01

    Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (−13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the −13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on −13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the −13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe. PMID:19714206

  8. Impact of selection and demography on the diffusion of lactase persistence.

    PubMed

    Gerbault, Pascale; Moret, Céline; Currat, Mathias; Sanchez-Mazas, Alicia

    2009-07-24

    The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches. We first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities. Our results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at

  9. Ancient DNA Analysis Reveals High Frequency of European Lactase Persistence Allele (T-13910) in Medieval Central Europe

    PubMed Central

    Akgül, Gülfirde; Della Casa, Philippe; Rühli, Frank; Warinner, Christina

    2014-01-01

    Ruminant milk and dairy products are important food resources in many European, African, and Middle Eastern societies. These regions are also associated with derived genetic variants for lactase persistence. In mammals, lactase, the enzyme that hydrolyzes the milk sugar lactose, is normally down-regulated after weaning, but at least five human populations around the world have independently evolved mutations regulating the expression of the lactase-phlorizin-hydrolase gene. These mutations result in a dominant lactase persistence phenotype and continued lactase tolerance in adulthood. A single nucleotide polymorphism (SNP) at C/T-13910 is responsible for most lactase persistence in European populations, but when and where the T-13910 polymorphism originated and the evolutionary processes by which it rose to high frequency in Europe have been the subject of strong debate. A history of dairying is presumed to be a prerequisite, but archaeological evidence is lacking. In this study, DNA was extracted from the dentine of 36 individuals excavated at a medieval cemetery in Dalheim, Germany. Eighteen individuals were successfully genotyped for the C/T-13910 SNP by molecular cloning and sequencing, of which 13 (72%) exhibited a European lactase persistence genotype: 44% CT, 28% TT. Previous ancient DNA-based studies found that lactase persistence genotypes fall below detection levels in most regions of Neolithic Europe. Our research shows that by AD 1200, lactase persistence frequency had risen to over 70% in this community in western Central Europe. Given that lactase persistence genotype frequency in present-day Germany and Austria is estimated at 71–80%, our results suggest that genetic lactase persistence likely reached modern levels before the historic population declines associated with the Black Death, thus excluding plague-associated evolutionary forces in the rise of lactase persistence in this region. This new evidence sheds light on the dynamic evolutionary

  10. Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?

    PubMed

    Dzialanski, Zbigniew; Barany, Michael; Engfeldt, Peter; Magnuson, Anders; Olsson, Lovisa A; Nilsson, Torbjörn K

    2016-02-01

    According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist. To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test. A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274). Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups. Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  11. Genetic Origins of Lactase Persistence and the Spread of Pastoralism in Africa

    PubMed Central

    Ranciaro, Alessia; Campbell, Michael C.; Hirbo, Jibril B.; Ko, Wen-Ya; Froment, Alain; Anagnostou, Paolo; Kotze, Maritha J.; Ibrahim, Muntaser; Nyambo, Thomas; Omar, Sabah A.; Tishkoff, Sarah A.

    2014-01-01

    In humans, the ability to digest lactose, the sugar in milk, declines after weaning because of decreasing levels of the enzyme lactase-phlorizin hydrolase, encoded by LCT. However, some individuals maintain high enzyme amounts and are able to digest lactose into adulthood (i.e., they have the lactase-persistence [LP] trait). It is thought that selection has played a major role in maintaining this genetically determined phenotypic trait in different human populations that practice pastoralism. To identify variants associated with the LP trait and to study its evolutionary history in Africa, we sequenced MCM6 introns 9 and 13 and ∼2 kb of the LCT promoter region in 819 individuals from 63 African populations and in 154 non-Africans from nine populations. We also genotyped four microsatellites in an ∼198 kb region in a subset of 252 individuals to reconstruct the origin and spread of LP-associated variants in Africa. Additionally, we examined the association between LP and genetic variability at candidate regulatory regions in 513 individuals from eastern Africa. Our analyses confirmed the association between the LP trait and three common variants in intron 13 (C-14010, G-13907, and G-13915). Furthermore, we identified two additional LP-associated SNPs in intron 13 and the promoter region (G-12962 and T-956, respectively). Using neutrality tests based on the allele frequency spectrum and long-range linkage disequilibrium, we detected strong signatures of recent positive selection in eastern African populations and the Fulani from central Africa. In addition, haplotype analysis supported an eastern African origin of the C-14010 LP-associated mutation in southern Africa. PMID:24630847

  12. Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations

    PubMed Central

    Hubácek, Jaroslav A.; Adámková, Věra; Šedová, Lenka; Olišarová, Věra; Adámek, Václav; Tóthová, Valérie

    2017-01-01

    Abstract Lactase non-persistence (leading to primary lactose intolerance) is a genetically dependent inability to digest lactose in adulthood. As part of the human adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates adult expression of lactase) developed, spread and participated in the adaptation to dairying. This variant is associated with lactase activity persistence, and its carriers are able to digest lactose. We compared the frequencies of lactase 13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma (N = 300), two ethnically different groups where this polymorphism has not yet been analysed. Allelic frequencies significantly differed between the populations (p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in 76% of the individuals, which is in agreement with frequencies among geographically neighbouring populations. In the Czech Gypsy/Roma population, only 27% of the adults were carriers of at least one lactase persistence allele, similar to the Indian population. In agreement with this result, dairy product consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs populations, the presence of carriers of the lactase persistence allele was similar in subjects self-reporting the consumption of unfermented/fresh milk, in comparison to the others. PMID:28497837

  13. Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations.

    PubMed

    Hubácek, Jaroslav A; Adámková, Věra; Šedová, Lenka; Olišarová, Věra; Adámek, Václav; Tóthová, Valérie

    2017-01-01

    Lactase non-persistence (leading to primary lactose intolerance) is a genetically dependent inability to digest lactose in adulthood. As part of the human adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates adult expression of lactase) developed, spread and participated in the adaptation to dairying. This variant is associated with lactase activity persistence, and its carriers are able to digest lactose. We compared the frequencies of lactase 13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma (N = 300), two ethnically different groups where this polymorphism has not yet been analysed. Allelic frequencies significantly differed between the populations (p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in 76% of the individuals, which is in agreement with frequencies among geographically neighbouring populations. In the Czech Gypsy/Roma population, only 27% of the adults were carriers of at least one lactase persistence allele, similar to the Indian population. In agreement with this result, dairy product consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs populations, the presence of carriers of the lactase persistence allele was similar in subjects self-reporting the consumption of unfermented/fresh milk, in comparison to the others.

  14. Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population

    PubMed Central

    Friedrich, Deise C.; Santos, Sidney E. B.; Ribeiro-dos-Santos, Ândrea K. C.; Hutz, Mara H.

    2012-01-01

    Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The −13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The −13779*C,−13910*T, −13937*A, −14010*C, −14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was −13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The −13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the −13910*T allele is an oversimplification. PMID:23029545

  15. Association of Lactase Persistence Genotypes with High Intake of Dairy Saturated Fat and High Prevalence of Lactase Non-Persistence among the Mexican Population.

    PubMed

    Ojeda-Granados, Claudia; Panduro, Arturo; Rebello Pinho, João Renato; Ramos-Lopez, Omar; Gleyzer, Ketti; Malta, Fernanda de Mello; Gonzalez-Aldaco, Karina; Roman, Sonia

    2016-01-01

    Lactase (LCT) -13910 C>T and -22018 G>A polymorphisms associated with the lactase non-persistence (LNP)/persistence (LP) phenotypes vary globally. LP has been associated with obesity in Europeans. However, it has not been genetically evaluated in Mexico, a country with admixed population, recent introduction of dairy, and a high prevalence of obesity. Thus, we aimed to determine the distribution of the LCT polymorphisms and their association with the nutritional profile of West Mexico's populations. Genotyping of 1,196 individuals (natives and mestizos) was carried out by a Taqman allelic discrimination assay. Descriptive statistics and interpopulation analyzes were performed by SPSS, Arlequin, and Structure software. Demographic, anthropometric, biochemical and dietary data were analyzed in 212 mestizos. LNP genotypes mainly prevailed (CC 68.7% and GG 68.2%); both predominated in native Huicholes and Nahuas (>97.7%). Among the mestizos, the LP genotypes were associated with a higher intake of saturated fat (9.9 ± 3.9% vs. 8.5 ± 4.0%, p = 0.018; OR = 2.55, 95% CI 1.29-5.03, p = 0.006) and a daily/more frequent consumption of dairy (88.8 vs. 78.0%; p = 0.049) than LNP genotypes. The LNP trait was predominant in Mexicans with a major Amerindian ancestry. A daily consumption of dairy was associated with a higher intake of saturated fat in LP individuals. © 2016 S. Karger AG, Basel.

  16. Functional Significance of Single Nucleotide Polymorphisms in the Lactase Gene in Diverse United States Subjects and Evidence for a Novel Lactase Persistence Allele at -13909 in Those of European Ancestry

    PubMed Central

    Baffour-Awuah, Nana Yaa; Fleet, Sarah; Baker, Susan S.; Butler, Johannah L.; Campbell, Catarina; Tischfield, Samuel; Mitchell, Paul D.; Moon, Jennifer E.; Allende-Richter, Sophie; Fishman, Laurie; Bousvaros, Athos; Fox, Victor; Kuokkanen, Mikko; Montgomery, Robert K.; Grand, Richard J.; Hirschhorn, Joel N.

    2014-01-01

    Objectives Recent data from mainly homogeneous European and African populations implicate a 140 bp region 5′ to the transcriptional start site of LCT (the lactase gene) as a regulatory site for lactase persistence and non-persistence. As there are no studies of United States non-homogeneous populations, we performed genotype/phenotype analysis of the -13910 and -22018 LCT SNPs in New England children, mostly of European ancestry. Methods Duodenal biopsies were processed for disaccharidase activities, RNA quantification by RT-PCR, allelic expression ratios by PCR, and genotyping and SNP analysis. Results were compared to clinical information. Results Lactase activity and mRNA levels, as well as sucrase-to-lactase ratios of enzyme activity and mRNA, showed robust correlations with genotype. None of the other LCT SNPs showed as strong a correlation with enzyme or mRNA activities as did -13910. Data were consistent with the -13910 being the causal sequence variant rather than -22018. Four individuals heterozygous for -13910T/C had allelic expression patterns similar to individuals with -13910C/C genotypes; of these, 2 showed equal LCT expression from the 2 alleles and a novel variant (-13909C>A) associated with lactase persistence. Conclusion The identification of -13910C/C genotype is very likely to predict lactase non-persistence, consistent with prior published studies. A -13910T/T genotype will frequently, but not perfectly, predict lactase persistence in this mixed European-ancestry population; a -13910T/C genotype will not predict the phenotype. A long, rare haplotype in 2 individuals with -13910T/C genotype but equal allele-specific expression contains a novel lactase persistence allele present at -13909. PMID:25625576

  17. Lactase Non-Persistence Genotyping: Comparison of Two Real-Time PCR Assays and Assessment of Concomitant Fructose/Sorbitol Malabsorption Rates.

    PubMed

    Enko, Dietmar; Pollheimer, Verena; Németh, Stefan; Pühringer, Helene; Stolba, Robert; Halwachs-Baumann, Gabriele; Kriegshäuser, Gernot

    2016-01-01

    Genetic testing is a standard technique for the diagnosis of primary adult-type hypolactasia, also referred to as lactase non-persistence. The aim of this study was to compare the lactase gene (LCT) C/T-13910 polymorphism genotyping results of two commercially available real-time (RT)-PCR assays in patients referred to our outpatient clinic for primary lactose malabsorption testing. Furthermore, concomitant conditions of fructose/sorbitol malabsorption were assessed. Samples obtained from 100 patients were tested in parallel using the LCT T-13910C ToolSet for Light Cycler (Roche, Rotkreuz, Switzerland) and the LCT-13910C>T RealFast Assay (ViennaLab Diagnostics GmbH, Vienna, Austria). Additionally, patients were also screened for the presence of fructose/sorbitol malabsorption by functional hydrogen (H2)/methane (CH4) breath testing (HMBT). Cohen's Kappa (κ) was used to calculate the agreement between the two genotyping methods. The exact Chi-Square test was performed to compare fructose/sorbitol HMBT with LCT genotyping results. Twenty-one (21.0%) patients had a LCT C/C-13910 genotype suggestive of lactase non-persistence, and 79 (79.0%) patients were identified with either a LCT T/C-13910 or T/T-13910 genotype (i.e., lactase persistence). In all genotype groups, concordance between the two RT-PCR assays was 100%. Cohen's κ demonstrated perfect observed agreement (p < 0.001, κ = 1). Fructose and sorbitol malabsorption was observed in 13/100 (13.0%) and 25/100 (25.0%) individuals, respectively. Both RT-PCR assays are robust and reliable LCT genotyping tools in a routine clinical setting. Concomitant fructose and/or sorbitol malabsorption should be considered in individuals with suspected lactase-non-persistence. However, standardization of clinical interpretation of laboratory HMBT results is required.

  18. The European lactase persistence genotype determines the lactase persistence state and correlates with gastrointestinal symptoms in the Hispanic and Amerindian Chilean population: a case–control and population-based study

    PubMed Central

    Morales, Eugenia; Azocar, Lorena; Maul, Ximena; Perez, Claudio; Chianale, José

    2011-01-01

    Background The lactase persistent (LP) or lactase non-persistent (LNP) state in European adults is genetically determined by a single nucleotide polymorphism (SNP) located 13.9 kb upstream of the lactase (LCT) gene, known as LCT C>T−13910 (rs4988235). The LNP condition leads to an inability to digest the milk sugar lactose leading to gastrointestinal symptoms and can affect nutrient and calcium intake in certain populations. Objectives The authors studied a group of 51 Chilean patients to assess whether this SNP influences the LP/LNP state in this population, and determined the prevalence of LCT C>T−13910 genotypes in a representative sample of 216 Hispanics and 43 Amerindians with correlation to digestive symptoms. Design Case–control study done in Chilean patients with clinical suspicion of LNP that were assessed using clinical survey, hydrogen breath test (HBT) and SNP genotyping. The population sample of Hispanics and Amerindians was assessed by clinical survey and SNP genotyping. Results Of the 51 patients with clinical suspicion of LNP, 29 were HBT-positive. The CC genotype (LNP) was present in 89.7% of the patients with positive HBT and in only 4.7% of those with negative HBT. The prevalence of the CC genotype was 56.9% in the Hispanic population and 88.3% in Amerindians, and was associated with a higher self-reported clinical intolerance to ingestion of dairy products. Conclusion The LP/LNP state is determined by the LCT C>T−13910 variant in Chileans. This variant predicts digestive symptoms associated with the ingestion of lactose and is a good tool for the diagnosis of primary adult hypolactasia. The LCT T−13910 allele is rare in the Amerindian population and is suggestive of European ancestry in this contemporary population. PMID:22021768

  19. Lactase persistence genotyping on whole blood by loop-mediated isothermal amplification and melting curve analysis.

    PubMed

    Abildgaard, Anders; Tovbjerg, Sara K; Giltay, Axel; Detemmerman, Liselot; Nissen, Peter H

    2018-03-26

    The lactase persistence phenotype is controlled by a regulatory enhancer region upstream of the Lactase (LCT) gene. In northern Europe, specifically the -13910C > T variant has been associated with lactase persistence whereas other persistence variants, e.g. -13907C > G and -13915 T > G, have been identified in Africa and the Middle East. The aim of the present study was to compare a previously developed high resolution melting assay (HRM) with a novel method based on loop-mediated isothermal amplification and melting curve analysis (LAMP-MC) with both whole blood and DNA as input material. To evaluate the LAMP-MC method, we used 100 whole blood samples and 93 DNA samples in a two tiered study. First, we studied the ability of the LAMP-MC method to produce specific melting curves for several variants of the LCT enhancer region. Next, we performed a blinded comparison between the LAMP-MC method and our existing HRM method with clinical samples of unknown genotype. The LAMP-MC method produced specific melting curves for the variants at position -13909, -13910, -13913 whereas the -13907C > G and -13915 T > G variants produced indistinguishable melting profiles. The LAMP-MC assay is a simple method for lactase persistence genotyping and compares well with our existing HRM method. Copyright © 2018. Published by Elsevier B.V.

  20. Lactase non-persistence and general patterns of dairy intake in indigenous and mestizo chilean populations.

    PubMed

    Fernández, Catalina I; Montalva, Nicolás; Arias, Macarena; Hevia, Macarena; Moraga, Mauricio L; Flores, Sergio V

    2016-01-01

    Lactase persistence (LP) is a genetic trait that has been studied among different countries and ethnic groups. In Latin America, the frequencies of this trait have been shown to vary according to the degree of admixture of the populations. The objective of this study is to better understand the relationship between this genetic trait and dairy intake in a multiethnic context through a synthesis of studies conducted in four regions of Chile. Genotypes frequencies for the SNP LCT-13910C>T (rs4988235) and frequency of dairy consumption were obtained from four populations: Polynesians from Easter Island (Rapanui); Amerindians (Mapuche) and Mestizos from the Araucanía region; urban Mestizos from Santiago; and rural Mestizos from the Coquimbo region. Genetic differentiation and association between milk consumption and genotype frequencies were estimated. Genetic differentiation between Native and Mestizo populations was significant; the LP frequency in Mapuche and Rapanui was 10% and 25%, respectively, whereas among the Mestizos, LP frequency was near 40%. Dairy intake was below the nutritional recommendations for the four groups, and extremely below recommendations among the indigenous populations. Association between milk intake and LP was found in Santiago and Rapanui populations. Although the frequency of LP varies among the populations according to their degree of admixture, dairy consumption was very low across the populations. Given that the association between milk consumption and expected phenotype was found only in two of the populations analyzed, it seems that lactase non-persistence (LNP) is not the only cause for dairy avoidance. Thus, it is suggested that SES and cultural preferences are likely affecting dairy consumption. © 2015 Wiley Periodicals, Inc.

  1. RFLP Analysis and Allelic Discrimination with Real-Time PCR Using the Human Lactase Persistence Trait: A Pair of Molecular Genetic Investigations

    ERIC Educational Resources Information Center

    Weinlander, Kenneth M.; Hall, David J.; De Stasio, Elizabeth A.

    2010-01-01

    We describe here two open-ended laboratory investigations for an undergraduate laboratory course that uses students' DNA as templates for quantitative real-time PCR and for traditional PCR followed by RFLP analysis. Students are captivated by the immediacy of the application and the relevance of the genotypes and traits, lactase persistence or…

  2. Frequency of LCT -13910C>T single nucleotide polymorphism associated with adult-type hypolactasia/lactase persistence among Brazilians of different ethnic groups.

    PubMed

    Mattar, Rejane; Monteiro, Maria S; Villares, Cibele A; Santos, Aníbal F; Silva, Joyce M K; Carrilho, Flair J

    2009-10-02

    Adult-type hypolactasia, the physiological decline of lactase some time after weaning, was previously associated with the LCT -13910C>T polymorphism worldwide except in Africa. Lactase non-persistence is the most common phenotype in humans, except in northwestern Europe with its long history of pastoralism and milking. We had previously shown association of LCT -13910C>T polymorphism with adult-type hypolactasia in Brazilians; thus, we assessed its frequency among different Brazilian ethnic groups. We investigated the ethnicity-related frequency of this polymorphism in 567 Brazilians [mean age, 42.1 +/- 16.8 years; 157 (27.7%) men]; 399 (70.4%) White, 50 (8.8%) Black, 65 (11.5%) Brown, and 53 (9.3%) Japanese-Brazilian. DNA was extracted from leukocytes; LCT -13910C>T polymorphism was analyzed by PCR-restriction fragment length polymorphism. Prevalence of the CC genotype associated with hypolactasia was similar (57%) among White and Brown groups; however, prevalence was higher among Blacks (80%) and those of Japanese descent (100%). Only 2 (4%) Blacks had TT genotype, and 8 (16%) had the CT genotype. Assuming an association between CC genotype and hypolactasia, and CT and TT genotypes with lactase persistence, 356 (62.8%) individuals had hypolactasia and 211 (37.2%) had lactase persistence. The White and Brown groups had the same hypolactasia prevalence (approximately 57%); nevertheless, was 80% among Black individuals and 100% among Japanese-Brazilians (P < 0.01). The lactase persistence allele, LCT -13910T, was found in about 43% of both White and Brown and 20% of the Black Brazilians, but was absent among all Japanese Brazilians studied.

  3. Body fat and dairy product intake in lactase persistent and non-persistent children and adolescents.

    PubMed

    Almon, Ricardo; Patterson, Emma; Nilsson, Torbjörn K; Engfeldt, Peter; Sjöström, Michael

    2010-06-16

    Lactase non-persistent (LNP) individuals may be lactose intolerant and therefore on a more restricted diet concerning milk and milk products compared to lactase persistent (LP) individuals. This may have an impact on body fat mass. This study examines if LP and LNP children and adolescents, defined by genotyping for the LCT-13910 C > T polymorphism, differ from each other with regard to milk and milk product intake, and measures of body fat mass. Children (n=298, mean age 9.6 years) and adolescents (n=386, mean age 15.6 years), belonging to the Swedish part of the European Youth Heart Study, were genotyped for the LCT-13910 C > T polymorphism. Dietary intakes of reduced and full-fat dairy varieties were determined. LNP (CC genotype) subjects consumed less milk, soured milk and yoghurt compared to LP (CT/TT genotype) subjects (p<0.001). Subsequent partitioning for age group attenuated this observation (p=0.002 for children and p=0.023 in adolescents). Six subjects were reported by parents to be 'lactose intolerant', none of whom were LNP. LNP children and adolescents consumed significantly less reduced fat milk and milk products than LP children and adolescents (p=0.009 for children and p=0.001 for adolescents). We conclude that LP is linked to an overall higher milk and dairy intake, but is not linked to higher body fat mass in children and adolescents.

  4. Lactase persistence and dairy intake in Mapuche and Mestizo populations from southern Chile.

    PubMed

    Fernández, Catalina I; Flores, Sergio V

    2014-11-01

    Lactase persistence (LP) occurs at a very low frequency in indigenous populations from Latin America, offering an opportunity to understand the relationship between this genetic trait and patterns of dairy consumption. Here, the frequency of LP is analyzed from Mapuche and -an adjacent- mestizo population inhabiting the Araucanía region. In addition to genotyping for LP, participants were surveyed in relation to general perception and consumption habits of dairy products. Low LP frequency (10%) and very low dairy intake was found among the Mapuche population as compared with Mestizo populations inhabiting Chile. The survey reported that the main reasons for avoidance of dairy were the gastrointestinal symptoms after dairy intake and cultural dietary habits. The interaction between low LP genotype frequency, low dairy intake, and sociocultural determinants is here discussed in the light of their potential health outcomes. © 2014 Wiley Periodicals, Inc.

  5. Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases.

    PubMed

    Szilagyi, Andrew

    2015-08-13

    Dairy foods contain complex nutrients which interact with the host. Yet, evolution of lactase persistence has divided the human species into those that can or cannot digest lactose in adulthood. Such a ubiquitous trait has differential effects on humanity. The literature is reviewed to explore how the divide affects lactose handling by lactase non persistent persons. There are two basic differences in digesters. Firstly, maldigesters consume less dairy foods, and secondly, excess lactose is digested by colonic microflora. Lactose intolerance in maldigesters may occur with random lactose ingestion. However, lactose intolerance without maldigestion tends to detract from gaining a clear understanding of the mechanisms of symptoms formation and leads to confusion with regards to dairy food consumption. The main consequence of intolerance is withholding dairy foods. However, regular dairy food consumption by lactase non persistent people could lead to colonic adaptation by the microbiome. This process may mimic a prebiotic effect and allows lactase non persistent people to consume more dairy foods enhancing a favorable microbiome. This process then could lead to alterations in outcome of diseases in response to dairy foods in lactose maldigesters. The evidence that lactose is a selective human prebiotic is reviewed and current links between dairy foods and some diseases are discussed within this context. Colonic adaptation has not been adequately studied, especially with modern microbiological techniques.

  6. Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases

    PubMed Central

    Szilagyi, Andrew

    2015-01-01

    Dairy foods contain complex nutrients which interact with the host. Yet, evolution of lactase persistence has divided the human species into those that can or cannot digest lactose in adulthood. Such a ubiquitous trait has differential effects on humanity. The literature is reviewed to explore how the divide affects lactose handling by lactase non persistent persons. There are two basic differences in digesters. Firstly, maldigesters consume less dairy foods, and secondly, excess lactose is digested by colonic microflora. Lactose intolerance in maldigesters may occur with random lactose ingestion. However, lactose intolerance without maldigestion tends to detract from gaining a clear understanding of the mechanisms of symptoms formation and leads to confusion with regards to dairy food consumption. The main consequence of intolerance is withholding dairy foods. However, regular dairy food consumption by lactase non persistent people could lead to colonic adaptation by the microbiome. This process may mimic a prebiotic effect and allows lactase non persistent people to consume more dairy foods enhancing a favorable microbiome. This process then could lead to alterations in outcome of diseases in response to dairy foods in lactose maldigesters. The evidence that lactose is a selective human prebiotic is reviewed and current links between dairy foods and some diseases are discussed within this context. Colonic adaptation has not been adequately studied, especially with modern microbiological techniques. PMID:26287234

  7. World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection.

    PubMed

    Liebert, Anke; López, Saioa; Jones, Bryony Leigh; Montalva, Nicolas; Gerbault, Pascale; Lau, Winston; Thomas, Mark G; Bradman, Neil; Maniatis, Nikolas; Swallow, Dallas M

    2017-11-01

    The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [-13910*T (rs4988235), -13907*G (rs41525747), -13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.

  8. The Frequency of the LCT*-13910C>T Polymorphism Associated with Lactase Persistence Diverges among Euro-Descendant Groups from Brazil.

    PubMed

    Boschmann, Stefanie Epp; Boldt, Angelica Beate; de Souza, Ilíada Rainha; Petzl-Erler, Maria Luiza; Messias-Reason, Iara Jose

    2016-01-01

    The aim of this study was to investigate the frequency of the LCT*-13910C>T polymorphism associated with a high expression of lactase in the small intestine during adulthood, and to infer the lactase persistence and adult-type hypolactasia phenotypes among Euro-Brazilians and Mennonites from South Brazil. A sequence-specific PCR method to genotype the LCT*-13910C>T polymorphism in 292 Euro-Brazilians and 151 Mennonites (a group with European ancestry and a long history of endogamy) was developed. Using an exact test of population differentiation, the genotype and allele frequency between these and other Brazilian populations were compared. The frequency of -13910*T was significantly higher among the Mennonites when compared to the Euro-Brazilian cohort (0.63 vs. 0.33, p < 0.000001). Accordingly, Mennonites had a higher prevalence of the lactase persistence genotype (88.1 vs. 55.5%, p < 0.000001). The distribution of -13910*T differed between Mennonites and all other Brazilian groups (p < 0.0001). The Euro-Brazilians from Curitiba displayed differences when compared to all other Brazilian groups (p < 0.0001), even to Euro-Brazilians from a different geographic region (p = 0.0003), but were similar to those from Porto Alegre (p = 0.2). Differences in the -13910*T-associated lactase persistence distribution among Euro-Brazilian groups reflect the ancestry and admixture of each particular group and should be considered for adult-type hypolactasia screening. © 2015 S. Karger AG, Basel.

  9. Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

    PubMed Central

    Mądry, Edyta; Fidler, Ewa; Sobczyńska-Tomaszewska, Agnieszka; Lisowska, Aleksandra; Krzyżanowska, Patrycja; Pogorzelski, Andrzej; Minarowski, Łukasz; Oralewska, Beata; Mojs, Ewa; Sapiejka, Ewa; Marciniak, Ryszard; Sands, Dorota; Korzon-Burakowska, Anna; Kwiecień, Jarosław; Walkowiak, Jarosław

    2011-01-01

    Taking into account the reported incidence of hypolactasia in cystic fibrosis (CF) and the possible impact of milk products on nutritional status we aimed to assess the genetic predisposition to adult-type hypolactasia (ATH) and its incidence in CF. Single nucleotide polymorphism upstream of the lactase gene (LCT) was assessed in 289 CF patients. In subject with −13910C/C genotype (C/C) predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted and clinical symptoms typical for lactose malabsorption were assessed. The percentage of CF patients with C/C was similar to that observed in healthy subjects (HS) (31.5 vs 32.5% ). Eleven out of 52 (24.5%) CF C/C patients had abnormal BT results. The recalculated frequency of lactose malabsorption was similar for the entire CF and HS populations (6.9 vs 7.2%). Similarly as in the control group, few CF patients have identified and linked to lactose consumption clinical symptoms. The frequency of LCT polymorphic variants in CF patients having and not having severe mutations of CFTR gene showed significant differences. The C allele was more frequent in homozygotes of the severe mutations than in patients carrying at least one mild/unknown mutation (P<0.0028) and in patients with at least one mild mutation (P<0.0377). In conclusion, CF patients carrying mild CFTR mutations seem to have lower genetic predisposition to ATH. Lactose malabsorption due to ATH in CF is not more frequent than in the general population. Symptomatic assessment of lactose malabsorption in CF is not reliable. PMID:21407263

  10. Comparison of Quick Lactose Intolerance Test in duodenal biopsies of dyspeptic patients with single nucleotide polymorphism LCT-13910C>T associated with primary hypolactasia/lactase-persistence.

    PubMed

    Mattar, Rejane; Basile-Filho, Anibal; Kemp, Rafael; Santos, José Sebastião dos

    2013-01-01

    To analyze the usefulness of Quick Lactose Intolerance Test in relation to the genetic test based on LCT-13910C>T genotypes, previously validated for clinical practice, for primary hypolactasia/lactase-persistence diagnosis. Thirty-two dyspeptic patients that underwent upper gastrointestinal endoscopy entered the study. Two postbulbar duodenal biopsies were taken for the Quick test, and gastric antral biopsy for DNA extraction and LCT-13910C>T polymorphism analysis. DNA was also extracted from biopsies after being used in the Quick Test that was kept frozen until extraction. Nine patients with lactase-persistence genotype (LCT-13910CT or LCT-13910TT) had normolactasia, eleven patients with hypolactasia genotype (LCT-13910CC) had severe hypolactasia, and among twelve with mild hypolactasia, except for one that had LCT-13910CT genotype, all the others had hypolactasia genotype. The agreement between genetic test and quick test was high (p<0.0001; Kappa Index 0.92). Most of the patients that reported symptoms with lactose-containing food ingestion had severe hypolactasia (p<0.05). Amplification with good quality PCR product was also obtained with DNA extracted from biopsies previously used in the Quick Test; thus, for the future studies antral gastric biopsies for genetic test would be unnecessary. Quick test is highly sensitive and specific for hypolactasia diagnosis and indicated those patients with symptoms of lactose intolerance.

  11. Positive selection of lactase persistence among people of Southern Arabia.

    PubMed

    Bayoumi, Riad; De Fanti, Sara; Sazzini, Marco; Giuliani, Cristina; Quagliariello, Andrea; Bortolini, Eugenio; Boattini, Alessio; Al-Habori, Molham; Al-Zubairi, Adel Sharaf; Rose, Jeffrey I; Romeo, Giovanni; Al-Abri, Abdulrahim; Luiselli, Donata

    2016-12-01

    Frequency patterns of the lactase persistence (LP)-associated -13,915 G allele and archaeological records pointing to substantial role played by southern regions in the peopling and domestication processes that involved the Arabian Peninsula suggest that Southern Arabia plausibly represented the center of diffusion of such adaptive variant. Nevertheless, a well-defined scenario for evolution of Arabian LP is still to be elucidated and the burgeoning archaeological picture of complex human migrations occurred through the peninsula is not matched by an equivalent high-resolution description of genetic variation underlying this adaptive trait. To fill this gap, we investigated diversity at a wide genomic interval surrounding the LCT gene in different Southern Arabian populations. 40 SNPs were genotyped to characterize LCT profiles of 630 Omani and Yemeni individuals to perform population structure, linkage disequilibrium, population differentiation-based and haplotype-based analyses. Typical Arabian LP-related variation was found in Dhofaris and Yemenis, being characterized by private haplotypes carrying the -13,915 G allele, unusual differentiation with respect to northern groups and conserved homozygous haplotype-blocks, suggesting that the adaptive allele was likely introduced in the Arabian gene pool in southern populations and was then subjected to prolonged selective pressure. By pointing to Yemen as one of the best candidate centers of diffusion of the Arabian-specific adaptive variant, obtained results indicate the spread of indigenous groups as the main process underlying dispersal of LP along the Arabian Peninsula, supporting a refugia model for Arabian demic movements occurred during the Terminal Pleistocene and Early Holocene. © 2016 Wiley Periodicals, Inc.

  12. Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

    PubMed Central

    Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

    2014-01-01

    A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system. PMID:25184300

  13. Lactase persistence and augmented salivary alpha-amylase gene copy numbers might have been selected by the combined toxic effects of gluten and (food born) pathogens.

    PubMed

    Pruimboom, Leo; Fox, Tom; Muskiet, Frits A J

    2014-03-01

    Various positively selected adaptations to new nutrients have been identified. Lactase persistence is among the best known, conferring the ability for drinking milk at post weaning age. An augmented number of amylase gene (AMY1) copies, giving rise to higher salivary amylase activity, has been implicated in the consumption of starch-rich foods. Higher AMY1 copy numbers have been demonstrated in populations with recent histories of starchy-rich diets. It is however questionable whether the resulting polymorphisms have exerted positive selection only by providing easily available sources of macro and micronutrients. Humans have explored new environments more than any other animal. Novel environments challenge the host, but especially its immune system with new climatic conditions, food and especially pathogens. With the advent of the agricultural revolution and the concurrent domestication of cattle came new pathogens. We contend that specific new food ingredients (e.g., gluten) and novel pathogens drove selection for lactase persistence and higher AMY gene copy numbers. Both adaptations provide ample glucose for activating the sodium glucose-dependent co-transporter 1 (SGLT1), which is the principal glucose, sodium and water transporter in the gastro-intestinal tract. Their rapid uptake confers protection against potentially lethal dehydration, hyponatremia and ultimately multiple organ failure. Oral rehydration therapy aims at SGLT1 activity and is the current treatment of choice for chronic diarrhoea and vomiting. We hypothesize that lifelong lactase activity and rapid starch digestion should be looked at as the evolutionary covalent of oral rehydration therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Analysis of a SNP linked to lactase persistence: An exercise for teaching molecular biology techniques to undergraduates.

    PubMed

    Schultheis, Patrick J; Bowling, Bethany V

    2011-01-01

    Recent experimental evidence indicates that the ability of adults to tolerate milk, cheese, and other lactose-containing dairy products is an autosomal dominant trait that co-evolved with dairy farming in Central Europe about 7,500 years ago. Among persons of European descent, this trait is strongly associated with a C to T substitution at a polymorphic site 13,910 bp upstream of the lactase gene. This mutation results in the persistent expression of lactase into adulthood enabling individuals carrying a T(-13,910) allele to digest lactose as adults. In this report, we describe a laboratory exercise for an undergraduate molecular biology course in which students determine their own genotype at the -13,910 polymorphic site and correlate this with their ability to tolerate dairy products. The exercise is used as a tool to teach basic molecular biology procedures such as agarose gel electrophoresis, PCR1, and DNA sequencing. Students are actively engaged in the learning process, not only by analyzing their own DNA but also by applying their knowledge and skills to answer an authentic question. The exercise is also integrated with lecture material on the control of gene expression at the transcriptional level, in particular, how transcription factors can influence the activity of a promoter by binding to cis-acting DNA regulatory elements located within the proximal promoter of a gene or distant enhancer regions. Copyright © 2010 Wiley Periodicals, Inc.

  15. Lactase persistence variants in Arabia and in the African Arabs.

    PubMed

    Priehodová, Edita; Abdelsawy, Abdelhay; Heyer, Evelyne; Cerný, Viktor

    2014-01-01

    Lactase persistence (LP), the state enabling the digestion of milk sugar in adulthood, occurs only in some human populations. The convergent and independent origin of this physiological ability in Europe and Africa is linked with animal domestication that either had started in both places independently or had spread from the Near East by acculturation. However, it has recently been shown that at least in its southern parts, the population of Arabia not only has a different LP-associated mutation profile than the rest of Africa and Europe but also had experienced an independent demographic expansion occurring before the Neolithic around the Pleistocene-Holocene boundary. In Arabia, LP is associated with mutation -13,915*G and not, as in Europe, with -13,910*T or, as in Africa, with -13,907*G and -14,010*C. We show here that, in Arabia, -13,915*G frequency conforms to a partial clinal pattern and that this specific mutation has likely been spread from Arabia to Africa only recently from the sixth century AD onward by nomadic Arabs (Bedouins) looking for new pastures. Arabic populations in Africa that still maintain a nomadic way of life also have more -13,915*G variants and fewer sub-Saharan L-type mitochondrial DNA haplogroups; this observation matches archaeological and historical records suggesting that the migration of Arabic pastoralists was accompanied by gradual sedentarization that allowed for admixture with the local African population. Copyright © 2014 Wayne State University Press, Detroit, Michigan 48201-1309.

  16. New insights into the history of the C-14010 lactase persistence variant in Eastern and Southern Africa.

    PubMed

    Macholdt, Enrico; Slatkin, Montgomery; Pakendorf, Brigitte; Stoneking, Mark

    2015-04-01

    Lactase persistence (LP), the ability to digest lactose into adulthood, is strongly associated with the cultural traits of pastoralism and milk-drinking among human populations, and several different genetic variants are known that confer LP. Recent studies of LP variants in Southern African populations, with a focus on Khoisan-speaking groups, found high frequencies of an LP variant (the C-14010 allele) that also occurs in Eastern Africa, and concluded that the C-14010 allele was brought to Southern Africa via a migration of pastoralists from Eastern Africa. However, this conclusion was based on indirect evidence; to date no study has jointly analyzed data on the C-14010 allele from both Southern African Khoisan-speaking groups and Eastern Africa. Here, we combine and analyze published data on the C-14010 allele in Southern and Eastern African populations, consisting of haplotypes with the C-14010 allele and four closely-linked short tandem repeat loci. Our results provide direct evidence for the previously-hypothesized Eastern African origin of the C-14010 allele in Southern African Khoisan-speaking groups. In addition, we find evidence for a separate introduction of the C-14010 allele into the Bantu-speaking Xhosa. The estimated selection intensity on the C-14010 allele in Eastern Africa is lower than that in Southern Africa, which suggests that in Eastern Africa the dietary changes conferring the fitness advantage associated with LP occurred some time after the origin of the C-14010 allele. Conversely, in Southern Africa the fitness advantage was present when the allele was introduced, as would be expected if pastoralism was introduced concomitantly. © 2014 Wiley Periodicals, Inc.

  17. Geographic associations between lactase phenotype, multiple sclerosis, and inflammatory bowel diseases; Does obesity trump geography?

    PubMed

    Szilagyi, Andew; Xue, Xiaoqing

    2016-11-01

    Geographic patterns with diminishing rates from north to south toward the equator have been described for a number of diseases, putatively related largely to "western" lifestyle. Among these the inflammatory bowel diseases; Crohn's (CD) and Ulcerative colitis (UC) have been prominent in sharing distributions with a number of autoimmune diseases. One of the interesting associations is the epidemiologic similarity with multiple sclerosis (MS). However, in addition, at least some of these diseases also correlated inversely with lactase non persistent population (LNP) distributions. It is hypothesized that MS should also have an inverse relationship with LNP. We provide support for this by comparing published MS, CD, UC and LNP national rates to the beginning of the new millennium. Possible links among these diseases may be an evolutionary signature of new genes which may have accompanied emergence of lactase persistence millennia ago. The emergent phenotypic dichotomy also forced different assimilation responses to lactose digestion. While intestinal retention of lactase results in direct host enzymatic digestion, in LNP persons intestinal bacterial metabolism of lactose impacts on the host micro-flora. These microbial changes may play some role in altering rates of diseases including IBD and MS. However, since the late 20th century previously observed patterns are changing. Although industrialization is considered to play an important modifying role, the rising rates of obesity with an emphasis on diet, and microfloral pathogenesis, but with an independent geographic pattern may also facilitate altering rates and geographic distributions of both of these and other diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Alginate Beads Containing Lactase: Stability and Microstructure.

    PubMed

    Traffano-Schiffo, Maria Victoria; Aguirre Calvo, Tatiana R; Castro-Giraldez, Marta; Fito, Pedro J; Santagapita, Patricio R

    2017-06-12

    β-Galactosidase (lactase) is a widely used enzyme in the food industry; however, it has low stability against thermal and mechanical treatments. Due to this, the purpose of the present research was to analyze the encapsulation of lactase in alginate-Ca(II) beads in order to maintain its enzymatic activity toward freezing, freezing/thawing, and storage. Also, the effect of the addition of trehalose, and arabic and guar gums and their influence on the microstructure as well as on thermal properties and molecular mobility were studied. Lactase was successfully encapsulated in alginate-Ca(II) beads, and the inclusion of trehalose was critical for activity preservation toward treatments, being improved in guar gum-containing systems. The gums increased the T m ' values, which represents a valuable technological improvement. Finally, the presence of secondary excipients affected the microstructure, showing rods with smaller outer diameter and with lower compactness than alginate-Ca(II) beads. Also, bead composition greatly affects the size, shape, and relaxation times.

  19. 21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Lactase enzyme preparation from Candida... Specific Substances Affirmed as GRAS § 184.1387 Lactase enzyme preparation from Candida pseudotropicalis. (a) This enzyme preparation is derived from the nonpathogenic, nontoxicogenic yeast C...

  20. Immobilization of Lactase onto Various Polymer Nanofibers for Enzyme Stabilization and Recycling.

    PubMed

    Jin, Lihua; Li, Ye; Ren, Xiang-Hao; Lee, Jung-Heon

    2015-08-01

    Five different polymer nanofibers, namely, polyaniline nanofiber (PANI), magnetically separable polyaniline nanofiber (PAMP), magnetically separable DEAE cellulose fiber (DEAE), magnetically separable CM cellulose fiber (CM), and polystyrene nanofiber (PSNF), have been used for the immobilization of lactase (E.C. 3.2.1.23). Except for CM and PSNF, three polymers showed great properties. The catalytic activities (kcat) of the free, PANI, PAMP, and magnetic DEAE-cellulose were determined to be 4.0, 2.05, 0.59, and 0.042 mM/min·mg protein, respectively. The lactase immobilized on DEAE, PANI, and PAMP showed improved stability and recyclability. PANI- and PAMP-lactase showed only a 0-3% decrease in activity after 3 months of vigorous shaking conditions (200 rpm) and at room temperature (25°C). PANI-, PAMP-, and DEAE-lactase showed a high percentage of conversion (100%, 47%, and 12%) after a 1 h lactose hydrolysis reaction. The residual activities of PANI-, PAMP-, and DEAE-lactase after 10 times of recycling were 98%, 96%, and 97%, respectively.

  1. Layer by layer assembly of a biocatalytic packaging film: lactase covalently bound to low-density polyethylene.

    PubMed

    Wong, Dana E; Talbert, Joey N; Goddard, Julie M

    2013-06-01

    Active packaging is utilized to overcome limitations of traditional processing to enhance the health, safety, economics, and shelf life of foods. Active packaging employs active components to interact with food constituents to give a desired effect. Herein we describe the development of an active package in which lactase is covalently attached to low-density polyethylene (LDPE) for in-package production of lactose-free dairy products. The specific goal of this work is to increase the total protein content loading onto LDPE using layer by layer (LbL) deposition, alternating polyethylenimine, glutaraldehyde (GL), and lactase, to enhance the overall activity of covalently attached lactase. The films were successfully oxidized via ultraviolet light, functionalized with polyethylenimine and glutaraldehyde, and layered with immobilized purified lactase. The total protein content increased with each additional layer of conjugated lactase, the 5-layer sample reaching up to 1.3 μg/cm2 . However, the increase in total protein did not lend to an increase in overall lactase activity. Calculated apparent Km indicated the affinity of immobilized lactase to substrate remains unchanged when compared to free lactase. Calculated apparent turnover numbers (kcat ) showed with each layer of attached lactase, a decrease in substrate turnover was experienced when compared to free lactase; with a decrease from 128.43 to 4.76 s(-1) for a 5-layer conjugation. Our results indicate that while LbL attachment of lactase to LDPE successfully increases total protein mass of the bulk material, the adverse impact in enzyme efficiency may limit the application of LbL immobilization chemistry for bioactive packaging use. © 2013 Institute of Food Technologists®

  2. Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD).

    PubMed

    Torniainen, Suvi; Freddara, Roberta; Routi, Taina; Gijsbers, Carolien; Catassi, Carlo; Höglund, Pia; Savilahti, Erkki; Järvelä, Irma

    2009-01-22

    Congenital lactase deficiency (CLD) is a severe gastrointestinal disorder of newborns. The diagnosis is challenging and based on clinical symptoms and low lactase activity in intestinal biopsy specimens. The disease is enriched in Finland but is also present in other parts of the world. Mutations encoding the lactase (LCT) gene have recently been shown to underlie CLD. The purpose of this study was to identify new mutations underlying CLD in patients with different ethnic origins, and to increase awareness of this disease so that the patients could be sought out and treated correctly. Disaccharidase activities in intestinal biopsy specimens were assayed and the coding region of LCT was sequenced from five patients from Europe with clinical features compatible with CLD. In the analysis and prediction of mutations the following programs: ClustalW, Blosum62, PolyPhen, SIFT and Panther PSEC were used. Four novel mutations in the LCT gene were identified. A single nucleotide substitution leading to an amino acid change S688P in exon 7 and E1612X in exon 12 were present in a patient of Italian origin. Five base deletion V565fsX567 leading to a stop codon in exon 6 was found in one and a substitution R1587H in exon 12 from another Finnish patient. Both Finnish patients were heterozygous for the Finnish founder mutation Y1390X. The previously reported mutation G1363S was found in a homozygous state in two siblings of Turkish origin. This is the first report of CLD mutations in patients living outside Finland. It seems that disease is more common than previously thought. All mutations in the LCT gene lead to a similar phenotype despite the location and/or type of mutation.

  3. Lactose intolerance: a non-allergic disorder often managed by allergologists.

    PubMed

    Perino, A; Cabras, S; Obinu, D; Cavalli Sforza, L

    2009-02-01

    Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world's population, while secondary bypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen may cause gastrointestinal symptoms. This condition is known as lactose intolerance. Lactase non-persistence is the ancestral state, whilst two single nucleotide polymorphisms in the lactase gene have been associated with lactase persistence. These are C/T 13910 and G/A 22018 substitutions. Lactase persistence, this Mendelian dominant trait, only became advantageous after the invention of agriculture, when milk from domesticated animals became available for adults to drink. Lactase persistence is then strongly correlated with the diary history of the population. Diagnosis is assessed clinically by elimination of dietary lactose or, better, by non-invasive tests including hydrogen breath test and genetic test. In patients with lactase non-persistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenous beta-galactosidase, yogurt and probiotics for their bacterial lactase activity, strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation.

  4. Milk intake is not associated with low risk of diabetes or overweight-obesity: a Mendelian randomization study in 97,811 Danish individuals.

    PubMed

    Bergholdt, Helle K M; Nordestgaard, Børge G; Ellervik, Christina

    2015-08-01

    High dairy/milk intake has been associated with a low risk of type 2 diabetes observationally, but whether this represents a causal association is unknown. We tested the hypothesis that high milk intake is associated with a low risk of type 2 diabetes and of overweight-obesity, observationally and genetically. In 97,811 individuals from the Danish general population, we examined the risk of incident type 2 diabetes and of overweight-obesity by milk intake observationally and by LCT-13910 C/T genotype [polymorphism (rs4988235) upstream from the lactase (LCT) gene], where TT and TC genotypes are associated with lactase persistence and CC with nonpersistence. Observationally for any compared with no milk intake, the HR for type 2 diabetes was 1.10 (95% CI: 0.98, 1.24; P = 0.11), whereas the OR for overweight-obesity was 1.06 (1.02, 1.09; P = 0.002). Median milk intake was 5 glasses/wk (IQR: 0-10) for lactase TT/TC persistence and 3 (0-7) for CC nonpersistence. Genetically for lactase TT/TC persistence compared with CC nonpersistence, the OR was 0.96 (0.86, 1.08; P = 0.50) for type 2 diabetes and 1.06 (1.00, 1.12; P = 0.04) for overweight-obesity. In a stratified analysis for type 2 diabetes, corresponding values in those with and without milk intake were 0.88 (0.76, 1.03; P = 0.11) and 1.35 (1.07, 1.70; P = 0.01) (P-interaction: 0.002), whereas no gene-milk interaction on overweight-obesity was found. For a 1-glass/wk higher milk intake, the genetic risk ratio for type 2 diabetes was 0.99 (0.93, 1.06), and the corresponding observational risk was 1.01 (1.00, 1.01). For overweight-obesity, the corresponding values were 1.01 (1.00, 1.02) genetically and 1.00 (1.00, 1.01) observationally. High milk intake is not associated with a low risk of type 2 diabetes or overweight-obesity, observationally or genetically via lactase persistence. The higher risk of type 2 diabetes in lactase-persistent individuals without milk intake likely is explained by collider stratification

  5. Ontogeny of intestinal safety factors: lactase capacities and lactose loads.

    PubMed

    O'Connor, T P; Diamond, J

    1999-03-01

    We measured intestinal safety factors (ratio of a physiological capacity to the load on it) for lactose digestion in developing rat pups. Specifically, we assessed the quantitative relationships between lactose load and the series capacities of lactase and the Na+-glucose cotransporter (SGLT-1). Both capacities increased significantly with age in suckling pups as a result of increasing intestinal mass and maintenance of mass-specific activities. The youngest pups examined (5 days) had surprisingly high safety factors of 8-13 for both lactase and SGLT-1, possibly because milk contains lactase substrates other than lactose; it also, however, suggests that their intestinal capacities were being prepared to meet future demands rather than just current ones. By day 10 (and also at day 15), increased lactose loads resulted in lower safety factors of 4-6, values more typical of adult intestines. The safety factor of SGLT-1 in day 30 (weanling) and day 100 (adult) rats was only approximately 1.0. This was initially unexpected, because most adult intestines maintain a modest reserve capacity beyond nutrient load values, but postweaning rats appear to use hindgut fermentation, assessed by gut morphology and hydrogen production assays, as a built-in reserve capacity. The series capacities of lactase and SGLT-1 varied in concert with each other over ontogeny and as lactose load was manipulated by experimental variation in litter size.

  6. Transformation of halogen-, alkyl-, and alkoxy-substituted anilines by a lactase of Trametes versicolor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoff, T.; Liu, S.Y.; Bollag, J.M.

    1985-05-01

    The lactase of the fungus Trametes versicolor was able to polymerize various halogen-, alkyl-, and alkoxy-substituted anilines, showing substrate specificity similar to that of horseradish peroxidase, whereas the lactase of Rhizoctonia praticola was active only with p-methoxyaniline. The substrate specificities of the enzymes were determined by using gas chromatography to measure the decrease in substrate concentration during incubation. With p-chloroaniline as the substrate, the peroxidase and the Trametes lactase showed maximum activity near pH 4.2. The transformation of this substrate gave rise to a number of oligomers, ranging from dimers to pentamers, as determined by mass spectrometry. The product profilesmore » obtained by high-pressure liquid chromatography were similar for the two enzymes. A chemical reaction was observed between p-chloroaniline and an enzymatically formed dimer, resulting in the formation of a trimer. All three enzymes oxidized p-methoxyaniline to 2-amino-5-p-anisidinobenzoquinone di-p-methoxyphenylimine, but only the T. versicolor lactase and the peroxidase caused the formation of a pentamer (2,5-di-p-anisidinobenzoquinone di-p-methoxyphenylimine). These results demonstrate that in addition to horseradish peroxidase, a T. versicolor lactase can also polymerize aniline derivatives.« less

  7. Gene–Dairy Food Interactions and Health Outcomes: A Review of Nutrigenetic Studies

    PubMed Central

    Pasin, Gonca

    2017-01-01

    Each person differs from the next by an average of over 3 million genetic variations in their DNA. This genetic diversity is responsible for many of the interindividual differences in food preferences, nutritional needs, and dietary responses between humans. The field of nutrigenetics aims to utilize this type of genetic information in order to personalize diets for optimal health. One of the most well-studied genetic variants affecting human dietary patterns and health is the lactase persistence mutation, which enables an individual to digest milk sugar into adulthood. Lactase persistence is one of the most influential Mendelian factors affecting human dietary patterns to occur since the beginning of the Neolithic Revolution. However, the lactase persistence mutation is only one of many mutations that can influence the relationship between dairy intake and disease risk. The purpose of this review is to summarize the available nutrigenetic literature investigating the relationships between genetics, dairy intake, and health outcomes. Nonetheless, the understanding of an individual’s nutrigenetic responses is just one component of personalized nutrition. In addition to nutrigenetic responses, future studies should also take into account nutrigenomic responses (epigenomic, transcriptomic, proteomic, metabolomic), and phenotypic/characteristic traits (age, gender, activity level, disease status, etc.), as these factors all interact with diet to influence health. PMID:28684688

  8. Genetically predicted milk consumption and bone health, ischemic heart disease and type 2 diabetes: a Mendelian randomization study.

    PubMed

    Yang, Q; Lin, S L; Au Yeung, S L; Kwok, M K; Xu, L; Leung, G M; Schooling, C M

    2017-08-01

    Milk provides protein and micronutrients, and is recommended by some dietary guidelines, particularly for bone health. Meta-analysis of small randomized controlled trials suggests that milk may increase bone mineral density, but they are very heterogeneous. No randomized controlled trial has assessed the effects of milk on major chronic diseases. Previous Mendelian randomization studies of milk did not consider bone health, found no effects on ischemic heart disease (IHD) or type 2 diabetes (T2D) but higher body mass index. Using larger genetic studies, we estimated the effects of milk on osteoporosis, IHD, T2D, adiposity, lipids and glycemic traits. Instrumental variable analysis based on a genetic variant endowing lactase persistence (rs4988235 (MCM6)) was used to obtain estimates for osteoporosis (GEFOS), IHD (CARDIoGRAMplusC4D), T2D (DIAGRAM), adiposity (GIANT), lipids (GLGC) and glycaemic traits (MAGIC). Eye color was a negative control for IHD, as it mirrors the distribution of lactase persistence and IHD in Western Europe. Genetically predicted adult milk consumption was not clearly associated with bone mineral density, IHD (odds ratio (OR): 1.03 per s.d., 95% confidence interval (CI): 0.95-1.12) and or T2D (OR: 0.92, 95% CI: 0.83-1.02) but was associated with higher log-transformed fasting insulin (0.05, 95% CI: 0.02-0.07) and body mass index (0.06, 95% CI: 0.03-0.09). Genetically predicted eye color was not associated with IHD. The lack of association of genetically predicted milk consumption with bone health, IHD or T2D suggests few beneficial effects but is more consistent with milk promoting adiposity.

  9. Genetics Home Reference: lactose intolerance

    MedlinePlus

    ... or Free article on PubMed Central Järvelä IE. Molecular genetics of adult-type hypolactasia. Ann Med. 2005;37( ... Citation on PubMed Robayo-Torres CC, Nichols BL. Molecular differentiation of congenital lactase ... Bulletins Genetics Home Reference Celebrates Its ...

  10. Clinical significance of enzymatic deficiencies in the gastrointestinal tract with particular reference to lactase deficiency.

    PubMed

    Rossi, E; Lentze, M J

    1984-12-01

    The study of deficiencies of small intestinal brush-border hydrolases increased our knowledge about the specific functions of hydrolases in the digestion of smaller molecules on the microvillus surface of the absorptive cells. The sucrase-isomaltase (SI) complex has been shown to be synthesized as a precursor (pro-sucrase-isomaltase) which is then incorporated into the membrane. The hydrophobic N-terminal end of the molecule is anchored in the lipid bilayer. In SI deficiency the molecular base of the disease is still not clear. Absence of SI activity could be due to complete lack of precursor synthesis or to structural changes within the N-terminal end of the SI-complex. Deficiencies of peptide hydrolases have not been reported with the exception of enteropeptidase (EP). Here a congenital deficiency of the enzyme was observed as the primary defect in enzyme synthesis within the enterocytes and as a secondary defect due to exocrine pancreatic insufficiency. In contrast to the primary EP deficiency, the activity of EP can be restored in the cases of exocrine pancreatic insufficiency by treatment with pancreatic extracts. Primary lactase deficiency exists in various forms. Besides congenital lactase deficiency, the late onset or adult type of lactase deficiency has been observed. The latter occurs in many different ethnic groups around the world. Here, using gel electrophoresis and immunoelectrophoresis, the lack of enzyme activity could be shown to be a primary defect in enzyme protein synthesis. In man and in the rat, two different lactases have been identified. In contrast to adult lactase, fetal lactase contains sialic acid at the end of carbohydrate side chains.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. 21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., nontoxicogenic yeast C. pseudotropicalis. It contains the enzyme lactase (β-D-galactoside galactohydrolase, EC 3.2.1.23), which converts lactose to glucose and galactose. It is prepared from yeast that has been...

  12. 21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., nontoxicogenic yeast C. pseudotropicalis. It contains the enzyme lactase (β-D-galactoside galactohydrolase, EC 3.2.1.23), which converts lactose to glucose and galactose. It is prepared from yeast that has been...

  13. Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

    PubMed

    Obermayer-Pietsch, Barbara M; Bonelli, Christine M; Walter, Daniela E; Kuhn, Regina J; Fahrleitner-Pammer, Astrid; Berghold, Andrea; Goessler, Walter; Stepan, Vinzenz; Dobnig, Harald; Leb, Georg; Renner, Wilfried

    2004-01-01

    Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose

  14. Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

    PubMed Central

    van de Heijning, Bert J. M.; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M.

    2015-01-01

    Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

  15. Diagnosis of genetic predisposition for lactose intolerance by high resolution melting analysis.

    PubMed

    Delacour, Hervé; Leduc, Amandine; Louçano-Perdriat, Andréa; Plantamura, Julie; Ceppa, Franck

    2017-02-01

    Lactose, the principle sugar in milk, is a disaccharide hydrolyzed by intestinal lactase into glucose and galactose, which are absorbed directly by diffusion in the intestine. The decline of lactase expression (or hypolactasia) in intestinal microvilli after weaning is a normal phenomenon in mammals known as lactase deficiency. It is observed in nearly 75% of the world population and is an inherited autosomal recessive trait with incomplete penetrance. It is caused by SNPs in a regulatory element for lactase gene. In Indo-European, lactase deficiency is associated with rs4982235 SNP (or -13910C>T). The aim of this study is to describe a method based on high resolution melting for rapidly detecting genetic predisposition to lactose intolerance. Analytical performance of the assay was assessed by evaluating within and betwwen-run precision and by comparing the results (n = 50 patients) obtained with the HRM assay to those obtained with the gold standard (Sanger sequencing of the region of interest). In silico prediction of HRM curves was performed to evaluate the potential impact of the other SNPs described within the PCR product on the HRM analytical performances. The assay has good performance (CV <0.2% during the between-run study). A perfect agreement with the gold standard method was observed. The presence of other polymorphisms within the amplified sequence is detected, the misclassification risk is low. This assay can be used for rapidly diagnosing genetic predisposition to lactose intolerance.

  16. Gums induced microstructure stability in Ca(II)-alginate beads containing lactase analyzed by SAXS.

    PubMed

    Traffano-Schiffo, Maria Victoria; Castro-Giraldez, Marta; Fito, Pedro J; Perullini, Mercedes; Santagapita, Patricio R

    2018-01-01

    Previous works show that the addition of trehalose and gums in β-galactosidase (lactase) Ca(II)-alginate encapsulation systems improved its intrinsic stability against freezing and dehydration processes in the pristine state. However, there is no available information on the evolution in microstructure due to the constraints imposed by the operational conditions. The aim of this research is to study the time course of microstructural changes of Ca(II)-alginate matrices driven by the presence of trehalose, arabic and guar gums as excipients and to discuss how these changes influence the diffusional transport (assessed by LF-NMR) and the enzymatic activity of the encapsulated lactase. The structural modifications at different scales were assessed by SAXS. The incorporation of gums as second excipients induces a significant stabilization in the microstructure not only at the rod scale, but also in the characteristic size and density of alginate dimers (basic units of construction of rods) and the degree of interconnection of rods at a larger scale, improving the performance in terms of lactase activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Significant positive correlation between sunshine and lactase nonpersistence in Europe may implicate both in similarly altering risks for some diseases.

    PubMed

    Szilagyi, Andrew; Leighton, Henry; Burstein, Barry; Shrier, Ian

    2011-01-01

    Decreasing latitude and increasing frequency of population lactase nonpersistence have been reported to diminish risks for several diseases, but the reason for overlap has not been explained. We evaluate, relationships between calculated national annual ultraviolet light B (UVB) exposure, latitude, and national lactose digestion frequencies. Annual UVB exposure and latitude were based on weighted averages from several cities in different countries. Lactase distribution status was based on published data that have been used previously to derive relations with diseases. We compare univariate regression analyses (r(2)(adj), slope) of percentage of lactase nonpersistence with UVB or latitude. We determine, differences between European and non-European sources by multiregression analysis of independent variables. Correlation between UVB and latitude is high (r(2) = 0.89), and between percentage of lactase nonpersistence and either latitude or UVB the correlation is moderately strong with r(2) = 0.51 and 0.46, respectively, with P ≤ 0.01 for both. A more detailed analysis shows that correlations between percentage of lactase nonpersistence and UVB are only significant in Europe, r(2) = 0.59, P < 0.001, whereas outside Europe: r(2) = 0.06, P = 0.16. These relationships raise hypothetical explanations to account for the observed overlap in similar risk modification by the 2 variables.

  18. Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis.

    PubMed

    Hartwig, Fernando Pires; Horta, Bernardo Lessa; Smith, George Davey; de Mola, Christian Loret; Victora, Cesar Gomes

    2016-10-01

    Milk intake has been associated with lower blood pressure (BP) in observational studies, and randomized controlled trials suggested that milk-derived tripeptides have BP-lowering effects. Milk intake has also been associated with body mass index (BMI). Nevertheless, it is unclear whether increasing milk consumption would reduce BP in the general population. We investigated the association of milk intake with obesity and BP using genetically-defined lactase persistence (LP) based on the rs4988235 polymorphism in a Mendelian randomization design in the 1982 Pelotas (Southern Brazil) Birth Cohort. These results were combined with published reports identified through a systematic review using meta-analysis. In the 1982 Pelotas Birth Cohort, milk intake was 42 [95% confidence interval (CI): 18; 67) ml/day higher in LP individuals. In conventional observational analysis, each 1-dl/day increase in milk intake was associated with -0.26 (95% CI: -0.33; -0.19) kg/m 2 in BMI and -0.31 (95% CI: -0.46; -0.16) and -0.35 (95% CI: -0.46; -0.23) mmHg in systolic and diastolic BP, respectively. These results were not corroborated when analysing LP status, but confidence intervals were large. In random effects meta-analysis, LP individuals presented higher BMI [0.17 (95% CI: 0.07; 0.27) kg/m 2 ] and higher odds of overweight-obesity [1.09 (95% CI: 1.02; 1.17)]. There were no reliable associations for BP. Our study supports that LP is positively associated with obesity, suggesting that the negative association of milk intake with obesity is likely due to limitations of conventional observational studies. Our findings also do not support that increased milk intake leads to lower BP. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  19. A combination of acid lactase from Aspergillus oryzae and yogurt bacteria improves lactose digestion in lactose maldigesters synergistically: A randomized, controlled, double-blind cross-over trial.

    PubMed

    de Vrese, Michael; Laue, Christiane; Offick, Birte; Soeth, Edlyn; Repenning, Frauke; Thoß, Angelika; Schrezenmeir, Jürgen

    2015-06-01

    Lactose digestion can be improved in subjects with impaired or completely absent intestinal lactase activity by administration of lactase preparations and particularly of acid lactase, which is active in the stomach, or by yogurt containing live lactic acid bacteria. It is the question, if lactose digestion can be further enhanced by combining these two approaches. We investigated in a randomised, placebo-controlled, double-blind, 5-arm crossover study on 24 lactose malabsorbers with variable degrees of lactase deficiency if different lactase preparations and freeze-dried yogurt culture affect gastrointestinal lactose digestion after consuming moderate amounts of lactose (12.5 g) by assessing hydrogen exhalation over 6 h. Furthermore, symptoms of lactose intolerance (excess gas production, abdominal pain, diarrhoea or nausea) were assessed using validated questionnaires. All preparations increased lactose digestion and reduced peak hydrogen exhalation by -27% (yogurt), -29/-33% (3300/9000 FCC(1) ((1) One FCC hydrolyses about 5 or 1.7-2.5 mg lactose in aquous solution or in (artificial) chyme, respectively, according to the FCC-III method of the Committee on Codex Specifications, Food and Nutrition Board, National Research Council. Food Chemicals Codex, 3rd edition. Washington, DC, National Academy Press, 1981 It cannot precisely be defined how much lactose can be hydrolysed in vivo by the consumption of a certain number of FCC units.) units acid lactase from Aspergillus oryzae) or -46%, respectively (3300 FCC units lactase plus yogurt culture combined), as compared with placebo (p < 0.001, Friedman test). The combination preparation had not only the strongest effect, but also showed the lowest variance in H(2)-exhalation values (less malabsorbers with no reduction of H(2)-exhalation) Apart from this, both the higher dose lactase and the combination preparation significantly reduced the symptoms most closely associated with H(2)-exhalation, namely flatulences and

  20. Study on influence of age, gender and genetic variants on lactose intolerance and its impact on milk intake in adult Asian Indians.

    PubMed

    Baadkar, Shruti V; Mukherjee, Manjari S; Lele, Smita S

    2014-01-01

    Lactase non-persistence (LNP) has been associated with the CC genotype of -13910C > T and GG genotype of -22018G > A polymorphisms present upstream of the lactase gene. Lactose intolerance (LI) is caused when gastrointestinal symptoms develop in individuals with low lactase activity. To analyse association of LNP genotype and LI symptoms with milk intake and determine whether factors such as age, gender and genotype affect LI status. Genetic analysis and lactose tolerance test (LTT) were performed on 205 healthy Indian adults. The pattern of milk consumption was recorded using a dietary questionnaire. LI was strongly associated with -13910CC genotype (OR = 10.28, 95% CI = 2.32-45.55, p = 0.002). Females were found to be at a higher risk of developing LI (OR = 2.47, 95% CI = 1.33-4.59, p = 0.004). The association of the ≥50 years age group with LI was marginally significant (OR = 1.86, 95% CI = 0.995-3.47, p = 0.05). Frequency and quantity of milk intake were lower in subjects belonging to the LNP genotype and LI groups (p < 0.05). Subject study suggests that gender and genotype may be associated with development of LI. Association of age with LI was marginal. The data also indicate that LNP genotype and LI may play a role in influencing milk intake in individuals.

  1. 21 CFR 184.1388 - Lactase enzyme preparation from Kluyveromyces lactis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-galactoside galactohydrase (CAS Reg. No. CBS 683), which converts lactose to glucose and galactose. It is... in § 170.3(o)(9) of this chapter to convert lactose to glucose and galactose. (2) The ingredient is... practice is to use this ingredient in milk to produce lactase-treated milk, which contains less lactose...

  2. 21 CFR 184.1388 - Lactase enzyme preparation from Kluyveromyces lactis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-galactoside galactohydrase (CAS Reg. No. CBS 683), which converts lactose to glucose and galactose. It is... in § 170.3(o)(9) of this chapter to convert lactose to glucose and galactose. (2) The ingredient is... practice is to use this ingredient in milk to produce lactase-treated milk, which contains less lactose...

  3. Using the Genetics Concept Assessment to Document Persistent Conceptual Difficulties in Undergraduate Genetics Courses

    PubMed Central

    Smith, Michelle K.; Knight, Jennifer K.

    2012-01-01

    To help genetics instructors become aware of fundamental concepts that are persistently difficult for students, we have analyzed the evolution of student responses to multiple-choice questions from the Genetics Concept Assessment. In total, we examined pretest (before instruction) and posttest (after instruction) responses from 751 students enrolled in six genetics courses for either majors or nonmajors. Students improved on all 25 questions after instruction, but to varying degrees. Notably, there was a subgroup of nine questions for which a single incorrect answer, called the most common incorrect answer, was chosen by >20% of students on the posttest. To explore response patterns to these nine questions, we tracked individual student answers before and after instruction and found that particular conceptual difficulties about genetics are both more likely to persist and more likely to distract students than other incorrect ideas. Here we present an analysis of the evolution of these incorrect ideas to encourage instructor awareness of these genetics concepts and provide advice on how to address common conceptual difficulties in the classroom. PMID:22367036

  4. Using the Genetics Concept Assessment to document persistent conceptual difficulties in undergraduate genetics courses.

    PubMed

    Smith, Michelle K; Knight, Jennifer K

    2012-05-01

    To help genetics instructors become aware of fundamental concepts that are persistently difficult for students, we have analyzed the evolution of student responses to multiple-choice questions from the Genetics Concept Assessment. In total, we examined pretest (before instruction) and posttest (after instruction) responses from 751 students enrolled in six genetics courses for either majors or nonmajors. Students improved on all 25 questions after instruction, but to varying degrees. Notably, there was a subgroup of nine questions for which a single incorrect answer, called the most common incorrect answer, was chosen by >20% of students on the posttest. To explore response patterns to these nine questions, we tracked individual student answers before and after instruction and found that particular conceptual difficulties about genetics are both more likely to persist and more likely to distract students than other incorrect ideas. Here we present an analysis of the evolution of these incorrect ideas to encourage instructor awareness of these genetics concepts and provide advice on how to address common conceptual difficulties in the classroom.

  5. From 'lactose intolerance' to 'lactose nutrition'.

    PubMed

    Lukito, Widjaja; Malik, Safarina G; Surono, Ingrid S; Wahlqvist, Mark L

    2015-01-01

    The concept of lactose intolerance has become embedded in Western medicine and developing economy medicine. It is based on evidence that intestinal lactase activity persists into later childhood and throughout life in only a minority of the world's population, notably northern European-derived populations. These people have the T single nucleotide polymorphism (SNP) of the rs49882359 allele (C/T), also known as C/T-13910, the MCM6 gene which positively influences the lactase LCT gene. Other lactase persistent (LP) populations are found in Africa and the Middle East with different genetic variants. These SNPs represent co-evolution with dairying since the agricultural revolution and nutrient-dependent ecological adaptation. That said, gastrointestinal symptoms considered due to small intestinal lactose malabsorption are poorly correlated with lactase non-persistence (LNP), the situation for most people. With LNP, colonic microbiome lactase enables lactose fermentation to occur so that none is found in faeces. Whether the short chain fatty acids (SCFAs) and gases (hydrogen, carbon dioxide and methane) produced cause symptoms is dose-dependent. Up to 25 g of lactose at any one time can usually be consumed by a LNP person, but its food and meal pattern context, the microbiomic characteristics, age and other factors may alter tolerance. Thus, the notion that lactose intolerance is a disorder or disease of LNP people is misplaced and has been one of cultural perspective. What actually matters is whether a particular dairy product as normally consumed give rise to symptoms. It is, therefore, proposed that lactose tolerance tests be replaced with dairy food tolerance tests.

  6. Genetic evaluation of lactation persistency for five breeds of dairy cattle.

    PubMed

    Cole, J B; Null, D J

    2009-05-01

    Cows with high lactation persistency tend to produce less milk than expected at the beginning of lactation and more than expected at the end. Best prediction of lactation persistency is calculated as a function of trait-specific standard lactation curves and linear regressions of test-day deviations on days in milk. Because regression coefficients are deviations from a tipping point selected to make yield and lactation persistency phenotypically uncorrelated it should be possible to use 305-d actual yield and lactation persistency to predict yield for lactations with later endpoints. The objectives of this study were to calculate (co)variance components and breeding values for best predictions of lactation persistency of milk (PM), fat (PF), protein (PP), and somatic cell score (PSCS) in breeds other than Holstein, and to demonstrate the calculation of prediction equations for 400-d actual milk yield. Data included lactations from Ayrshire, Brown Swiss, Guernsey (GU), Jersey (JE), and Milking Shorthorn (MS) cows calving since 1997. The number of sires evaluated ranged from 86 (MS) to 3,192 (JE), and mean sire estimated breeding value for PM ranged from 0.001 (Ayrshire) to 0.10 (Brown Swiss); mean estimated breeding value for PSCS ranged from -0.01 (MS) to -0.043 (JE). Heritabilities were generally highest for PM (0.09 to 0.15) and lowest for PSCS (0.03 to 0.06), with PF and PP having intermediate values (0.07 to 0.13). Repeatabilities varied considerably between breeds, ranging from 0.08 (PSCS in GU, JE, and MS) to 0.28 (PM in GU). Genetic correlations of PM, PF, and PP with PSCS were moderate and favorable (negative), indicating that increasing lactation persistency of yield traits is associated with decreases in lactation persistency of SCS, as expected. Genetic correlations among yield and lactation persistency were low to moderate and ranged from -0.55 (PP in GU) to 0.40 (PP in MS). Prediction equations for 400-d milk yield were calculated for each breed by

  7. Lactose intolerance: diagnosis, genetic, and clinical factors

    PubMed Central

    Mattar, Rejane; de Campos Mazo, Daniel Ferraz; Carrilho, Flair José

    2012-01-01

    Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately 75% of the world’s population loses this ability at some point, while others can digest lactose into adulthood. This review discusses the lactase-persistence alleles that have arisen in different populations around the world, diagnosis of lactose intolerance, and its symptomatology and management. PMID:22826639

  8. Adult lactose digestion status and effects on disease.

    PubMed

    Szilagyi, Andrew

    2015-04-01

    Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes. To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions. A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic. The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide. The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases. Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing.

  9. Immobilized Lactase in the Biochemistry Laboratory

    NASA Astrophysics Data System (ADS)

    Allison, Matthew J.; Bering, C. Larry

    1998-10-01

    Immobilized enzymes have many practical applications. They may be used in clinical, industrial, and biotechnological laboratories and in many clinical diagnostic kits. For educational purposes, use of immobilized enzymes can easily be taught at the undergraduate or even secondary level. We have developed an immobilized enzyme experiment that combines many practical techniques used in the biochemistry laboratory and fits within a three-hour time frame. In this experiment, lactase from over-the-counter tablets for patients with lactose intolerance is immobilized in polyacrylamide, which is then milled into small beads and placed into a chromatography column. A lactose solution is added to the column and the eluant is assayed using the glucose oxidase assay, available as a kit. We have determined the optimal conditions to give the greatest turnover of lactose while allowing the immobilized enzymes to be active for long periods at room temperature.

  10. Effect of probiotic strain Lactobacillus acidophilus (LBKV-3) on fecal residual lactase activity in undernourished children below 10 years.

    PubMed

    Hajare, Sunil Tulshiram; Bekele, Genene

    2017-01-01

    Clinically proven Lactobacillus acidophilus strain LBKV-3 intended as probiotic for humans was used to test its effect on fecal residual lactase activity in undernourished children below 10 years of age. The children were selected from malnutrition-declared area of Maharashtra (India). One of the major causes of malnutrition is lactose intolerance which leads to diarrhea. The basic consideration in selecting the probiotic strain of L. acidophilus (LBKV-3) in this investigation was the fact that the organism is isolated from human vaginal surface swab and it was found extensively studied for probiotic characteristic. LBKB 3 is tested by several workers as probiotic for hypocholesterolemic activity, implantation ability, therapeutic effects on gastrointestinal (GI) and related ailments. The results of present investigation have shown that the fecal residual lactase activity significantly increased than its initial value (which was almost zero). It appeared that the fecal residual β-galactosidase activity is an indication of positive implementation abilities of the cultures under investigation. These trends were compared with the control and blank group of children receiving Dahi and buffalo milk (BM). It was observed that both these products failed to exert any significant impact on increase in residual lactase activity.

  11. Adult lactose digestion status and effects on disease

    PubMed Central

    Szilagyi, Andrew

    2015-01-01

    BACKGROUND: Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes. OBJECTIVES: To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions. METHODS: A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic. RESULTS: The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide. DISCUSSION: The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases. CONCLUSIONS: Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing. PMID:25855879

  12. The Diverse Forms of Lactose Intolerance and the Putative Linkage to Several Cancers

    PubMed Central

    Amiri, Mahdi; Diekmann, Lena; von Köckritz-Blickwede, Maren; Naim, Hassan Y.

    2015-01-01

    Lactase-phlorizin hydrolase (LPH) is a membrane glycoprotein and the only β-galactosidase of the brush border membrane of the intestinal epithelium. Besides active transcription, expression of the active LPH requires different maturation steps of the polypeptide through the secretory pathway, including N- and O-glycosylation, dimerization and proteolytic cleavage steps. The inability to digest lactose due to insufficient lactase activity results in gastrointestinal symptoms known as lactose intolerance. In this review, we will concentrate on the structural and functional features of LPH protein and summarize the cellular and molecular mechanism required for its maturation and trafficking. Then, different types of lactose intolerance are discussed, and the molecular aspects of lactase persistence/non-persistence phenotypes are investigated. Finally, we will review the literature focusing on the lactase persistence/non-persistence populations as a comparative model in order to determine the protective or adverse effects of milk and dairy foods on the incidence of colorectal, ovarian and prostate cancers. PMID:26343715

  13. The Diverse Forms of Lactose Intolerance and the Putative Linkage to Several Cancers.

    PubMed

    Amiri, Mahdi; Diekmann, Lena; von Köckritz-Blickwede, Maren; Naim, Hassan Y

    2015-08-28

    Lactase-phlorizin hydrolase (LPH) is a membrane glycoprotein and the only β-galactosidase of the brush border membrane of the intestinal epithelium. Besides active transcription, expression of the active LPH requires different maturation steps of the polypeptide through the secretory pathway, including N- and O-glycosylation, dimerization and proteolytic cleavage steps. The inability to digest lactose due to insufficient lactase activity results in gastrointestinal symptoms known as lactose intolerance. In this review, we will concentrate on the structural and functional features of LPH protein and summarize the cellular and molecular mechanism required for its maturation and trafficking. Then, different types of lactose intolerance are discussed, and the molecular aspects of lactase persistence/non-persistence phenotypes are investigated. Finally, we will review the literature focusing on the lactase persistence/non-persistence populations as a comparative model in order to determine the protective or adverse effects of milk and dairy foods on the incidence of colorectal, ovarian and prostate cancers.

  14. Modeling and optimization of fermentation variables for enhanced production of lactase by isolated Bacillus subtilis strain VUVD001 using artificial neural networking and response surface methodology.

    PubMed

    Venkateswarulu, T C; Prabhakar, K Vidya; Kumar, R Bharath; Krupanidhi, S

    2017-07-01

    Modeling and optimization were performed to enhance production of lactase through submerged fermentation by Bacillus subtilis VUVD001 using artificial neural networks (ANN) and response surface methodology (RSM). The effect of process parameters namely temperature (°C), pH, and incubation time (h) and their combinational interactions on production was studied in shake flask culture by Box-Behnken design. The model was validated by conducting an experiment at optimized process variables which gave the maximum lactase activity of 91.32 U/ml. Compared to traditional activity, 3.48-folds improved production was obtained after RSM optimization. This study clearly shows that both RSM and ANN models provided desired predictions. However, compared with RSM (R 2  = 0.9496), the ANN model (R 2  = 0.99456) gave a better prediction for the production of lactase.

  15. Persistence of genetic variants of the arctic fox strain of Rabies virus in southern Ontario.

    PubMed

    Nadin-Davis, Susan A; Muldoon, Frances; Wandeler, Alexander I

    2006-01-01

    Genetic-variant analysis of rabies viruses provides the most sensitive epidemiologic tool for following the spread and persistence of these viruses in their wildlife hosts. Since its introduction by a southern epizootic movement that began in the far north, the arctic fox (AFX) strain of Rabies virus has been enzootic in Ontario for almost 50 y. Prior genetic studies identified 4 principal genetic variants (ONT.T1 to ONT.T4) that were localized to different regions of the province; furthermore, these viruses could be distinguished from the variant circulating in northern regions of Quebec, Newfoundland, and arctic zones, ARC.T5. Despite an intensive provincial control program undertaken over the last decade that involved aerial distribution of baits laden with rabies vaccine to combat fox rabies throughout the enzootic zone of Ontario, pockets of rabies activity persist. Re-evaluation of the genetic characteristics of the viral variants circulating in these areas of persistence has been undertaken. These data demonstrate that the recent outbreaks are, with 1 exception, due to persistence of the regional variant first identified in the area in the early 1990s. In contrast, the disease in the Georgian Bay area is a consequence of the incursion of a variant previously found further south. An outbreak that occurred in northern Ontario north and west of North Bay and in the neighboring border areas of Quebec in 2000-2001 was due to renewed incursion of the ARC.T5 variant from more northerly areas.

  16. Persistence of genetic variants of the arctic fox strain of Rabies virus in southern Ontario

    PubMed Central

    2006-01-01

    Abstract Genetic-variant analysis of rabies viruses provides the most sensitive epidemiologic tool for following the spread and persistence of these viruses in their wildlife hosts. Since its introduction by a southern epizootic movement that began in the far north, the arctic fox (AFX) strain of Rabies virus has been enzootic in Ontario for almost 50 y. Prior genetic studies identified 4 principal genetic variants (ONT.T1 to ONT.T4) that were localized to different regions of the province; furthermore, these viruses could be distinguished from the variant circulating in northern regions of Quebec, Newfoundland, and arctic zones, ARC.T5. Despite an intensive provincial control program undertaken over the last decade that involved aerial distribution of baits laden with rabies vaccine to combat fox rabies throughout the enzootic zone of Ontario, pockets of rabies activity persist. Re-evaluation of the genetic characteristics of the viral variants circulating in these areas of persistence has been undertaken. These data demonstrate that the recent outbreaks are, with 1 exception, due to persistence of the regional variant first identified in the area in the early 1990s. In contrast, the disease in the Georgian Bay area is a consequence of the incursion of a variant previously found further south. An outbreak that occurred in northern Ontario north and west of North Bay and in the neighboring border areas of Quebec in 2000–2001 was due to renewed incursion of the ARC.T5 variant from more northerly areas. PMID:16548327

  17. A Cross-Sectional Behavioral Genetic Analysis of Task Persistence in the Transition to Middle Childhood

    ERIC Educational Resources Information Center

    Deater-Deckard, Kirby; Petrill, Stephen A.; Thompson, Lee A.; DeThorne, Laura S.

    2005-01-01

    Task persistence, measured by a composite score of independent teacher, tester and observer reports, was examined using behavioral genetic analysis. Participants included 92 monozygotic and 137 same-sex dizygotic twin pairs in Kindergarten or 1st grade (4.3 to 7.9 years old). Task persistence was widely distributed, higher among older children,…

  18. ORAL ADMINISTRATION OF EXOGENOUS LACTASE IN TABLETS FOR PATIENTS DIAGNOSED WITH LACTOSE INTOLERANCE DUE TO PRIMARY HYPOLACTASIA.

    PubMed

    Francesconi, Carlos Fernando de Magalhães; Machado, Marta Brenner; Steinwurz, Flavio; Nones, Rodrigo Bremer; Quilici, Flávio Antonio; Catapani, Wilson Roberto; Miszputen, Sender Jankiel; Bafutto, Mauro

    2016-01-01

    Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance

  19. Differential impact of lactose/lactase phenotype on colonic microflora

    PubMed Central

    Szilagyi, Andrew; Shrier, Ian; Heilpern, Debra; Je, Jung Sung; Park, Sunghoon; Chong, George; Lalonde, Catherine; Cote, Louis-Francois; Lee, Byong

    2010-01-01

    BACKGROUND: The ability to digest lactose divides the world’s population into two phenotypes that may be risk variability markers for several diseases. Prebiotic effects likely favour lactose maldigesters who experience lactose spilling into their colon. OBJECTIVE: To evaluate the effects of fixed-dose lactose solutions on fecal bifidobacteria and lactobacilli in digesters and maldigesters, and to determine whether the concept of a difference in ability to digest lactose is supported. METHODS: A four-week study was performed in 23 lactose mal-digesters and 18 digesters. Following two weeks of dairy food withdrawal, subjects ingested 25 g of lactose twice a day for two weeks. Stool bifidobacteria and lactobacilli counts pre- and postintervention were measured as the primary outcome. For secondary outcomes, total anaerobes, Enterobacteriaceae, beta-galactosidase and N-acetyl-beta-D-glucosaminidase activity in stool, as well as breath hydrogen and symptoms following lactose challenge tests, were measured. RESULTS: Lactose maldigesters had a mean change difference (0.72 log10 colony forming units/g stool; P=0.04) in bifidobacteria counts compared with lactose digesters. Lactobacilli counts were increased, but not significantly. Nevertheless, reduced breath hydrogen after lactose ingestion correlated with lactobacilli (r=−0.5; P<0.001). Reduced total breath hydrogen and symptom scores together, with a rise in fecal enzymes after intervention, were appropriate, but not significant. CONCLUSIONS: Despite failure to achieve full colonic adaptation, the present study provided evidence for a differential impact of lactose on microflora depending on genetic lactase status. A prebiotic effect was evident in lactose maldigesters but not in lactose digesters. This may play a role in modifying the mechanisms of certain disease risks related to dairy food consumption between the two phenotypes. PMID:20559580

  20. Genetic Parameters for Milk Yield and Lactation Persistency Using Random Regression Models in Girolando Cattle

    PubMed Central

    Canaza-Cayo, Ali William; Lopes, Paulo Sávio; da Silva, Marcos Vinicius Gualberto Barbosa; de Almeida Torres, Robledo; Martins, Marta Fonseca; Arbex, Wagner Antonio; Cobuci, Jaime Araujo

    2015-01-01

    A total of 32,817 test-day milk yield (TDMY) records of the first lactation of 4,056 Girolando cows daughters of 276 sires, collected from 118 herds between 2000 and 2011 were utilized to estimate the genetic parameters for TDMY via random regression models (RRM) using Legendre’s polynomial functions whose orders varied from 3 to 5. In addition, nine measures of persistency in milk yield (PSi) and the genetic trend of 305-day milk yield (305MY) were evaluated. The fit quality criteria used indicated RRM employing the Legendre’s polynomial of orders 3 and 5 for fitting the genetic additive and permanent environment effects, respectively, as the best model. The heritability and genetic correlation for TDMY throughout the lactation, obtained with the best model, varied from 0.18 to 0.23 and from −0.03 to 1.00, respectively. The heritability and genetic correlation for persistency and 305MY varied from 0.10 to 0.33 and from −0.98 to 1.00, respectively. The use of PS7 would be the most suitable option for the evaluation of Girolando cattle. The estimated breeding values for 305MY of sires and cows showed significant and positive genetic trends. Thus, the use of selection indices would be indicated in the genetic evaluation of Girolando cattle for both traits. PMID:26323397

  1. Fine-scale human genetic structure in Western France.

    PubMed

    Karakachoff, Matilde; Duforet-Frebourg, Nicolas; Simonet, Floriane; Le Scouarnec, Solena; Pellen, Nadine; Lecointe, Simon; Charpentier, Eric; Gros, Françoise; Cauchi, Stéphane; Froguel, Philippe; Copin, Nane; Le Tourneau, Thierry; Probst, Vincent; Le Marec, Hervé; Molinaro, Sabrina; Balkau, Beverley; Redon, Richard; Schott, Jean-Jacques; Blum, Michael Gb; Dina, Christian

    2015-06-01

    The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.S.I.R and CavsGen. We found that fine-scale population structure occurs at the scale of Western France, with distinct admixture proportions for individuals originating from the Brittany Region and the Vendée Department. Genetic differentiation increases with distance at a high rate in these two parts of Northwestern France and linkage disequilibrium is higher in Brittany suggesting a lower effective population size. When looking for genomic regions informative about Breton origin, we found two prominent associated regions that include the lactase region and the HLA complex. For both the lactase and the HLA regions, there is a low differentiation between Bretons and Irish, and this is also found at the genome-wide level. At a more refined scale, and within the Pays de la Loire Region, we also found evidence of fine-scale population structure, although principal component analysis showed that individuals from different departments cannot be confidently discriminated. Because of the evidence for fine-scale genetic structure in Western France, we anticipate that rare and geographically localized variants will be identified in future full-sequence analyses.

  2. Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.

    PubMed

    Yang, Wan-Lin; Kouyos, Roger D; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Scherrer, Alexandra U; Shilaih, Mohaned; Hinkley, Trevor; Petropoulos, Christos; Bonhoeffer, Sebastian; Günthard, Huldrych F

    2015-03-01

    Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V) to 2.7/100-person-years;[0.7, 10.9] (for 215D). RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

  3. Economic weights for genetic improvement of lactation persistency and milk yield.

    PubMed

    Togashi, K; Lin, C Y

    2009-06-01

    This study aimed to establish a criterion for measuring the relative weight of lactation persistency (the ratio of yield at 280 d in milk to peak yield) in restricted selection index for the improvement of net merit comprising 3-parity total yield and total lactation persistency. The restricted selection index was compared with selection based on first-lactation total milk yield (I(1)), the first-two-lactation total yield (I(2)), and first-three-lactation total yield (I(3)). Results show that genetic response in net merit due to selection on restricted selection index could be greater than, equal to, or less than that due to the unrestricted index depending upon the relative weight of lactation persistency and the restriction level imposed. When the relative weight of total lactation persistency is equal to the criterion, the restricted selection index is equal to the selection method compared (I(1), I(2), or I(3)). The restricted selection index yielded a greater response when the relative weight of total lactation persistency was above the criterion, but a lower response when it was below the criterion. The criterion varied depending upon the restriction level (c) imposed and the selection criteria compared. A curvilinear relationship (concave curve) exists between the criterion and the restricted level. The criterion increases as the restriction level deviates in either direction from 1.5. Without prior information of the economic weight of lactation persistency, the imposition of the restriction level of 1.5 on lactation persistency would maximize change in net merit. The procedure presented allows for simultaneous modification of multi-parity lactation curves.

  4. Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis

    PubMed Central

    de Campos Mazo, Daniel Ferraz; Mattar, Rejane; Stefano, José Tadeu; da Silva-Etto, Joyce Matie Kinoshita; Diniz, Márcio Augusto; Duarte, Sebastião Mauro Bezerra; Rabelo, Fabíola; Lima, Rodrigo Vieira Costa; de Campos, Priscila Brizolla; Carrilho, Flair José; Oliveira, Claudia P

    2016-01-01

    AIM To assess lactase gene (LCT)-13910C>T polymorphisms in Brazilian non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients in comparison with healthy controls. METHODS This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clínicas, São Paulo, Brazil. The polymorphism of lactase non-persistence/lactase persistence (LCT-13910C>T) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients (steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher’s exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were performed. RESULTS No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients (66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls (59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism (LCT-13910C>T) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase non-persistence (low lactase activity or hypolactasia) phenotype was associated with higher insulin levels (23.47 ± 15.94 μU/mL vs 15.8 ± 8.33 μU/mL, P = 0.027) and a higher frequency of insulin resistance (91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes (P = 0

  5. Association of HLA-DRB1 genetic variants with the persistence of atopic dermatitis

    PubMed Central

    Margolis, David J.; Mitra, Nandita; Kim, Brian; Gupta, Jayanta; Hoffstad, Ole J; Papadopoulos, Maryte; Wubbenhorst, Bradley; Nathanson, Katherine L; Duke, Jamie L.; Monos, Dimtri.; Kamoun, Malek

    2015-01-01

    Atopic dermatitis (AD) is a waxing and waning illness of childhood that is likely caused by interactions between an altered skin barrier and immune dysregulation. The goal of our study was to evaluate the association of DRB1 genetic variants and the persistence of AD using whole exome sequencing and high resolution typing. DRB1 was interrogated based on previous reports that utilized high throughput techniques. We evaluated an ongoing nation-wide long-term cohort of children with AD in which patients are asked every 6 months about their medication use and their AD symptoms. In total, 87 African-American and 50 European-American children were evaluated. Genetic association analysis was performed using a software tool focusing on amino acid variable positions shared by HLA-DRB1 alleles covering the antigen presenting domain. Amino acid variations at position 9 (pocket 9), position 26, and position 78 (pocket 4) were marginally associated with the prevalence of AD. However, the odds ratio was 0.30 (0.14, 0.68; p=0.003) for residue 78, 0.27 (0.10, 0.69; p=0.006) for residue 26 and not significant for residue 9 with respect to the persistence of AD. In conclusion, amino acid variations at peptide-binding pockets of HLA-DRB1 were associated with the persistence of AD in African-American children. PMID:26307177

  6. Genetic Variability of Smoking Persistence in African Americans

    PubMed Central

    Hamidovic, A; Kasberger, J; Young, T; Goodloe, R; Redline, S; Buxbaum, S; Benowitz, N; Bergen, A; Butler, K; Franceschini, N; Gharib, S; Hitsman, B; Levy, D; Meng, Y; Papanicolaou, G; Preiss, S; Spring, B; Styn, M; Tong, E; White, W; Wiggins, K; Jorgenson, E

    2011-01-01

    To date, most genetic association analyses of smoking behaviors have been conducted in populations of European ancestry and many of these studies focused on the phenotype that measures smoking quantity, i.e. cigarettes per day. Additional association studies in diverse populations with different linkage disequilibrium (LD) patterns and an alternate phenotype, such as total tobacco exposure which accounts for intermittent periods of smoking cessation within a larger smoking period as measured in large cardiovascular risk studies, can aid the search for variants relevant to smoking behavior. For these reasons, we undertook an association analysis using a genotyping array that includes 2100 genes to analyze smoking persistence in unrelated African-American participants from The Atherosclerosis Risk in Communities (ARIC) study. A locus located ~ 4 Kb downstream from the 3’ UTR of the Brain-Derived Neurotrophic Factor (BDNF) significantly influenced smoking persistence. In addition, independent variants rs12915366 and rs12914385 in the cluster of genes encoding nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4) on 15q25.1 were also associated with the phenotype in this sample of African American subjects. To our knowledge, this is the first study to more extensively evaluate the genome in the African American population as a limited number of previous studies of smoking behavior in this population included evaluations of only single genomic regions. PMID:21436384

  7. De Novo Emergence of Genetically Resistant Mutants of Mycobacterium tuberculosis from the Persistence Phase Cells Formed against Antituberculosis Drugs In Vitro

    PubMed Central

    Sebastian, Jees; Swaminath, Sharmada; Nair, Rashmi Ravindran; Jakkala, Kishor; Pradhan, Atul

    2016-01-01

    ABSTRACT Bacterial persisters are a subpopulation of cells that can tolerate lethal concentrations of antibiotics. However, the possibility of the emergence of genetically resistant mutants from antibiotic persister cell populations, upon continued exposure to lethal concentrations of antibiotics, remained unexplored. In the present study, we found that Mycobacterium tuberculosis cells exposed continuously to lethal concentrations of rifampin (RIF) or moxifloxacin (MXF) for prolonged durations showed killing, RIF/MXF persistence, and regrowth phases. RIF-resistant or MXF-resistant mutants carrying clinically relevant mutations in the rpoB or gyrA gene, respectively, were found to emerge at high frequency from the RIF persistence phase population. A Luria-Delbruck fluctuation experiment using RIF-exposed M. tuberculosis cells showed that the rpoB mutants were not preexistent in the population but were formed de novo from the RIF persistence phase population. The RIF persistence phase M. tuberculosis cells carried elevated levels of hydroxyl radical that inflicted extensive genome-wide mutations, generating RIF-resistant mutants. Consistent with the elevated levels of hydroxyl radical-mediated genome-wide random mutagenesis, MXF-resistant M. tuberculosis gyrA de novo mutants could be selected from the RIF persistence phase cells. Thus, unlike previous studies, which showed emergence of genetically resistant mutants upon exposure of bacteria for short durations to sublethal concentrations of antibiotics, our study demonstrates that continuous prolonged exposure of M. tuberculosis cells to lethal concentrations of an antibiotic generates antibiotic persistence phase cells that form a reservoir for the generation of genetically resistant mutants to the same antibiotic or another antibiotic. These findings may have clinical significance in the emergence of drug-resistant tubercle bacilli. PMID:27895008

  8. A cat's tale: the impact of genetic restoration on Florida panther population dynamics and persistence.

    PubMed

    Hostetler, Jeffrey A; Onorato, David P; Jansen, Deborah; Oli, Madan K

    2013-05-01

    1. Genetic restoration has been suggested as a management tool for mitigating detrimental effects of inbreeding depression in small, inbred populations, but the demographic mechanisms underlying population-level responses to genetic restoration remain poorly understood. 2. We studied the dynamics and persistence of the endangered Florida panther Puma concolor coryi population and evaluated the potential influence of genetic restoration on population growth and persistence parameters. As part of the genetic restoration programme, eight female Texas pumas P. c. stanleyana were released into Florida panther habitat in southern Florida in 1995. 3. The overall asymptotic population growth rate (λ) was 1.04 (5th and 95th percentiles: 0.95-1.14), suggesting an increase in the panther population of approximately 4% per year. Considering the effects of environmental and demographic stochasticities and density-dependence, the probability that the population will fall below 10 panthers within 100 years was 0.072 (0-0.606). 4. Our results suggest that the population would have declined at 5% per year (λ = 0.95; 0.83-1.08) in the absence of genetic restoration. Retrospective life table response experiment analysis revealed that the positive effect of genetic restoration on survival of kittens was primarily responsible for the substantial growth of the panther population that would otherwise have been declining. 5. For comparative purposes, we also estimated probability of quasi-extinction under two scenarios - implementation of genetic restoration and no genetic restoration initiative - using the estimated abundance of panthers in 1995, the year genetic restoration was initiated. Assuming no density-dependence, the probability that the panther population would fall below 10 panthers by 2010 was 0.098 (0.002-0.332) for the restoration scenario and 0.445 (0.032-0.944) for the no restoration scenario, providing further evidence that the panther population would have faced a

  9. Lactose intolerance and gastrointestinal cow's milk allergy in infants and children - common misconceptions revisited.

    PubMed

    Heine, Ralf G; AlRefaee, Fawaz; Bachina, Prashant; De Leon, Julie C; Geng, Lanlan; Gong, Sitang; Madrazo, José Armando; Ngamphaiboon, Jarungchit; Ong, Christina; Rogacion, Jossie M

    2017-01-01

    Lactose is the main carbohydrate in human and mammalian milk. Lactose requires enzymatic hydrolysis by lactase into D-glucose and D-galactose before it can be absorbed. Term infants express sufficient lactase to digest about one liter of breast milk daily. Physiological lactose malabsorption in infancy confers beneficial prebiotic effects, including the establishment of Bifidobacterium-rich fecal microbiota. In many populations, lactase levels decline after weaning (lactase non-persistence; LNP). LNP affects about 70% of the world's population and is the physiological basis for primary lactose intolerance (LI). Persistence of lactase beyond infancy is linked to several single nucleotide polymorphisms in the lactase gene promoter region on chromosome 2. Primary LI generally does not manifest clinically before 5 years of age. LI in young children is typically caused by underlying gut conditions, such as viral gastroenteritis, giardiasis, cow's milk enteropathy, celiac disease or Crohn's disease. Therefore, LI in childhood is mostly transient and improves with resolution of the underlying pathology. There is ongoing confusion between LI and cow's milk allergy (CMA) which still leads to misdiagnosis and inappropriate dietary management. In addition, perceived LI may cause unnecessary milk restriction and adverse nutritional outcomes. The treatment of LI involves the reduction, but not complete elimination, of lactose-containing foods. By contrast, breastfed infants with suspected CMA should undergo a trial of a strict cow's milk protein-free maternal elimination diet. If the infant is not breastfed, an extensively hydrolyzed or amino acid-based formula and strict cow's milk avoidance are the standard treatment for CMA. The majority of infants with CMA can tolerate lactose, except when an enteropathy with secondary lactase deficiency is present.

  10. Persistence and innovation effects in genetic and environmental factors in negative emotionality during infancy: A twin study.

    PubMed

    Schumann, Lyndall; Boivin, Michel; Paquin, Stéphane; Lacourse, Eric; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard E; Booij, Linda

    2017-01-01

    Difficult temperament in infancy is a risk factor for forms of later internalizing and externalizing psychopathology, including depression and anxiety. A better understanding of the roots of difficult temperament requires assessment of its early development with a genetically informative design. The goal of this study was to estimate genetic and environmental contributions to individual differences in infant negative emotionality, their persistence over time and their influences on stability between 5 and 18 months of age. Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male) recruited from birth. Mothers rated their twins for negative emotionality at 5 and 18 months. Longitudinal analysis of stability and innovation between the two time points was performed in Mplus. There were substantial and similar heritability (approximately 31%) and shared environmental (57.3%) contributions to negative emotionality at both 5 and 18 months. The trait's interindividual stability across time was both genetically- and environmentally- mediated. Evidence of innovative effects (i.e., variance at 18 months independent from variance at 5 months) indicated that negative emotionality is developmentally dynamic and affected by persistent and new genetic and environmental factors at 18 months. In the first two years of life, ongoing genetic and environmental influences support temperamental negative emotionality but new genetic and environmental factors also indicate dynamic change of those factors across time. A better understanding of the source and timing of factors on temperament in early development, and role of sex, could improve efforts to prevent related psychopathology.

  11. A comparison between lactose breath test and quick test on duodenal biopsies for diagnosing lactase deficiency in patients with self-reported lactose intolerance.

    PubMed

    Furnari, Manuele; Bonfanti, Daria; Parodi, Andrea; Franzè, Jolanda; Savarino, Edoardo; Bruzzone, Luca; Moscatelli, Alessandro; Di Mario, Francesco; Dulbecco, Pietro; Savarino, Vincenzo

    2013-02-01

    A lactose breath test (LBT) is usually used to diagnose lactase deficiency, and a lactose quick test (LQT) has been proposed as a new test on duodenal biopsies to detect this disorder. We aimed to assess the diagnostic accuracy of LBT and LQT and their ability to predict the clinical response to a lactose-free diet in patients with self-reported lactose intolerance. Fifty-five patients (age 47 ± 14 y; M/F 15/36) underwent upper gastrointestinal endoscopy and 25g-LBT. Two duodenal biopsies were taken to determine lactase deficiency (normal, mild, or severe) by LQT and to rule out other causes of secondary lactose malabsorption. Patients with a positive LBT and normal LQT also underwent a glucose breath test to exclude small intestinal bacterial overgrowth as a cause of the former result. The severity of gastrointestinal symptoms was measured with a GSS questionnaire, under basal condition and 1 month after a lactose-free diet. Lactose malabsorption was detected in 31/51 patients with LBT and in 37/51 patients with LQT (P = NS). Celiac disease was found in 2 patients. Two LBT+ patients showed a positive glucose breath test for small intestinal bacterial overgrowth. Eight patients had a mild hypolactasia by LQT and a negative LBT, but they had a significant improvement of symptoms after diet. LQT and LBT were concordant in 83% of cases and predicted the response to a lactose-free diet in 98% and 81% of the cases, respectively (P = 0.03). LQT is as sensitive as LBT in detecting lactase deficiency; however, it seems to be more accurate than LBT in predicting the clinical response to a lactose-free diet.

  12. Persistence and innovation effects in genetic and environmental factors in negative emotionality during infancy: A twin study

    PubMed Central

    Boivin, Michel; Paquin, Stéphane; Lacourse, Eric; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Tremblay, Richard E.; Booij, Linda

    2017-01-01

    Background Difficult temperament in infancy is a risk factor for forms of later internalizing and externalizing psychopathology, including depression and anxiety. A better understanding of the roots of difficult temperament requires assessment of its early development with a genetically informative design. The goal of this study was to estimate genetic and environmental contributions to individual differences in infant negative emotionality, their persistence over time and their influences on stability between 5 and 18 months of age. Method Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male) recruited from birth. Mothers rated their twins for negative emotionality at 5 and 18 months. Longitudinal analysis of stability and innovation between the two time points was performed in Mplus. Results There were substantial and similar heritability (approximately 31%) and shared environmental (57.3%) contributions to negative emotionality at both 5 and 18 months. The trait’s interindividual stability across time was both genetically- and environmentally- mediated. Evidence of innovative effects (i.e., variance at 18 months independent from variance at 5 months) indicated that negative emotionality is developmentally dynamic and affected by persistent and new genetic and environmental factors at 18 months. Conclusions In the first two years of life, ongoing genetic and environmental influences support temperamental negative emotionality but new genetic and environmental factors also indicate dynamic change of those factors across time. A better understanding of the source and timing of factors on temperament in early development, and role of sex, could improve efforts to prevent related psychopathology. PMID:28448561

  13. Genetic Predisposition to Persistent Apical Periodontitis

    PubMed Central

    Morsani, Jussara M.; Aminoshariae, Anita; Han, Yiping Weng; Montagnese, Thomas A.; Mickel, Andre

    2013-01-01

    Introduction The proinflammatory cytokine interleukin (IL)-1 is a key regulator of host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption. Allele2 of IL-1b is associated with a four-fold increase in IL-1β production. The aim of this case-control study was to evaluate the gene polymorphism of IL-1β in the pathogenesis of endodontic failure. We hypothesized that the gene polymorphism (allele2 of IL-1β) would influence host response and enhance inflammatory reactions predisposing to persistent apical periodontitis (PAP). Materials and Methods Subjects with at least 1 year of follow-up after root canal therapy (RCT) were recalled. Inclusion and exclusion criteria were applied, and 34 subjects with signs/symptoms of PAP with otherwise acceptable RCT were included. Sixty-one controls showed healing with acceptable RCT. Genomic DNA from buccal mucosa was amplified by polymerase chain reaction followed by restriction fragment length polymorphism to distinguish the alleles of IL-1β gene polymorphism. Results A significant difference in the distribution of the polymorphic genotype among cases (70.6%) and controls (24.6%) (P < .001, Pearson χ2) was shown. Conclusions These findings suggest that specific genetic markers associated with increased IL-1β production may contribute to increased susceptibility to PAP. PMID:21419289

  14. Genetics of Persister Formation in Pseudomonas aeruginosa

    DTIC Science & Technology

    2012-12-14

    RNA endonuclease toxin-anti-toxin modules must be knocked out before there is an observable effect on persister formation (Maisonneuve, Shakespeare et...multidrug tolerance in Escherichia coli." J Bacteriol 186(24): 8172-8180. Maisonneuve, E., L. J. Shakespeare , et al. (2011). "Bacterial persistence by RNA...endonuclease toxin-anti-toxin modules must be knocked out before there is an observable effect on persister formation (Maisonneuve, Shakespeare et al. 2011

  15. 4-O-beta-D-galactopyranosyl-D-xylose: a new synthesis and application to the evaluation of intestinal lactase.

    PubMed

    Rivera-Sagredo, A; Fernández-Mayoralas, A; Jiménez-Barbero, J; Martín-Lomas, M; Villanueva, D; Aragón, J J

    1992-04-10

    4-O-beta-D-Galactopyranosyl-D-xylose (2) was prepared from benzyl 2,3-O-isopropylidene-beta-D-xylopyranoside by glycosylation with 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl bromide and subsequent deprotection. Compound 2 was hydrolyzed in vitro by intestinal lactase; the Vmax was 25% of that with lactose and the Km was 370mM (cf. 27mM for lactose). Oral administration of 2 suckling rats led to urinary excretion of D-xylose which could be estimated colorimetrically.

  16. Persistent genetic signatures of historic climatic events in an Antarctic octopus.

    PubMed

    Strugnell, J M; Watts, P C; Smith, P J; Allcock, A L

    2012-06-01

    Repeated cycles of glaciation have had major impacts on the distribution of genetic diversity of the Antarctic marine fauna. During glacial periods, ice cover limited the amount of benthic habitat on the continental shelf. Conversely, more habitat and possibly altered seaways were available during interglacials when the ice receded and the sea level was higher. We used microsatellites and partial sequences of the mitochondrial cytochrome oxidase 1 gene to examine genetic structure in the direct-developing, endemic Southern Ocean octopod Pareledone turqueti sampled from a broad range of areas that circumvent Antarctica. We find that, unusually for a species with poor dispersal potential, P. turqueti has a circumpolar distribution and is also found off the islands of South Georgia and Shag Rocks. The overriding pattern of spatial genetic structure can be explained by hydrographic (with ocean currents both facilitating and hindering gene flow) and bathymetric features. The Antarctic Peninsula region displays a complex population structure, consistent with its varied topographic and oceanographic influences. Genetic similarities between the Ross and Weddell Seas, however, are interpreted as a persistent historic genetic signature of connectivity during the hypothesized Pleistocene West Antarctic Ice Sheet collapses. A calibrated molecular clock indicates two major lineages within P. turqueti, a continental lineage and a sub-Antarctic lineage, that diverged in the mid-Pliocene with no subsequent gene flow. Both lineages survived subsequent major glacial cycles. Our data are indicative of potential refugia at Shag Rocks and South Georgia and also around the Antarctic continent within the Ross Sea, Weddell Sea and off Adélie Land. The mean age of mtDNA diversity within these main continental lineages coincides with Pleistocene glacial cycles. © 2012 Blackwell Publishing Ltd.

  17. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence

    PubMed Central

    1984-01-01

    We studied the mechanism of lymphocytic choriomeningitis virus (LCMV) persistence and the suppression of cytotoxic T lymphocyte (CTL) responses in BALB/c WEHI mice infected at birth with LCMV Armstrong strain. Using adoptive transfer experiments we found that spleen cells from persistently infected (carrier) mice actively suppressed the expected LCMV-specific CTL response of spleen cells from normal adult mice. The suppression was specific for the CTL response and LCMV - specific antibody responses were not affected. Associated with the specific CTL suppression was the establishment of persistent LCMV infection. The transfer of spleen or lymph node cells containing LCMV - specific CTL resulted in virus clearance and prevented establishment of the carrier state. The suppression of LCMV -specific CTL responses by carrier spleen cells is not mediated by a suppressor cell, but is due to the presence of genetic variants of LCMV in spleens of carrier mice. Such virus variants selectively suppress LCMV-specific CTL responses and cause persistent infections in immunocompetent mice. In striking contrast, wild-type LCMV Armstrong, from which these variants were generated, induces a potent CTL response in immunocompetent mice and the LCMV infection is rapidly cleared. Our results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence. PMID:6332167

  18. Self-reported lactose intolerance in clinic patients with functional gastrointestinal symptoms: prevalence, risk factors, and impact on food choices.

    PubMed

    Zheng, X; Chu, H; Cong, Y; Deng, Y; Long, Y; Zhu, Y; Pohl, D; Fried, M; Dai, N; Fox, M

    2015-08-01

    Many patients complain of abdominal symptoms with dairy products; however, clinical and psychosocial factors associated with self-reported lactose intolerance (SLI) have not been assessed in large studies. In particular, data are lacking from lactase deficient populations. This prospective cohort study assessed the prevalence of, and risk factors for, SLI in Chinese patients attending a gastroenterology clinic. Consecutive patients completed questionnaires to assess digestive health (Rome III), psychological state (HADS), life event stress (LES), food intake, and quality-of-life (SF-8). A representative sample completed genetic studies and hydrogen breath testing (HBT) at the clinically relevant dose of 20 g lactose. SLI was present in 411/910 (45%) clinic patients with functional abdominal symptoms. The genotype in all subjects was C/C-13910. A small number of novel SNPs in lactase promoter region were identified, including C/T-13908 which appeared to confer lactase persistence. Over half of the patients (54%) completed the 20 g lactose HBT with 58% (285/492) reporting typical symptoms. Positive and negative predictive values of SLI for abdominal symptoms during HBT were 60% and 44%, respectively. Psychological state and stress were not associated with SLI in clinic patients. SLI impacted on physical quality-of-life and was associated with reduced ingestion of dairy products, legumes, and dried fruit (p ≤ 0.05). In a lactase deficient population, approximately half of patients attending clinic with functional gastrointestinal symptoms reported intolerance to dairy products; however, SLI did not predict findings on 20 g lactose HBT. Independent of psychosocial factors, SLI impacted on quality-of-life and impacted on food choices with restrictions not limited to dairy products. © 2015 John Wiley & Sons Ltd.

  19. Genetic etiology in cases of recovered and persistent stuttering in an unselected, longitudinal sample of young twins.

    PubMed

    Dworzynski, Katharina; Remington, Anna; Rijsdijk, Frühling; Howell, Peter; Plomin, Robert

    2007-05-01

    The contribution of genetic factors in the persistence of and early recovery from stuttering was assessed. Data from the Twins Early Development Study were employed. Parental reports regarding stuttering were collected at ages 2, 3, 4, and 7 years, and were used to classify speakers into recovered and persistent groups. Of 12,892 children with at least 2 ratings, 950 children had recovered and 135 persisted in their stutter. Logistic regressions showed that the rating at age 2 was not predictive of later stuttering, whereas ratings at ages 3 and 4 were. Concordance rates were consistently higher for monozygotic than for dizygotic twin pairs (with the exception of girls at age 3). At 3, 4, and 7 years, the liability to stuttering was highly heritable (h2 estimates of between .58 and .66). Heritability for the recovered and persistent groups was also high but did not differ from each other. Stuttering appears to be a disorder that has high heritability and little shared environment effect in early childhood and for recovered and persistent groups of children, by age 7. The clinical implications of the findings are discussed.

  20. Genetic etiology in cases of recovered and persistent stuttering in an unselected, longitudinal sample of young twins

    PubMed Central

    Dworzynski, Katharina; Remington, Anna; Rijsdijk, Frühling; Howell, Peter; Plomin, Robert

    2007-01-01

    Purpose The contribution of genetic factors in persistence and early recovery from stuttering was assessed.. Method Data from the Twins Early Development Study were employed. Parental reports regarding stuttering were collected at ages 2, 3, 4 and 7 years and were used to classify speakers into recovered and persistent groups. Of 12,892 children with at least two ratings, 950 children had recovered and 135 persisted in their stutter. Results Logistic regressions showed that the rating at age 2 was not predictive of later stuttering, whereas ratings at ages 3 and 4 were. Concordance rates were consistently higher for monozygotic than for dizygotic twin pairs (with the exception of girls at age 3). At 3, 4 and 7 years, the liability to stuttering was highly heritable (h2 estimates of between .58 and .66). Heritability for the recovered and persistent groups was also high, but did not differ from each other. Conclusion Stuttering appears to be a disorder that has high heritability and little shared environment effect in early childhood and for recovered and persistent groups of children, by age 7. The clinical implications of the findings are discussed. PMID:17456895

  1. Persistence of Multiple Genetic Lineages within Intrahost Populations of Ross River Virus▿

    PubMed Central

    Liu, Wen J.; Rourke, Michelle F.; Holmes, Edward C.; Aaskov, John G.

    2011-01-01

    We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances. PMID:21430052

  2. Tracing Technological Development Trajectories: A Genetic Knowledge Persistence-Based Main Path Approach.

    PubMed

    Park, Hyunseok; Magee, Christopher L

    2017-01-01

    The aim of this paper is to propose a new method to identify main paths in a technological domain using patent citations. Previous approaches for using main path analysis have greatly improved our understanding of actual technological trajectories but nonetheless have some limitations. They have high potential to miss some dominant patents from the identified main paths; nonetheless, the high network complexity of their main paths makes qualitative tracing of trajectories problematic. The proposed method searches backward and forward paths from the high-persistence patents which are identified based on a standard genetic knowledge persistence algorithm. We tested the new method by applying it to the desalination and the solar photovoltaic domains and compared the results to output from the same domains using a prior method. The empirical results show that the proposed method can dramatically reduce network complexity without missing any dominantly important patents. The main paths identified by our approach for two test cases are almost 10x less complex than the main paths identified by the existing approach. The proposed approach identifies all dominantly important patents on the main paths, but the main paths identified by the existing approach miss about 20% of dominantly important patents.

  3. Comparison of geographic distributions of Irritable Bowel Syndrome with Inflammatory Bowel Disease fail to support common evolutionary roots: Irritable Bowel Syndrome and Inflammatory Bowel Diseases are not related by evolution.

    PubMed

    Szilagyi, Andrew; Xue, Xiaoqing

    2018-01-01

    Irritable Bowel Syndrome (IBS) shares overlapping symptoms and some features of pathogenesis with Inflammatory Bowel Diseases (IBD: Crohn's disease [CD], and Ulcerative Colitis [UC]). Geographic markers such as latitude/sunshine and more recently lactase population distributions are found to be correlated with IBD. As a result of clinical and pathogenic similarities between the 2 conditions, some authorities questioned whether a connection exists between them. We compare IBS directly with IBD, and indirectly with geographic markers associated with IBD, in order to evaluate possible evolutionary links between IBS and IBD. Similar correlations may link IBS as a precursor to IBD and possibly other conditions which are geographically connected with IBD. Data from four systematic reviews on IBD incidence and prevalence, IBS prevalence, and lactase distributions were included. Pearson's correlations were used for comparisons, with IBD values log-transformed because of skewed distribution. The articles provided 18-28 complete set of national data. Direct comparison between IBS and IBD showed no significant correlations (r = -0.14, r = -0.06 for CD and UC prevalence, r = -0.10 for CD incidence). Indirect comparisons also failed to show correlations of IBS with lactase distributions (r = -0.17), sunshine (r = -0.2) or latitude (r = 0.097); however, there was significant correlation between lactase distributions and CD incidence (r = -0.84), prevalence (r = -0.55) and UC prevalence (r = -0.59). Both sunshine (r= -0.53) and latitude (r = 0.58) are also significantly related to CD incidence. It is concluded that IBS and IBD do not follow similar global geographic patterns. This suggests a lack of an evolutionary genetic background coincident with emergence of lactase persistence. As well, vitamin D has no obvious impact on development of IBS. Similarities with IBD may result from sub groups (not yet identified) within the current Rome

  4. Tracing Technological Development Trajectories: A Genetic Knowledge Persistence-Based Main Path Approach

    PubMed Central

    2017-01-01

    The aim of this paper is to propose a new method to identify main paths in a technological domain using patent citations. Previous approaches for using main path analysis have greatly improved our understanding of actual technological trajectories but nonetheless have some limitations. They have high potential to miss some dominant patents from the identified main paths; nonetheless, the high network complexity of their main paths makes qualitative tracing of trajectories problematic. The proposed method searches backward and forward paths from the high-persistence patents which are identified based on a standard genetic knowledge persistence algorithm. We tested the new method by applying it to the desalination and the solar photovoltaic domains and compared the results to output from the same domains using a prior method. The empirical results show that the proposed method can dramatically reduce network complexity without missing any dominantly important patents. The main paths identified by our approach for two test cases are almost 10x less complex than the main paths identified by the existing approach. The proposed approach identifies all dominantly important patents on the main paths, but the main paths identified by the existing approach miss about 20% of dominantly important patents. PMID:28135304

  5. Heritability and quantitative genetic divergence of serotiny, a fire-persistence plant trait

    PubMed Central

    Hernández-Serrano, Ana; Verdú, Miguel; Santos-del-Blanco, Luís; Climent, José; González-Martínez, Santiago C.; Pausas, Juli G.

    2014-01-01

    Background and Aims Although it is well known that fire acts as a selective pressure shaping plant phenotypes, there are no quantitative estimates of the heritability of any trait related to plant persistence under recurrent fires, such as serotiny. In this study, the heritability of serotiny in Pinus halepensis is calculated, and an evaluation is made as to whether fire has left a selection signature on the level of serotiny among populations by comparing the genetic divergence of serotiny with the expected divergence of neutral molecular markers (QST–FST comparison). Methods A common garden of P. halepensis was used, located in inland Spain and composed of 145 open-pollinated families from 29 provenances covering the entire natural range of P. halepensis in the Iberian Peninsula and Balearic Islands. Narrow-sense heritability (h2) and quantitative genetic differentiation among populations for serotiny (QST) were estimated by means of an ‘animal model’ fitted by Bayesian inference. In order to determine whether genetic differentiation for serotiny is the result of differential natural selection, QST estimates for serotiny were compared with FST estimates obtained from allozyme data. Finally, a test was made of whether levels of serotiny in the different provenances were related to different fire regimes, using summer rainfall as a proxy for fire regime in each provenance. Key Results Serotiny showed a significant narrow-sense heritability (h2) of 0·20 (credible interval 0·09–0·40). Quantitative genetic differentiation among provenances for serotiny (QST = 0·44) was significantly higher than expected under a neutral process (FST = 0·12), suggesting adaptive differentiation. A significant negative relationship was found between the serotiny level of trees in the common garden and summer rainfall of their provenance sites. Conclusions Serotiny is a heritable trait in P. halepensis, and selection acts on it, giving rise to contrasting serotiny levels

  6. A Longitudinal Behavioral Genetic Analysis of Task Persistence

    ERIC Educational Resources Information Center

    Deater-Deckard, Kirby; Petrill, Stephen A.; Thompson, Lee A.; DeThorne, Laura S.

    2006-01-01

    Change in task persistence was assessed in two annual assessments using teachers', testers', and observers' ratings. Participants included 79 monozygotic and 116 same-sex dizygotic twin pairs who were in Kindergarten or 1st grade (4.3 to 7.9 years old) at the initial assessment. Task persistence was widely distributed and higher among older…

  7. The Genetic Legacy of the Indian Ocean Slave Trade: Recent Admixture and Post-admixture Selection in the Makranis of Pakistan.

    PubMed

    Laso-Jadart, Romuald; Harmant, Christine; Quach, Hélène; Zidane, Nora; Tyler-Smith, Chris; Mehdi, Qasim; Ayub, Qasim; Quintana-Murci, Lluis; Patin, Etienne

    2017-12-07

    From the eighth century onward, the Indian Ocean was the scene of extensive trade of sub-Saharan African slaves via sea routes controlled by Muslim Arab and Swahili traders. Several populations in present-day Pakistan and India are thought to be the descendants of such slaves, yet their history of admixture and natural selection remains largely undefined. Here, we studied the genome-wide diversity of the African-descent Makranis, who reside on the Arabian Sea coast of Pakistan, as well that of four neighboring Pakistani populations, to investigate the genetic legacy, population dynamics, and tempo of the Indian Ocean slave trade. We show that the Makranis are the result of an admixture event between local Baluch tribes and Bantu-speaking populations from eastern or southeastern Africa; we dated this event to ∼300 years ago during the Omani Empire domination. Levels of parental relatedness, measured through runs of homozygosity, were found to be similar across Pakistani populations, suggesting that the Makranis rapidly adopted the traditional practice of endogamous marriages. Finally, we searched for signatures of post-admixture selection at traits evolving under positive selection, including skin color, lactase persistence, and resistance to malaria. We demonstrate that the African-specific Duffy-null blood group-believed to confer resistance against Plasmodium vivax infection-was recently introduced to Pakistan through the slave trade and evolved adaptively in this P. vivax malaria-endemic region. Our study reconstructs the genetic and adaptive history of a neglected episode of the African Diaspora and illustrates the impact of recent admixture on the diffusion of adaptive traits across human populations. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Association of lactase 13910 C/T polymorphism with bone mineral density and fracture risk: a meta-analysis.

    PubMed

    Wu, Yougen; Li, Yinghua; Cui, Yunqing; Zhou, Yunjiao; Qian, Qingqing; Hong, Yang

    2017-12-01

    A number of studies have investigated the association of lactase (LCT,C/T-13910) gene polymorphismwith bonemineral density (BMD) and fracture risk, but previous results were inconclusive. In this study, a meta-analysis was performed to quantify the association of LCT (C/T-13910) polymorphism with BMD and fracture risk. Eligible publications were searched in the PubMed, Web of Science, Embase databases, Google Scholar, Yahoo and Baidu. Pooled weighed mean difference (WMD) or odds ratio (OR) with their 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. A total of nine articles with 8871 subjects were investigated in the presentmeta-analysis. Overall, the TT/TC genotypes of LCT 13910 C/T polymorphism showed significantly higher BMD than those with the CC genotype at femur neck (FN) (WMD = 0.011 g/cm 2 , 95% CI = 0.004-0.018, P = 0.003). Besides, LCT 13910 C/T polymorphism may decrease the risk of any site fractures (for TT versus TC+CC, OR = 0.813, 95% CI = 0.704-0.938, P = 0.005; for T allele versus C allele, OR = 0.885, 95% CI = 0.792-0.989, P = 0.032). However, there was no significant association of LCT 13910 C/T polymorphism with BMD at lumbar spine and risk of vertebral fractures under all genetic contrast models (all P values were >0.05). The meta-analysis suggests that there are significant effects of LCT 13910 C/T polymorphism on BMD and fracture risk. Large-scale studies with different ethnic populations will be needed to further investigate the possible race-specific effect of LCT 13910 C/T polymorphism on BMD and fracture risk.

  9. PERSISTENCE OF A SURROGATE FOR A GENETICALLY ENGINEERED CELLULOLYTIC MICROORGANISM AND EFFECTS ON AQUATIC COMMUNITY AND ECOSYSTEM PROPERTIES: MICROCOSM AND STREAM COMPARISONS

    EPA Science Inventory

    Our research objectives were to: (1) determine the persistence of an introduced surrogate (Cellulomonas sp NRC 2406) for a genetically engineered microorganism (GEM) in three streamlined habitats; sediments, growths of Cladophora (Chlorophyta), and leaf packs, (2) test ommunity a...

  10. Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications.

    PubMed

    Tabor, M P; Brakenhoff, R H; van Houten, V M; Kummer, J A; Snel, M H; Snijders, P J; Snow, G B; Leemans, C R; Braakhuis, B J

    2001-06-01

    In 1953, Slaughter et al. [D. P. Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] proposed the concept of field cancerization in patients with squamous cell carcinoma of the head and neck (HNSCC) and discussed its clinical significance for the development of second primary tumors and local recurrences. To define the process of field cancerization and its putative clinical implications, we analyzed genetic aberrations in HNSCC and the accompanying macroscopically normal mucosa. In 28 HNSCC patients, loss of heterozygosity was determined in tumor and five noncontiguous mucosal biopsies using eight microsatellite markers at 9p, 3p, and 17p. For patients who showed loss of heterozygosity in their mucosal biopsies, all margins of the surgical specimen were subsequently analyzed to determine the extension of the field. In these cases, additional markers at 8p, 13q, and 18q as well as p53 mutations were included to determine subclonal differences between field and tumor. Genetically altered fields were detected in 36% (10 of 28) of the HNSCC patients. The field varied in size between patients and consisted of genetically different subclones. In 7 of 10 cases, the field extended into the surgical margins. One particular patient with a genetically altered field in a surgical margin developed a local recurrence after 28 months of follow-up. Microsatellite analysis showed that this recurrence had more molecular markers in common with the nonresected premalignant field than with the original tumor, suggesting that this persistent field has progressed further into a new malignancy. Our data show that genetically altered mucosa remains after treatment in a significant proportion of HNSCC patients, which may explain in part the high frequency of local recurrences and second primary tumors. Adequate identification and risk assessment of these genetically altered fields may have profound implications for future patient management.

  11. Genetic redundancy and persistence of plasmid-mediated trimethoprim/sulfamethoxazole resistant effluent and stream water Escherichia coli.

    PubMed

    Suhartono, Suhartono; Savin, Mary; Gbur, Edward E

    2016-10-15

    Antibiotic resistant bacteria may persist in effluent receiving surface water in the presence of low (sub-inhibitory) antibiotic concentrations if the bacteria possess multiple genes encoding resistance to the same antibiotic. This redundancy of antibiotic resistance genes may occur in plasmids harboring conjugation and mobilization (mob) and integrase (intI) genes. Plasmids extracted from 76 sulfamethoxazole-trimethoprim resistant Escherichia coli originally isolated from effluent and an effluent-receiving stream were used as DNA template to identify sulfamethoxazole (sul) and trimethoprim (dfr) resistances genes plus detect the presence of intI and mob genes using PCR. Sulfamethoxazole and trimethoprim resistance was plasmid-mediated with three sul (sul1, sul2 and sul3 genes) and four dfr genes (dfrA12, dfrA8, dfrA17, and dfrA1 gene) the most prevalently detected. Approximately half of the plasmids carried class 1 and/or 2 integron and, although unrelated, half were also transmissible. Sampling site in relationship to effluent input significantly affected the number of intI and mob but not the number of sul and dfr genes. In the presence of low (sub-inhibitory) sulfamethoxazole concentration, isolates persisted regardless of integron and mobilization gene designation, whereas in the presence of trimethoprim, the presence of both integron and mobilization genes made isolates less persistent than in the absence of both or the presence of a gene from either group individually. Regardless, isolates persisted in large concentrations throughout the experiment. Treated effluent containing antibiotic resistant bacteria may be an important source of integrase and mobilization genes into the stream environment. Sulfamethoxazole-trimethoprim resistant bacteria may have a high degree of genetic redundancy and diversity carrying resistance to each antibiotic, although the role of integrase and mobilization genes towards persistence is unclear. Copyright © 2016 Elsevier Ltd

  12. Lactose digestion from flavored and frozen yogurts, ice milk, and ice cream by lactase-deficient persons.

    PubMed

    Martini, M C; Smith, D E; Savaiano, D A

    1987-10-01

    Lactose digestion from and tolerance to flavored and frozen yogurts, ice cream, and ice milk were evaluated (20 g lactose/meal) in lactase-deficient subjects by use of breath hydrogen techniques. Unflavored yogurt caused significantly less hydrogen production than milk (37 vs 185 delta ppm X h, n = 9). Flavored yogurt was intermediate (77 delta ppm X h). Subjects were free of symptoms after consuming flavored and unflavored yogurts. Of seven commercial yogurts tested, all contained significant levels of microbial beta-galactosidase (beta-gal). In addition, eight subjects were fed meals of milk, ice milk, ice cream, and frozen yogurts with and without cultures containing high levels of beta-gal. Peak hydrogen excretion after consumption of frozen yogurt with high beta-gal was less than one-half of that observed after the other five test meals and intolerance symptoms were absent. Tolerance to frozen yogurt, produced under usual commercial procedures, was found to be similar to that of ice milk and ice cream.

  13. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study

    USDA-ARS?s Scientific Manuscript database

    Objective: To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. Design: Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable...

  14. Genome flux and stasis in a five millennium transect of European prehistory.

    PubMed

    Gamba, Cristina; Jones, Eppie R; Teasdale, Matthew D; McLaughlin, Russell L; Gonzalez-Fortes, Gloria; Mattiangeli, Valeria; Domboróczki, László; Kővári, Ivett; Pap, Ildikó; Anders, Alexandra; Whittle, Alasdair; Dani, János; Raczky, Pál; Higham, Thomas F G; Hofreiter, Michael; Bradley, Daniel G; Pinhasi, Ron

    2014-10-21

    The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (~22 × ) and seven to ~1 × coverage, to investigate the impact of these on Europe's genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence.

  15. Persistence of the same genetic type of Mycoplasma hyopneumoniae in a closed herd for at least two years.

    PubMed

    Rebaque, Florencia; Camacho, Pablo; Parada, Julián; Lucchesi, Paula; Ambrogi, Arnaldo; Tamiozzo, Pablo

    2017-10-20

    Two cross-sectional studies were carried out in 2013 and 2015 monitoring for Mycoplasma hyopneumoniae presence in a swine farm. In these studies, the genetic diversity of M. hyopneumoniae was assessed in clinical specimens using a Multiple Locus Variable-number tandem repeat Analysis (MLVA) targeting P97 R1, P146 R3 and H4 loci. The samples from August 2015 showed the MLVA profile prevalent in June 2013, therefore it can be concluded that a same genetic type of M. hyopneumoniae can persist for at least two years in a closed herd. In addition, the nested PCR reactions implemented in this study showed to be useful for MLVA typing in non-invasive clinical samples. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Participation and performance in INSTAND multi-analyte molecular genetics external quality assessment schemes from 2006 to 2012.

    PubMed

    Maly, Friedrich E; Fried, Roman; Spannagl, Michael

    2014-01-01

    INSTAND e.V. has provided Molecular Genetics Multi-Analyte EQA schemes since 2006. EQA participation and performance were assessed from 2006 - 2012. From 2006 to 2012, the number of analytes in the Multi-Analyte EQA schemes rose from 17 to 53. Total number of results returned rose from 168 in January 2006 to 824 in August 2012. The overall error rate was 1.40 +/- 0.84% (mean +/- SD, N = 24 EQA dates). From 2006 to 2012, no analyte was reported 100% correctly. Individual participant performance was analysed for one common analyte, Lactase (LCT) T-13910C. From 2006 to 2012, 114 laboratories participated in this EQA. Of these, 10 laboratories (8.8%) reported at least one wrong result during the whole observation period. All laboratories reported correct results after their failure incident. In spite of the low overall error rate, EQA will continue to be important for Molecular Genetics.

  17. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study

    USDA-ARS?s Scientific Manuscript database

    This study examined whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. A Mendelian randomization study was employed, using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental var...

  18. Bacterial persistence by RNA endonucleases

    PubMed Central

    Maisonneuve, Etienne; Shakespeare, Lana J.; Jørgensen, Mikkel Girke; Gerdes, Kenn

    2011-01-01

    Bacteria form persisters, individual cells that are highly tolerant to different types of antibiotics. Persister cells are genetically identical to nontolerant kin but have entered a dormant state in which they are recalcitrant to the killing activity of the antibiotics. The molecular mechanisms underlying bacterial persistence are unknown. Here, we show that the ubiquitous Lon (Long Form Filament) protease and mRNA endonucleases (mRNases) encoded by toxin-antitoxin (TA) loci are required for persistence in Escherichia coli. Successive deletion of the 10 mRNase-encoding TA loci of E. coli progressively reduced the level of persisters, showing that persistence is a phenotype common to TA loci. In all cases tested, the antitoxins, which control the activities of the mRNases, are Lon substrates. Consistently, cells lacking lon generated a highly reduced level of persisters. Moreover, Lon overproduction dramatically increased the levels of persisters in wild-type cells but not in cells lacking the 10 mRNases. These results support a simple model according to which mRNases encoded by TA loci are activated in a small fraction of growing cells by Lon-mediated degradation of the antitoxins. Activation of the mRNases, in turn, inhibits global cellular translation, and thereby induces dormancy and persistence. Many pathogenic bacteria known to enter dormant states have a plethora of TA genes. Therefore, in the future, the discoveries described here may lead to a mechanistic understanding of the persistence phenomenon in pathogenic bacteria. PMID:21788497

  19. Adaptations to local environments in modern human populations.

    PubMed

    Jeong, Choongwon; Di Rienzo, Anna

    2014-12-01

    After leaving sub-Saharan Africa around 50000-100000 years ago, anatomically modern humans have quickly occupied extremely diverse environments. Human populations were exposed to further environmental changes resulting from cultural innovations, such as the spread of farming, which gave rise to new selective pressures related to pathogen exposures and dietary shifts. In addition to changing the frequency of individual adaptive alleles, natural selection may also shape the overall genetic architecture of adaptive traits. Here, we review recent advances in understanding the genetic architecture of adaptive human phenotypes based on insights from the studies of lactase persistence, skin pigmentation and high-altitude adaptation. These adaptations evolved in parallel in multiple human populations, providing a chance to investigate independent realizations of the evolutionary process. We suggest that the outcome of adaptive evolution is often highly variable even under similar selective pressures. Finally, we highlight a growing need for detecting adaptations that did not follow the classical sweep model and for incorporating new sources of genetic evidence such as information from ancient DNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Genome flux and stasis in a five millennium transect of European prehistory

    PubMed Central

    Gamba, Cristina; Jones, Eppie R.; Teasdale, Matthew D.; McLaughlin, Russell L.; Gonzalez-Fortes, Gloria; Mattiangeli, Valeria; Domboróczki, László; Kővári, Ivett; Pap, Ildikó; Anders, Alexandra; Whittle, Alasdair; Dani, János; Raczky, Pál; Higham, Thomas F. G.; Hofreiter, Michael; Bradley, Daniel G; Pinhasi, Ron

    2014-01-01

    The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (~22 × ) and seven to ~1 × coverage, to investigate the impact of these on Europe’s genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence. PMID:25334030

  1. The danger within: the role of genetic, behavioural and ecological factors in population persistence of colour polymorphic species.

    PubMed

    Bolton, Peri E; Rollins, Lee A; Griffith, Simon C

    2015-06-01

    Polymorphic species have been the focus of important work in evolutionary biology. It has been suggested that colour polymorphic species have specific evolutionary and population dynamics that enable them to persist through environmental changes better than less variable species. We suggest that recent empirical and theoretical work indicates that polymorphic species may be more vulnerable to extinction than previously thought. This vulnerability arises because these species often have a number of correlated sexual, behavioural, life history and ecological traits, which can have a simple genetic underpinning. When exacerbated by environmental change, these alternate strategies can lead to conflict between morphs at the genomic and population levels, which can directly or indirectly affect population and evolutionary dynamics. In this perspective, we identify a number of ways in which the nature of the correlated traits, their underpinning genetic architecture, and the inevitable interactions between colour morphs can result in a reduction in population fitness. The principles illustrated here apply to all kinds of discrete polymorphism (e.g. behavioural syndromes), but we focus primarily on colour polymorphism because they are well studied. We urge further empirical investigation of the genetic architecture and interactions in polymorphic species to elucidate the impact on population fitness. © 2015 John Wiley & Sons Ltd.

  2. Genetic and palaeo-climatic evidence for widespread persistence of the coastal tree species Eucalyptus gomphocephala (Myrtaceae) during the Last Glacial Maximum.

    PubMed

    Nevill, Paul G; Bradbury, Donna; Williams, Anna; Tomlinson, Sean; Krauss, Siegfried L

    2014-01-01

    Few phylogeographic studies have been undertaken of species confined to narrow, linear coastal systems where past sea level and geomorphological changes may have had a profound effect on species population sizes and distributions. In this study, a phylogeographic analysis was conducted of Eucalyptus gomphocephala (tuart), a tree species restricted to a 400 × 10 km band of coastal sand-plain in south west Australia. Here, there is little known about the response of coastal vegetation to glacial/interglacial climate change, and a test was made as to whether this species was likely to have persisted widely through the Last Glacial Maximum (LGM), or conforms to a post-LGM dispersal model of recovery from few refugia. The genetic structure over the entire range of tuart was assessed using seven nuclear (21 populations; n = 595) and four chloroplast (24 populations; n = 238) microsatellite markers designed for eucalypt species. Correlative palaeodistribution modelling was also conducted based on five climatic variables, within two LGM models. The chloroplast markers generated six haplotypes, which were strongly geographically structured (GST = 0·86 and RST = 0·75). Nuclear microsatellite diversity was high (overall mean HE 0·75) and uniformly distributed (FST = 0·05), with a strong pattern of isolation by distance (r(2) = 0·362, P = 0·001). Distribution models of E. gomphocephala during the LGM showed a wide distribution that extended at least 30 km westward from the current distribution to the palaeo-coastline. The chloroplast and nuclear data suggest wide persistence of E. gomphocephala during the LGM. Palaeodistribution modelling supports the conclusions drawn from genetic data and indicates a widespread westward shift of E. gomphocephala onto the exposed continental shelf during the LGM. This study highlights the importance of the inclusion of complementary, non-genetic data (information on geomorphology and palaeoclimate) to interpret phylogeographic patterns.

  3. Long-Term Monitoring of Field Trial Sites with Genetically Modified Oilseed Rape (Brassica napus L.) in Saxony-Anhalt, Germany. Fifteen Years Persistence to Date but No Spatial Dispersion

    PubMed Central

    Belter, Anke

    2016-01-01

    Oilseed rape is known to persist in arable fields because of its ability to develop secondary seed dormancy in certain agronomic and environmental conditions. If conditions change, rapeseeds are able to germinate up to 10 years later to build volunteers in ensuing crops. Extrapolations of experimental data acted on the assumption of persistence periods for more than 20 years after last harvest of rapeseed. Genetically-modified oilseed rape—cultivated widely in Northern America since 1996—is assumed not to differ from its conventional form in this property. Here, experimental data are reported from official monitoring activities that verify these assumptions. At two former field trial sites in Saxony-Anhalt genetically-modified herbicide-resistant oilseed rape volunteers are found up to fifteen years after harvest. Nevertheless, spatial dispersion or establishment of GM plants outside of the field sites was not observed within this period. PMID:26784233

  4. Fumarate-Mediated Persistence of Escherichia coli against Antibiotics

    PubMed Central

    Kim, Jun-Seob; Cho, Da-Hyeong; Heo, Paul; Jung, Suk-Chae; Park, Myungseo; Oh, Eun-Joong; Sung, Jaeyun; Kim, Pan-Jun; Lee, Suk-Chan; Lee, Dae-Hee; Lee, Sarah; Lee, Choong Hwan; Shin, Dongwoo

    2016-01-01

    Bacterial persisters are a small fraction of quiescent cells that survive in the presence of lethal concentrations of antibiotics. They can regrow to give rise to a new population that has the same vulnerability to the antibiotics as did the parental population. Although formation of bacterial persisters in the presence of various antibiotics has been documented, the molecular mechanisms by which these persisters tolerate the antibiotics are still controversial. We found that amplification of the fumarate reductase operon (FRD) in Escherichia coli led to a higher frequency of persister formation. The persister frequency of E. coli was increased when the cells contained elevated levels of intracellular fumarate. Genetic perturbations of the electron transport chain (ETC), a metabolite supplementation assay, and even the toxin-antitoxin-related hipA7 mutation indicated that surplus fumarate markedly elevated the E. coli persister frequency. An E. coli strain lacking succinate dehydrogenase (SDH), thereby showing a lower intracellular fumarate concentration, was killed ∼1,000-fold more effectively than the wild-type strain in the stationary phase. It appears that SDH and FRD represent a paired system that gives rise to and maintains E. coli persisters by producing and utilizing fumarate, respectively. PMID:26810657

  5. Joining forces for genetic conservation

    Treesearch

    Gary Man; Emily Boes; Rhoda Maurer; Michael Dosmann; Matt Lobdell; Kevin Conrad; Mike Kintgen; Rebecca Sucher; Martin Nicholson; David Stevenson; Brianna McTeague; Evan Heck; Richard A. Sniezko

    2017-01-01

    Facing a Challenge Non-native diseases and insects as well as a changing climate pose serious threats to native trees in North America. Genetic variation in a species is key to its enduring persistence in the face of these abiotic and biotic threats. Efforts to conserve genetic diversity of North American tree at-risk species will ensure the genetic...

  6. The social transmission of metacontrol policies: Mechanisms underlying the interpersonal transfer of persistence and flexibility.

    PubMed

    Hommel, Bernhard; Colzato, Lorenza S

    2017-10-01

    Humans often face binary cognitive-control dilemmas, with the choice between persistence and flexibility being a crucial one. Tackling these dilemmas requires metacontrol, i.e., the control of the current cognitive-control policy. As predicted from functional, psychometric, neuroscientific, and modeling approaches, interindividual variability in metacontrol biases towards persistence or flexibility could be demonstrated in metacontrol-sensitive tasks. These biases covary systematically with genetic predispositions regarding mesofrontal and nigrostriatal dopaminergic functioning and the individualistic or collectivistic nature of the cultural background. However, there is also evidence for mood- and meditation-induced intraindividual variability (with negative mood and focused-attention meditation being associated with a bias towards persistence, and positive mood and open-monitoring meditation being associated with a bias towards flexibility), suggesting that genetic and cultural factors do not determine metacontrol settings entirely. We suggest a theoretical framework that explains how genetic predisposition and cultural learning can lead to the implementation of metacontrol defaults, which however can be shifted towards persistence or flexibility by situational factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Polar bear use of a persistent food subsidy: insights from non-invasive genetic sampling in Alaska

    USGS Publications Warehouse

    Peacock, Elizabeth; Herreman, Jason

    2013-01-01

    Remains of bowhead whales (Balaena mysticetus) harvested by Iñupiat whalers are deposited in bone piles along the coast of Alaska and have become persistent and reliable food sources for polar bears (Ursus maritimus). The importance of bone piles to individuals and the population, the patterns of use, and the number, sex, and age of bears using these resources are poorly understood. We implemented barbed-wire hair snaring to obtain genetic identities from bears using the Point Barrow bone pile in winter 2010–11. Eighty-three percent of genotyped samples produced individual and sex identification. We identified 97 bears from 200 samples. Using genetic mark–recapture techniques, we estimated that 228 bears used the bone pile during November to February, which would represent approximately 15% of the Southern Beaufort Sea polar bear subpopulation, if all bears were from this subpopulation. We found that polar bears of all age and sex classes simultaneously used the bone pile. More males than females used the bone pile, and males predominated in February, likely because 1/3 of adult females would be denning during this period. On average, bears spent 10 days at the bone pile (median  =  5 days); the probability that an individual bear remained at the bone pile from week to week was 63% for females and 45% for males. Most bears in the sample were detected visiting the bone pile once or twice. We found some evidence of matrilineal fidelity to the bone pile, but the group of animals visiting the bone pile did not differ genetically from the Southern Beaufort Sea subpopulation, nor did patterns of relatedness. We demonstrate that bowhead whale bone piles may be an influential food subsidy for polar bears in the Barrow region in autumn and winter for all sex and age classes.

  8. The relationship between the human genome and microbiome comes into view

    PubMed Central

    Goodrich, Julia K.; Davenport, Emily R.; Clark, Andrew G.; Ley, Ruth E.

    2017-01-01

    The microbiome’s involvement in health and disease, and the complexity of its composition and function, make it intriguing to consider human genetic factors that impact microbiome composition. Genes may influence health through their ability to promote a stable microbial community in the gut. Studies of heritability yield a consistent subset of microbes that are impacted by genes, but the use of genome-wide association studies (GWAS) to identify specific genetic variants associated with microbiota phenotypes has proven challenging. Processing microbiome datasets into traits to be modeled and reducing the burden of multiple testing are just some of the technical hurdles in microbiome GWAS. Studies to date are small by GWAS standards, making cross-study comparisons and validations particularly important in identifying authentic signals. Cross-study comparisons are hampered by differences in analytical approaches. Nevertheless, some consistent associations have emerged between populations, most notably between Bifidobacteria and the lactase non-persister genotype. These early successes open the way for the microbiome to be incorporated into studies that quantify interactions among genotype, environment, and the microbiome for predicting disease susceptibility. PMID:28934590

  9. Automated Sampling Procedures Supported by High Persistence of Bacterial Fecal Indicators and Bacteroidetes Genetic Microbial Source Tracking Markers in Municipal Wastewater during Short-Term Storage at 5°C

    PubMed Central

    Mayer, R. E.; Vierheilig, J.; Egle, L.; Reischer, G. H.; Saracevic, E.; Mach, R. L.; Kirschner, A. K. T.; Zessner, M.; Farnleitner, A. H.

    2015-01-01

    Because of high diurnal water quality fluctuations in raw municipal wastewater, the use of proportional autosampling over a period of 24 h at municipal wastewater treatment plants (WWTPs) to evaluate carbon, nitrogen, and phosphorus removal has become a standard in many countries. Microbial removal or load estimation at municipal WWTPs, however, is still based on manually recovered grab samples. The goal of this study was to establish basic knowledge regarding the persistence of standard bacterial fecal indicators and Bacteroidetes genetic microbial source tracking markers in municipal wastewater in order to evaluate their suitability for automated sampling, as the potential lack of persistence is the main argument against such procedures. Raw and secondary treated wastewater of municipal origin from representative and well-characterized biological WWTPs without disinfection (organic carbon and nutrient removal) was investigated in microcosm experiments at 5 and 21°C with a total storage time of 32 h (including a 24-h autosampling component and an 8-h postsampling phase). Vegetative Escherichia coli and enterococci, as well as Clostridium perfringens spores, were selected as indicators for cultivation-based standard enumeration. Molecular analysis focused on total (AllBac) and human-associated genetic Bacteroidetes (BacHum-UCD, HF183 TaqMan) markers by using quantitative PCR, as well as 16S rRNA gene-based next-generation sequencing. The microbial parameters showed high persistence in both raw and treated wastewater at 5°C under the storage conditions used. Surprisingly, and in contrast to results obtained with treated wastewater, persistence of the microbial markers in raw wastewater was also high at 21°C. On the basis of our results, 24-h autosampling procedures with 5°C storage conditions can be recommended for the investigation of fecal indicators or Bacteroidetes genetic markers at municipal WWTPs. Such autosampling procedures will contribute to better

  10. Inevitability of Genetic Parasites

    PubMed Central

    Iranzo, Jaime; Puigbò, Pere; Lobkovsky, Alexander E.; Wolf, Yuri I.

    2016-01-01

    Abstract Almost all cellular life forms are hosts to diverse genetic parasites with various levels of autonomy including plasmids, transposons and viruses. Theoretical modeling of the evolution of primordial replicators indicates that parasites (cheaters) necessarily evolve in such systems and can be kept at bay primarily via compartmentalization. Given the (near) ubiquity, abundance and diversity of genetic parasites, the question becomes pertinent: are such parasites intrinsic to life? At least in prokaryotes, the persistence of parasites is linked to the rate of horizontal gene transfer (HGT). We mathematically derive the threshold value of the minimal transfer rate required for selfish element persistence, depending on the element duplication and loss rates as well as the cost to the host. Estimation of the characteristic gene duplication, loss and transfer rates for transposons, plasmids and virus-related elements in multiple groups of diverse bacteria and archaea indicates that most of these rates are compatible with the long term persistence of parasites. Notably, a small but non-zero rate of HGT is also required for the persistence of non-parasitic genes. We hypothesize that cells cannot tune their horizontal transfer rates to be below the threshold required for parasite persistence without experiencing highly detrimental side-effects. As a lower boundary to the minimum DNA transfer rate that a cell can withstand, we consider the process of genome degradation and mutational meltdown of populations through Muller’s ratchet. A numerical assessment of this hypothesis suggests that microbial populations cannot purge parasites while escaping Muller’s ratchet. Thus, genetic parasites appear to be virtually inevitable in cellular organisms. PMID:27503291

  11. DNA in soil: adsorption, genetic transformation, molecular evolution and genetic microchip.

    PubMed

    Trevors, J T

    1996-07-01

    This review examines interactions between DNA and soil with an emphasis on the persistence and stability of DNA in soil. The role of DNA in genetic transformation in soil microorganisms will also be discussed. In addition, a postulated mechanism for stabilization and elongation/assembly of primitive genetic material and the role of soil particles, salt concentrations, temperature cycling and crystal formation is examined.

  12. Genetic and palaeo-climatic evidence for widespread persistence of the coastal tree species Eucalyptus gomphocephala (Myrtaceae) during the Last Glacial Maximum

    PubMed Central

    Nevill, Paul G.; Bradbury, Donna; Williams, Anna; Tomlinson, Sean; Krauss, Siegfried L.

    2014-01-01

    Background and Aims Few phylogeographic studies have been undertaken of species confined to narrow, linear coastal systems where past sea level and geomorphological changes may have had a profound effect on species population sizes and distributions. In this study, a phylogeographic analysis was conducted of Eucalyptus gomphocephala (tuart), a tree species restricted to a 400 × 10 km band of coastal sand-plain in south west Australia. Here, there is little known about the response of coastal vegetation to glacial/interglacial climate change, and a test was made as to whether this species was likely to have persisted widely through the Last Glacial Maximum (LGM), or conforms to a post-LGM dispersal model of recovery from few refugia. Methods The genetic structure over the entire range of tuart was assessed using seven nuclear (21 populations; n = 595) and four chloroplast (24 populations; n = 238) microsatellite markers designed for eucalypt species. Correlative palaeodistribution modelling was also conducted based on five climatic variables, within two LGM models. Key Results The chloroplast markers generated six haplotypes, which were strongly geographically structured (GST = 0·86 and RST = 0·75). Nuclear microsatellite diversity was high (overall mean HE 0·75) and uniformly distributed (FST = 0·05), with a strong pattern of isolation by distance (r2 = 0·362, P = 0·001). Distribution models of E. gomphocephala during the LGM showed a wide distribution that extended at least 30 km westward from the current distribution to the palaeo-coastline. Conclusions The chloroplast and nuclear data suggest wide persistence of E. gomphocephala during the LGM. Palaeodistribution modelling supports the conclusions drawn from genetic data and indicates a widespread westward shift of E. gomphocephala onto the exposed continental shelf during the LGM. This study highlights the importance of the inclusion of complementary, non-genetic data (information on geomorphology and

  13. Genetic improvement of total milk yield and total lactation persistency of the first three lactations in dairy cattle.

    PubMed

    Togashi, K; Lin, C Y

    2008-07-01

    The objective of this study was to compare 6 selection criteria in terms of 3-parity total milk yield and 9 selection criteria in terms of total net merit (H) comprising 3-parity total milk yield and total lactation persistency. The 6 selection criteria compared were as follows: first-parity milk estimated breeding value (EBV; M1), first 2-parity milk EBV (M2), first 3-parity milk EBV (M3), first-parity eigen index (EI(1)), first 2-parity eigen index (EI(2)), and first 3-parity eigen index (EI(3)). The 9 selection criteria compared in terms of H were M1, M2, M3, EI(1), EI(2), EI(3), and first-parity, first 2-parity, and first 3-parity selection indices (I(1), I(2), and I(3), respectively). In terms of total milk yield, selection on M3 or EI(3) achieved the greatest genetic response, whereas selection on EI(1) produced the largest genetic progress per day. In terms of total net merit, selection on I(3) brought the largest response, whereas selection EI(1) yielded the greatest genetic progress per day. A multiple-lactation random regression test-day model simultaneously yields the EBV of the 3 lactations for all animals included in the analysis even though the younger animals do not have the opportunity to complete the first 3 lactations. It is important to use the first 3 lactation EBV for selection decision rather than only the first lactation EBV in spite of the fact that the first-parity selection criteria achieved a faster genetic progress per day than the 3-parity selection criteria. Under a multiple-lactation random regression animal model analysis, the use of the first 3 lactation EBV for selection decision does not prolong the generation interval as compared with the use of only the first lactation EBV. Thus, it is justified to compare genetic response on a lifetime basis rather than on a per-day basis. The results suggest the use of M3 or EI(3) for genetic improvement of total milk yield and the use of I(3) for genetic improvement of total net merit H

  14. Phenotypic and genetic heterogeneity within biofilms with particular emphasis on persistence and antimicrobial tolerance.

    PubMed

    Sadiq, Faizan A; Flint, Steve; Li, YanJun; Ou, Kai; Yuan, Lei; He, Guo Qing

    2017-09-01

    Phenotypic changes or phase variation within biofilms is an important feature of bacterial dormant life. Enhanced resistance to antimicrobials is one of the distinct features displayed by a fraction of cells within biofilms. It is believed that persisters are mainly responsible for this phenotypic heterogeneity. However, there is still an unresolved debate on the formation of persisters. In this short review, we highlight all known genomic and proteomic changes encountered by bacterial cells within biofilms. We have also described all phenotypic changes displayed by bacterial cells within biofilms with particular emphasis on enhanced antimicrobial tolerance of biofilms with particular reference to persisters. In addition, all currently known models of persistence have been succinctly discussed.

  15. A machine-learned analysis of human gene polymorphisms modulating persisting pain points at major roles of neuroimmune processes.

    PubMed

    Kringel, Dario; Lippmann, Catharina; Parnham, Michael J; Kalso, Eija; Ultsch, Alfred; Lötsch, Jörn

    2018-06-19

    Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analyzed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signaling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. The present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Transcriptomic study on persistence and survival of Listeria monocytogenes following lethal treatment with Nisin.

    PubMed

    Wu, Shuyan; Yu, Pak-Lam; Wheeler, Dave; Flint, Steve

    2018-06-19

    The aim of this study was to determine the gene expression associated with the persistence of a Listeria monocytogenes stationary phase population when facing lethal nisin treatment METHODS: RNA Seq analysis was used for gene expression profiling of the persister cells in rich medium (persister TN) compared with untreated cells (non-persister).The results were confirmed using RT PCR. Functional genes associated with the persister populations were identified in multiple systems, such as heat shock related stress response, cell wall synthesis, ATP-binding cassette (ABC) transport system, phosphotransferase system (PTS system), and SOS/DNA repair. This study pointed to genetic regulation of persister cells exposed to lethal nisin and provides some insight into possible mechanisms of impeding bacterial persistence. Copyright © 2018. Published by Elsevier Ltd.

  17. Characterization of multi-drug tolerant persister cells in Streptococcus suis

    PubMed Central

    2014-01-01

    Background Persister cells constitute a subpopulation of dormant cells within a microbial population which are genetically identical but phenotypically different to regular cells. Notably, persister cells show an elevated tolerance to antimicrobial agents. Thus, they are considered to represent a microbial ‘bet-hedging’ strategy and are of particular importance in pathogenic bacteria. Results We studied the ability of the zoonotic pathogen Streptococcus (S.) suis to form multi-drug tolerant variants and identified persister cells dependent on the initial bacterial growth phase. We observed lower numbers of persisters in exponential phase cultures than in stationary growth phase populations. S. suis persister cells showed a high tolerance to a variety of antibiotics, and the phenotype was not inherited as tested with four passages of S. suis populations. Furthermore, we provide evidence that the persister phenotype is related to expression of genes involved in general metabolic pathways since we found higher numbers of persister cells in a mutant strain defective in the catabolic arginine deiminase system as compared to its parental wild type strain. Finally, we observed persister cell formation also in other S. suis strains and pathogenic streptococcal species. Conclusions Taken together, this is the first study that reports multi-drug tolerant persister cells in the zoonotic pathogen S. suis. PMID:24885389

  18. Characterization of multi-drug tolerant persister cells in Streptococcus suis.

    PubMed

    Willenborg, Jörg; Willms, Daniela; Bertram, Ralph; Goethe, Ralph; Valentin-Weigand, Peter

    2014-05-12

    Persister cells constitute a subpopulation of dormant cells within a microbial population which are genetically identical but phenotypically different to regular cells. Notably, persister cells show an elevated tolerance to antimicrobial agents. Thus, they are considered to represent a microbial 'bet-hedging' strategy and are of particular importance in pathogenic bacteria. We studied the ability of the zoonotic pathogen Streptococcus (S.) suis to form multi-drug tolerant variants and identified persister cells dependent on the initial bacterial growth phase. We observed lower numbers of persisters in exponential phase cultures than in stationary growth phase populations. S. suis persister cells showed a high tolerance to a variety of antibiotics, and the phenotype was not inherited as tested with four passages of S. suis populations. Furthermore, we provide evidence that the persister phenotype is related to expression of genes involved in general metabolic pathways since we found higher numbers of persister cells in a mutant strain defective in the catabolic arginine deiminase system as compared to its parental wild type strain. Finally, we observed persister cell formation also in other S. suis strains and pathogenic streptococcal species. Taken together, this is the first study that reports multi-drug tolerant persister cells in the zoonotic pathogen S. suis.

  19. Biotic Interactions and Sunlight Affect Persistence of Fecal Indicator Bacteria and Microbial Source Tracking Genetic Markers in the Upper Mississippi River

    PubMed Central

    McMinn, Brian R.; Shanks, Orin C.; Sivaganesan, Mano; Fout, G. Shay; Ashbolt, Nicholas J.

    2014-01-01

    The sanitary quality of recreational waters that may be impacted by sewage is assessed by enumerating fecal indicator bacteria (FIB) (Escherichia coli and enterococci); these organisms are found in the gastrointestinal tracts of humans and many other animals, and hence their presence provides no information about the pollution source. Microbial source tracking (MST) methods can discriminate between different pollution sources, providing critical information to water quality managers, but relatively little is known about factors influencing the decay of FIB and MST genetic markers following release into aquatic environments. An in situ mesocosm was deployed at a temperate recreational beach in the Mississippi River to evaluate the effects of ambient sunlight and biotic interactions (predation, competition, and viral lysis) on the decay of culture-based FIB, as well as molecularly based FIB (Entero1a and GenBac3) and human-associated MST genetic markers (HF183 and HumM2) measured by quantitative real-time PCR (qPCR). In general, culturable FIB decayed the fastest, while molecularly based FIB and human-associated genetic markers decayed more slowly. There was a strong correlation between the decay of molecularly based FIB and that of human-associated genetic markers (r2, 0.96 to 0.98; P < 0.0001) but not between culturable FIB and any qPCR measurement. Overall, exposure to ambient sunlight may be an important factor in the early-stage decay dynamics but generally was not after continued exposure (i.e., after 120 h), when biotic interactions tended to be the only/major influential determinant of persistence. PMID:24747902

  20. Long-term in situ persistence of biodiversity in tropical sky islands revealed by landscape genomics.

    PubMed

    Mastretta-Yanes, Alicia; Xue, Alexander T; Moreno-Letelier, Alejandra; Jorgensen, Tove H; Alvarez, Nadir; Piñero, Daniel; Emerson, Brent C

    2018-01-01

    Tropical mountains are areas of high species richness and endemism. Two historical phenomena may have contributed to this: (i) fragmentation and isolation of habitats may have promoted the genetic differentiation of populations and increased the possibility of allopatric divergence and speciation and (ii) the mountain areas may have allowed long-term population persistence during global climate fluctuations. These two phenomena have been studied using either species occurrence data or estimating species divergence times. However, only few studies have used intraspecific genetic data to analyse the mechanisms by which endemism may emerge at the microevolutionary scale. Here, we use landscape analysis of genomic SNP data sampled from two high-elevation plant species from an archipelago of tropical sky islands (the Trans-Mexican Volcanic Belt) to test for population genetic differentiation, synchronous demographic changes and habitat persistence. We show that genetic differentiation can be explained by the degree of glacial habitat connectivity among mountains and that mountains have facilitated the persistence of populations throughout glacial/interglacial cycles. Our results support the ongoing role of tropical mountains as cradles for biodiversity by uncovering cryptic differentiation and limits to gene flow. © 2017 John Wiley & Sons Ltd.

  1. High turnover drives prolonged persistence of influenza in managed pig herds

    PubMed Central

    Aguas, Ricardo; Riley, Steven; Loeffen, Willie L. A.; Wood, James L. N.; Grenfell, Bryan T.

    2016-01-01

    Pigs have long been hypothesized to play a central role in the emergence of novel human influenza A virus (IAV) strains, by serving as mixing vessels for mammalian and avian variants. However, the key issue of viral persistence in swine populations at different scales is ill understood. We address this gap using epidemiological models calibrated against seroprevalence data from Dutch finishing pigs to estimate the ‘critical herd size’ (CHS) for IAV persistence. We then examine the viral phylogenetic evidence for persistence by comparing human and swine IAV. Models suggest a CHS of approximately 3000 pigs above which influenza was likely to persist, i.e. orders of magnitude lower than persistence thresholds for IAV and other acute viruses in humans. At national and regional scales, we found much stronger empirical signatures of prolonged persistence of IAV in swine compared with human populations. These striking levels of persistence in small populations are driven by the high recruitment rate of susceptible piglets, and have significant implications for management of swine and for overall patterns of genetic diversity of IAV. PMID:27358277

  2. Genetic Virulence Profile of Enteroaggregative Escherichia coli Strains Isolated from Danish Children with Either Acute or Persistent Diarrhea.

    PubMed

    Hebbelstrup Jensen, Betina; Poulsen, Anja; Hebbelstrup Rye Rasmussen, Stig; Struve, Carsten; Engberg, Jørgen H; Friis-Møller, Alice; Boisen, Nadia; Jønsson, Rie; Petersen, Randi F; Petersen, Andreas M; Krogfelt, Karen A

    2017-01-01

    Enteroaggregative Escherichia coli (EAEC) is frequently found in diarrheal stools worldwide. It has been associated with persistent diarrhea, weight loss, and failure to thrive in children living in developing countries. A number of important EAEC virulence genes are identified; however, their roles in acute and persistent diarrhea have not been previously investigated. The aim of this study was to identify specific EAEC virulence genes associated with duration and type of diarrhea in Danish children. We aimed to improve the current diagnostics of EAEC and enable targeting of strains with an expected severe disease course. Questionnaires answered by parents provided information regarding duration of diarrhea and presence of blood or mucus. A total of 295 EAEC strains were collected from children with acute (≤7 days) and persistent diarrhea (≥14 days) and were compared by using multiplex PCR targeting the genes sat, sepA, pic, sigA, pet, astA, aatA, aggR, aaiC, aap, agg3/4C, ORF3, aafA, aggA, agg3A, agg4A , and agg5A . Furthermore, the distribution of EAEC genes in strains collected from cases of bloody, mucoid, and watery diarrhea was investigated. The classification and regression tree analysis (CART) was applied to investigate the relationship between EAEC virulence genes and diarrheal duration and type. Persistent diarrhea was associated with strains lacking the pic gene ( p = 0.002) and with the combination of the genes pic, sat , and absence of the aggA gene ( p = 0.05). Prolonged diarrhea was associated with the combination of the genes aatA and astA ( p = 0.03). Non-mucoid diarrhea was associated with strains lacking the aatA gene ( p = 0.004). Acute diarrhea was associated with the genes aggR, aap , and aggA by individual odds ratios. Resistance toward gentamicin and ciprofloxacin was observed in 7.5 and 3% of strains, respectively. Multi-drug resistance was observed in 38% of strains. Genetic host factors have been associated with an increased risk of

  3. Genetic Virulence Profile of Enteroaggregative Escherichia coli Strains Isolated from Danish Children with Either Acute or Persistent Diarrhea

    PubMed Central

    Hebbelstrup Jensen, Betina; Poulsen, Anja; Hebbelstrup Rye Rasmussen, Stig; Struve, Carsten; Engberg, Jørgen H.; Friis-Møller, Alice; Boisen, Nadia; Jønsson, Rie; Petersen, Randi F.; Petersen, Andreas M.; Krogfelt, Karen A.

    2017-01-01

    Enteroaggregative Escherichia coli (EAEC) is frequently found in diarrheal stools worldwide. It has been associated with persistent diarrhea, weight loss, and failure to thrive in children living in developing countries. A number of important EAEC virulence genes are identified; however, their roles in acute and persistent diarrhea have not been previously investigated. The aim of this study was to identify specific EAEC virulence genes associated with duration and type of diarrhea in Danish children. We aimed to improve the current diagnostics of EAEC and enable targeting of strains with an expected severe disease course. Questionnaires answered by parents provided information regarding duration of diarrhea and presence of blood or mucus. A total of 295 EAEC strains were collected from children with acute (≤7 days) and persistent diarrhea (≥14 days) and were compared by using multiplex PCR targeting the genes sat, sepA, pic, sigA, pet, astA, aatA, aggR, aaiC, aap, agg3/4C, ORF3, aafA, aggA, agg3A, agg4A, and agg5A. Furthermore, the distribution of EAEC genes in strains collected from cases of bloody, mucoid, and watery diarrhea was investigated. The classification and regression tree analysis (CART) was applied to investigate the relationship between EAEC virulence genes and diarrheal duration and type. Persistent diarrhea was associated with strains lacking the pic gene (p = 0.002) and with the combination of the genes pic, sat, and absence of the aggA gene (p = 0.05). Prolonged diarrhea was associated with the combination of the genes aatA and astA (p = 0.03). Non-mucoid diarrhea was associated with strains lacking the aatA gene (p = 0.004). Acute diarrhea was associated with the genes aggR, aap, and aggA by individual odds ratios. Resistance toward gentamicin and ciprofloxacin was observed in 7.5 and 3% of strains, respectively. Multi-drug resistance was observed in 38% of strains. Genetic host factors have been associated with an increased risk of EAEC

  4. Estimates of genetic parameters and eigenvector indices for milk production of Holstein cows.

    PubMed

    Savegnago, R P; Rosa, G J M; Valente, B D; Herrera, L G G; Carneiro, R L R; Sesana, R C; El Faro, L; Munari, D P

    2013-01-01

    The objectives of the present study were to estimate genetic parameters of monthly test-day milk yield (TDMY) of the first lactation of Brazilian Holstein cows using random regression (RR), and to compare the genetic gains for milk production and persistency, derived from RR models, using eigenvector indices and selection indices that did not consider eigenvectors. The data set contained monthly TDMY of 3,543 first lactations of Brazilian Holstein cows calving between 1994 and 2011. The RR model included the fixed effect of the contemporary group (herd-month-year of test days), the covariate calving age (linear and quadratic effects), and a fourth-order regression on Legendre orthogonal polynomials of days in milk (DIM) to model the population-based mean curve. Additive genetic and nongenetic animal effects were fit as RR with 4 classes of residual variance random effect. Eigenvector indices based on the additive genetic RR covariance matrix were used to evaluate the genetic gains of milk yield and persistency compared with the traditional selection index (selection index based on breeding values of milk yield until 305 DIM). The heritability estimates for monthly TDMY ranged from 0.12 ± 0.04 to 0.31 ± 0.04. The estimates of additive genetic and nongenetic animal effects correlation were close to 1 at adjacent monthly TDMY, with a tendency to diminish as the time between DIM classes increased. The first eigenvector was related to the increase of the genetic response of the milk yield and the second eigenvector was related to the increase of the genetic gains of the persistency but it contributed to decrease the genetic gains for total milk yield. Therefore, using this eigenvector to improve persistency will not contribute to change the shape of genetic curve pattern. If the breeding goal is to improve milk production and persistency, complete sequential eigenvector indices (selection indices composite with all eigenvectors) could be used with higher economic

  5. QUANTIFICATION OF TRANSGENIC PLANT MARKER GENE PERSISTENCE IN THE FIELD

    EPA Science Inventory

    Methods were developed to monitor persistence of genomic DNA in decaying plants in the field. As a model, we used recombinant neomycin phosphotransferase II (rNPT-II) marker genes present in genetically engineered plants. Polymerase chain reaction (PCR) primers were designed, com...

  6. Postepizootic Persistence of Venezuelan Equine Encephalitis Virus, Venezuela

    PubMed Central

    Navarro, Juan-Carlos; Medina, Gladys; Vasquez, Clovis; Coffey, Lark L.; Wang, Eryu; Suárez, Alexander; Biord, Hernán; Salas, Marlene

    2005-01-01

    Five years after the apparent end of the major 1995 Venezuelan equine encephalitis (VEE) epizootic/epidemic, focal outbreaks of equine encephalitis occurred in Carabobo and Barinas States of western Venezuela. Virus isolates from horses in each location were nearly identical in sequence to 1995 isolates, which suggests natural persistence of subtype IC VEE virus (VEEV) strains in a genetically stable mode. Serologic evidence indicated that additional outbreaks occurred in Barinas State in 2003. Field studies identified known Culex (Melanoconion) spp. vectors and reservoir hosts of enzootic VEEV but a dearth of typical epidemic vectors. Cattle serosurveys indicated the recent circulation of enzootic VEEV strains, and possibly of epizootic strains. Persistence of VEEV subtype IC strains and infection of horses at the end of the rainy season suggest the possibility of an alternative, cryptic transmission cycle involving survival through the dry season of infected vectors or persistently infected vertebrates. PMID:16485478

  7. Population genetic signatures of a climate change driven marine range extension.

    PubMed

    Ramos, Jorge E; Pecl, Gretta T; Moltschaniwskyj, Natalie A; Semmens, Jayson M; Souza, Carla A; Strugnell, Jan M

    2018-06-22

    Shifts in species distribution, or 'range shifts', are one of the most commonly documented responses to ocean warming, with important consequences for the function and structure of ecosystems, and for socio-economic activities. Understanding the genetic signatures of range shifts can help build our knowledge of the capacity of species to establish and persist in colonised areas. Here, seven microsatellite loci were used to examine the population connectivity, genetic structure and diversity of Octopus tetricus, which has extended its distribution several hundred kilometres polewards associated with the southwards extension of the warm East Australian Current along south-eastern Australia. The historical distribution and the range extension zones had significant genetic differences but levels of genetic diversity were comparable. The population in the range extension zone was sub-structured, contained relatively high levels of self-recruitment and was sourced by migrants from along the entire geographic distribution. Genetic bottlenecks and changes in population size were detected throughout the range extension axis. Persistent gene flow from throughout the historical zone and moderate genetic diversity may buffer the genetic bottlenecks and favour the range extension of O. tetricus. These characteristics may aid adaptation, establishment, and long-term persistence of the population in the range extension zone.

  8. Persistent hyperlactacidaemia: about a clinical case.

    PubMed

    Oliveira, Ana Rita Saraiva; Valente, Rosalina; Ramos, José; Ventura, Lurdes

    2013-05-22

    Lactate is the endogenous end product of the anaerobic glycolysis, whose production is favoured in situations of hypoperfusion or mitochondrial dysfunction. Leigh syndrome is a rare, progressive encephalomyopathy that represents a spectrum of mitochondrial genetic diseases phenotypically distinct, but with neuroradiological and pathological uniform presentation. We present the case of a 7-month-old infant, with a history of prematurity, psychomotor retardation and epilepsy, admitted to the paediatric intensive care unit (PICU) due to cardio-respiratory arrest because of respiratory infection. Hyperlactacidaemia was detected and was persistent. The study of redox potential was normal but MRI with spectroscopy identified bilateral and symmetrical lesions involving thalamic and basal ganglia, with small lactate peaks at T2 flair, findings that were suggestive of Leigh syndrome. Subsequent enzymatic study identified lack of pyruvate dehydrogenase. Persistent hyperlactacidaemia, in the appropriate clinical context, should lead to the screening of mitochondrial diseases.

  9. Lactose (mal)digestion evaluated by the 13C-lactose digestion test.

    PubMed

    Vonk, R J; Lin, Y; Koetse, H A; Huang, C; Zeng, G; Elzinga, H; Antoine, J; Stellaard, F

    2000-02-01

    The prevalence of genetically determined lactase nonpersistence is based on the results of the lactose H2 breath test. This test, however, is an indirect test, which might lead to misinterpretation. We determined lactase activity in healthy Chinese and Dutch students using a novel 13C-lactose digestion test. The cut-off value of this test was established in a Chinese population with a homogenous genetic background of lactase nonpersistence and was compared with the results obtained in a Caucasian population. Twenty-five grams of a 13C-lactose solution was consumed by 12 known H2-positive and 5 H2-negative Chinese students and 48 Dutch students and, subsequently, 13C-glucose concentration in plasma and H2 excretion in breath were measured. A similar 13C-glucose response curve was found in all Chinese students. The mean response curve in the Dutch students was more pronounced (P < 0.01). The 1 h (peak) plasma 13C-glucose concentration was the best discriminator between lactose digesting and maldigesting subjects. The cut-off level of 2 mmol L-1 13C-glucose in plasma was defined in the H2-positive Chinese students group. Based on the 13C-glucose response the prevalence of lactose maldigestion in the Dutch subjects was 25%; based on the lactose H2 breath test 17%. Using the 13C-lactose digestion test the results demonstrate a higher prevalence of lactose maldigestion in a Caucasian population than indicated by the results of the H2 breath test. A moderate increase in the plasma 13C-glucose concentration after consumption of 13C-lactose in the young adult Chinese subjects indicates a residual lactase activity in that age group, even when a positive H2 breath test result is obtained. These results indicate that the 13C-glucose concentration in plasma more accurately reflects the small intestinal lactose digestion capacity than the lactose H2 breath test.

  10. Prevalence of the AMHR2 mutation in Miniature Schnauzers and genetic investigation of a Belgian Malinois with persistent Müllerian duct syndrome.

    PubMed

    Smit, M M; Ekenstedt, K J; Minor, K M; Lim, C K; Leegwater, Paj; Furrow, E

    2018-04-01

    Persistent Müllerian duct syndrome (PMDS) is a sex-limited disorder in which males develop portions of the female reproductive tract. Important consequences of PMDS are cryptorchidism and its sequelae of infertility and increased risk of testicular cancer. Anti-Müllerian hormone (AMH) and its receptor (AMHR2) induce the regression of the Müllerian ducts in male embryos. In Miniature Schnauzer dogs, the genetic basis has been identified as an autosomal recessive nonsense mutation in AMHR2, but the allele frequency of the mutation is unknown. Thus, the primary objective of this study was to estimate the prevalence of the AMHR2 mutation in North American Miniature Schnauzers, in order to ascertain the value of genetic testing in this breed. An additional objective was to determine whether mutations in AMH or AMHR2 were responsible for PMDS in a Belgian Malinois; this would aid development of a genetic test for the Belgian Malinois breed. Genomic DNA from 216 Miniature Schnauzers (including one known PMDS case) was genotyped for the AMHR2 mutation, and DNA from a single PMDS-affected Belgian Malinois was sequenced for all coding exons of AMH and AMHR2. The Miniature Schnauzer cohort had an AMHR2 mutation allele frequency of 0.16 and a carrier genotypic frequency of 0.27. The genetic basis for PMDS in the Belgian Malinois was not determined, as no coding or splicing mutations were identified in either AMH or AMHR2. These findings support a benefit to AMHR2 mutation testing Miniature Schnauzers used for breeding or with cryptorchidism. © 2017 Blackwell Verlag GmbH.

  11. Genomic analysis of lactation persistency in four breeds of dairy cattle

    USDA-ARS?s Scientific Manuscript database

    The objectives of this study were to determine gains in reliability from the addition of genomic information to genetic evaluations for best predictions of lactation persistency in US Ayrshire (AY), Brown Swiss (BS), Holstein (HO), and Jersey (JE) cattle, and to identify genomic regions with large e...

  12. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment.

    PubMed

    Misselwitz, Benjamin; Pohl, Daniel; Frühauf, Heiko; Fried, Michael; Vavricka, Stephan R; Fox, Mark

    2013-06-01

    Lactose malabsorption is a common condition caused by reduced expression or activity of lactase in the small intestine. In such patients, lactose intolerance is characterized by abdominal symptoms (e.g. nausea, bloating, and pain) after ingestion of dairy products. The genetic basis of lactose malabsorption is established and several tests for this condition are available, including genetic, endoscopic, and H2-breath tests. In contrast, lactose intolerance is less well understood. Recent studies show that the risk of symptoms after lactose ingestion depends on the dose of lactose, lactase expression, intestinal flora, and sensitivity of the gastrointestinal tract. Lactose intolerance has recently been defined as symptoms developing after ingestion of lactose which do not develop after placebo challenge in a person with lactose maldigestion. Such blinded testing might be especially important in those with functional gastrointestinal diseases in whom self-reported lactose intolerance is common. However, placebo-controlled testing is not part of current clinical practice. Updated protocols and high-quality outcome studies are needed. Treatment options of lactose intolerance include lactose-reduced diet and enzyme replacement. Documenting the response to multiple doses can guide rational dietary management; however, the clinical utility of this strategy has not been tested. This review summarizes the genetic basis, diagnosis, and treatment of lactose malabsorption and intolerance.

  13. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment

    PubMed Central

    Pohl, Daniel; Frühauf, Heiko; Fried, Michael; Vavricka, Stephan R; Fox, Mark

    2013-01-01

    Lactose malabsorption is a common condition caused by reduced expression or activity of lactase in the small intestine. In such patients, lactose intolerance is characterized by abdominal symptoms (e.g. nausea, bloating, and pain) after ingestion of dairy products. The genetic basis of lactose malabsorption is established and several tests for this condition are available, including genetic, endoscopic, and H2-breath tests. In contrast, lactose intolerance is less well understood. Recent studies show that the risk of symptoms after lactose ingestion depends on the dose of lactose, lactase expression, intestinal flora, and sensitivity of the gastrointestinal tract. Lactose intolerance has recently been defined as symptoms developing after ingestion of lactose which do not develop after placebo challenge in a person with lactose maldigestion. Such blinded testing might be especially important in those with functional gastrointestinal diseases in whom self-reported lactose intolerance is common. However, placebo-controlled testing is not part of current clinical practice. Updated protocols and high-quality outcome studies are needed. Treatment options of lactose intolerance include lactose-reduced diet and enzyme replacement. Documenting the response to multiple doses can guide rational dietary management; however, the clinical utility of this strategy has not been tested. This review summarizes the genetic basis, diagnosis, and treatment of lactose malabsorption and intolerance. PMID:24917953

  14. Drosophila Insulin receptor regulates the persistence of injury-induced nociceptive sensitization

    PubMed Central

    Patel, Atit A.

    2018-01-01

    ABSTRACT Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury. However, their acute thermal hypersensitivity persists and fails to return to baseline, unlike in controls. Remarkably, injury-induced persistent hypersensitivity is also observed in larvae that exhibit either type 1 or type 2 diabetes. Cell type-specific genetic analysis indicates that InR function is required in multidendritic sensory neurons including nociceptive class IV neurons. In these same nociceptive sensory neurons, only modest changes in dendritic morphology were observed in the InRRNAi-expressing and diabetic larvae. At the cellular level, InR-deficient nociceptive sensory neurons show elevated calcium responses after injury. Sensory neuron-specific expression of InR rescues the persistent thermal hypersensitivity of InR mutants and constitutive activation of InR in sensory neurons ameliorates the hypersensitivity observed with a type 2-like diabetic state. Our results suggest that a sensory neuron-specific function of InR regulates the persistence of injury-associated hypersensitivity. It is likely that this new system will be an informative genetically tractable model of diabetes-associated hypersensitivity. PMID:29752280

  15. Salt stress-induced transcription of σB- and CtsR-regulated genes in persistent and non-persistent Listeria monocytogenes strains from food processing plants.

    PubMed

    Ringus, Daina L; Ivy, Reid A; Wiedmann, Martin; Boor, Kathryn J

    2012-03-01

    Listeria monocytogenes is a foodborne pathogen that can persist in food processing environments. Six persistent and six non-persistent strains from fish processing plants and one persistent strain from a meat plant were selected to determine if expression of genes in the regulons of two stress response regulators, σ(B) and CtsR, under salt stress conditions is associated with the ability of L. monocytogenes to persist in food processing environments. Subtype data were also used to categorize the strains into genetic lineages I or II. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure transcript levels for two σ(B)-regulated genes, inlA and gadD3, and two CtsR-regulated genes, lmo1138 and clpB, before and after (t=10 min) salt shock (i.e., exposure of exponential phase cells to BHI+6% NaCl for 10 min at 37°C). Exposure to salt stress induced higher transcript levels relative to levels under non-stress conditions for all four stress and virulence genes across all wildtype strains tested. Analysis of variance (ANOVA) of induction data revealed that transcript levels for one gene (clpB) were induced at significantly higher levels in non-persistent strains compared to persistent strains (p=0.020; two-way ANOVA). Significantly higher transcript levels of gadD3 (p=0.024; two-way ANOVA) and clpB (p=0.053; two-way ANOVA) were observed after salt shock in lineage I strains compared to lineage II strains. No clear association between stress gene transcript levels and persistence was detected. Our data are consistent with an emerging model that proposes that establishment of L. monocytogenes persistence in a specific environment occurs as a random, stochastic event, rather than as a consequence of specific bacterial strain characteristics.

  16. Coral reef fish populations can persist without immigration

    PubMed Central

    Salles, Océane C.; Maynard, Jeffrey A.; Joannides, Marc; Barbu, Corentin M.; Saenz-Agudelo, Pablo; Almany, Glenn R.; Berumen, Michael L.; Thorrold, Simon R.; Jones, Geoffrey P.; Planes, Serge

    2015-01-01

    Determining the conditions under which populations may persist requires accurate estimates of demographic parameters, including immigration, local reproductive success, and mortality rates. In marine populations, empirical estimates of these parameters are rare, due at least in part to the pelagic dispersal stage common to most marine organisms. Here, we evaluate population persistence and turnover for a population of orange clownfish, Amphiprion percula, at Kimbe Island in Papua New Guinea. All fish in the population were sampled and genotyped on five occasions at 2-year intervals spanning eight years. The genetic data enabled estimates of reproductive success retained in the same population (reproductive success to self-recruitment), reproductive success exported to other subpopulations (reproductive success to local connectivity), and immigration and mortality rates of sub-adults and adults. Approximately 50% of the recruits were assigned to parents from the Kimbe Island population and this was stable through the sampling period. Stability in the proportion of local and immigrant settlers is likely due to: low annual mortality rates and stable egg production rates, and the short larval stages and sensory capacities of reef fish larvae. Biannual mortality rates ranged from 0.09 to 0.55 and varied significantly spatially. We used these data to parametrize a model that estimated the probability of the Kimbe Island population persisting in the absence of immigration. The Kimbe Island population was found to persist without significant immigration. Model results suggest the island population persists because the largest of the subpopulations are maintained due to having low mortality and high self-recruitment rates. Our results enable managers to appropriately target and scale actions to maximize persistence likelihood as disturbance frequencies increase. PMID:26582017

  17. Coral reef fish populations can persist without immigration.

    PubMed

    Salles, Océane C; Maynard, Jeffrey A; Joannides, Marc; Barbu, Corentin M; Saenz-Agudelo, Pablo; Almany, Glenn R; Berumen, Michael L; Thorrold, Simon R; Jones, Geoffrey P; Planes, Serge

    2015-11-22

    Determining the conditions under which populations may persist requires accurate estimates of demographic parameters, including immigration, local reproductive success, and mortality rates. In marine populations, empirical estimates of these parameters are rare, due at least in part to the pelagic dispersal stage common to most marine organisms. Here, we evaluate population persistence and turnover for a population of orange clownfish, Amphiprion percula, at Kimbe Island in Papua New Guinea. All fish in the population were sampled and genotyped on five occasions at 2-year intervals spanning eight years. The genetic data enabled estimates of reproductive success retained in the same population (reproductive success to self-recruitment), reproductive success exported to other subpopulations (reproductive success to local connectivity), and immigration and mortality rates of sub-adults and adults. Approximately 50% of the recruits were assigned to parents from the Kimbe Island population and this was stable through the sampling period. Stability in the proportion of local and immigrant settlers is likely due to: low annual mortality rates and stable egg production rates, and the short larval stages and sensory capacities of reef fish larvae. Biannual mortality rates ranged from 0.09 to 0.55 and varied significantly spatially. We used these data to parametrize a model that estimated the probability of the Kimbe Island population persisting in the absence of immigration. The Kimbe Island population was found to persist without significant immigration. Model results suggest the island population persists because the largest of the subpopulations are maintained due to having low mortality and high self-recruitment rates. Our results enable managers to appropriately target and scale actions to maximize persistence likelihood as disturbance frequencies increase. © 2015 The Author(s).

  18. The persistence and ecological impacts of a cyanobacterium genetically engineered to express mosquitocidal Bacillus thuringiensis toxins.

    PubMed

    Ketseoglou, Irene; Bouwer, Gustav

    2016-05-10

    The cyanobacterium Anabaena PCC 7120#11 has been genetically engineered to act as a delivery vehicle for Bacillus thuringiensis subspecies israelensis mosquitocidal toxins. To address ecological concerns about releasing this genetically engineered microorganism into the environment for mosquito larva control, the persistence and ecological impacts of PCC 7120#11 was evaluated using multi-species, standardized aquatic microcosms. The microcosms were set up as described in ASTM E1366-02 (Standard Practice for Standardized Aquatic Microcosms: Fresh Water), with a few modifications. The treatment group microcosms were inoculated with PCC 7120#11 and key water quality parameters and non-target effects were compared between the treatment and control groups over a period of 35 days. PCC 7120#11 decreased from a concentration of 4.50 × 10(6) cells/ml (at inoculation) to 1.32 × 10(3) cells/ml after 4 weeks and larvicidal activity against third instar larvae of Anopheles arabiensis was only evident for two weeks after treatment. Both treatment and the interaction of treatment and time had a significant effect on nitrate, phosphate and photosynthetic microorganism concentrations. Treatment with PCC 7120#11 caused a temporary spike in ammonia in the microcosms a week after treatment, but the concentrations were well below acute and chronic criteria values for ammonia in freshwater ecosystems. Cyprinotus vidua concentrations were not significantly different between PCC 7120#11 and control microcosms. In PCC 7120#11 microcosms, Daphnia pulex concentrations were significantly lower than control concentrations between days 18 and 25. By the end of the experiment, none of the measured variables were significantly different between the treatment groups. The standard aquatic microcosm experiments provided more data on the ecological impacts of PCC 7120#11 than single-organism assessments would have. On the basis of the relatively minor, short-term effects that PCC 7120

  19. In Vitro Emergence of High Persistence upon Periodic Aminoglycoside Challenge in the ESKAPE Pathogens

    PubMed Central

    Verstraeten, Natalie; Fauvart, Maarten

    2016-01-01

    Health care-associated infections present a major threat to modern medical care. Six worrisome nosocomial pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—are collectively referred to as the “ESKAPE bugs.” They are notorious for extensive multidrug resistance, yet persistence, or the phenotypic tolerance displayed by a variant subpopulation, remains underappreciated in these pathogens. Importantly, persistence can prevent eradication of antibiotic-sensitive bacterial populations and is thought to act as a catalyst for the development of genetic resistance. Concentration- and time-dependent aminoglycoside killing experiments were used to investigate persistence in the ESKAPE pathogens. Additionally, a recently developed method for the experimental evolution of persistence was employed to investigate adaptation to high-dose, extended-interval aminoglycoside therapy in vitro. We show that ESKAPE pathogens exhibit biphasic killing kinetics, indicative of persister formation. In vitro cycling between aminoglycoside killing and persister cell regrowth, evocative of clinical high-dose extended-interval therapy, caused a 37- to 213-fold increase in persistence without the emergence of resistance. Increased persistence also manifested in biofilms and provided cross-tolerance to different clinically important antibiotics. Together, our results highlight a possible drawback of intermittent, high-dose antibiotic therapy and suggest that clinical diagnostics might benefit from taking into account persistence. PMID:27185802

  20. Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization.

    PubMed

    Smith, Caren E; Coltell, Oscar; Sorlí, Jose V; Estruch, Ramón; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Fitó, Montserrat; Arós, Fernando; Dashti, Hassan S; Lai, Chao Q; Miró, Leticia; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Fiol, Miquel; Ros, Emilio; Aslibekyan, Stella; Hidalgo, Bertha; Neuhouser, Marian L; Di, Chongzhi; Tucker, Katherine L; Arnett, Donna K; Ordovás, José M; Corella, Dolores

    2016-09-14

    Controversy persists on the association between dairy products, especially milk, and cardiovascular diseases (CVD). Genetic proxies may improve dairy intake estimations, and clarify diet-disease relationships through Mendelian randomization. We meta-analytically (n ≤ 20,089) evaluated associations between a lactase persistence (LP) SNP, the minichromosome maintenance complex component 6 (MCM6)-rs3754686C>T (nonpersistence>persistence), dairy intake, and CVD biomarkers in American (Hispanics, African-American and Whites) and Mediterranean populations. Moreover, we analyzed longitudinal associations with milk, CVD and mortality in PREDIMED), a randomized Mediterranean diet (MedDiet) intervention trial (n = 7185). The MCM6-rs3754686/MCM6-rs309180 (as proxy), LP-allele (T) was strongly associated with higher milk intake, but inconsistently associated with glucose and lipids, and not associated with CVD or total mortality in the whole population. Heterogeneity analyses suggested some sex-specific associations. The T-allele was associated with higher CVD and mortality risk in women but not in men (P-sex interaction:0.005 and 0.032, respectively), mainly in the MedDiet group. However, milk intake was not associated with CVD biomarkers, CVD or mortality either generally or in sub-groups. Although MCM6-rs3754686 is a good milk intake proxy in these populations, attributing its associations with CVD and mortality in Mediterranean women to milk is unwarranted, as other factors limiting the assumption of causality in Mendelian randomization may exist.

  1. The Persistence of American Indian Health Disparities

    PubMed Central

    Jones, David S.

    2006-01-01

    Disparities in health status between American Indians and other groups in the United States have persisted throughout the 500 years since Europeans arrived in the Americas. Colonists, traders, missionaries, soldiers, physicians, and government officials have struggled to explain these disparities, invoking a wide range of possible causes. American Indians joined these debates, often suggesting different explanations. Europeans and Americans also struggled to respond to the disparities, sometimes working to relieve them, sometimes taking advantage of the ill health of American Indians. Economic and political interests have always affected both explanations of health disparities and responses to them, influencing which explanations were emphasized and which interventions were pursued. Tensions also appear in ongoing debates about the contributions of genetic and socioeconomic forces to the pervasive health disparities. Understanding how these economic and political forces have operated historically can explain both the persistence of the health disparities and the controversies that surround them. PMID:17077399

  2. Milk Intake at Midlife and Cognitive Decline over 20 Years. The Atherosclerosis Risk in Communities (ARIC) Study.

    PubMed

    Petruski-Ivleva, Natalia; Kucharska-Newton, Anna; Palta, Priya; Couper, David; Meyer, Katie; Graff, Misa; Haring, Bernhard; Sharrett, Richey; Heiss, Gerardo

    2017-10-17

    Background : Faster rates of cognitive decline are likely to result in earlier onset of cognitive impairment and dementia. d-galactose, a derivative of lactose, is used in animal studies to induce neurodegeneration. Milk is the primary source of lactose in the human diet, and its effects on cognitive decline have not been fully evaluated. Objective : Assess the association of milk intake with change in cognitive function over 20 years. Methods : A total of 13,751 participants of the Atherosclerosis Risk in Communities (ARIC) cohort completed a food frequency questionnaire and three neurocognitive evaluations from 1990 through 2013. Two single nucleotide polymorphisms (SNPs) were used to determine lactase persistence (LCT-13910 C/T for Whites and LCT-14010 G/C for Blacks). Mixed-effects models were used to study the association of milk intake with cognitive change. Multiple imputations by chained equations were used to account for attrition. Results : Milk intake greater than 1 glass/day was associated with greater decline in the global z-score over a 20-year period. The difference in decline was 0.10 (95% CI: 0.16, 0.03) z-scores, or an additional 10% decline, relative to the group reporting "almost never" consuming milk. Conclusions : Replication of these results is warranted in diverse populations with greater milk intake and higher variability of lactase persistence genotype.

  3. Milk Intake at Midlife and Cognitive Decline over 20 Years. The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Petruski-Ivleva, Natalia; Kucharska-Newton, Anna; Palta, Priya; Meyer, Katie; Graff, Misa; Haring, Bernhard; Sharrett, Richey; Heiss, Gerardo

    2017-01-01

    Background: Faster rates of cognitive decline are likely to result in earlier onset of cognitive impairment and dementia. d-galactose, a derivative of lactose, is used in animal studies to induce neurodegeneration. Milk is the primary source of lactose in the human diet, and its effects on cognitive decline have not been fully evaluated. Objective: Assess the association of milk intake with change in cognitive function over 20 years. Methods: A total of 13,751 participants of the Atherosclerosis Risk in Communities (ARIC) cohort completed a food frequency questionnaire and three neurocognitive evaluations from 1990 through 2013. Two single nucleotide polymorphisms (SNPs) were used to determine lactase persistence (LCT-13910 C/T for Whites and LCT-14010 G/C for Blacks). Mixed-effects models were used to study the association of milk intake with cognitive change. Multiple imputations by chained equations were used to account for attrition. Results: Milk intake greater than 1 glass/day was associated with greater decline in the global z-score over a 20-year period. The difference in decline was 0.10 (95% CI: 0.16, 0.03) z-scores, or an additional 10% decline, relative to the group reporting “almost never” consuming milk. Conclusions: Replication of these results is warranted in diverse populations with greater milk intake and higher variability of lactase persistence genotype. PMID:29039795

  4. Anger/Frustration, Task Persistence, and Conduct Problems in Childhood: A Behavioral Genetic Analysis

    ERIC Educational Resources Information Center

    Deater-Deckard, Kirby; Petrill, Stephen A.; Thompson, Lee A.

    2007-01-01

    Background: Individual differences in conduct problems arise in part from proneness to anger/frustration and poor self-regulation of behavior. However, the genetic and environmental etiology of these connections is not known. Method: Using a twin design, we examined genetic and environmental covariation underlying the well-documented correlations…

  5. Neglect of genetic diversity in implementation of the Convention on Biological Diversity

    Treesearch

    Linda Laikre; Fred W. Allendorf; Laurel C. Aroner; C. Scott Baker; David P. Gregovich; Michael M. Hansen; Jennifer A. Jackson; Katherine C. Kendall; Kevin Mckelvey; Maile C. Neel; Isabelle Olivieri; Nils Ryman; Michael K. Schwartz; Ruth Short Bull; Jeffrey B. Stetz; David A. Tallmon; Barbara L. Taylor; Christina D. Vojta; Donald M. Waller; Robin S. Waples

    2009-01-01

    Genetic diversity is the foundation for all biological diversity; the persistence and evolutionary potential of species depend on it. World leaders have agreed on the conservation of genetic diversity as an explicit goal of the Convention on Biological Diversity (CBD). Nevertheless, actions to protect genetic diversity are largely lacking. With only months left to the...

  6. Interspecies transmission and limited persistence of low pathogenic avian influenza genomes among Alaska dabbling ducks

    USGS Publications Warehouse

    Reeves, Andrew B.; Pearce, John M.; Ramey, Andy M.; Meixell, Brandt W.; Runstadler, Jonathan A.

    2011-01-01

    The reassortment and geographic distribution of low pathogenic avian influenza (LPAI) virus genes are well documented, but little is known about the persistence of intact LPAI genomes among species and locations. To examine persistence of entire LPAI genome constellations in Alaska, we calculated the genetic identities among 161 full-genome LPAI viruses isolated across 4 years from five species of duck: northern pintail (Anas acuta), mallard (Anas platyrhynchos), American green-winged teal (Anas crecca), northern shoveler (Anas clypeata) and American wigeon (Anas americana). Based on pairwise genetic distance, highly similar LPAI genomes (>99% identity) were observed within and between species and across a range of geographic distances (up to and >1000 km), but most often between isolates collected 0–10 km apart. Highly similar viruses were detected between years, suggesting inter-annual persistence, but these were rare in our data set with the majority occurring within 0–9 days of sampling. These results identify LPAI transmission pathways in the context of species, space and time, an initial perspective into the extent of regional virus distribution and persistence, and insight into why no completely Eurasian genomes have ever been detected in Alaska. Such information will be useful in forecasting the movement of foreign-origin avian influenza strains should they be introduced to North America.

  7. Interspecies transmission and limited persistence of low pathogenic avian influenza genomes among Alaska dabbling ducks.

    PubMed

    Reeves, Andrew B; Pearce, John M; Ramey, Andrew M; Meixell, Brandt W; Runstadler, Jonathan A

    2011-12-01

    The reassortment and geographic distribution of low pathogenic avian influenza (LPAI) virus genes are well documented, but little is known about the persistence of intact LPAI genomes among species and locations. To examine persistence of entire LPAI genome constellations in Alaska, we calculated the genetic identities among 161 full-genome LPAI viruses isolated across 4 years from five species of duck: northern pintail (Anas acuta), mallard (Anas platyrhynchos), American green-winged teal (Anas crecca), northern shoveler (Anas clypeata) and American wigeon (Anas americana). Based on pairwise genetic distance, highly similar LPAI genomes (>99% identity) were observed within and between species and across a range of geographic distances (up to and >1000 km), but most often between isolates collected 0-10 km apart. Highly similar viruses were detected between years, suggesting inter-annual persistence, but these were rare in our data set with the majority occurring within 0-9 days of sampling. These results identify LPAI transmission pathways in the context of species, space and time, an initial perspective into the extent of regional virus distribution and persistence, and insight into why no completely Eurasian genomes have ever been detected in Alaska. Such information will be useful in forecasting the movement of foreign-origin avian influenza strains should they be introduced to North America. Published by Elsevier B.V.

  8. In Vitro Emergence of High Persistence upon Periodic Aminoglycoside Challenge in the ESKAPE Pathogens.

    PubMed

    Michiels, Joran Elie; Van den Bergh, Bram; Verstraeten, Natalie; Fauvart, Maarten; Michiels, Jan

    2016-08-01

    Health care-associated infections present a major threat to modern medical care. Six worrisome nosocomial pathogens-Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.-are collectively referred to as the "ESKAPE bugs." They are notorious for extensive multidrug resistance, yet persistence, or the phenotypic tolerance displayed by a variant subpopulation, remains underappreciated in these pathogens. Importantly, persistence can prevent eradication of antibiotic-sensitive bacterial populations and is thought to act as a catalyst for the development of genetic resistance. Concentration- and time-dependent aminoglycoside killing experiments were used to investigate persistence in the ESKAPE pathogens. Additionally, a recently developed method for the experimental evolution of persistence was employed to investigate adaptation to high-dose, extended-interval aminoglycoside therapy in vitro We show that ESKAPE pathogens exhibit biphasic killing kinetics, indicative of persister formation. In vitro cycling between aminoglycoside killing and persister cell regrowth, evocative of clinical high-dose extended-interval therapy, caused a 37- to 213-fold increase in persistence without the emergence of resistance. Increased persistence also manifested in biofilms and provided cross-tolerance to different clinically important antibiotics. Together, our results highlight a possible drawback of intermittent, high-dose antibiotic therapy and suggest that clinical diagnostics might benefit from taking into account persistence. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut.

    PubMed

    Porse, Andreas; Gumpert, Heidi; Kubicek-Sutherland, Jessica Z; Karami, Nahid; Adlerberth, Ingegerd; Wold, Agnes E; Andersson, Dan I; Sommer, Morten O A

    2017-01-01

    Elucidating the adaptive strategies and plasticity of bacterial genomes in situ is crucial for understanding the epidemiology and evolution of pathogens threatening human health. While much is known about the evolution of Escherichia coli in controlled laboratory environments, less effort has been made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut during the first year of life. One E. coli lineage causes a urinary tract infection (UTI) and experiences several alterations of its genomic content during subsequent antibiotic treatment. Interestingly, all isolates of this uropathogenic E. coli strain carried a highly stable plasmid implicated in virulence of diverse pathogenic strains from all over the world. While virulence elements are certainly beneficial during infection scenarios, their role in gut colonization and pathogen persistence is poorly understood. We performed in vivo competitive fitness experiments to assess the role of this highly disseminated virulence plasmid in gut colonization, but found no evidence for a direct benefit of plasmid carriage. Through plasmid stability assays, we demonstrate that this plasmid is maintained in a parasitic manner, by strong first-line inheritance mechanisms, acting on the single-cell level, rather than providing a direct survival advantage in the gut. Investigating the ecology of endemic accessory genetic elements, in their pathogenic hosts and native environment, is of vital importance if we want to understand the evolution and persistence of highly virulent and drug resistant bacterial isolates.

  10. Genetic Structure and Diversity of the Endangered Fir Tree of Lebanon (Abies cilicica Carr.): Implications for Conservation

    PubMed Central

    Awad, Lara; Fady, Bruno; Khater, Carla; Roig, Anne; Cheddadi, Rachid

    2014-01-01

    The threatened conifer Abies cilicica currently persists in Lebanon in geographically isolated forest patches. The impact of demographic and evolutionary processes on population genetic diversity and structure were assessed using 10 nuclear microsatellite loci. All remnant 15 local populations revealed a low genetic variation but a high recent effective population size. FST-based measures of population genetic differentiation revealed a low spatial genetic structure, but Bayesian analysis of population structure identified a significant Northeast-Southwest population structure. Populations showed significant but weak isolation-by-distance, indicating non-equilibrium conditions between dispersal and genetic drift. Bayesian assignment tests detected an asymmetric Northeast-Southwest migration involving some long-distance dispersal events. We suggest that the persistence and Northeast-Southwest geographic structure of Abies cilicica in Lebanon is the result of at least two demographic processes during its recent evolutionary history: (1) recent migration to currently marginal populations and (2) local persistence through altitudinal shifts along a mountainous topography. These results might help us better understand the mechanisms involved in the species response to expected climate change. PMID:24587219

  11. Interpreting phenotypic antibiotic tolerance and persister cells as evolution via epigenetic inheritance.

    PubMed

    Day, Troy

    2016-04-01

    Epigenetic inheritance is the transmission of nongenetic material such as gene expression levels, RNA and other biomolecules from parents to offspring. There is a growing realization that such forms of inheritance can play an important role in evolution. Bacteria represent a prime example of epigenetic inheritance because a large array of cellular components is transmitted to offspring, in addition to genetic material. Interestingly, there is an extensive and growing empirical literature showing that many bacteria can form 'persister' cells that are phenotypically resistant or tolerant to antibiotics, but most of these results are not interpreted within the context of epigenetic inheritance. Instead, persister cells are usually viewed as a genetically encoded bet-hedging strategy that has evolved in response to a fluctuating environment. Here I show, using a relatively simple model, that many of these empirical findings can be more simply understood as arising from a combination of epigenetic inheritance and cellular noise. I therefore suggest that phenotypic drug tolerance in bacteria might represent one of the best-studied examples of evolution under epigenetic inheritance. © 2016 John Wiley & Sons Ltd.

  12. Systems Biology-Based Identification of Mycobacterium tuberculosis Persistence Genes in Mouse Lungs

    PubMed Central

    Dutta, Noton K.; Bandyopadhyay, Nirmalya; Veeramani, Balaji; Lamichhane, Gyanu; Karakousis, Petros C.; Bader, Joel S.

    2014-01-01

    ABSTRACT Identifying Mycobacterium tuberculosis persistence genes is important for developing novel drugs to shorten the duration of tuberculosis (TB) treatment. We developed computational algorithms that predict M. tuberculosis genes required for long-term survival in mouse lungs. As the input, we used high-throughput M. tuberculosis mutant library screen data, mycobacterial global transcriptional profiles in mice and macrophages, and functional interaction networks. We selected 57 unique, genetically defined mutants (18 previously tested and 39 untested) to assess the predictive power of this approach in the murine model of TB infection. We observed a 6-fold enrichment in the predicted set of M. tuberculosis genes required for persistence in mouse lungs relative to randomly selected mutant pools. Our results also allowed us to reclassify several genes as required for M. tuberculosis persistence in vivo. Finally, the new results implicated additional high-priority candidate genes for testing. Experimental validation of computational predictions demonstrates the power of this systems biology approach for elucidating M. tuberculosis persistence genes. PMID:24549847

  13. Studies on Monitoring and Tracking Genetic Resources: An Executive Summary

    PubMed Central

    Garrity, George M.; Thompson, Lorraine M.; Ussery, David W.; Paskin, Norman; Baker, Dwight; Desmeth, Philippe; Schindel, D.E.; Ong, P.S.

    2009-01-01

    The principles underlying fair and equitable sharing of benefits derived from the utilization of genetic resources are set out in Article 15 of the UN Convention on Biological Diversity, which stipulate that access to genetic resources is subject to the prior informed consent of the country where such resources are located and to mutually agreed terms regarding the sharing of benefits that could be derived from such access. One issue of particular concern for provider countries is how to monitor and track genetic resources once they have left the provider country and enter into use in a variety of forms. This report was commissioned to provide a detailed review of advances in DNA sequencing technologies, as those methods apply to identification of genetic resources, and the use of globally unique persistent identifiers for persistently linking to data and other forms of digital documentation that is linked to individual genetic resources. While the report was written for an audience with a mixture of technical, legal, and policy backgrounds it is relevant to the genomics community as it is an example of downstream application of genomics information. PMID:21304641

  14. Association of genetic and psychological factors with persistent pain after cosmetic thoracic surgery

    PubMed Central

    Dimova, Violeta; Lötsch, Jörn; Hühne, Kathrin; Winterpacht, Andreas; Heesen, Michael; Parthum, Andreas; Weber, Peter G; Carbon, Roman; Griessinger, Norbert; Sittl, Reinhard; Lautenbacher, Stefan

    2015-01-01

    The genetic control of pain has been repeatedly demonstrated in human association studies. In the present study, we assessed the relative contribution of 16 single nucleotide polymorphisms in pain-related genes, such as cathechol-O-methyl transferase gene (COMT), fatty acid amino hydrolase gene (FAAH), transient receptor potential cation channel, subfamily V, member 1 gene (TRPV1), and δ-opioid receptor gene (OPRD1), for postsurgical pain chronification. Ninety preoperatively pain-free male patients were assigned to good or poor outcome groups according to their intensity or disability score assessed at 1 week, 3 months, 6 months, and 1 year after funnel chest correction. The genetic effects were compared with those of two psychological predictors, the attentional bias toward positive words (dot-probe task) and the self-reported pain vigilance (Pain Vigilance and Awareness Questionnaire [PVAQ]), which were already shown to be the best predictors for pain intensity and disability at 6 months after surgery in the same sample, respectively. Cox regression analyses revealed no significant effects of any of the genetic predictors up to the end point of survival time at 1 year after surgery. Adding the genetics to the prediction by the attentional bias to positive words for pain intensity and the PVAQ for pain disability, again no significant additional explanation could be gained by the genetic predictors. In contrast, the preoperative PVAQ score was also, in the present enlarged sample, a meaningful predictor for lasting pain disability after surgery. Effect size measures suggested some genetic variables, for example, the polymorphism rs1800587G>A in the interleukin 1 alpha gene (IL1A) and the COMT haplotype rs4646312T>C/rs165722T>C/rs6269A>G/rs4633T>C/rs4818C>G/rs4680A>G, as possible relevant modulators of long-term postsurgical pain outcome. A comparison between pathophysiologically different predictor groups appears to be helpful in identifying clinically relevant

  15. [Lactose intolerance: past and present. Part 1].

    PubMed

    Buzás, György Miklós

    2015-09-20

    Lactose intolerance is the most prevalent intestinal malabsorption disorder. After presentation of its history, the author describes the emergence of lactose intolerance during the evolution of species, and the biochemistry of lactose as well as features of human and bacterial lactase enzymes are then described. The unequal distribution of lactose intolerance in different continents and population is discussed, followed by presentation of past and present prevalence data in Hungary. Adult-type hypolactasia is caused by a polymorphism of the MCM6 gene located upstream from the lactase gene on the long arm of the chromosome 2. It can be determined with the polymerase chain reaction. The intestinal symptoms of lactose intolerance are well known, but its extra-intestinal manifestations are less recognised. Invasive diagnostic methods (determination of lactase activity from small intestinal biopsies, lactose tolerance test), are accurate, but have been replaced by the non-invasive methods; their gold standard is the H2 breath test. Genetic testing is being used more and more frequently in Hungary too, and, presumably, the methane breath test will be also available in the near future. Lactose intolerance can be accompanied by inflammatory bowel diseases, coeliac disease and irritable bowel syndrome; it could be established whether this association is causal or not in order to start a correct diet and therapy.

  16. Persistence of Agrobacterium tumefaciens in transformed conifers.

    PubMed

    Charity, Julia A; Klimaszewska, Krystyna

    2005-01-01

    Previous studies have shown that the widely used plant transformation vector Agrobacterium tumefaciens can persist in genetically engineered plants in vitro and in transgenic greenhouse-grown plants, despite the use of counter-selective antibiotics. However, little is known regarding Agrobacterium persistence in tree species. To understand the kinetics of A. tumefaciens decline and persistence in transformation experiments, we assayed for the presence of A. tumefaciens in spruce and pine embryogenic tissue for up to 10 weeks post-transformation. The A. tumefaciens populations declined rapidly in the first five days post-cocultivation but generally declined more slowly in pine, relative to spruce. No bacteria were detected in spruce embryogenic tissue beyond four weeks after cocultivation, however in pine there were -100 colony forming units per g tissue at 10 weeks post-cocultivation. We present evidence that the detection limit for PCR using virD2 primers to detect A. tumefaciens in a background of pine needle DNA was approximately 10(9)-10(10) A. tumefaciens cells per g of tissue. We also assayed for A. tumefaciens in transgenic pine and spruce embryogenic tissue and from needles, branches, stems and roots of transformed plants, up to four years post-inoculation. Occasionally A. tumefaciens was detected in embryogenic tissue up to 12 months post-inoculation. A. tumefaciens was never detected in cultured embryogenic tissue more than twelve months after inoculation, nor in developing somatic embryos or germinating plantlets, nor any of the parts of greenhouse-grown plants. From these data we conclude that if A. tumefaciens persists in transgenic conifers, it does so beneath our ability to detect it.

  17. [Persistence of Pseudomonas aeruginosa strains in patients of Federal Scientific Center of Transplantology and Artificial Organs].

    PubMed

    Avetisian, L R; Voronina, O L; Chernukha, M Iu; Kunda, M S; Gabrielian, N I; Lunin, V G; Shaginian, I A

    2012-01-01

    Study genetic diversity of P. aeruginosa strains persisting in patients of Federal Scientific Center of Transplantology and Artificial Organs, and main factors facilitating persistence of strains in the hospital. 136 P. aeruginosa strains isolated from patients of the center for 3 years 6 months were genotyped by RAPD-PCR and MLST methods and studied for antibiotics resistance and presence of integrons. Genetic diversity of strains persisting in hospital was established. Strains of main genotypes ST235, ST446, ST598 were isolated from patients of various surgical departments. Patients were shown to be colonized by these strains during stay in reanimation and intensive therapy department (RITD) of the hospital. Strains of dominant genotype 235 were isolated from 47% of examined patients during more than 3 years. Only genotype 235 strains contained integron with cassettes of antibiotics resistance genes blaGES5 and aadA6 in the genome. The data obtained show that over the period of observation in the center 1 clone of P. aeruginosa that belonged to genotype 235 dominated. This clone was endemic for this hospital and in the process of prolonged persistence became more resistant to antibiotics. Colonization of patients with these strains occurs in RITD. This confirms the necessity of constant monitoring of hospital microflora for advance detection of potentially dangerous epidemic hospital strains able to cause hospital infections.

  18. Strategies used by helicobacter pylori to establish persistent infection

    PubMed Central

    Abadi, Amin Talebi Bezmin

    2017-01-01

    Helicobacter pylori (H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host’s entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium

  19. Fisher population and landscape genetics

    Treesearch

    Michael Schwartz; Joel Saunder; Kristine L. Pilgrim; Ray Vinkey; Michael K. Lucid; Sean Parks; Nathan Albrecht

    2013-01-01

    This talk provides a population and landscape genetic overview of fishers in Idaho and Montana. We start by discussing some of our initial findings using mitochondrial DNA (Vinkey et al. 2006, Schwartz 2007, Knaus et al. 2011). On balance these results demonstrate the uniqueness of a native haplotype that persisted in the Bitterroot-Selway Ecosystem. They also show the...

  20. Genetic erosion impedes adaptive responses to stressful environments

    PubMed Central

    Bijlsma, R; Loeschcke, Volker

    2012-01-01

    Biodiversity is increasingly subjected to human-induced changes of the environment. To persist, populations continually have to adapt to these often stressful changes including pollution and climate change. Genetic erosion in small populations, owing to fragmentation of natural habitats, is expected to obstruct such adaptive responses: (i) genetic drift will cause a decrease in the level of adaptive genetic variation, thereby limiting evolutionary responses; (ii) inbreeding and the concomitant inbreeding depression will reduce individual fitness and, consequently, the tolerance of populations to environmental stress. Importantly, inbreeding generally increases the sensitivity of a population to stress, thereby increasing the amount of inbreeding depression. As adaptation to stress is most often accompanied by increased mortality (cost of selection), the increase in the ‘cost of inbreeding’ under stress is expected to severely hamper evolutionary adaptive processes. Inbreeding thus plays a pivotal role in this process and is expected to limit the probability of genetically eroded populations to successfully adapt to stressful environmental conditions. Consequently, the dynamics of small fragmented populations may differ considerably from large nonfragmented populations. The resilience of fragmented populations to changing and deteriorating environments is expected to be greatly decreased. Alleviating inbreeding depression, therefore, is crucial to ensure population persistence. PMID:25568035

  1. Landscape-scale distribution and persistence of genetically modified oilseed rape (Brassica napus) in Manitoba, Canada.

    PubMed

    Knispel, Alexis L; McLachlan, Stéphane M

    2010-01-01

    Genetically modified herbicide-tolerant (GMHT) oilseed rape (OSR; Brassica napus L.) was approved for commercial cultivation in Canada in 1995 and currently represents over 95% of the OSR grown in western Canada. After a decade of widespread cultivation, GMHT volunteers represent an increasing management problem in cultivated fields and are ubiquitous in adjacent ruderal habitats, where they contribute to the spread of transgenes. However, few studies have considered escaped GMHT OSR populations in North America, and even fewer have been conducted at large spatial scales (i.e. landscape scales). In particular, the contribution of landscape structure and large-scale anthropogenic dispersal processes to the persistence and spread of escaped GMHT OSR remains poorly understood. We conducted a multi-year survey of the landscape-scale distribution of escaped OSR plants adjacent to roads and cultivated fields. Our objective was to examine the long-term dynamics of escaped OSR at large spatial scales and to assess the relative importance of landscape and localised factors to the persistence and spread of these plants outside of cultivation. From 2005 to 2007, we surveyed escaped OSR plants along roadsides and field edges at 12 locations in three agricultural landscapes in southern Manitoba where GMHT OSR is widely grown. Data were analysed to examine temporal changes at large spatial scales and to determine factors affecting the distribution of escaped OSR plants in roadside and field edge habitats within agricultural landscapes. Additionally, we assessed the potential for seed dispersal between escaped populations by comparing the relative spatial distribution of roadside and field edge OSR. Densities of escaped OSR fluctuated over space and time in both roadside and field edge habitats, though the proportion of GMHT plants was high (93-100%). Escaped OSR was positively affected by agricultural landscape (indicative of cropping intensity) and by the presence of an

  2. Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease.

    PubMed

    Middelveen, Marianne J; Sapi, Eva; Burke, Jennie; Filush, Katherine R; Franco, Agustin; Fesler, Melissa C; Stricker, Raphael B

    2018-04-14

    Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi , in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

  3. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management

    PubMed Central

    Deng, Yanyong; Misselwitz, Benjamin; Dai, Ning; Fox, Mark

    2015-01-01

    Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance. PMID:26393648

  4. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management.

    PubMed

    Deng, Yanyong; Misselwitz, Benjamin; Dai, Ning; Fox, Mark

    2015-09-18

    Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance.

  5. The capture of heritable variation for genetic quality through social competition.

    PubMed

    Wolf, Jason B; Harris, W Edwin; Royle, Nick J

    2008-09-01

    In theory, females of many species choose mates based on traits that are indicators of male genetic quality. A fundamental question in evolutionary biology is why genetic variation for such indicator traits persists despite strong persistent selection imposed by female preference, which is known as the lek paradox. One potential solution to the lek paradox suggests that the traits that are targets of mate choice should evolve condition-dependent expression and that condition should have a large genetic variance. Condition is expected to exhibit high genetic variance because it is affected by a large number of physiological processes and hence, condition-dependent traits should 'capture' variation contributed by a large number of loci. We suggest that a potentially important cause of variation in condition is competition for limited resources. Here, we discuss a pair of models to analyze the evolutionary genetics of traits affected by success in social competition for resources. We show that competition can contribute to genetic variation of 'competition-dependent' traits that have fundamentally different evolutionary properties than other sources of variation. Competition dependence can make traits honest indicators of genetic quality by revealing the relative competitive ability of males, can provide a component of heritable variation that does not contribute to trait evolution, and can help maintain heritable variation under directional selection. Here we provide a general introduction to the concept of competition dependence and briefly introduce two models to demonstrate the potential evolutionary consequences of competition-dependent trait expression.

  6. The elephants of Gash-Barka, Eritrea: nuclear and mitochondrial genetic patterns.

    PubMed

    Brandt, Adam L; Hagos, Yohannes; Yacob, Yohannes; David, Victor A; Georgiadis, Nicholas J; Shoshani, Jeheskel; Roca, Alfred L

    2014-01-01

    Eritrea has one of the northernmost populations of African elephants. Only about 100 elephants persist in the Gash-Barka administrative zone. Elephants in Eritrea have become completely isolated, with no gene flow from other elephant populations. The conservation of Eritrean elephants would benefit from an understanding of their genetic affinities to elephants elsewhere on the continent and the degree to which genetic variation persists in the population. Using dung samples from Eritrean elephants, we examined 18 species-diagnostic single nucleotide polymorphisms in 3 nuclear genes, sequences of mitochondrial HVR1 and ND5, and genotyped 11 microsatellite loci. The sampled Eritrean elephants carried nuclear and mitochondrial DNA markers establishing them as savanna elephants, with closer genetic affinity to Eastern than to North Central savanna elephant populations, and contrary to speculation by some scholars that forest elephants were found in Eritrea. Mitochondrial DNA diversity was relatively low, with 2 haplotypes unique to Eritrea predominating. Microsatellite genotypes could only be determined for a small number of elephants but suggested that the population suffers from low genetic diversity. Conservation efforts should aim to protect Eritrean elephants and their habitat in the short run, with restoration of habitat connectivity and genetic diversity as long-term goals.

  7. Genetics Show Current Decline and Pleistocene Expansion in Northern Spotted Owls

    USGS Publications Warehouse

    Funk, W. Chris; Forsman, Eric D.; Mullins, Thomas D.; Haig, Susan M.

    2008-01-01

    The northern spotted owl (Strix occidentalis caurina) is one of the most controversial threatened subspecies ever listed under the U.S. Endangered Species Act. Because of concern for persistence of the subspecies, logging on Federal lands in the U.S. Pacific Northwest was dramatically reduced under the Northwest Forest Plan in 1994. Despite protection of its remaining forest habitat, recent field studies show continued demographic declines of northern spotted owls. One potential threat to northern spotted owls that has not yet been shown is loss of genetic variation from population bottlenecks that can increase inbreeding depression and decrease adaptive potential. Here, we show recent genetic bottlenecks in northern spotted owls using a large genetic dataset (352 individuals from across the subspecies' range and 11 microsatellite loci). The signature of bottlenecks was strongest in Washington State, in agreement with field data. Interestingly, we also found a genetic signature of Pleistocene expansion in the same study areas where recent bottlenecks were shown. Our results provide independent evidence that northern spotted owls have recently declined, and suggest that loss of genetic variation is an emerging threat to the subspecies' persistence. Reduced effective population size (Ne), shown here in addition to field evidence for demographic decline, highlights the increasing vulnerability of this bird to extinction.

  8. Prefrontal Cortex HCN1 Channels Enable Intrinsic Persistent Neural Firing and Executive Memory Function

    PubMed Central

    Thuault, Sébastien J.; Malleret, Gaël; Constantinople, Christine M.; Nicholls, Russell; Chen, Irene; Zhu, Judy; Panteleyev, Andrey; Vronskaya, Svetlana; Nolan, Matthew F.; Bruno, Randy

    2013-01-01

    In many cortical neurons, HCN1 channels are the major contributors to Ih, the hyperpolarization-activated current, which regulates the intrinsic properties of neurons and shapes their integration of synaptic inputs, paces rhythmic activity, and regulates synaptic plasticity. Here, we examine the physiological role of Ih in deep layer pyramidal neurons in mouse prefrontal cortex (PFC), focusing on persistent activity, a form of sustained firing thought to be important for the behavioral function of the PFC during working memory tasks. We find that HCN1 contributes to the intrinsic persistent firing that is induced by a brief depolarizing current stimulus in the presence of muscarinic agonists. Deletion of HCN1 or acute pharmacological blockade of Ih decreases the fraction of neurons capable of generating persistent firing. The reduction in persistent firing is caused by the membrane hyperpolarization that results from the deletion of HCN1 or Ih blockade, rather than a specific role of the hyperpolarization-activated current in generating persistent activity. In vivo recordings show that deletion of HCN1 has no effect on up states, periods of enhanced synaptic network activity. Parallel behavioral studies demonstrate that HCN1 contributes to the PFC-dependent resolution of proactive interference during working memory. These results thus provide genetic evidence demonstrating the importance of HCN1 to intrinsic persistent firing and the behavioral output of the PFC. The causal role of intrinsic persistent firing in PFC-mediated behavior remains an open question. PMID:23966682

  9. Anticipating persistent infection

    NASA Astrophysics Data System (ADS)

    Moitra, Promit; Jain, Kanishk; Sinha, Sudeshna

    2018-03-01

    We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual within a given range. We focus on the role of synchronization in the persistence of contagion. Our key result is that higher degree of synchronization, both globally in the population and locally in the neighbourhoods, hinders persistence of infection. Importantly, we find that early short-time asynchrony appears to be a consistent precursor to future persistence of infection, and can potentially provide valuable early warnings for sustained contagion in a population patch. Thus, transient synchronization can help anticipate the long-term persistence of infection. Further we demonstrate that when the range of influence of an infected individual is wider, one obtains lower persistent infection. This counterintuitive observation can also be understood through the relation between synchronization and infection burn-out.

  10. Genetic and Environmental Factors in Invasive Cervical Cancer: Design and Methods of a Classical Twin Study.

    PubMed

    Machalek, Dorothy A; Wark, John D; Tabrizi, Sepehr N; Hopper, John L; Bui, Minh; Dite, Gillian S; Cornall, Alyssa M; Pitts, Marian; Gertig, Dorota; Erbas, Bircan; Garland, Suzanne M

    2017-02-01

    Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role. The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors. The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression.

  11. Persistence of butterfly populations in fragmented habitats along urban density gradients: motility helps

    PubMed Central

    Rochat, E; Manel, S; Deschamps-Cottin, M; Widmer, I; Joost, S

    2017-01-01

    In a simulation study of genotypes conducted over 100 generations for more than 1600 butterfly’s individuals, we evaluate how the increase of anthropogenic fragmentation and reduction of habitat size along urbanisation gradients (from 7 to 59% of impervious land cover) influences genetic diversity and population persistence in butterfly species. We show that in areas characterised by a high urbanisation rate (>56% impervious land cover), a large decrease of both genetic diversity (loss of 60–80% of initial observed heterozygosity) and population size (loss of 70–90% of individuals) is observed over time. This is confirmed by empirical data available for the mobile butterfly species Pieris rapae in a subpart of the study area. Comparing simulated data for P. rapae with its normal dispersal ability and with a reduced dispersal ability, we also show that a higher dispersal ability can be an advantage to survive in an urban or highly fragmented environment. The results obtained here suggest that it is of high importance to account for population persistence, and confirm that it is crucial to maintain habitat size and connectivity in the context of land-use planning. PMID:28792492

  12. Molecular findings and approaches spotlighting Mycobacterium bovis persistence in cattle.

    PubMed

    Alvarez, Angel H; Estrada-Chávez, Ciro; Flores-Valdez, Mario Alberto

    2009-01-01

    Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis (M. bovis) are the etiological agents of human and bovine tuberculosis (TB, bTB) respectively, and share genetic identity over 99% at the whole genome level. Progress has been made towards explaining how mycobacteria and their infected hosts remain in balance without producing clinical symptoms of disease, a phenomenon referred to as latency or persistence, which can be mimicked by certain in vitro conditions. Latency/persistence has mainly been studied using Mtb, where the two-component signalling system, dosRS, has been assigned an instrumental role, and even constitutes the current basis for development of new diagnostic methods and treatment addressing this particular stage of TB. M. bovis conserves homolog genes that in Mtb play a role in human latent TB infection and that, by analogy, would allow it to enter a persistent state in infected cattle; nevertheless, little attention has been paid to this stage in bovine hosts. We suggest that many of the advances acquired through the study of Mtb can and should be taken into consideration by research groups and veterinary professionals dealing with bTB. The study of the infection in bovines, paying particular attention to defining the molecular and cellular markers of a M. bovis persistent infection in cattle, presents great opportunities for the development and trial of new diagnostic tests and vaccines, tools that will surely help in promoting eradication of bTB in high-burden settings.

  13. An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics

    ERIC Educational Resources Information Center

    Molenaar, Peter C. M.

    2015-01-01

    The main theme of this paper concerns the persistent critique of Gilbert Gottlieb on developmental behavior genetics and my reactions to this critique, the latter changing from rejection to complete acceptation. Concise characterizations of developmental behavior genetics, developmental systems theory (to which Gottlieb made essential…

  14. Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds

    PubMed Central

    Badosa, Anna; Frisch, Dagmar; Green, Andy J.; Rico, Ciro; Gómez, Africa

    2017-01-01

    Understanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks. PMID:28276459

  15. Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds

    NASA Astrophysics Data System (ADS)

    Badosa, Anna; Frisch, Dagmar; Green, Andy J.; Rico, Ciro; Gómez, Africa

    2017-03-01

    Understanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks.

  16. Population-level genetic variation and climate change in a biodiversity hotspot

    PubMed Central

    2017-01-01

    Introduction Estimated future climate scenarios can be used to predict where hotspots of endemism may occur over the next century, but life history, ecological and genetic traits will be important in informing the varying responses within myriad taxa. Essential to predicting the consequences of climate change to individual species will be an understanding of the factors that drive genetic structure within and among populations. Here, I review the factors that influence the genetic structure of plant species in California, but are applicable elsewhere; existing levels of genetic variation, life history and ecological characteristics will affect the ability of an individual taxon to persist in the presence of anthropogenic change. Factors influencing the distribution of genetic variation Persistence in the face of climate change is likely determined by life history characteristics: dispersal ability, generation time, reproductive ability, degree of habitat specialization, plant–insect interactions, existing genetic diversity and availability of habitat or migration corridors. Existing levels of genetic diversity in plant populations vary based on a number of evolutionary scenarios that include endemism, expansion since the last glacial maximum, breeding system and current range sizes. Regional priorities and examples A number of well-documented examples are provided from the California Floristic Province. Some predictions can be made for the responses of plant taxa to rapid environmental changes based on geographic position, evolutionary history, existing genetic variation, and ecological amplitude. Conclusions, Solutions and Recommendations The prediction of how species will respond to climate change will require a synthesis drawing from population genetics, geography, palaeontology and ecology. The important integration of the historical factors that have shaped the distribution and existing genetic structure of California’s plant taxa will enable us to predict

  17. Alcohol-related Genes Show an Enrichment of Associations with a Persistent Externalizing Factor

    PubMed Central

    Ashenhurst, James R.; Harden, K. Paige; Corbin, William R.; Fromme, Kim

    2016-01-01

    Research using twins has found that much of the variability in externalizing phenotypes – including alcohol and drug use, impulsive personality traits, risky sex and property crime – is explained by genetic factors. Nevertheless, identification of specific genes and variants associated with these traits has proven to be difficult, likely because individual differences in externalizing are explained by many genes of small individual effect. Moreover, twin research indicates that heritable variance in externalizing behaviors is mostly shared across the externalizing spectrum rather than specific to any behavior. We use a longitudinal, “deep phenotyping” approach to model a general externalizing factor reflecting persistent engagement in a variety of socially problematic behaviors measured at eleven assessment occasions spanning early adulthood (ages 18 to 28). In an ancestrally homogenous sample of non-Hispanic Whites (N = 337), we then tested for enrichment of associations between the persistent externalizing factor and a set of 3,281 polymorphisms within 104 genes that were previously identified as associated with alcohol-use behaviors. Next we tested for enrichment among domain-specific factors (e.g., property crime) composed of residual variance not accounted for by the common factor. Significance was determined relative to bootstrapped empirical thresholds derived from permutations of phenotypic data. Results indicated significant enrichment of genetic associations for persistent externalizing, but not for domain-specific factors. Consistent with twin research findings, these results suggest that genetic variants are broadly associated with externalizing behaviors rather than unique to specific behaviors. General Scientific Summary This study shows that variation in 104 genes is associated with socially problematic “externalizing” behavior, including substance misuse, property crime, risky sex, and aspects of impulsive personality. Importantly, this

  18. Polygenic risk accelerates the developmental progression to heavy, persistent smoking and nicotine dependence: Evidence from a 4-Decade Longitudinal Study

    PubMed Central

    Moffitt, Terrie E; Baker, Timothy B; Biddle, Andrea K; Evans, James P; Harrington, HonaLee; Houts, Renate; Meier, Madeline; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    OBJECTIVE To test how genomic loci identified in genome-wide association studies (GWAS) influence the developmental progression of smoking behavior. DESIGN A 38-year prospective longitudinal study of a representative birth-cohort. SETTING The Dunedin Multidisciplinary Health and Development Study, New Zealand. PARTICIPANTS N=1037 male and female study members. MAIN EXPOSURES We assessed genetic risk with a multi-locus genetic risk score (GRS). The GRS was composed of single-nucleotide polymorphisms identified in three meta-analyses of GWAS of smoking quantity phenotypes. OUTCOME MEASURES Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerstrom Test of Nicotine Dependence), and cessation difficulties were evaluated at eight assessments spanning ages 11-38 years. RESULTS Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that two adolescent developmental phenotypes—early conversion to daily smoking and rapid progression to heavy smoking--mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history. CONCLUSIONS Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers. PMID:23536134

  19. Identifying environmental correlates of intraspecific genetic variation.

    PubMed

    Harrisson, K A; Yen, J D L; Pavlova, A; Rourke, M L; Gilligan, D; Ingram, B A; Lyon, J; Tonkin, Z; Sunnucks, P

    2016-09-01

    Genetic variation is critical to the persistence of populations and their capacity to adapt to environmental change. The distribution of genetic variation across a species' range can reveal critical information that is not necessarily represented in species occurrence or abundance patterns. We identified environmental factors associated with the amount of intraspecific, individual-based genetic variation across the range of a widespread freshwater fish species, the Murray cod Maccullochella peelii. We used two different approaches to statistically quantify the relative importance of predictor variables, allowing for nonlinear relationships: a random forest model and a Bayesian approach. The latter also accounted for population history. Both approaches identified associations between homozygosity by locus and both disturbance to the natural flow regime and mean annual flow. Homozygosity by locus was negatively associated with disturbance to the natural flow regime, suggesting that river reaches with more disturbed flow regimes may support larger, more genetically diverse populations. Our findings are consistent with the hypothesis that artificially induced perennial flows in regulated channels may provide greater and more consistent habitat and reduce the frequency of population bottlenecks that can occur frequently under the highly variable and unpredictable natural flow regime of the system. Although extensive river regulation across eastern Australia has not had an overall positive effect on Murray cod numbers over the past century, regulation may not represent the primary threat to Murray cod survival. Instead, pressures other than flow regulation may be more critical to the persistence of Murray cod (for example, reduced frequency of large floods, overfishing and chemical pollution).

  20. Fragmentation reduces regional-scale spatial genetic structure in a wind-pollinated tree because genetic barriers are removed.

    PubMed

    Wang, Rong; Compton, Stephen G; Shi, Yi-Su; Chen, Xiao-Yong

    2012-09-01

    Gene flow strongly influences the regional genetic structuring of plant populations. Seed and pollen dispersal patterns can respond differently to the increased isolation resulting from habitat fragmentation, with unpredictable consequences for gene flow and population structuring. In a recently fragmented landscape we compared the pre- and post-fragmentation genetic structure of populations of a tree species where pollen and seed dispersal respond differentially to forest fragmentation generated by flooding. Castanopsis sclerophylla is wind-pollinated, with seeds that are dispersed by gravity and rodents. Using microsatellites, we found no significant difference in genetic diversity between pre- and post-fragmentation cohorts. Significant genetic structure was observed in pre-fragmentation cohorts, due to an unknown genetic barrier that had isolated one small population. Among post-fragmentation cohorts this genetic barrier had disappeared and genetic structure was significantly weakened. The strengths of genetic structuring were at a similar level in both cohorts, suggesting that overall gene flow of C. sclerophylla has been unchanged by fragmentation at the regional scale. Fragmentation has blocked seed dispersal among habitats, but this appears to have been compensated for by enhanced pollen dispersal, as indicated by the disappearance of a genetic barrier, probably as a result of increased wind speeds and easier pollen movement over water. Extensive pollen flow can counteract some negative effects of fragmentation and assist the long-term persistence of small remnant populations.

  1. Central role of a bacterial two-component gene regulatory system of previously unknown function in pathogen persistence in human saliva.

    PubMed

    Shelburne, Samuel A; Sumby, Paul; Sitkiewicz, Izabela; Granville, Chanel; DeLeo, Frank R; Musser, James M

    2005-11-01

    The molecular genetic mechanisms used by bacteria to persist in humans are poorly understood. Group A Streptococcus (GAS) causes the majority of bacterial pharyngitis cases in humans and is prone to persistently inhabit the upper respiratory tract. To gain information about how GAS survives in and infects the oropharynx, we analyzed the transcriptome of a serotype M1 strain grown in saliva. The dynamic pattern of changes in transcripts of genes [spy0874/0875, herein named sptR and sptS (sptR/S), for saliva persistence] encoding a two-component gene regulatory system of unknown function suggested that SptR/S contributed to persistence of GAS in saliva. Consistent with this idea, an isogenic nonpolar mutant strain (DeltasptR) was dramatically less able to survive in saliva compared with the parental strain. Iterative expression microarray analysis of bacteria grown in saliva revealed that transcripts of several known and putative GAS virulence factor genes were decreased significantly in the DeltasptR mutant strain. Compared with the parental strain, the isogenic mutant strain also had altered transcripts of multiple genes encoding proteins involved in complex carbohydrate acquisition and utilization pathways. Western immunoblot analysis and real-time PCR analysis of GAS in throat swabs taken from humans with pharyngitis confirmed the findings. We conclude that SptR/S optimizes persistence of GAS in human saliva, apparently by strategically influencing metabolic pathways and virulence factor production. The discovery of a genetic program that significantly increased persistence of a major human pathogen in saliva enhances understanding of how bacteria survive in the host and suggests new therapeutic strategies.

  2. Rapid genetic restoration of a keystone species exhibiting delayed demographic response.

    PubMed

    Cosentino, Bradley J; Schooley, Robert L; Bestelmeyer, Brandon T; McCarthy, Alison J; Sierzega, Kevin

    2015-12-01

    Genetic founder effects are often expected when animals colonize restored habitat in fragmented landscapes, but empirical data on genetic responses to restoration are limited. We examined the genetic response of banner-tailed kangaroo rats (Dipodomys spectabilis) to landscape-scale grassland restoration in the Chihuahuan Desert of New Mexico, USA. Dipodomys spectabilis is a grassland specialist and keystone species. At sites treated with herbicide to remove shrubs, colonization by D. spectabilis is slow and populations persist at low density for ≥10 years (≥6 generations). Persistence at low density and low gene flow may cause strong founder effects. We compared genetic structure of D. spectabilis populations between treated sites and remnant grasslands, and we examined how the genetic response to restoration depended on treatment age, area, and connectivity to source populations. Allelic richness and heterozygosity were similar between treated sites and remnant grasslands. Allelic richness at treated sites was greatest early in the restoration trajectory, and genetic divergence did not differ between recently colonized and established populations. These results indicated that founder effects during colonization of treated sites were weak or absent. Moreover, our results suggested founder effects were not mitigated by treatment area or connectivity. Dispersal is negatively density-dependent in D. spectabilis, and we hypothesize that high gene flow may occur early in the restoration trajectory when density is low. Our study shows genetic diversity can be recovered more rapidly than demographic components of populations after habitat restoration and that founder effects are not inevitable for animals colonizing restored habitat in fragmented landscapes. © 2015 John Wiley & Sons Ltd.

  3. Dairy foods and health in Asians: Taiwanese considerations.

    PubMed

    Lee, Meei-Shyuan; Wahlqvist, Mark L; Peng, Cheau-Jane

    2015-01-01

    The health relevance of dairy products has mostly been judged by their abundant nutrients (protein, calcium and riboflavin) and recommendations for these derived in lactase-persistent Caucasian populations. Extrapolation to Asians who are generally lactase non-persisters may not be biologically, culturally or environmentally sound. A number of studies, especially among north-east Asians as in Taiwan, provide guidance for their optimal dairy intakes. In Taiwan, the NAHSIT (Nutrition and Health Surveys in Taiwan) linked to the National Health Insurance and Death Registry data bases provide most of the evidence. Cultural and socio-economic barriers create population resistance to increase dairy consumption beyond one serving per day as reflected in food balance sheet and repeat survey trend analyses. For the morbidity and mortality patterns principally seen in Asia, some, but not too much, dairy is to be preferred. This applies to all-cause and cardiovascular, especially stroke, mortality, to the risk of overfatness (by BMI and abdominal circumference) and diabetes and very likely to fracture and its sequelae. In Taiwan, there is no apparent association with total cancer mortality, but among Europeans, there may be protection. Historically, while fermented mammalian milks have been consumed in south Asia and various Asian subgroups and regions, most of the uptake of dairy in Asia after World War 2 has been from imported powdered milk or fresh liquid milk, encouraged further by the use of yogurts and popularization of milk teas and coffee. Asian dietary guidelines and clinical nutrition protocols need to encourage a modest, asymptomatic dairy intake.

  4. Population genetics features for persistent, but transient, Botryllus schlosseri (Urochordata) congregations in a central Californian marina.

    PubMed

    Karahan, Arzu; Douek, Jacob; Paz, Guy; Rinkevich, Baruch

    2016-08-01

    The colonial tunicate Botryllus schlosseri is a globally distributed, invasive ascidian that has colonized the Californian coasts of the USA during the mid-late 1940s and has, since the late 1980s, spread north to Washington. This study analyzes the population genetic characteristics of transient populations residing at the Elkhorn Yacht-Club (EYC), in central California (seven sessions, 1996-2008), which suffered periodic catastrophes caused by episodic fresh-water floods and a single sampling session (in the year 2001) of five West-Coast populations using the mtDNA COI gene and five microsatellite markers. EYC microsatellite results were further compared with the closely situated but persistent population of the Santa Cruz Harbor (SCH) to understand the impact on EYC population regeneration processes after the 2005-flood catastrophe. All microsatellites were highly polymorphic, revealing a large number of unique alleles at different sampling dates. Whereas pairwise θ did not reveal significant differences between the EYC time-series samplings, the overall θ was significant, as it was between all the 2001 West Coast populations. The most likely cluster number was 3 for the EYC samples whereas two K values were obtained (2 and 5) for the 2001 samples. Tajima's D and Fu's/Fs tests did not reject the null hypothesis for COI neutral evolution, except for in the EYC-2000, 2007 and two 2001 samplings. The wide geographical range of the analyses has indicated that following the EYC 2005-flood catastrophe, newcomers could have originated from neighboring populations, from deep-water colonies that may have escaped the 2005 low salinity event, or less expectedly, from far away West-Coast populations, while revealing that the SCH population is the most probable source for the EYC population. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Cellar-Associated Saccharomyces cerevisiae Population Structure Revealed High-Level Diversity and Perennial Persistence at Sauternes Wine Estates

    PubMed Central

    Börlin, Marine; Venet, Pauline; Claisse, Olivier; Salin, Franck

    2016-01-01

    ABSTRACT Three wine estates (designated A, B, and C) were sampled in Sauternes, a typical appellation of the Bordeaux wine area producing sweet white wine. From those wine estates, 551 yeast strains were collected between 2012 and 2014, added to 102 older strains from 1992 to 2011 from wine estate C. All the strains were analyzed through 15 microsatellite markers, resulting in 503 unique Saccharomyces cerevisiae genotypes, revealing high genetic diversity and a low presence of commercial yeast starters. Population analysis performed using Fst genetic distance or ancestry profiles revealed that the two closest wine estates, B and C, which have juxtaposed vineyard plots and common seasonal staff, share more related isolates with each other than with wine estate A, indicating exchange between estates. The characterization of isolates collected 23 years ago at wine estate C in relation to recent isolates obtained at wine estate B revealed the long-term persistence of isolates. Last, during the 2014 harvest period, a temporal succession of ancestral subpopulations related to the different batches associated with the selective picking of noble rotted grapes was highlighted. IMPORTANCE High genetic diversity of S. cerevisiae isolates from spontaneous fermentation on wine estates in the Sauternes appellation of Bordeaux was revealed. Only 7% of all Sauternes strains were considered genetically related to specific commercial strains. The long-term persistence (over 20 years) of S. cerevisiae profiles on a given wine estate is highlighted. PMID:26969698

  6. Cellar-Associated Saccharomyces cerevisiae Population Structure Revealed High-Level Diversity and Perennial Persistence at Sauternes Wine Estates.

    PubMed

    Börlin, Marine; Venet, Pauline; Claisse, Olivier; Salin, Franck; Legras, Jean-Luc; Masneuf-Pomarede, Isabelle

    2016-05-15

    Three wine estates (designated A, B, and C) were sampled in Sauternes, a typical appellation of the Bordeaux wine area producing sweet white wine. From those wine estates, 551 yeast strains were collected between 2012 and 2014, added to 102 older strains from 1992 to 2011 from wine estate C. All the strains were analyzed through 15 microsatellite markers, resulting in 503 unique Saccharomyces cerevisiae genotypes, revealing high genetic diversity and a low presence of commercial yeast starters. Population analysis performed using Fst genetic distance or ancestry profiles revealed that the two closest wine estates, B and C, which have juxtaposed vineyard plots and common seasonal staff, share more related isolates with each other than with wine estate A, indicating exchange between estates. The characterization of isolates collected 23 years ago at wine estate C in relation to recent isolates obtained at wine estate B revealed the long-term persistence of isolates. Last, during the 2014 harvest period, a temporal succession of ancestral subpopulations related to the different batches associated with the selective picking of noble rotted grapes was highlighted. High genetic diversity of S. cerevisiae isolates from spontaneous fermentation on wine estates in the Sauternes appellation of Bordeaux was revealed. Only 7% of all Sauternes strains were considered genetically related to specific commercial strains. The long-term persistence (over 20 years) of S. cerevisiae profiles on a given wine estate is highlighted. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Comparative riverscape genetics reveals reservoirs of genetic diversity for conservation and restoration of Great Plains fishes.

    PubMed

    Osborne, Megan J; Perkin, Joshuah S; Gido, Keith B; Turner, Thomas F

    2014-12-01

    We used comparative landscape genetics to examine the relative roles of historical events, intrinsic traits and landscape factors in determining the distribution of genetic diversity of river fishes across the North American Great Plains. Spatial patterns of diversity were overlaid on a patch-based graphical model and then compared within and among three species that co-occurred across five Great Plains watersheds. Species differing in reproductive strategy (benthic vs. pelagic-spawning) were hypothesized to have different patterns of genetic diversity, but the overriding factor shaping contemporary patterns of diversity was the signature of past climates and geological history. Allelic diversity was significantly higher at southern latitudes for Cyprinella lutrensis and Hybognathus placitus, consistent with northward expansion from southern Pleistocene refugia. Within the historical context, all species exhibited lowered occupancy and abundance in heavily fragmented and drier upstream reaches, particularly H. placitus; a pelagic-spawning species, suggesting rates of extirpation have outpaced losses of genetic diversity in this species. Within most tributary basins, genetically diverse populations of each species persisted. Hence, reconnecting genetically diverse populations with those characterized by reduced diversity (regardless of their position within the riverine network) would provide populations with greater genetic and demographic resilience. We discuss cases where cross-basin transfer may be appropriate to enhance genetic diversity and mitigate negative effects of climate change. Overall, striking similarities in genetic patterns and in response to fragmentation and dewatering suggest a common strategy for genetic resource management in this unique riverine fish assemblage. © 2014 John Wiley & Sons Ltd.

  8. Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior.

    PubMed

    Wertz, J; Caspi, A; Belsky, D W; Beckley, A L; Arseneault, L; Barnes, J C; Corcoran, D L; Hogan, S; Houts, R M; Morgan, N; Odgers, C L; Prinz, J A; Sugden, K; Williams, B S; Poulton, R; Moffitt, T E

    2018-05-01

    Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.

  9. Genetics and crime: Integrating new genomic discoveries into psychological research about antisocial behavior

    PubMed Central

    Wertz, J.; Caspi, A.; Belsky, D. W.; Beckley, A. L.; Arseneault, L.; Barnes, J. C.; Corcoran, D. L.; Hogan, S.; Houts, R. M.; Morgan, N.; Odgers, C. L.; Prinz, J. A.; Sugden, K.; Williams, B. S.; Poulton, R.; Moffitt, T. E.

    2018-01-01

    Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and E-Risk birth cohorts of individuals growing up 20 years and 20,000 kilometres apart, education polygenic scores predicted risk of a criminal record, with modest effects. Polygenic risk manifested during primary schooling, in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and predicted a life-course persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature/nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest the hypothesis that improving school experiences might prevent genetic influences on crime from unfolding. PMID:29513605

  10. Molecular Darwinism: The Contingency of Spontaneous Genetic Variation

    PubMed Central

    Arber, Werner

    2011-01-01

    The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions. PMID:21979160

  11. Molecular Darwinism: the contingency of spontaneous genetic variation.

    PubMed

    Arber, Werner

    2011-01-01

    The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions.

  12. Persistent inhibition of hippocampal long-term potentiation in vivo by learned helplessness stress.

    PubMed

    Ryan, Benedict K; Vollmayr, Barbara; Klyubin, Igor; Gass, Peter; Rowan, Michael J

    2010-06-01

    The persistent cognitive disruptive effects of stress have been strongly implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (<3 h), inhibited induction of both NMDA receptor-dependent LTP induced by a standard high frequency (200 Hz) conditioning stimulus and an additional LTP that required voltage-dependent Ca(2+) channel activation triggered by strong (400 Hz) conditioning stimulation. In contrast, acute inescapable footshock stress, used to study learned helplessness, inhibited LTP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LTP inhibition. Moreover, LTP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress.

  13. Review: domestic animal forensic genetics - biological evidence, genetic markers, analytical approaches and challenges.

    PubMed

    Kanthaswamy, S

    2015-10-01

    This review highlights the importance of domestic animal genetic evidence sources, genetic testing, markers and analytical approaches as well as the challenges this field is facing in view of the de facto 'gold standard' human DNA identification. Because of the genetic similarity between humans and domestic animals, genetic analysis of domestic animal hair, saliva, urine, blood and other biological material has generated vital investigative leads that have been admitted into a variety of court proceedings, including criminal and civil litigation. Information on validated short tandem repeat, single nucleotide polymorphism and mitochondrial DNA markers and public access to genetic databases for forensic DNA analysis is becoming readily available. Although the fundamental aspects of animal forensic genetic testing may be reliable and acceptable, animal forensic testing still lacks the standardized testing protocols that human genetic profiling requires, probably because of the absence of monetary support from government agencies and the difficulty in promoting cooperation among competing laboratories. Moreover, there is a lack in consensus about how to best present the results and expert opinion to comply with court standards and bear judicial scrutiny. This has been the single most persistent challenge ever since the earliest use of domestic animal forensic genetic testing in a criminal case in the mid-1990s. Crime laboratory accreditation ensures that genetic test results have the courts' confidence. Because accreditation requires significant commitments of effort, time and resources, the vast majority of animal forensic genetic laboratories are not accredited nor are their analysts certified forensic examiners. The relevance of domestic animal forensic genetics in the criminal justice system is undeniable. However, further improvements are needed in a wide range of supporting resources, including standardized quality assurance and control protocols for sample

  14. Persistent natural infection of a Culex tritaeniorhynchus cell line with a novel Culex tritaeniorhynchus rhabdovirus strain.

    PubMed

    Gillich, Nadine; Kuwata, Ryusei; Isawa, Haruhiko; Horie, Masayuki

    2015-09-01

    Culex tritaeniorhynchus rhabdovirus (CTRV) is a mosquito virus that establishes persistent infection without any obvious cell death. Therefore, occult infection by CTRV can be present in mosquito cell lines. In this study, it is shown that NIID-CTR cells, which were derived from Cx. tritaeniorhynchus, are persistently infected with a novel strain of CTRV. Complete genome sequencing of the infecting strain revealed that it is genetically similar but distinct from the previously isolated CTRV strain, excluding the possibility of contamination. These findings raise the importance of further CTRV studies, such as screening of CTRV in other mosquito cell lines. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  15. Future climate change is predicted to shift long-term persistence zones in the cold-temperate kelp Laminaria hyperborea.

    PubMed

    Assis, Jorge; Lucas, Ana Vaz; Bárbara, Ignacio; Serrão, Ester Álvares

    2016-02-01

    Global climate change is shifting species distributions worldwide. At rear edges (warmer, low latitude range margins), the consequences of small variations in environmental conditions can be magnified, producing large negative effects on species ranges. A major outcome of shifts in distributions that only recently received attention is the potential to reduce the levels of intra-specific diversity and consequently the global evolutionary and adaptive capacity of species to face novel disturbances. This is particularly important for low dispersal marine species, such as kelps, that generally retain high and unique genetic diversity at rear ranges resulting from long-term persistence, while ranges shifts during climatic glacial/interglacial cycles. Using ecological niche modelling, we (1) infer the major environmental forces shaping the distribution of a cold-temperate kelp, Laminaria hyperborea (Gunnerus) Foslie, and we (2) predict the effect of past climate changes in shaping regions of long-term persistence (i.e., climatic refugia), where this species might hypothetically harbour higher genetic diversity given the absence of bottlenecks and local extinctions over the long term. We further (3) assessed the consequences of future climate for the fate of L. hyperborea using different scenarios of greenhouse gas emissions (RCP 2.6 and RCP 8.5). Results show NW Iberia, SW Ireland and W English Channel, Faroe Islands and S Iceland, as regions where L. hyperborea may have persisted during past climate extremes until present day. All predictions for the future showed expansions to northern territories coupled with the significant loss of suitable habitats at low latitude range margins, where long-term persistence was inferred (e.g., NW Iberia). This pattern was particularly evident in the most agressive scenario of climate change (RCP 8.5), likely driving major biodiversity loss, changes in ecosystem functioning and the impoverishment of the global gene pool of L

  16. Persistent Genetic and Family-Wide Environmental Contributions to Early Number Knowledge and Later Achievement in Mathematics.

    PubMed

    Garon-Carrier, Gabrielle; Boivin, Michel; Kovas, Yulia; Feng, Bei; Brendgen, Mara; Vitaro, Frank; Séguin, Jean R; Tremblay, Richard E; Dionne, Ginette

    2017-12-01

    This study investigated the stable and transient genetic and environmental contributions to individual differences in number knowledge in the transition from preschool (age 5) to Grade 1 (age 7) and to the predictive association between early number knowledge and later math achievement (age 10-12). We conducted genetic simplex modeling across these three time points. Genetic variance was transmitted from preschool number knowledge to late-elementary math achievement; in addition, significant genetic innovation (i.e., new influence) occurred at ages 10 through 12 years. The shared and nonshared environmental contributions decreased during the transition from preschool to school entry, but shared and nonshared environment contributed to the continuity across time from preschool number knowledge to subsequent number knowledge and math achievement. There was no new environmental contribution at time points subsequent to preschool. Results are discussed in light of their practical implications for children who have difficulties with mathematics, as well as for preventive intervention.

  17. Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

    PubMed Central

    Ramirez-Carvajal, Lisbeth; Pauszek, Steven J.; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S.; Stockwell, Timothy B.; Rodriguez, Luis L.

    2018-01-01

    Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008–2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008–2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region. PMID:29390015

  18. Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

    PubMed

    Ramirez-Carvajal, Lisbeth; Pauszek, Steven J; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S; Stockwell, Timothy B; Rodriguez, Luis L

    2018-01-01

    Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

  19. A test of genetic models for the evolutionary maintenance of same-sex sexual behaviour.

    PubMed

    Hoskins, Jessica L; Ritchie, Michael G; Bailey, Nathan W

    2015-06-22

    The evolutionary maintenance of same-sex sexual behaviour (SSB) has received increasing attention because it is perceived to be an evolutionary paradox. The genetic basis of SSB is almost wholly unknown in non-human animals, though this is key to understanding its persistence. Recent theoretical work has yielded broadly applicable predictions centred on two genetic models for SSB: overdominance and sexual antagonism. Using Drosophila melanogaster, we assayed natural genetic variation for male SSB and empirically tested predictions about the mode of inheritance and fitness consequences of alleles influencing its expression. We screened 50 inbred lines derived from a wild population for male-male courtship and copulation behaviour, and examined crosses between the lines for evidence of overdominance and antagonistic fecundity selection. Consistent variation among lines revealed heritable genetic variation for SSB, but the nature of the genetic variation was complex. Phenotypic and fitness variation was consistent with expectations under overdominance, although predictions of the sexual antagonism model were also supported. We found an unexpected and strong paternal effect on the expression of SSB, suggesting possible Y-linkage of the trait. Our results inform evolutionary genetic mechanisms that might maintain low but persistently observed levels of male SSB in D. melanogaster, but highlight a need for broader taxonomic representation in studies of its evolutionary causes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  20. Effect of pregnancy on the genetic evaluation of dairy cattle.

    PubMed

    Pereira, R J; Santana, M L; Bignardi, A B; Verneque, R S; El Faro, L; Albuquerque, L G

    2011-09-26

    We investigated the effect of stage of pregnancy on estimates of breeding values for milk yield and milk persistency in Gyr and Holstein dairy cattle in Brazil. Test-day milk yield records were analyzed using random regression models with or without the effect of pregnancy. Models were compared using residual variances, heritabilities, rank correlations of estimated breeding values of bulls and cows, and number of nonpregnant cows in the top 200 for milk yield and milk persistency. The estimates of residual variance and heritabilities obtained with the models with or without the effect of pregnancy were similar for the two breeds. Inclusion of the effect of pregnancy in genetic evaluation models for these populations did not affect the ranking of cows and sires based on their predicted breeding values for 305-day cumulative milk yield. In contrast, when we examined persistency of milk yield, lack of adjustment for the effect of pregnancy overestimated breeding values of nonpregnant cows and cows with a long days open period and underestimated breeding values of cows with a short days open period. We recommend that models include the effect of days of pregnancy for estimation of adjustment factors for the effect of pregnancy in genetic evaluations of Dairy Gyr and Holstein cattle.

  1. Lactose digestion from yogurt: mechanism and relevance.

    PubMed

    Savaiano, Dennis A

    2014-05-01

    Yogurt is traditionally consumed throughout the world among populations who are seemingly unable to digest lactose. This review provides a historical overview of the studies that show lactose digestion and tolerance from yogurt by lactose-intolerant people. The lactose in yogurt is digested more efficiently than other dairy sources of lactose because the bacteria inherent in yogurt assist with its digestion. The bacterial lactase survives the acidic conditions of the stomach, apparently being physically protected within the bacterial cells and facilitated by the buffering capacity of yogurt. The increasing pH as the yogurt enters the small intestine and a slower gastrointestinal transit time allow the bacterial lactase to be active, digesting lactose from yogurt sufficiently to prevent symptoms in lactose-intolerant people. There is little difference in the lactase capability of different commercial yogurts, because they apparently contain Lactobacillus bulgaricus and Streptococcus thermophilus in sufficient quantities (10(8) bacteria/mL). However, Lactobacillus acidophilus appears to require cell membrane disruption to physically release the lactase. Compared with unflavored yogurts, flavored yogurts appear to exhibit somewhat reduced lactase activity but are still well tolerated.

  2. Numeric invariants from multidimensional persistence

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Skryzalin, Jacek; Carlsson, Gunnar

    2017-05-19

    In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be usedmore » to study data.« less

  3. Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice.

    PubMed

    Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu; Hsu, Sheng-Min; Chen, Shun-Hua

    2017-02-15

    Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484-490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised

  4. Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice

    PubMed Central

    Huang, Chih-Yu; Yao, Hui-Wen; Wang, Li-Chiu; Shen, Fang-Hsiu

    2016-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484–490, 1994, https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1. IMPORTANCE Acyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of

  5. Persistent Short-Term Memory Defects Following Sleep Deprivation in a Drosophila Model of Parkinson Disease

    PubMed Central

    Seugnet, Laurent; Galvin, James E.; Suzuki, Yasuko; Gottschalk, Laura; Shaw, Paul J.

    2009-01-01

    Study Objectives: Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on short-term memory using a Drosophila model of Parkinson disease. Participants: Transgenic strains of Drosophila melanogaster. Design: Using the GAL4-UAS system, human α-synuclein was expressed throughout the nervous system of adult flies. α-Synuclein expressing flies (αS flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry. Measurments and Results: When sleep deprived at an intermediate stage of the pathology, αS flies showed persistent short-term memory deficits that lasted ≥ 3 days. Cognitive deficits were not observed in younger αS flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived αS flies. Blocking D1-like receptors during sleep deprivation prevented persistent short-term memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits. Conclusions: These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics. Citation: Seugnet L

  6. Object-oriented Persistent Homology

    PubMed Central

    Wang, Bao; Wei, Guo-Wei

    2015-01-01

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  7. Population-level genetic variation and climate change in a biodiversity hotspot.

    PubMed

    Schierenbeck, Kristina A

    2017-01-01

    Estimated future climate scenarios can be used to predict where hotspots of endemism may occur over the next century, but life history, ecological and genetic traits will be important in informing the varying responses within myriad taxa. Essential to predicting the consequences of climate change to individual species will be an understanding of the factors that drive genetic structure within and among populations. Here, I review the factors that influence the genetic structure of plant species in California, but are applicable elsewhere; existing levels of genetic variation, life history and ecological characteristics will affect the ability of an individual taxon to persist in the presence of anthropogenic change. Persistence in the face of climate change is likely determined by life history characteristics: dispersal ability, generation time, reproductive ability, degree of habitat specialization, plant-insect interactions, existing genetic diversity and availability of habitat or migration corridors. Existing levels of genetic diversity in plant populations vary based on a number of evolutionary scenarios that include endemism, expansion since the last glacial maximum, breeding system and current range sizes. A number of well-documented examples are provided from the California Floristic Province. Some predictions can be made for the responses of plant taxa to rapid environmental changes based on geographic position, evolutionary history, existing genetic variation, and ecological amplitude. The prediction of how species will respond to climate change will require a synthesis drawing from population genetics, geography, palaeontology and ecology. The important integration of the historical factors that have shaped the distribution and existing genetic structure of California's plant taxa will enable us to predict and prioritize the conservation of species and areas most likely to be impacted by rapid climate change, human disturbance and invasive species.

  8. Sex, Gender, Genetics, and Health

    PubMed Central

    Yang, Yang Claire; Jenkins, Tania M.

    2013-01-01

    This article addresses 2 questions. First, to what extent are sex and gender incorporated into research on genetics and health? Second, how might social science understandings of sex and gender, and gender differences in health, become more integrated into scholarship in this area? We review articles on genetics and health published in selected peer-reviewed journals. Although sex is included frequently as a control or stratifying variable, few articles articulate a conceptual frame or methodological justification for conducting research in this way, and most are not motivated by sex or gender differences in health. Gender differences in health are persistent, unexplained, and shaped by multilevel social factors. Future scholarship on genetics and health needs to incorporate more systematic attention to sex and gender, gender as an environment, and the intertwining of social and biological variation over the life course. Such integration will advance understandings of gender differences in health, and may yield insight regarding the processes and circumstances that make genomic variation relevant for health and well-being. PMID:23927517

  9. Using HexSim to link demography and genetics in animal and plant simulations

    EPA Science Inventory

    Simulation models are essential for understanding the effects of land management practices and environmental drivers, including landscape change, shape population genetic structure and persistence probabilities. The emerging field of eco-evolutionary modeling is beginning to dev...

  10. Lifestyle, Genetics, and Disease in Sami

    PubMed Central

    Ross, Alastair B.; Johansson, Åsa; Ingman, Max; Gyllensten, Ulf

    2006-01-01

    Aim To present a summary of the lifestyle, genetic origin, diet, and disease in the population of Sami, indigenous people of northern Fennoscandia. Method A survey of the available scientific literature and preliminary results from our own study of the Swedish Sami population. Results The Sami probably have a heterogeneous genetic origin, with a major contribution of continental or Eastern European tribes and a smaller contribution from Asia. The traditional Sami diet, high in animal products, persists in Sami groups still involved with reindeer herding, but others have adopted a diet typical of Western cultures. Early reports indicated a lower prevalence of heart disease and most cancers, except stomach cancer. Recent studies have not found a lower risk of heart disease, but have consistently shown an overall reduced cancer risk. Sami have been reported to share some specific health-related genetic polymorphisms with other European populations, but none that would explain the observed differences in disease risk. Conclusion The genetic structure of the Sami population makes it suitable for studies of the genetic and environmental factors influencing the development of common diseases. The difference in incidence of heart disease between studies may reflect the ongoing transition from a traditional to a more Westernized lifestyle. The ability to compare population segments with different lifestyles, combined with the genetic structure of the population, creates unusual possibilities for studies of the genetic and environmental factors involved in the development of common disease. PMID:16909452

  11. Habitat fragmentation in coastal southern California disrupts genetic connectivity in the cactus wren (Campylorhynchus brunneicapillus)

    USGS Publications Warehouse

    Barr, Kelly R.; Kus, Barbara E.; Preston, Kristine; Howell, Scarlett; Perkins, Emily; Vandergast, Amy

    2015-01-01

    Achieving long-term persistence of species in urbanized landscapes requires characterizing population genetic structure to understand and manage the effects of anthropogenic disturbance on connectivity. Urbanization over the past century in coastal southern California has caused both precipitous loss of coastal sage scrub habitat and declines in populations of the cactus wren (Campylorhynchus brunneicapillus). Using 22 microsatellite loci, we found that remnant cactus wren aggregations in coastal southern California comprised 20 populations based on strict exact tests for population differentiation, and 12 genetic clusters with hierarchical Bayesian clustering analyses. Genetic structure patterns largely mirrored underlying habitat availability, with cluster and population boundaries coinciding with fragmentation caused primarily by urbanization. Using a habitat model we developed, we detected stronger associations between habitat-based distances and genetic distances than Euclidean geographic distance. Within populations, we detected a positive association between available local habitat and allelic richness and a negative association with relatedness. Isolation-by-distance patterns varied over the study area, which we attribute to temporal differences in anthropogenic landscape development. We also found that genetic bottleneck signals were associated with wildfire frequency. These results indicate that habitat fragmentation and alterations have reduced genetic connectivity and diversity of cactus wren populations in coastal southern California. Management efforts focused on improving connectivity among remaining populations may help to ensure population persistence.

  12. Parsing apart the persisters: Etiological mechanisms and criminal offense patterns of moderate- and high-level persistent offenders.

    PubMed

    Amemiya, Jamie; Vanderhei, Susan; Monahan, Kathryn C

    2017-08-01

    Longitudinal investigations that have applied Moffitt's dual taxonomic framework to criminal offending have provided support for the existence of adolescent-limited and life-course persistent antisocial individuals, but have also identified additional trajectories. For instance, rather than a single persistent trajectory, studies have found both high-level and moderate-level persistent offenders. To inform theory and progress our understanding of chronic antisocial behavior, the present study used a sample of serious adolescent offenders (N =1,088) followed from middle adolescence to early adulthood (14-25 years), and examined how moderate-level persistent offenders differed from low-rate, desisting, and high-level persistent offenders. Results indicated that moderate-level persisters' etiology and criminal offense patterns were most similar to high-level persisters, but there were notable differences. Specifically, increasing levels of contextual adversity characterized both moderate-level and high-level persisting trajectories, but moderate-level persisters reported consistently lower levels of environmental risk. While both high- and moderate-level persisters committed more drug-related offenses in early adulthood compared to adolescence, moderate-level persisters engaged in lower levels of antisocial behavior across all types of criminal offenses. Taken cumulatively, the findings of this study suggest that sociocontextual interventions may be powerful in reducing both moderate- and high-level persistence in crime.

  13. The genetic and environmental etiology of antisocial behavior from childhood to emerging adulthood.

    PubMed

    Tuvblad, Catherine; Narusyte, Jurgita; Grann, Martin; Sarnecki, Jerzy; Lichtenstein, Paul

    2011-09-01

    Previous research suggests that both genetic and environmental influences are important for antisocial behavior across the life span, even though the prevalence and incidence of antisocial behavior varies considerably across ages. However, little is known of how genetic and environmental effects influence the development of antisocial behavior. A total of 2,600 male and female twins from the population-based Swedish Twin Registry were included in the present study. Antisocial behavior was measured on four occasions, when twins were 8-9, 13-14, 16-17, and 19-20 years old. Longitudinal analyses of the data were conducted using structural equation modeling. The stability of antisocial behavior over time was explained by a common latent persistent antisocial behavior factor. A common genetic influence accounted for 67% of the total variance in this latent factor, the shared environment explained 26%, and the remaining 7% was due to the non-shared environment. Significant age-specific shared environmental factors were found at ages 13-14 years, suggesting that common experiences (e.g., peers) are important for antisocial behavior at this age. Results from this study show that genetic as well as shared environmental influences are important in antisocial behavior that persists from childhood to emerging adulthood.

  14. Genesis and genetic constellations of swine influenza viruses in Thailand.

    PubMed

    Poonsuk, Sukontip; Sangthong, Pradit; Petcharat, Nantawan; Lekcharoensuk, Porntippa

    2013-12-27

    Swine influenza virus (SIV) is one of the most important zoonotic agents and the origin of the most recent pandemic virus. Asia is considered to be the epicenter for genetic exchanging of influenza A viruses and Southeast Asia including Thailand serves as a reservoir to maintain the persistence of the viruses for seeding other regions. Therefore, searching for new reassortants in this area has been routinely required. Although SIVs in Thailand have been characterized, collective information regarding their genetic evolution and gene constellations is limited. In this study, whole genomes of 30 SIVs isolated during clinical target surveillance plus all available sequences of past and currently circulating Thai SIVs were genetically characterized based on their evolutionary relationships. All genetic pools of Thai SIVs are comprised of four lineages including classical swine (CS), Eurasian swine (EAs), Triple reassortants (TRIG) and Seasonal human (Shs). Out of 84 isolates, nine H1N1, six H3N2 and one H1N2 strains were identified. Gene constellations of SIVs in Thailand are highly complex resulting from multiple reassortments among concurrently circulating SIVs and temporally introduced foreign genes. Most strains contain gene segments from both EAs and CS lineages and appeared transiently. TRIG lineage has been recently introduced into Thai SIV gene pools. The existence of EAs and TRIG lineages in this region may increase rates of genetic exchange and diversity while Southeast Asia is a persistent reservoir for influenza A viruses. Continual monitoring of SIV evolution in this region is crucial in searching for the next potential pandemic viruses. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Microsatellite variation reveals weak genetic structure and retention of genetic variability in threatened Chinook salmon (Oncorhynchus tshawytscha) within a Snake River watershed

    USGS Publications Warehouse

    Neville, Helen; Issacs, Frank B.; Thurow, Russel; Dunham, J.B.; Rieman, B.

    2007-01-01

    Pacific salmon (Oncorhynchus spp.) have been central to the development of management concepts associated with evolutionarily significant units (ESUs), yet there are still relatively few studies of genetic diversity within threatened and endangered ESUs for salmon or other species. We analyzed genetic variation at 10 microsatellite loci to evaluate spatial population structure and genetic variability in indigenous Chinook salmon (Oncorhynchus tshawytscha) across a large wilderness basin within a Snake River ESU. Despite dramatic 20th century declines in abundance, these populations retained robust levels of genetic variability. No significant genetic bottlenecks were found, although the bottleneck metric (M ratio) was significantly correlated with average population size and variability. Weak but significant genetic structure existed among tributaries despite evidence of high levels of gene flow, with the strongest genetic differentiation mirroring the physical segregation of fish from two sub-basins. Despite the more recent colonization of one sub-basin and differences between sub-basins in the natural level of fragmentation, gene diversity and genetic differentiation were similar between sub-basins. Various factors, such as the (unknown) genetic contribution of precocial males, genetic compensation, lack of hatchery influence, and high levels of current gene flow may have contributed to the persistence of genetic variability in this system in spite of historical declines. This unique study of indigenous Chinook salmon underscores the importance of maintaining natural populations in interconnected and complex habitats to minimize losses of genetic diversity within ESUs.

  16. Persistence of West Nile virus.

    PubMed

    Garcia, Melissa N; Hasbun, Rodrigo; Murray, Kristy O

    2015-02-01

    West Nile virus (WNV) is a widespread global pathogen that results in significant morbidity and mortality. Data from animal models provide evidence of persistent renal and neurological infection from WNV; however, the possibility of persistent infection in humans and long-term neurological and renal outcomes related to viral persistence remain largely unknown. In this paper, we provide a review of the literature related to persistent infection in parallel with the findings from cohorts of patients with a history of WNV infection. The next steps for enhancing our understanding of WNV as a persistent pathogen are discussed. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  17. Bilateral persistent fetal vasculature due to a mutation in the Norrie disease protein gene

    PubMed Central

    Payabvash, Seyedmehdi; Anderson, Jill S

    2015-01-01

    We report a case of a 7-week-old boy with bilateral leukocoria and asymmetric microphthalmia who was found to have Norrie disease. Symmetrically hyperdense globes with no evidence of calcification were seen on CT scan. The MRI showed bilateral retinal hemorrhages resulting in conical vitreous chambers—narrow at the optic disc and widened toward the lens—characteristic of persistent fetal vasculature. Genetic evaluation revealed a previously undescribed mutation in the Norrie disease protein gene. PMID:26459204

  18. Successive Respiratory Syncytial Virus Epidemics in Local Populations Arise from Multiple Variant Introductions, Providing Insights into Virus Persistence

    PubMed Central

    Otieno, James R.; Ngama, Mwanajuma; Mwihuri, Alexander G.; Medley, Graham F.; Cane, Patricia A.; Nokes, D. James

    2015-01-01

    ABSTRACT Respiratory syncytial virus (RSV) is a global respiratory pathogen of humans, with infection occurring characteristically as recurrent seasonal epidemics. Unlike influenza viruses, little attention has been paid to the mechanism underlying worldwide spread and persistence of RSV and how this may be discerned through an improved understanding of the introduction and persistence of RSV in local communities. We analyzed 651 attachment (G) glycoprotein nucleotide sequences of RSV B collected over 11 epidemics (2002 to 2012) in Kilifi, Kenya, and contemporaneous data collected elsewhere in Kenya and 18 other countries worldwide (2002 to 2012). Based on phylogeny, genetic distance and clustering patterns, we set out pragmatic criteria to classify local viruses into distinct genotypes and variants, identifying those newly introduced and those locally persisting. Three genotypes were identified in the Kilifi data set: BA (n = 500), SAB1 (n = 148), and SAB4 (n = 3). Recurrent RSV epidemics in the local population were composed of numerous genetic variants, most of which have been newly introduced rather than persisting in the location from season to season. Global comparison revealed that (i) most Kilifi variants do not cluster closely with strains from outside Kenya, (ii) some Kilifi variants were closely related to those observed outside Kenya (mostly Western Europe), and (iii) many variants were circulating elsewhere but were never detected in Kilifi. These results are consistent with the hypothesis that year-to-year presence of RSV at the local level (i.e., Kilifi) is achieved primarily, but not exclusively, through introductions from a pool of variants that are geographically restricted (i.e., to Kenya or to the region) rather than global. IMPORTANCE The mechanism by which RSV persists and reinvades local populations is poorly understood. We investigated this by studying the temporal patterns of RSV variants in a rural setting in tropical Africa and comparing

  19. Persistence of the single lineage of transmissible 'social cancer' in an asexual ant.

    PubMed

    Dobata, S; Sasaki, T; Mori, H; Hasegawa, E; Shimada, M; Tsuji, K

    2011-02-01

    How cooperation can arise and persist, given the threat of cheating phenotypes, is a central problem in evolutionary biology, but the actual significance of cheating in natural populations is still poorly understood. Theories of social evolution predict that cheater lineages are evolutionarily short-lived. However, an exception comes from obligate socially parasitic species, some of which thought to have arisen as cheaters within cooperator colonies and then diverged through sympatric speciation. This process requires the cheater lineage to persist by avoiding rapid extinction that would result from the fact that the cheaters inflict fitness cost on their host. We examined whether this prerequisite is fulfilled, by estimating the persistence time of cheaters in a field population of the parthenogenetic ant Pristomyrmex punctatus. Population genetic analysis found that the cheaters belong to one monophyletic lineage which we infer has persisted for 200-9200 generations. We show that the cheaters migrate and are thus horizontally transmitted between colonies, a trait allowing the lineage to avoid rapid extinction with its host colony. Although horizontal transmission of disruptive cheaters has the potential to induce extinction of the entire population, such collapse is likely averted when there is spatially restricted migration in a structured population, a scenario that matches the observed isolation by distance pattern that we found. We compare our result with other examples of disruptive and horizontally transmissible cheater lineages in nature. © 2010 Blackwell Publishing Ltd.

  20. The conservation genetics juggling act: Integrating genetics and ecology, science and policy

    USGS Publications Warehouse

    Haig, Susan M.; Miller, Mark P.; Bellinger, Renee; Draheim, Hope M.; Mercer, Dacey; Mullins, Tom

    2016-01-01

    The field of conservation genetics, when properly implemented, is a constant juggling act integrating molecular genetics, ecology, and demography with applied aspects concerning managing declining species or implementing conservation laws and policies. This young field has grown substantially since the 1980’s following development of the polymerase chain reaction and now into the genomics era. Our lab has “grown up” with the field, having worked on these issues for over three decades. Our multi-disciplinary approach entails understanding the behavior and ecology of species as well as the underlying processes that contribute to genetic viability. Taking this holistic approach provides a comprehensive understanding of factors that influence species persistence and evolutionary potential while considering annual challenges that occur throughout their life cycle. As a federal lab, we are often addressing the needs of the U.S. Fish and Wildlife Service in their efforts to list, de-list or recover species. Nevertheless, there remains an overall communication gap between research geneticists and biologists who are charged with implementing their results. Therefore, we outline the need for a National Center for Small Population Biology to ameliorate this problem and provide organizations charged with making status decisions firmer ground from which to make their critical decisions. 

  1. Persistent arm pain is distinct from persistent breast pain following breast cancer surgery.

    PubMed

    Langford, Dale J; Paul, Steven M; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D; Hamolsky, Deborah; Luce, Judith A; Kober, Kord M; Neuhaus, John M; Cooper, Bruce A; Aouizerat, Bradley E; Miaskowski, Christine

    2014-12-01

    Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  2. PERSISTENT ARM PAIN IS DISTINCT FROM PERSISTENT BREAST PAIN FOLLOWING BREAST CANCER SURGERY

    PubMed Central

    Langford, Dale J.; Paul, Steven M.; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D.; Hamolsky, Deborah; Luce, Judith A.; Kober, Kord M.; Neuhaus, John M.; Cooper, Bruce A.; Aouizerat, Bradley E.; Miaskowski, Christine

    2014-01-01

    Persistent pain following breast cancer surgery is well-documented. However, it is not well characterized in terms of the anatomic site effected (i.e., breast, arm). In two separate growth mixture modeling analyses, we identified subgroups of women (n=398) with distinct breast pain and arm pain trajectories. Based on the fact that these latent classes differed by anatomic site, types if tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. Purposes of this companion study were to identify demographic and clinical characteristics that differed between the two arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection (ALND) sites, pain qualities, pain interference, and hand and arm function; as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the Moderate Arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and ALND site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. Perspective: For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. PMID:25439319

  3. Loss of Genetic Diversity and Increased Subdivision in an Endemic Alpine Stonefly Threatened by Climate Change

    PubMed Central

    Jordan, Steve; Giersch, J. Joseph; Muhlfeld, Clint C.; Hotaling, Scott; Fanning, Liz; Tappenbeck, Tyler H.; Luikart, Gordon

    2016-01-01

    Much remains unknown about the genetic status and population connectivity of high-elevation and high-latitude freshwater invertebrates, which often persist near snow and ice masses that are disappearing due to climate change. Here we report on the conservation genetics of the meltwater stonefly Lednia tumana (Ricker) of Montana, USA, a cold-water obligate species. We sequenced 1530 bp of mtDNA from 116 L. tumana individuals representing “historic” (>10 yr old) and 2010 populations. The dominant haplotype was common in both time periods, while the second-most-common haplotype was found only in historic samples, having been lost in the interim. The 2010 populations also showed reduced gene and nucleotide diversity and increased genetic isolation. We found lower genetic diversity in L. tumana compared to two other North American stonefly species, Amphinemura linda (Ricker) and Pteronarcys californica Newport. Our results imply small effective sizes, increased fragmentation, limited gene flow, and loss of genetic variation among contemporary L. tumana populations, which can lead to reduced adaptive capacity and increased extinction risk. This study reinforces concerns that ongoing glacier loss threatens the persistence of L. tumana, and provides baseline data and analysis of how future environmental change could impact populations of similar organisms. PMID:27348125

  4. Loss of genetic diversity and increased subdivision in an endemic Alpine Stonefly threatened by climate change

    USGS Publications Warehouse

    Jordan, Steve; Giersch, J. Joseph; Muhlfeld, Clint C.; Hotalling, Scott; Fanning, Liz; Tappenbeck, Tyler H.; Luikart, Gordon

    2016-01-01

    Much remains unknown about the genetic status and population connectivity of high-elevation and high-latitude freshwater invertebrates, which often persist near snow and ice masses that are disappearing due to climate change. Here we report on the conservation genetics of the meltwater stonefly Lednia tumana (Ricker) of Montana, USA, a cold-water obligate species. We sequenced 1530 bp of mtDNA from 116 L. tumana individuals representing “historic” (>10 yr old) and 2010 populations. The dominant haplotype was common in both time periods, while the second-most-common haplotype was found only in historic samples, having been lost in the interim. The 2010 populations also showed reduced gene and nucleotide diversity and increased genetic isolation. We found lower genetic diversity in L. tumana compared to two other North American stonefly species, Amphinemura linda (Ricker) and Pteronarcys californica Newport. Our results imply small effective sizes, increased fragmentation, limited gene flow, and loss of genetic variation among contemporary L. tumana populations, which can lead to reduced adaptive capacity and increased extinction risk. This study reinforces concerns that ongoing glacier loss threatens the persistence of L. tumana, and provides baseline data and analysis of how future environmental change could impact populations of similar organisms.

  5. Numeric invariants from multidimensional persistence

    DOE PAGES

    Skryzalin, Jacek; Carlsson, Gunnar

    2017-05-19

    Topological data analysis is the study of data using techniques from algebraic topology. Often, one begins with a finite set of points representing data and a “filter” function which assigns a real number to each datum. Using both the data and the filter function, one can construct a filtered complex for further analysis. For example, applying the homology functor to the filtered complex produces an algebraic object known as a “one-dimensional persistence module”, which can often be interpreted as a finite set of intervals representing various geometric features in the data. If one runs the above process incorporating multiple filtermore » functions simultaneously, one instead obtains a multidimensional persistence module. Unfortunately, these are much more difficult to interpret. In this article, we analyze the space of multidimensional persistence modules from the perspective of algebraic geometry. First we build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence instead of one-dimensional persistence. Fruthermore, we argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Finally, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be used to study data. This paper extends the results of Adcock et al. (Homol Homotopy Appl 18(1), 381–402, 2016) by constructing numeric invariants from the computation of a multidimensional persistence module as given by Carlsson et al. (J Comput Geom 1(1), 72–100, 2010).« less

  6. Looking for the Primordial Genetic Honeycomb

    NASA Astrophysics Data System (ADS)

    Gallori, Enzo; Biondi, Elisa; Branciamore, Sergio

    2006-12-01

    All life forms on Earth share the same biological program based on the DNA/RNA genomes and proteins. The genetic information, recorded in the nucleotide sequence of the DNA and RNA molecule, supplies the language of life which is transferred through the different generations, thus ensuring the perpetuation of genetic information on Earth. The presence of a genetic system is absolutely essential to life. Thus, the appearance in an ancestral era of a nucleic acid-like polymer able to undergo Darwinian evolution indicates the beginning of life on our planet. The building of primordial genetic molecules, whatever they were, required the presence of a protected environment, allowing the synthesis and concentration of precursors (nucleotides), their joining into larger molecules (polynucleotides), the protection of forming polymers against degradation (i.e. by cosmic and UV radiation), thus ensuring their persistence in a changing environment, and the expression of the “biological” potential of the molecule (its capacity to self-replicate and evolve). Determining how these steps occurred and how the primordial genetic molecules originated on Earth is a very difficult problem that still must be resolved. It has long been proposed that surface chemistry, i.e. on clay minerals, could have played a crucial role in the prebiotic formation of molecules basic to life. In the present work, we discuss results obtained in different fields that strengthen the hypothesis of a clay-surface-mediated origin of genetic material.

  7. Recent advances on lactose intolerance: Tolerance thresholds and currently available answers.

    PubMed

    Corgneau, M; Scher, J; Ritie-Pertusa, L; Le, D T L; Petit, J; Nikolova, Y; Banon, S; Gaiani, C

    2017-10-13

    The genetically programmed reduction in lactase activity during adulthood affects 70% of the world adult population and can cause severe digestive disorders, which are the sign of lactose intolerance. Lactose intolerance symptoms vary depending on the residual lactase activity, the small bowel transit time, and especially the amount of ingested lactose. To formulate dairy products suitable for the vast majority of lactose intolerants, it is essential to define lactose intolerance threshold. A recent meta-analysis permitted to show that almost all lactose intolerants tolerate 12 g of lactose in one intake and approximately 18 g of lactose spread over the day. The prevalence and severity of lactose intolerance are probably overestimated by the general public. This misconception usually leads to an unnecessary reduction of dairy foodstuff consumption. Nevertheless, dairy products are essential for health mainly due to their calcium content and the positive influence of probiotic bacteria. The formulation of dairy products suitable for most intolerant and suspicious subjects seems necessary. The use of exogenous enzyme preparations, as well as the consumption of lactose-free products or products rich in probiotic bacteria are proposed as symptom-reducing strategies.

  8. Caspase 3 promotes genetic instability and carcinogenesis

    PubMed Central

    Liu, Xinjian; He, Yujun; Li, Fang; Huang, Qian; Kato, Takamitsu A.; Hall, Russell P; Li, Chuan-Yuan

    2015-01-01

    Summary Apoptosis is typically considered an anti-oncogenic process since caspase activation can promote the elimination of genetically unstable or damaged cells. We report that a central effector of apoptosis, caspase 3, facilitates, rather than suppresses, chemical and radiation-induced genetic instability and carcinogenesis. We found that a significant fraction of mammalian cells treated with ionizing radiation can survive, despite caspase 3 activation. Moreover, this sublethal activation of caspase 3 promoted persistent DNA damage and oncogenic transformation. In addition, chemically-induced skin carcinogenesis was significantly reduced in mice genetically deficient in caspase 3. Furthermore, attenuation of Endo G activity significantly reduced radiation-induced DNA damage and oncogenic transformation, identifying Endo G as a downstream effector of caspase 3 in this pathway. Our findings suggest that rather than acting as a broad inhibitor of carcinogenesis, caspase 3 activation may contribute to genome instability and play a pivotal role in tumor formation following damage. PMID:25866249

  9. Habitat fragmentation in coastal southern California disrupts genetic connectivity in the cactus wren (Campylorhynchus brunneicapillus).

    PubMed

    Barr, Kelly R; Kus, Barbara E; Preston, Kristine L; Howell, Scarlett; Perkins, Emily; Vandergast, Amy G

    2015-05-01

    Achieving long-term persistence of species in urbanized landscapes requires characterizing population genetic structure to understand and manage the effects of anthropogenic disturbance on connectivity. Urbanization over the past century in coastal southern California has caused both precipitous loss of coastal sage scrub habitat and declines in populations of the cactus wren (Campylorhynchus brunneicapillus). Using 22 microsatellite loci, we found that remnant cactus wren aggregations in coastal southern California comprised 20 populations based on strict exact tests for population differentiation, and 12 genetic clusters with hierarchical Bayesian clustering analyses. Genetic structure patterns largely mirrored underlying habitat availability, with cluster and population boundaries coinciding with fragmentation caused primarily by urbanization. Using a habitat model we developed, we detected stronger associations between habitat-based distances and genetic distances than Euclidean geographic distance. Within populations, we detected a positive association between available local habitat and allelic richness and a negative association with relatedness. Isolation-by-distance patterns varied over the study area, which we attribute to temporal differences in anthropogenic landscape development. We also found that genetic bottleneck signals were associated with wildfire frequency. These results indicate that habitat fragmentation and alterations have reduced genetic connectivity and diversity of cactus wren populations in coastal southern California. Management efforts focused on improving connectivity among remaining populations may help to ensure population persistence. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  10. A comparative study on the metabolism of Epimedium koreanum Nakai-prenylated flavonoids in rats by an intestinal enzyme (lactase phlorizin hydrolase) and intestinal flora.

    PubMed

    Zhou, Jing; Chen, Yan; Wang, Ying; Gao, Xia; Qu, Ding; Liu, Congyan

    2013-12-24

    The aim of this study was to compare the significance of the intestinal hydrolysis of prenylated flavonoids in Herba Epimedii by an intestinal enzyme and flora. Flavonoids were incubated at 37 °C with rat intestinal enzyme and intestinal flora. HPLC-UV was used to calculate the metabolic rates of the parent drug in the incubation and LC/MS/MS was used to determine the chemical structures of metabolites generated by different flavonoid glycosides. Rates of flavonoid metabolism by rat intestinal enzyme were quicker than those of intestinal flora. The sequence of intestinal flora metabolic rates was icariin>epimedin B>epimedin A>epimedin C>baohuoside I, whereas the order of intestinal enzyme metabolic rates was icariin>epimedin A>epimedin C>epimedin B>baohuoside I. Meanwhile, the LC/MS/MS graphs showed that icariin produced three products, epimedin A/B/C had four and baohuoside I yielded one product in incubations of both intestinal enzyme and flora, which were more than the results of HPLC-UV due to the fact LC/MS/MS has lower detectability and higher sensitivity. Moreover, the outcomes indicated that the rate of metabolization of flavonoids by intestinal enzyme were faster than those of intestinal flora, which was consistent with the HPLC-UV results. In conclusion, the metabolic pathways of the same components by intestinal flora and enzyme were the same. What's more, an intestinal enzyme such as lactase phlorizin hydrolase exhibited a more significant metabolic role in prenylated flavonoids of Herba Epimedi compared with intestinal flora.

  11. Bilateral persistent fetal vasculature due to a mutation in the Norrie disease protein gene.

    PubMed

    Payabvash, Seyedmehdi; Anderson, Jill S; Nascene, David R

    2015-12-01

    We report a case of a 7-week-old boy with bilateral leukocoria and asymmetric microphthalmia who was found to have Norrie disease. Symmetrically hyperdense globes with no evidence of calcification were seen on CT scan. The MRI showed bilateral retinal hemorrhages resulting in conical vitreous chambers-narrow at the optic disc and widened toward the lens-characteristic of persistent fetal vasculature. Genetic evaluation revealed a previously undescribed mutation in the Norrie disease protein gene. © The Author(s) 2015.

  12. Rodent Models of Genetic Contributions to Motivation to Abuse Alcohol

    PubMed Central

    Crabbe, John C.

    2016-01-01

    The distinction between alcohol use (normative) and abuse (unfortunately common) implies dysregulation of motivation directed toward the drug. Genetic contributions to abuse risk are mediated through personality differences, other predispositions to drink excessively, and differences in sensitivity to the acute and chronic consequences of the drug. How to assess motivation in laboratory animals is not straightforward but risk factors for and consequences of alcohol abuse can be modeled with reasonable fidelity in laboratory rodents. Remarkably few rodent studies focus on the genetic contributions to alcohol’s reinforcing value: almost all examine preferential drinking of unflavored alcohol over water. Such studies will likely never avoid the confounding role of taste preferences and most often yield intake levels insufficient to yield a pharmacologically significant blood alcohol level. Genotypes that avoid alcohol probably do so based on pre-ingestive sensory cues; however, post-ingestive consequences are also important. Thus, the quest for improved measures of reinforcing value continues. We have genetic differences aplenty, but still lack evidence that any genotype will readily self-administer alcohol to the devastating extent that many alcoholics will. Encouraging results that are emerging include improved behavioral methods for elevating alcohol intake and inferring alcohol reinforcement, as well as new genetic animal models. Several ingenious assays to index alcohol’s motivational effects have been used extensively. Alcoholic drinking that attempts to prevent or to alleviate withdrawal symptoms has been modeled. Another characteristic of alcoholic drinking is its persistence despite abundant evidence to the drinker of the damaging effects of the excessive drinking on work, relationships, and/or health. Modeling such persistence in rodents has been uncommon to date. New genetic animal models include lines of mice selectively bred for chronic high drinking

  13. Cannabis Controversies: How genetics can inform the study of comorbidity

    PubMed Central

    Agrawal, Arpana; Lynskey, Michael T.

    2014-01-01

    Aims To review three key and controversial comorbidities of cannabis use – other illicit drug use, psychosis and depression as well as suicide, from a genetically informed perspective. Design Selective review. Results Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Conclusions Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. PMID:24438181

  14. Diverse Geno- and Phenotypes of Persistent Listeria monocytogenes Isolates from Fermented Meat Sausage Production Facilities in Portugal ▿

    PubMed Central

    Ferreira, V.; Barbosa, J.; Stasiewicz, M.; Vongkamjan, K.; Moreno Switt, A.; Hogg, T.; Gibbs, P.; Teixeira, P.; Wiedmann, M.

    2011-01-01

    The persistence of Listeria monocytogenes in food-associated environments represents a key factor in transmission of this pathogen. To identify persistent and transient strains associated with production of fermented meat sausages in northern Portugal, 1,723 L. monocytogenes isolates from raw material and finished products from 11 processors were initially characterized by random amplification of polymorphic DNA (RAPD), PCR-based molecular serotyping, and epidemic clone characterization, as well as cadmium, arsenic, and tetracycline resistance typing. Pulsed-field gel electrophoresis (PFGE) typing of 240 representative isolates provided evidence for persistence of L. monocytogenes for periods of time ranging from 10 to 32 months for all seven processors for which isolates from different production dates were available. Among 50 L. monocytogenes isolates that included one representative for each PFGE pattern obtained from a given sample, 12 isolates showed reduced invasion efficiency in Caco-2 cells, including 8 isolates with premature stop codons in inlA. Among 41 isolates representing sporadic and persistent PFGE types, 22 isolates represented lysogens. Neither strains with reduced invasion nor lysogens were overrepresented among persistent isolates. While the susceptibility of isolates to lysogenic phages also did not correlate with persistence, it appeared to be associated with molecular serotype. Our data show the following. (i) RAPD may not be suitable for analysis of large sets of L. monocytogenes isolates. (ii) While a large diversity of L. monocytogenes subtypes is found in Portuguese fermented meat sausages, persistence of L. monocytogenes in this food chain is common. (iii) Persistent L. monocytogenes strains are diverse and do not appear to be characterized by unique genetic or phenotypic characteristics. PMID:21378045

  15. Drought Persistence in Models and Observations

    NASA Astrophysics Data System (ADS)

    Moon, Heewon; Gudmundsson, Lukas; Seneviratne, Sonia

    2017-04-01

    Many regions of the world have experienced drought events that persisted several years and caused substantial economic and ecological impacts in the 20th century. However, it remains unclear whether there are significant trends in the frequency or severity of these prolonged drought events. In particular, an important issue is linked to systematic biases in the representation of persistent drought events in climate models, which impedes analysis related to the detection and attribution of drought trends. This study assesses drought persistence errors in global climate model (GCM) simulations from the 5th phase of Coupled Model Intercomparison Project (CMIP5), in the period of 1901-2010. The model simulations are compared with five gridded observational data products. The analysis focuses on two aspects: the identification of systematic biases in the models and the partitioning of the spread of drought-persistence-error into four possible sources of uncertainty: model uncertainty, observation uncertainty, internal climate variability and the estimation error of drought persistence. We use monthly and yearly dry-to-dry transition probabilities as estimates for drought persistence with drought conditions defined as negative precipitation anomalies. For both time scales we find that most model simulations consistently underestimated drought persistence except in a few regions such as India and Eastern South America. Partitioning the spread of the drought-persistence-error shows that at the monthly time scale model uncertainty and observation uncertainty are dominant, while the contribution from internal variability does play a minor role in most cases. At the yearly scale, the spread of the drought-persistence-error is dominated by the estimation error, indicating that the partitioning is not statistically significant, due to a limited number of considered time steps. These findings reveal systematic errors in the representation of drought persistence in current

  16. Agroecosystems shape population genetic structure of the greenhouse whitefly in Northern and Southern Europe

    PubMed Central

    2014-01-01

    Background To predict further invasions of pests it is important to understand what factors contribute to the genetic structure of their populations. Cosmopolitan pest species are ideal for studying how different agroecosystems affect population genetic structure within a species at different climatic extremes. We undertook the first population genetic study of the greenhouse whitefly (Trialeurodes vaporariorum), a cosmopolitan invasive herbivore, and examined the genetic structure of this species in Northern and Southern Europe. In Finland, cold temperatures limit whiteflies to greenhouses and prevent them from overwintering in nature, and in Greece, milder temperatures allow whiteflies to inhabit both fields and greenhouses year round, providing a greater potential for connectivity among populations. Using nine microsatellite markers, we genotyped 1274 T. vaporariorum females collected from 18 greenhouses in Finland and eight greenhouses as well as eight fields in Greece. Results Populations from Finland were less diverse than those from Greece, suggesting that Greek populations are larger and subjected to fewer bottlenecks. Moreover, there was significant population genetic structure in both countries that was explained by different factors. Habitat (field vs. greenhouse) together with longitude explained genetic structure in Greece, whereas in Finland, genetic structure was explained by host plant species. Furthermore, there was no temporal genetic structure among populations in Finland, suggesting that year-round populations are able to persist in greenhouses. Conclusions Taken together our results show that greenhouse agroecosystems can limit gene flow among populations in both climate zones. Fragmented populations in greenhouses could allow for efficient pest management. However, pest persistence in both climate zones, coupled with increasing opportunities for naturalization in temperate latitudes due to climate change, highlight challenges for the

  17. Persistent luminescence nanothermometers

    NASA Astrophysics Data System (ADS)

    Martín Rodríguez, Emma; López-Peña, Gabriel; Montes, Eduardo; Lifante, Ginés; García Solé, José; Jaque, Daniel; Diaz-Torres, Luis Armando; Salas, Pedro

    2017-08-01

    Persistent phosphorescence nanoparticles emitting in the red and near-infrared spectral regions are strongly demanded as contrast nanoprobes for autofluorescence free bioimaging and biosensing. In this work, we have developed Sr4Al14O25:Eu2+, Cr3+, Nd3+ nanopowders that produce persistent red phosphorescence peaking at 694 nm generated by Cr3+ ions. This emission displays temperature sensitivity in the physiological temperature range (20-60 °C), which makes these nanoparticles potentially useful as fluorescence (contactless) nanothermometers operating without requiring optical excitation. Nd3+ ions, which act as shallow electron traps for the red Cr3+ persistent emission, also display infrared emission bands, extending the fluorescence imaging capability to the second biological window. This unique combination of properties makes these nanoparticles multifunctional luminescent probes with great potential applications in nanomedicine.

  18. STEM Field Persistence: The Impact of Engagement on Postsecondary STEM Persistence for Underrepresented Minority Students

    ERIC Educational Resources Information Center

    Flynn, Daniel T.

    2016-01-01

    Persistence studies in science, technology, engineering, and math (STEM) fields indicate that the pipeline to degree attainment is "leaky" and underrepresented minorities are not persisting in the STEM fields. Those students who do not persist in the STEM fields either migrate to other fields of study or drop out of higher education…

  19. A Guided-Inquiry pH Laboratory Exercise for Introductory Biological Science Laboratories

    ERIC Educational Resources Information Center

    Snodgrass, Meagan A.; Lux, Nicholas; Metz, Anneke M.

    2011-01-01

    There is a continuing need for engaging inquiry-based laboratory experiences for advanced high school and undergraduate biology courses. The authors describe a guided-inquiry exercise investigating the pH-dependence of lactase enzyme that uses an inexpensive, wide-range buffering system, lactase dietary supplement, over-the-counter glucose test…

  20. Intestinal Disaccharidase Activity in Patients with Autism: Effect of Age, Gender, and Intestinal Inflammation

    ERIC Educational Resources Information Center

    Kushak, Rafail I.; Lauwers, Gregory Y.; Winter, Harland S.; Buie, Timothy M.

    2011-01-01

    Intestinal disaccharidase activities were measured in 199 individuals with autism to determine the frequency of enzyme deficiency. All patients had duodenal biopsies that were evaluated morphologically and assayed for lactase, sucrase, and maltase activity. Frequency of lactase deficiency was 58% in autistic children less than or equal to 5 years…

  1. Measurement of Enzyme Kinetics by Use of a Blood Glucometer: Hydrolysis of Sucrose and Lactose

    ERIC Educational Resources Information Center

    Heinzerling, Peter; Schrader, Frank; Schanze, Sascha

    2012-01-01

    An alternative analytical method for measuring the kinetic parameters of the enzymes invertase and lactase is described. Invertase hydrolyzes sucrose to glucose and fructose and lactase hydrolyzes lactose to glucose and galactose. In most enzyme kinetics studies, photometric methods or test strips are used to quantify the derivates of the…

  2. Increasing persistency in lay and stabilising egg quality in longer laying cycles. What are the challenges?

    PubMed Central

    Bain, M. M.; Nys, Y.; Dunn, I.C.

    2016-01-01

    Abstract In the past 50 years, selection starting initially at the breed level and then using quantitative genetics coupled with a sophisticated breeding pyramid, has resulted in a very productive hybrid for a variety of traits associated with egg production.One major trait currently being developed further is persistency of lay and the concept of the “long life” layer. Persistency in lay however cannot be achieved without due consideration of how to sustain egg quality and the health and welfare of the birds in longer laying cycles. These multiple goals require knowledge and consideration of the bird’s physiology, nutritional requirements, which vary depending on age and management system, reproductive status and choice of the selection criteria applied.The recent advent of molecular genetics offers considerable hope that these multiple elements can be balanced for the good of all in the industry including the hens.The “long life” layer, which will be capable of producing 500 eggs in a laying cycle of 100 weeks, is therefore on the horizon, bringing with it the benefits of a more efficient utilisation of diminishing resources, including land, water, raw materials for feed as well as a reduction in waste, and an overall reduced carbon footprint. PMID:26982003

  3. Increasing persistency in lay and stabilising egg quality in longer laying cycles. What are the challenges?

    PubMed

    Bain, M M; Nys, Y; Dunn, I C

    2016-06-01

    In the past 50 years, selection starting initially at the breed level and then using quantitative genetics coupled with a sophisticated breeding pyramid, has resulted in a very productive hybrid for a variety of traits associated with egg production. One major trait currently being developed further is persistency of lay and the concept of the "long life" layer. Persistency in lay however cannot be achieved without due consideration of how to sustain egg quality and the health and welfare of the birds in longer laying cycles. These multiple goals require knowledge and consideration of the bird's physiology, nutritional requirements, which vary depending on age and management system, reproductive status and choice of the selection criteria applied. The recent advent of molecular genetics offers considerable hope that these multiple elements can be balanced for the good of all in the industry including the hens. The "long life" layer, which will be capable of producing 500 eggs in a laying cycle of 100 weeks, is therefore on the horizon, bringing with it the benefits of a more efficient utilisation of diminishing resources, including land, water, raw materials for feed as well as a reduction in waste, and an overall reduced carbon footprint.

  4. Novel genomic rearrangements mediated by multiple genetic elements in Streptococcus pyogenes M23ND confer potential for evolutionary persistence

    PubMed Central

    Bao, Yun-Juan; Liang, Zhong; Mayfield, Jeffrey A.; McShan, William M.; Lee, Shaun W.; Ploplis, Victoria A.; Castellino, Francis J.

    2016-01-01

    Symmetric genomic rearrangements around replication axes in genomes are commonly observed in prokaryotic genomes, including Group A Streptococcus (GAS). However, asymmetric rearrangements are rare. Our previous studies showed that the hypervirulent invasive GAS strain, M23ND, containing an inactivated transcriptional regulator system, covRS, exhibits unique extensive asymmetric rearrangements, which reconstructed a genomic structure distinct from other GAS genomes. In the current investigation, we identified the rearrangement events and examined the genetic consequences and evolutionary implications underlying the rearrangements. By comparison with a close phylogenetic relative, M18-MGAS8232, we propose a molecular model wherein a series of asymmetric rearrangements have occurred in M23ND, involving translocations, inversions and integrations mediated by multiple factors, viz., rRNA-comX (factor for late competence), transposons and phage-encoded gene segments. Assessments of the cumulative gene orientations and GC skews reveal that the asymmetric genomic rearrangements did not affect the general genomic integrity of the organism. However, functional distributions reveal re-clustering of a broad set of CovRS-regulated actively transcribed genes, including virulence factors and metabolic genes, to the same leading strand, with high confidence (p-value ~10−10). The re-clustering of the genes suggests a potential selection advantage for the spatial proximity to the transcription complexes, which may contain the global transcriptional regulator, CovRS, and other RNA polymerases. Their proximities allow for efficient transcription of the genes required for growth, virulence and persistence. A new paradigm of survival strategies of GAS strains is provided through multiple genomic rearrangements, while, at the same time, maintaining genomic integrity. PMID:27329479

  5. A KCNQ1 mutation causes age-dependant bradycardia and persistent atrial fibrillation.

    PubMed

    Ki, Chang-Seok; Jung, Chae Lim; Kim, Hyun-ji; Baek, Kwan-Hyuck; Park, Seung Jung; On, Young Keun; Kim, Ki-Suk; Noh, Su Jin; Youm, Jae Boum; Kim, June Soo; Cho, Hana

    2014-03-01

    Atrial fibrillation (AF) is the most common arrhythmia. Gain-of-function mutations in KCNQ1, the pore-forming α-subunit of the slow delayed rectifier K current (IKs) channel, have been associated with AF. The purpose of this study was functional assessment of a mutation in KCNQ1 identified in a family with persistent AF and sinus bradycardia. We investigated whether this KCNQ1 missense mutation could form the genetic basis for AF and bradycardia simultaneously in this family. Sanger sequencing in a family with hereditary persistent AF identified a novel KCNQ1 variant (V241F) in a highly conserved region of S4 domain. The proband and her son developed bradycardia and persistent AF in an age-dependent fashion. The other son was a mutation carrier but he showed sinus bradycardia and not AF. Whole-cell patch clamp electrophysiology showed that V241F mutation in KCNQ1 shifted the activation curve to the left and dramatically slowed deactivation, leading to a constitutively open-like phenotype. Computer modeling showed that V241F would slow pacemaker activity. Also, simulations of atrial excitation predicted that V241F results in extreme shortening of action potential duration, possibly resulting in AF. Our study indicates that V241F might cause sinus bradycardia by increasing IKs. Additionally, V241F likely shortens atrial refractoriness to promote a substrate for reentry. KCNQ1 mutations have previously been described in AF, yet this is the first time a mutation in KCNQ1 is associated with age-dependent bradycardia and persistent AF. This finding further supports the hypothesis that sinus node dysfunction contributes to the development of AF.

  6. Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury

    PubMed Central

    Polimanti, Renato; Chen, Chia-Yen; Ursano, Robert J.; Heeringa, Steven G.; Jain, Sonia; Kessler, Ronald C.; Nock, Matthew K.; Smoller, Jordan W.; Sun, Xiaoying; Gelernter, Joel

    2017-01-01

    Abstract Traumatic brain injury (TBI) contributes to the increased rates of suicide and post-traumatic stress disorder in military personnel and veterans, and it is also associated with the risk for neurodegenerative and psychiatric disorders. A cross-phenotype high-resolution polygenic risk score (PRS) analysis of persistent post-concussive symptoms (PCS) was conducted in 845 U.S. Army soldiers who sustained TBI during their deployment. We used a prospective longitudinal survey of three brigade combat teams to assess deployment-acquired TBI and persistent physical, cognitive, and emotional PCS. PRS was derived from summary statistics of large genome-wide association studies of Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, and major depressive disorder (MDD); and for years of schooling, college completion, childhood intelligence, infant head circumference (IHC), and adult intracranial volume. Although our study had more than 95% of statistical power to detect moderate-to-large effect sizes, no association was observed with neurodegenerative and psychiatric disorders, suggesting that persistent PCS does not share genetic components with these traits to a moderate-to-large degree. We observed a significant finding: subjects with high IHC PRS recovered better from cognitive/emotional persistent PCS than the other individuals (R2 = 1.11%; p = 3.37 × 10−3). Enrichment analysis identified two significant Gene Ontology (GO) terms related to this result: GO:0050839∼Cell adhesion molecule binding (p = 8.9 × 10−6) and GO:0050905∼Neuromuscular process (p = 9.8 × 10−5). In summary, our study indicated that the genetic predisposition to persistent PCS after TBI does not have substantial overlap with neurodegenerative and psychiatric diseases, but mechanisms related to early brain growth may be involved. PMID:27439997

  7. Persistent homology and non-Gaussianity

    NASA Astrophysics Data System (ADS)

    Cole, Alex; Shiu, Gary

    2018-03-01

    In this paper, we introduce the topological persistence diagram as a statistic for Cosmic Microwave Background (CMB) temperature anisotropy maps. A central concept in 'Topological Data Analysis' (TDA), the idea of persistence is to represent a data set by a family of topological spaces. One then examines how long topological features 'persist' as the family of spaces is traversed. We compute persistence diagrams for simulated CMB temperature anisotropy maps featuring various levels of primordial non-Gaussianity of local type. Postponing the analysis of observational effects, we show that persistence diagrams are more sensitive to local non-Gaussianity than previous topological statistics including the genus and Betti number curves, and can constrain Δ fNLloc= 35.8 at the 68% confidence level on the simulation set, compared to Δ fNLloc= 60.6 for the Betti number curves. Given the resolution of our simulations, we expect applying persistence diagrams to observational data will give constraints competitive with those of the Minkowski Functionals. This is the first in a series of papers where we plan to apply TDA to different shapes of non-Gaussianity in the CMB and Large Scale Structure.

  8. Persistent Distress after Water Contamination.

    PubMed

    Schade, Charles P; Gupta, Rahul; Jha, Ayan; Wright, Nasandra

    2016-01-01

    A chemical spill contaminated the public water supply of Charleston, West Virginia in January 2014 for at least a week. Psychological distress is common after disasters. We surveyed the exposed population to assess psychological distress during and three months after the incident. We inquired about stressors that might predict distress, adequacy of communication from public officials, and use of the water supply and perceptions of its safety three months after the incident. Twenty six percent of interviewees had persistent symptoms of distress. Female sex, negative household experiences during the episode (especially having someone sick), and poor perception of communication increased odds of persistent distress. Households of respondents without persistent distress were significantly more likely to report drinking tap water (RR=1.95) than those with persistent distress. Distress in Charleston area residents persisted and may have resulted in continuing mistrust of the water supply.

  9. Predominant effect of host genetics on levels of Lactobacillus johnsonii bacteria in the mouse gut.

    PubMed

    Buhnik-Rosenblau, Keren; Danin-Poleg, Yael; Kashi, Yechezkel

    2011-09-01

    The gut microbiota is strongly associated with the well-being of the host. Its composition is affected by environmental factors, such as food and maternal inoculation, while the relative impact of the host's genetics have been recently uncovered. Here, we studied the effect of the host genetic background on the composition of intestinal bacteria in a murine model, focusing on lactic acid bacteria (LAB) as an important group that includes many probiotic strains. Based on 16S rRNA gene genotyping, variation was observed in fecal LAB populations of BALB/c and C57BL/6J mouse lines. Lactobacillus johnsonii, a potentially probiotic bacterium, appeared at significantly higher levels in C57BL/6J versus BALB/c mouse feces. In the BALB/c gut, the L. johnsonii level decreased rapidly after oral administration, suggesting that some selective force does not allow its persistence at higher levels. The genetic inheritance of L. johnsonii levels was further tested in reciprocal crosses between the two mouse lines. The resultant F1 offspring presented similar L. johnsonii levels, confirming that mouse genetics plays a major role in determining these levels compared to the smaller maternal effect. Our findings suggest that mouse genetics has a major effect on the composition of the LAB population in general and on the persistence of L. johnsonii in the gut in particular. Concentrating on a narrow spectrum of culturable LAB enables the isolation and characterization of such potentially probiotic bacterial strains, which might be specifically oriented to the genetic background of the host as part of a personalized-medicine approach.

  10. The future of subalpine forests in the Southern Rocky Mountains: Trajectories for Pinus aristata genetic lineages

    PubMed Central

    2018-01-01

    Like many other high elevation alpine tree species, Rocky Mountain bristlecone pine (Pinus aristata Engelm.) may be particularly vulnerable to climate change. To evaluate its potential vulnerability to shifts in climate, we defined the suitable climate space for each of four genetic lineages of bristlecone pine and for other subalpine tree species in close proximity to bristlecone pine forests. Measuring changes in the suitable climate space for lineage groups is an important step beyond models that assume species are genetically homogenous. The suitable climate space for bristlecone pine in the year 2090 is projected to decline by 74% and the proportional distribution of suitable climate space for genetic lineages shifts toward those associated with warmer and wetter conditions. The 2090 climate space for bristlecone pine exhibits a bimodal distribution along an elevation gradient, presumably due to the persistence of the climate space in the Southern Rocky Mountains and exclusion at mid-elevations by conditions that favor the climate space of other species. These shifts have implications for changes in fire regimes, vulnerability to pest and pathogens, and altered carbon dynamics across the southern Rockies, which may reduce the likelihood of bristlecone pine trees achieving exceptional longevity in the future. The persistence and expansion of climate space for southern bristlecone pine genetic lineage groups in 2090 suggests that these sources may be the least vulnerable in the future. While these lineages may be more likely to persist and therefore present opportunities for proactive management (e.g., assisted migration) to maintain subalpine forest ecosystem services in a warmer world, our findings also imply heighted conservation concern for vulnerable northern lineages facing range contractions. PMID:29554097

  11. COMT Val(158)Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study.

    PubMed

    Olsson, C A; Byrnes, G B; Anney, R J L; Collins, V; Hemphill, S A; Williamson, R; Patton, G C

    2007-10-01

    We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val(158)Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose-response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met(158) [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76-0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79-0.99, P = 0.033). There was no evidence for a dose-response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29-0.70, P < 0.001) among carriers homozygous for both the COMT Met(158) and the 5HTTLPR Short alleles (Met(158)Met + Short-Short) compared with the remaining cohort. The double-recessive effect remained after multivariate adjustment for a range of psychosocial predictors of anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.

  12. A study of the role of the FOXP2 and CNTNAP2 genes in persistent developmental stuttering.

    PubMed

    Han, Tae-Un; Park, John; Domingues, Carlos F; Moretti-Ferreira, Danilo; Paris, Emily; Sainz, Eduardo; Gutierrez, Joanne; Drayna, Dennis

    2014-09-01

    A number of speech disorders including stuttering have been shown to have important genetic contributions, as indicated by high heritability estimates from twin and other studies. We studied the potential contribution to stuttering from variants in the FOXP2 gene, which have previously been associated with developmental verbal dyspraxia, and from variants in the CNTNAP2 gene, which have been associated with specific language impairment (SLI). DNA sequence analysis of these two genes in a group of 602 unrelated cases, all with familial persistent developmental stuttering, revealed no excess of potentially deleterious coding sequence variants in the cases compared to a matched group of 487 well characterized neurologically normal controls. This was compared to the distribution of variants in the GNPTAB, GNPTG, and NAGPA genes which have previously been associated with persistent stuttering. Using an expanded subject data set, we again found that NAGPA showed significantly different mutation frequencies in North Americans of European descent (p=0.0091) and a significant difference existed in the mutation frequency of GNPTAB in Brazilians (p=0.00050). No significant differences in mutation frequency in the FOXP2 and CNTNAP2 genes were observed between cases and controls. To examine the pattern of expression of these five genes in the human brain, real time quantitative reverse transcription PCR was performed on RNA purified from 27 different human brain regions. The expression patterns of FOXP2 and CNTNAP2 were generally different from those of GNPTAB, GNPTG and NAPGA in terms of relatively lower expression in the cerebellum. This study provides an improved estimate of the contribution of mutations in GNPTAB, GNPTG and NAGPA to persistent stuttering, and suggests that variants in FOXP2 and CNTNAP2 are not involved in the genesis of familial persistent stuttering. This, together with the different brain expression patterns of GNPTAB, GNPTG, and NAGPA compared to that of

  13. Interaction of Staphylococcus aureus persister cells with the host when in a persister state and following awakening.

    PubMed

    Mina, Elin G; Marques, Cláudia N H

    2016-08-10

    Persister cells, a tolerant cell sub-population, are commonly associated with chronic and recurrent infections. However, little is known about their ability to actually initiate or establish an infection, become virulent and cause pathogenicity within a host. Here we investigated whether Staphylococcus aureus persister cells initiate an infection and are recognized by macrophages, while in a persister cell status, and upon awakening due to exposure to cis-2-decenoic acid (cis-DA). Our results show that S. aureus persister cells are not able to initiate infections in A. thaliana and present significantly reduced virulence towards C. elegans compared to total populations. In contrast, awakened S. aureus persister cells are able to initiate infections in A. thaliana and in C. elegans albeit, with lower mortality than total population. Furthermore, exposure of S. aureus persister cells to cis-DA led to a loss of tolerance to ciprofloxacin, and an increase of the bacterial fluorescence to levels found in total population. In addition, macrophage engulfment of persister cells was significantly lower than engulfment of total population, both before and following awakening. Overall our findings indicate that upon awakening of a persister population the cells regain their ability to infect hosts despite the absence of an increased immune response.

  14. Genetically Engineering Entomopathogenic Fungi.

    PubMed

    Zhao, H; Lovett, B; Fang, W

    2016-01-01

    Entomopathogenic fungi have been developed as environmentally friendly alternatives to chemical insecticides in biocontrol programs for agricultural pests and vectors of disease. However, mycoinsecticides currently have a small market share due to low virulence and inconsistencies in their performance. Genetic engineering has made it possible to significantly improve the virulence of fungi and their tolerance to adverse conditions. Virulence enhancement has been achieved by engineering fungi to express insect proteins and insecticidal proteins/peptides from insect predators and other insect pathogens, or by overexpressing the pathogen's own genes. Importantly, protein engineering can be used to mix and match functional domains from diverse genes sourced from entomopathogenic fungi and other organisms, producing insecticidal proteins with novel characteristics. Fungal tolerance to abiotic stresses, especially UV radiation, has been greatly improved by introducing into entomopathogens a photoreactivation system from an archaean and pigment synthesis pathways from nonentomopathogenic fungi. Conversely, gene knockout strategies have produced strains with reduced ecological fitness as recipients for genetic engineering to improve virulence; the resulting strains are hypervirulent, but will not persist in the environment. Coupled with their natural insect specificity, safety concerns can also be mitigated by using safe effector proteins with selection marker genes removed after transformation. With the increasing public concern over the continued use of synthetic chemical insecticides and growing public acceptance of genetically modified organisms, new types of biological insecticides produced by genetic engineering offer a range of environmentally friendly options for cost-effective control of insect pests. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Cannabis controversies: how genetics can inform the study of comorbidity.

    PubMed

    Agrawal, Arpana; Lynskey, Michael T

    2014-03-01

    To review three key and controversial comorbidities of cannabis use-other illicit drug use, psychosis and depression, as well as suicide, from a genetically informed perspective. Selective review. Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression, as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. © 2014 Society for the Study of Addiction.

  16. Early vitrectomy effective for bilateral combined anterior and posterior persistent fetal vasculature syndrome.

    PubMed

    Walsh, Mark K; Drenser, Kimberly A; Capone, Antonio; Trese, Michael T

    2010-04-01

    The purpose of this study was to review our surgical experience with patients with bilateral combined anterior and posterior persistent fetal vasculature syndrome (PFVS). We retrospectively reviewed the charts of all patients seen in our tertiary care pediatric retinal practice from 1988 to 2008 with a potential diagnosis of bilateral PFVS with posterior involvement. Clinical diagnosis required the presence of either bilateral persistent hyaloidal stalk tissue with retinal involvement or bilateral dense retrolental fibrovascular plaques (usually with no posterior view preoperatively) without a family history or genetic testing consistent with Norrie disease or familial exudative vitreoretinopathy. Chart review showed 22 vitrectomized patients with clinical findings consistent with bilateral PFVS with posterior involvement who did not have a family history or genetic testing consistent with Norrie disease or familial exudative vitreoretinopathy. All 22 of these patients with posterior retinal involvement also had anterior findings and thus can be classified as combined anterior and posterior PFVS. Of the 13 patients with visual acuity follow-up data, 9 patients (69%) maintained at least light perception vision in at least 1 eye at last follow-up. Of the 28 operated eyes in 16 patients with follow-up data, 3 eyes (11%) were phthisical at last follow-up. Children with bilateral PFVS with posterior retinal involvement have a dismal visual prognosis if left unoperated. In this relatively large series of a rare condition, we find that vitrectomy with or without lensectomy is beneficial in bilateral combined anterior and posterior PFVS in two regards: maintenance or restoration of vision and avoidance of phthisis bulbi.

  17. GENETIC DIVERSITY AND STRUCTURE OF AN ESTUARINE FISH (FUNDULUS HETEROCLITUS) INDIGENOUS TO A HIGHLY CONTAMINATED URBAN HARBOR

    EPA Science Inventory

    Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...

  18. Phylogenetics, phylogeography and population genetics of North American sea ducks (tribe: Mergini)

    USGS Publications Warehouse

    Talbot, Sandra L.; Sonsthagen, Sarah A.; Pearce, John M.; Scribner, Kim T.

    2015-01-01

    Many environments occupied by North American sea ducks are remote and difficult to access, and as a result, detailed information about life history characteristics that drive population dynamics within and across species is limited. Nevertheless, progress on this front during the past several decades has benefited by the application of genetic technologies, and for several species, these technologies have allowed for concomitant tracking of population trends and genetic diversity, delineation of populations, assessment of gene flow among metapopulations, and understanding of migratory connectivity between breeding and wintering grounds. This chapter provides an overview of phylogenetic, phylogeographic, and population genetics studies of North American sea duck species, many of which have sought to understand the major and minor genetic divisions within and among sea duck species, and most of which have been conducted with the understanding that the maintenance of genetic variation in wild sea duck populations is fundamental to the group’s long-term persistence.

  19. DNA hypomethylation at ALOX12 is associated with persistent wheezing in childhood.

    PubMed

    Morales, Eva; Bustamante, Mariona; Vilahur, Nadia; Escaramis, Georgia; Montfort, Magda; de Cid, Rafael; Garcia-Esteban, Raquel; Torrent, Maties; Estivill, Xavier; Grimalt, Joan O; Sunyer, Jordi

    2012-05-01

    Epigenetic changes may play a role in the occurrence of asthma-related phenotypes. To identify epigenetic marks in terms of DNA methylation of asthma-related phenotypes in childhood, and to assess the effect of prenatal exposures and genetic variation on these epigenetic marks. Data came from two cohorts embedded in the Infancia y Medio Ambiente (INMA) PROJECT: Menorca (n = 122) and Sabadell (n = 236). Wheezing phenotypes were defined at age 4-6 years. Cytosine-guanine (CpG) dinucleotide site DNA methylation differences associated with wheezing phenotypes were screened in children of the Menorca study using the Illumina GoldenGate Panel I. Findings were validated and replicated using pyrosequencing. Information on maternal smoking and folate supplement use was obtained through questionnaires. Dichlorodiphenyldichloroethylene was measured in cord blood or maternal serum. Genotypes were extracted from genome-wide data. Screening identified lower DNA methylation at a CpG site in the arachidonate 12-lipoxygenase (ALOX12) gene in children having persistent wheezing compared with those never wheezed (P = 0.003). DNA hypomethylation at ALOX12 loci was associated with higher risk of persistent wheezing in the Menorca study (odds ratio per 1% methylation decrease, 1.13; 95% confidence interval, 0.99-1.29; P = 0.077) and in the Sabadell study (odds ratio, 1.16; 95% confidence interval, 1.03-1.37; P = 0.017). Higher levels of prenatal dichlorodiphenyldichloroethylene were associated with DNA hypomethylation of ALOX12 in the Menorca study (P = 0.033), but not in the Sabadell study (P = 0.377). ALOX12 DNA methylation was strongly determined by underlying genetic polymorphisms. DNA methylation of ALOX12 may be an epigenetic biomarker for the risk of asthma-related phenotypes.

  20. Persistence of vigilance and flight response behaviour in wild reindeer with varying domestic ancestry.

    PubMed

    Reimers, E; Røed, K H; Colman, J E

    2012-08-01

    Knowledge about changes in behavioural traits related to wildness and tameness is for most mammals lacking, despite the increased trend of using domestic stock to re-establish wild populations into historical ranges. To test for persistence of behavioural traits of wild reindeer (Rangifer tarandus L.) exposed to hunting, we sampled DNA, vigilance and flight responses in wild reindeer herds with varying domestic ancestry. Analyses of 14 DNA microsatellite loci revealed a dichotomous main genetic structure reflecting their native origin, with the Rondane reindeer genetically different from the others and with least differentiation towards the Hardangervidda reindeer. The genetic clustering of the reindeer in Norefjell-Reinsjøfjell, Ottadalen and Forollhogna, together with domestic reindeer, supports a predominant domestic origin of these herds. Despite extensive hunting in all herds, the behavioural measures indicate increasing vigilance, alert and flight responses with increasing genetic dissimilarity with domestic herds. Vigilance frequency and time spent vigilant were higher in Rondane compared to Hardangervidda, which again were higher than herds with a domestic origin. We conclude that previous domestication has preserved a hard wired behavioural trait in some reindeer herds exhibiting less fright responses towards humans that extensive hunting has, but only slightly, altered. This brings novel and relevant knowledge to discussions about genetic diversity of wildlife in general and wild reindeer herds in Norway in specific. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

  1. Persistent short-term memory defects following sleep deprivation in a drosophila model of Parkinson disease.

    PubMed

    Seugnet, Laurent; Galvin, James E; Suzuki, Yasuko; Gottschalk, Laura; Shaw, Paul J

    2009-08-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on shortterm memory using a Drosophila model of Parkinson disease. Transgenic strains of Drosophila melanogaster. Using the GAL4-UAS system, human alpha-synuclein was expressed throughout the nervous system of adult flies. Alpha-synuclein expressing flies (alpha S flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry. MEASURMENTS AND RESULTS: When sleep deprived at an intermediate stage of the pathology, alpha S flies showed persistent short-term memory deficits that lasted > or = 3 days. Cognitive deficits were not observed in younger alpha S flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived alpha S flies. Blocking D1-like receptors during sleep deprivation prevented persistent shortterm memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits. These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics.

  2. Epigenetic regulation of persistent pain

    PubMed Central

    Bai, Guang; Ren, Ke; Dubner, Ronald

    2014-01-01

    Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development/maintenance of persistent pain and, possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain. PMID:24948399

  3. [From persistence to symbiosis of microorganisms].

    PubMed

    Bukharin, O V

    2012-01-01

    Primary results of study of problem of microorganism persistence over the last 2 decades on 7 all-Russian conferences in Orenburg are examined in the article. Milestones of both fundamental research and practically significant studies are designated, the role of persistent potential of microorganisms in infectious pathology is evaluated. The emerging turn of studies from persistence to symbiosis is consonant with the idea of international project "Human microbiom" and allows to use the persistent potential of microorganisms as one of the instruments of resolving issues of infectology.

  4. Kinship structures create persistent channels for language transmission

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lansing, J. Stephen; Abundo, Cheryl; Jacobs, Guy S.

    Here, languages are transmitted through channels created by kinship systems. Given sufficient time, these kinship channels can change the genetic and linguistic structure of populations. In traditional societies of eastern Indonesia, finely resolved cophylogenies of languages and genes reveal persistent movements between stable speech communities facilitated by kinship rules. When multiple languages are present in a region and postmarital residence rules encourage sustained directional movement between speech communities, then languages should be channeled along uniparental lines. We find strong evidence for this pattern in 982 individuals from 25 villages on two adjacent islands, where different kinship rules have been followed.more » Core groups of close relatives have stayed together for generations, while remaining in contact with, and marrying into, surrounding groups. Over time, these kinship systems shaped their gene and language phylogenies: Consistently following a postmarital residence rule turned social communities into speech communities.« less

  5. Kinship structures create persistent channels for language transmission.

    PubMed

    Lansing, J Stephen; Abundo, Cheryl; Jacobs, Guy S; Guillot, Elsa G; Thurner, Stefan; Downey, Sean S; Chew, Lock Yue; Bhattacharya, Tanmoy; Chung, Ning Ning; Sudoyo, Herawati; Cox, Murray P

    2017-12-05

    Languages are transmitted through channels created by kinship systems. Given sufficient time, these kinship channels can change the genetic and linguistic structure of populations. In traditional societies of eastern Indonesia, finely resolved cophylogenies of languages and genes reveal persistent movements between stable speech communities facilitated by kinship rules. When multiple languages are present in a region and postmarital residence rules encourage sustained directional movement between speech communities, then languages should be channeled along uniparental lines. We find strong evidence for this pattern in 982 individuals from 25 villages on two adjacent islands, where different kinship rules have been followed. Core groups of close relatives have stayed together for generations, while remaining in contact with, and marrying into, surrounding groups. Over time, these kinship systems shaped their gene and language phylogenies: Consistently following a postmarital residence rule turned social communities into speech communities. Copyright © 2017 the Author(s). Published by PNAS.

  6. Kinship structures create persistent channels for language transmission

    DOE PAGES

    Lansing, J. Stephen; Abundo, Cheryl; Jacobs, Guy S.; ...

    2017-11-20

    Here, languages are transmitted through channels created by kinship systems. Given sufficient time, these kinship channels can change the genetic and linguistic structure of populations. In traditional societies of eastern Indonesia, finely resolved cophylogenies of languages and genes reveal persistent movements between stable speech communities facilitated by kinship rules. When multiple languages are present in a region and postmarital residence rules encourage sustained directional movement between speech communities, then languages should be channeled along uniparental lines. We find strong evidence for this pattern in 982 individuals from 25 villages on two adjacent islands, where different kinship rules have been followed.more » Core groups of close relatives have stayed together for generations, while remaining in contact with, and marrying into, surrounding groups. Over time, these kinship systems shaped their gene and language phylogenies: Consistently following a postmarital residence rule turned social communities into speech communities.« less

  7. Persistence of transferable extended-spectrum-β-lactamase resistance in the absence of antibiotic pressure.

    PubMed

    Cottell, Jennifer L; Webber, Mark A; Piddock, Laura J V

    2012-09-01

    The treatment of infections caused by antibiotic-resistant bacteria is one of the great challenges faced by clinicians in the 21st century. Antibiotic resistance genes are often transferred between bacteria by mobile genetic vectors called plasmids. It is commonly believed that removal of antibiotic pressure will reduce the numbers of antibiotic-resistant bacteria due to the perception that carriage of resistance imposes a fitness cost on the bacterium. This study investigated the ability of the plasmid pCT, a globally distributed plasmid that carries an extended-spectrum-β-lactamase (ESBL) resistance gene (bla(CTX-M-14)), to persist and disseminate in the absence of antibiotic pressure. We investigated key attributes in plasmid success, including conjugation frequencies, bacterial-host growth rates, ability to cause infection, and impact on the fitness of host strains. We also determined the contribution of the bla(CTX-M-14) gene itself to the biology of the plasmid and host bacterium. Carriage of pCT was found to impose no detectable fitness cost on various bacterial hosts. An absence of antibiotic pressure and inactivation of the antibiotic resistance gene also had no effect on plasmid persistence, conjugation frequency, or bacterial-host biology. In conclusion, plasmids such as pCT have evolved to impose little impact on host strains. Therefore, the persistence of antibiotic resistance genes and their vectors is to be expected in the absence of antibiotic selective pressure regardless of antibiotic stewardship. Other means to reduce plasmid stability are needed to prevent the persistence of these vectors and the antibiotic resistance genes they carry.

  8. Persistence-Retention. Snapshot™ Report, Spring 2014

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2014

    2014-01-01

    This snapshot report provides information on student persistence and retention rates for Spring 2014. Data is presented in tabular format on the following: (1) First-Year Persistence and Retention Rates by Starting Enrollment Intensity (all institutional sectors); (2) First-Year Persistence and Retention Rates by Age at College Entry (all…

  9. Evidence for the establishment and persistence of genetically modified canola populations in the U.S.

    EPA Science Inventory

    Background/Questions/Methods Concerns surrounding the commercial release of genetically modified crops include the risks of escape from cultivation, naturalization, and the transfer of beneficial traits to native and weedy species. Among the crops commonly grown in the U.S., a l...

  10. Persistence of interest in science, technology, engineering and mathematics: An analysis of persisting and non-persisting students

    NASA Astrophysics Data System (ADS)

    White, Jeffry L.

    While there has been an increase in enrollment, interest in science, technology, engineering, and mathematics (STEM) has been declining on college campuses since 1967. Higher enrollment does not transfer to an increase in the number of minorities in the STEM fields. The majority-minority enrollment ratio is nearly 2:1 but the gap widens to 4:1 when it comes to graduation. In fact, underrepresented minorities (URM) earned only 12% of the STEM degrees awarded in 1998. When the higher attrition and lower graduation rates of URM are scrutinized, upwards of 60% changed majors or dropped out of STEM. Further investigation reveals the most frequently cited reasons for departure were loss of initial interest, developed a greater interest in another field, or were turned off by the STEM disciplines. A primarily exploratory study was conducted into the conditions necessary for academic interest in the STEM fields to persist. A model based on student engagement (Astin, 1977) and interest operations (Prenzel, 1988a) theories was used with a random sample of URM at universities participating in the Ohio Science and Engineering Alliance. Survey research was employed to investigate interest development and the effect of student retention programs and activities on such interest. The latter part of the study could not be fully examined when 95% reported not utilizing retention services. For the section on interest, an online survey using a 5-point Likert scale was validated using principal components analysis. A binominal logistic regression was used to predict membership in one of two possible groups: persisters and students at-risk for not persisting. The major conclusions are: (1) While 3 variables (feelings, learning and difficulty) were statistically significant only one, feelings was substantively significant. (2) Persistence increased 80.9% for each 1-unit increase in feelings and 9.9% for learning. (3) Persistence decreased 19.8% for each one-unit increase in difficulty

  11. IN-STREAM AND WATERSHED PREDICTORS OF GENETIC DIVERSITY, EFFECTIVE POPULATION SIZE AND IMMIGRATION ACROSS RIVER-STREAM NETWORKS

    EPA Science Inventory

    The influence of spatial processes on population dynamics within river-stream networks is poorly understood. Utilizing spatially explicit analyses of temporal genetic variance, we examined whether persistence of Central Stonerollers (Campostoma anomalum) reflects differences in h...

  12. Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.

    PubMed

    Li, Yibo; Amarachintha, Surya; Wilson, Andrew F; Li, Xue; Du, Wei

    2017-06-18

    Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G 2 /M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.

  13. Metagenomic analysis reveals the prevalence and persistence of antibiotic- and heavy metal-resistance genes in wastewater treatment plant.

    PubMed

    Gupta, Sachin Kumar; Shin, Hanseob; Han, Dukki; Hur, Hor-Gil; Unno, Tatsuya

    2018-06-01

    The increased antibiotic resistance among microorganisms has resulted into growing interest for investigating the wastewater treatment plants (WWTPs) as they are reported to be the major source in the dissemination of antibiotic resistance genes (ARGs) and heavy metal resistance genes (HMRGs) in the environment. In this study, we investigated the prevalence and persistence of ARGs and HMRGs as well as bacterial diversity and mobile genetic elements (MGEs) in influent and effluent at the WWTP in Gwangju, South Korea, using high-throughput sequencing based metagenomic approach. A good number of broad-spectrum of resistance genes (both ARG and HMRG) were prevalent and likely persistent, although large portion of them were successfully removed at the wastewater treatment process. The relative abundance of ARGs and MGEs was higher in effluent as compared to that of influent. Our results suggest that the resistance genes with high abundance and bacteria harbouring ARGs and MGEs are likely to persist more through the treatment process. On analyzing the microbial community, the phylum Proteobacteria, especially potentially pathogenic species belonging to the genus Acinetobacter, dominated in WWTP. Overall, our study demonstrates that many ARGs and HMRGs may persist the treatment processes in WWTPs and their association to MGEs may contribute to the dissemination of resistance genes among microorganisms in the environment.

  14. Mean wind speed persistence over China

    NASA Astrophysics Data System (ADS)

    Jiang, Lei

    2018-07-01

    The wind speed persistence is an important factor in the assessment of wind energy potential. In this paper, we explore the persistence of Mean Wind Speed (MWS) with many years of record using Detrended Fluctuation Analysis (DFA) over China. The results illustrate that there exist irregular high-frequency fluctuations for daily MWS anomaly records. Long-term persistence of MWS is found for all meteorological observed sites. We also make some numerical tests in order to verify the significance of long-term persistence by shuffling the data records many times. These facts prove that the MWS anomaly records have long-term persistence over all the stations in China. The mean value 0.64 in DFA-exponents for all stations over China is also obviously higher than the value 0.53 according to interval threshold of 95% confidence level after shuffling the MWS records many times. In addition, the values of scaling exponent vary from station to station over China. Long-term persistence of MWS in spatial distributions seems to be downward trends from east to west China. Many factors may affect long-term persistence of MWS such as southwest monsoon, Tibetan Plateau landform and atmosphere-ocean-land interaction and so on. Possible physical mechanism need further analysis in the future.

  15. Persistence-Retention. Snapshot™ Report, Spring 2015

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2015

    2015-01-01

    This Snapshot Report offers information on student persistence and retention rates for 2009-2013. It offers data on the following: (1) First-Year Persistence and Retention Rates for Students Who Start College at Four-Year Private Nonprofit Institutions; (2) First-Year Persistence and Retention Rates for Students Who Start College at Four-Year…

  16. Persistence Characteristics of Australian Rainfall Anomalies

    NASA Astrophysics Data System (ADS)

    Simmonds, Ian; Hope, Pandora

    1997-05-01

    Using 79 years (1913-1991) of Australian monthly precipitation data we examined the nature of the persistence of rainfall anomalies. Analyses were performed for four climate regions covering the country, as well as for the entire Australian continent. We show that rainfall over these regions has high temporal variability and that annual rainfall amounts over all five sectors vary in phase and are, with the exception of the north-west region, significantly correlated with the Southern Oscillation Index (SOI). These relationships were particularly strong during the spring season.It is demonstrated that Australian rainfall exhibits statistically significant persistence on monthly, seasonal, and (to a limited extent) annual time-scales, up to lags of 3 months and one season and 1 year. The persistence showed strong seasonal dependence, with each of the five regions showing memory out to 4 or 5 months from winter and spring. Many aspects of climate in the Australasian region are known to have undergone considerable changes about 1950. We show this to be true for persistence also; its characteristics identified for the entire record were present during the 1951--1980 period, but virtually disappeared in the previous 30-year period.Much of the seasonal distribution of rainfall persistence on monthly time-scales, particularly in the east, is due to the influence of the SOI. However, most of the persistence identified in winter and spring in the north-west is independent of the ENSO phenomenon.Rainfall anomalies following extreme dry and wet months, seasons and years (lowest and highest two deciles) persisted more than would be expected by chance. For monthly extreme events this was more marked in the winter semester for the wet events, except in the south-east region. In general, less persistence was found for the extreme seasons. Although the persistence of dry years was less than would have been expected by chance, the wet years appear to display persistence.

  17. Genetic variation in westslope cutthroat trout Oncorhynchusclarkii lewisi: implications for conservation

    USGS Publications Warehouse

    Daniel P. Drinan,; Kalinowski, Steven T.; Vu, Ninh V.; Shepard, Bradley B.; Muhlfeld, Clint C.; Campbell, Matthew R.

    2011-01-01

    Twenty-five populations of westslope cutthroat trout from throughout their native range were genotyped at 20 microsatellite loci to describe the genetic structure of westslope cutthroat trout. The most genetic diversity (heterozygosity, allelic richness, and private alleles) existed in populations from the Snake River drainage, while populations from the Missouri River drainage had the least. Neighbor-joining trees grouped populations according to major river drainages. A great amount of genetic differentiation was present among and within all drainages. Based on Nei’s DS, populations in the Snake River were the most differentiated, while populations in the Missouri River were the least. This pattern of differentiation is consistent with a history of sequential founding events through which westslope cutthroat trout may have experienced a genetic bottleneck as they colonized each river basin from the Snake to the Clark Fork to the Missouri river. These data should serve as a starting point for a discussion on management units and possible distinct population segments. Given the current threats to the persistence of westslope cutthroat trout, and the substantial genetic differentiation between populations, these topics warrant attention.

  18. Potential Genetic Risk Factors for Chronic TMD: Genetic Associations from the OPPERA Case Control Study

    PubMed Central

    Smith, Shad B.; Maixner, Dylan; Greenspan, Joel; Dubner, Ron; Fillingim, Roger; Ohrbach, Richard; Knott, Charles; Slade, Gary; Bair, Eric; Gibson, Dustin G.; Zaykin, Dmitri V.; Weir, Bruce; Maixner, William; Diatchenko, Luda

    2011-01-01

    Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously-reported associations between TMD and two genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD and they identify potential targets for therapeutic intervention. PMID:22074755

  19. Perceived Stress and an Elaborated Structural Model of Adult Student Persistence: An Examination of Financial Aid, Financial Satisfaction, Intent To Persist and Persistence.

    ERIC Educational Resources Information Center

    Sandler, Martin E.

    Researchers used cross-sectional survey research to reexamine the problem of adult persistence within undergraduate degree programs. They identified a variable--perceived stress--that permitted a richer explanation of the process of student persistence. A model was presented that examined the attitudinal and behavioral impacts of unmet need,…

  20. Does the seed bank contribute to the build-up of a genetic extinction debt in the grassland perennial Campanula rotundifolia?

    PubMed

    Plue, Jan; Vandepitte, Katrien; Honnay, Olivier; Cousins, Sara A O

    2017-09-01

    Habitat fragmentation threatens global biodiversity. Many plant species persist in habitat fragments via persistent life cycle stages such as seed banks, generating a species extinction debt. Here, seed banks are hypothesized to cause a temporal delay in the expected loss of genetic variation, which can be referred to as a genetic extinction debt, as a possible mechanism behind species extinction debts. Fragmented grassland populations of Campanula rotundifolia were examined for evidence of a genetic extinction debt, investigating if the seed bank contributed to the extinction debt build-up. The genetic make-up of 15 above- and below-ground populations was analysed in relation to historical and current levels of habitat fragmentation, both separately and combined. Genetic diversity was highest in above-ground populations, though below-ground populations contained 8 % of unique alleles that were absent above-ground. Above-ground genetic diversity and composition were related to historical patch size and connectivity, but not current patch characteristics, suggesting the presence of a genetic extinction debt in the above-ground populations. No such relationships were found for the below-ground populations. Genetic diversity measures still showed a response to historical but not present landscape characteristics when combining genetic diversity of the above- and below-ground populations. The fragmented C. rotundifolia populations exhibited a genetic extinction debt. However, the role of the seed banks in the build-up of this extinction debt is probably small, since the limited, unique genetic diversity of the seed bank alone seems unable to counter the detrimental effects of habitat fragmentation on the population genetic structure of C. rotundifolia. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  1. Demographic mechanisms underpinning genetic assimilation of remnant groups of a large carnivore

    USGS Publications Warehouse

    Mikle, Nathaniel; Graves, Tabitha A.; Kovach, Ryan P.; Kendall, Katherine C.; Macleod, Amy C.

    2016-01-01

    Current range expansions of large terrestrial carnivores are occurring following human-induced range contraction. Contractions are often incomplete, leaving small remnant groups in refugia throughout the former range. Little is known about the underlying ecological and evolutionary processes that influence how remnant groups are affected during range expansion. We used data from a spatially explicit, long-term genetic sampling effort of grizzly bears (Ursus arctos) in the Northern Continental Divide Ecosystem (NCDE), USA, to identify the demographic processes underlying spatial and temporal patterns of genetic diversity. We conducted parentage analysis to evaluate how reproductive success and dispersal contribute to spatio-temporal patterns of genetic diversity in remnant groups of grizzly bears existing in the southwestern (SW), southeastern (SE) and east-central (EC) regions of the NCDE. A few reproductively dominant individuals and local inbreeding caused low genetic diversity in peripheral regions that may have persisted for multiple generations before eroding rapidly (approx. one generation) during population expansion. Our results highlight that individual-level genetic and reproductive dynamics play critical roles during genetic assimilation, and show that spatial patterns of genetic diversity on the leading edge of an expansion may result from historical demographic patterns that are highly ephemeral.

  2. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation.

    PubMed

    Merfa, Marcus V; Niza, Bárbara; Takita, Marco A; De Souza, Alessandra A

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis-CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions.

  3. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation

    PubMed Central

    Merfa, Marcus V.; Niza, Bárbara; Takita, Marco A.; De Souza, Alessandra A.

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis—CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID:27375608

  4. Americamysis bahia: A New Laboratory Model for Conservation Genetics in a Changing Environment (AGA09)

    EPA Science Inventory

    Levels of population genetic diversity are expected to play an important role in species persistence during periods of environmental change, yet our understanding of how to quantify relevant aspects of this diversity is not well developed. We are conducting a long-term study wit...

  5. Metapopulation Dynamics Enable Persistence of Influenza A, Including A/H5N1, in Poultry

    PubMed Central

    Hosseini, Parviez Rana; Fuller, Trevon; Harrigan, Ryan; Zhao, Delong; Arriola, Carmen Sofia; Gonzalez, Armandoe; Miller, Matthew Joshua; Xiao, Xiangming; Smith, Tom B.; Jones, Jamie Holland; Daszak, Peter

    2013-01-01

    Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified. PMID:24312455

  6. Genetic Architecture of Conspicuous Red Ornaments in Female Threespine Stickleback

    PubMed Central

    Yong, Lengxob; Peichel, Catherine L.; McKinnon, Jeffrey S.

    2015-01-01

    Explaining the presence of conspicuous female ornaments that take the form of male-typical traits has been a longstanding challenge in evolutionary biology. Such female ornaments have been proposed to evolve via both adaptive and nonadaptive evolutionary processes. Determining the genetic underpinnings of female ornaments is important for elucidating the mechanisms by which such female traits arise and persist in natural populations, but detailed information about their genetic basis is still scarce. In this study, we investigated the genetic architecture of two ornaments, the orange-red throat and pelvic spine, in the threespine stickleback (Gasterosteus aculeatus). Throat coloration is male-specific in ancestral marine populations but has evolved in females in some derived stream populations, whereas sexual dimorphism in pelvic spine coloration is variable among populations. We find that ornaments share a common genetic architecture between the sexes. At least three independent genomic regions contribute to red throat coloration, and harbor candidate genes related to pigment production and pigment cell differentiation. One of these regions is also associated with spine coloration, indicating that both ornaments might be mediated partly via pleiotropic genetic mechanisms. PMID:26715094

  7. The Genetic Basis of Peyronie Disease: A Review.

    PubMed

    Herati, Amin S; Pastuszak, Alexander W

    2016-01-01

    Peyronie disease (PD) is a progressive fibrotic disorder of the penile tunica albuginea that results in fibrotic penile plaques and can lead to penile deformity. Characterized by aberrant fibrosis resulting in part from the persistence of myofibroblasts and altered gene expression, the molecular factors underpinning PD and other related fibrotic diatheses are just being elucidated. A genetic link to PD was first identified three decades ago using pedigree analyses. However, the specific genetic factors that predispose patients to aberrant fibrosis remain unknown, and the relations between these fibrotic conditions and other heritable diseases, including malignancy, are uncharacterized. To review the current landscape linking molecular and genetic factors to aberrant fibrosis in PD and related fibrotic diatheses, including Dupuytren disease. Review and evaluation of the literature from 1970 to the present for genetic factors associated with PD were performed. Data describing the genetic factors associated with PD were obtained. We describe the known structural chromosomal abnormalities and single-nucleotide polymorphisms associated with fibrotic diatheses and discuss the spectrum of differential gene expression data comparing normal tissues with those derived from men with PD or Dupuytren disease. We discuss epigenetic mechanisms that might regulate gene expression and alter predisposition to fibrosis. Although the current understanding of the genetic factors associated with PD is limited, significant advances have been made during the past three decades. Further research is necessary to provide a more comprehensive understanding of the landscape of genetic factors responsible for the development of PD. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  8. Using Benchmarking To Strengthen the Assessment of Persistence.

    PubMed

    McLachlan, Michael S; Zou, Hongyan; Gouin, Todd

    2017-01-03

    Chemical persistence is a key property for assessing chemical risk and chemical hazard. Current methods for evaluating persistence are based on laboratory tests. The relationship between the laboratory based estimates and persistence in the environment is often unclear, in which case the current methods for evaluating persistence can be questioned. Chemical benchmarking opens new possibilities to measure persistence in the field. In this paper we explore how the benchmarking approach can be applied in both the laboratory and the field to deepen our understanding of chemical persistence in the environment and create a firmer scientific basis for laboratory to field extrapolation of persistence test results.

  9. Genetic architecture and temporal patterns of biomass accumulation in spring barley revealed by image analysis.

    PubMed

    Neumann, Kerstin; Zhao, Yusheng; Chu, Jianting; Keilwagen, Jens; Reif, Jochen C; Kilian, Benjamin; Graner, Andreas

    2017-08-10

    Genetic mapping of phenotypic traits generally focuses on a single time point, but biomass accumulates continuously during plant development. Resolution of the temporal dynamics that affect biomass recently became feasible using non-destructive imaging. With the aim to identify key genetic factors for vegetative biomass formation from the seedling stage to flowering, we explored growth over time in a diverse collection of two-rowed spring barley accessions. High heritabilities facilitated the temporal analysis of trait relationships and identification of quantitative trait loci (QTL). Biomass QTL tended to persist only a short period during early growth. More persistent QTL were detected around the booting stage. We identified seven major biomass QTL, which together explain 55% of the genetic variance at the seedling stage, and 43% at the booting stage. Three biomass QTL co-located with genes or QTL involved in phenology. The most important locus for biomass was independent from phenology and is located on chromosome 7HL at 141 cM. This locus explained ~20% of the genetic variance, was significant over a long period of time and co-located with HvDIM, a gene involved in brassinosteroid synthesis. Biomass is a dynamic trait and is therefore orchestrated by different QTL during early and late growth stages. Marker-assisted selection for high biomass at booting stage is most effective by also including favorable alleles from seedling biomass QTL. Selection for dynamic QTL may enhance genetic gain for complex traits such as biomass or, in the future, even grain yield.

  10. Geographic and temporal genetic patterns of Aedes aegypti populations in Rio de Janeiro, Brazil.

    PubMed

    da Costa-Ribeiro, Magda C V; Lourenço-de-Oliveira, Ricardo; Failloux, Anna-Bella

    2006-08-01

    Rio de Janeiro is considered as the most important entry point for dengue viruses in Brazil. Using isoenzyme markers, we investigated the genetic structure of the mosquito vector Aedes aegypti sampled at three-month intervals in 14 districts in Rio de Janeiro from December 2002 to December 2003. We detected high levels of genetic differentiation (i.e. high F(ST) values and significant P values), which tended to persist throughout the year. The species does not take advantage of routes and railways to disperse. Genetic structuring was higher in the rainy season, suggesting low dispersion of Ae. aegypti at this time of year when all dengue epidemics have been reported in the city.

  11. Decay Of Bacterial Pathogens, Fecal Indicators, And Real-Time Quantitative PCR Genetic Markers In Manure-Amended Soils

    EPA Science Inventory

    This study examined persistence and decay of bacterial pathogens, fecal indicator bacteria (FIB), and emerging real-time quantitative PCR (qPCR) genetic markers for rapid detection of fecal pollution in manure-amended agricultural soils. Known concentrations of transformed green...

  12. Decay Of Bacterial Pathogen, Fecal Indicators, And Real-Time Quantitative PCR Genetic Markers In Manure Amended Soils

    EPA Science Inventory

    This study examined persistence and decay of bacterial pathogens, fecal indicator bacteria, and emerging real-time quantitative PCR (qPCR) genetic markers for rapid detection of fecal pollution in manre-amended agricultural soils. Known concentrations of transformed green fluore...

  13. Persistence of seeds from crops of conventional and herbicide tolerant oilseed rape (Brassica napus).

    PubMed

    Lutman, Peter J W; Berry, Kate; Payne, Roger W; Simpson, Euan; Sweet, Jeremy B; Champion, Gillian T; May, Mike J; Wightman, Pat; Walker, Kerr; Lainsbury, Martin

    2005-09-22

    A series of rotation experiments at five sites over four years has explored the environmental and agronomic implications of growing herbicide tolerant oilseed rape and sugar beet. This paper reports on the population dynamics of volunteer rape (Brassica napus). The experiments compared four winter oilseed rape (WOSR) cultivars: a conventional cultivar (Apex) and three developmental cultivars either genetically modified (GM) to be tolerant to glyphosate or glufosinate, or conventionally bred to be tolerant to herbicides of the imidazolinone group. Seed losses at harvest averaged 3575 seeds m(-2) but ranged from less than 2000 up to more than 10000 seeds m(-2). There was a rapid decline in seed numbers during the first few months after harvest, resulting in a mean loss of seeds of 60%. In subsequent seasons, the seedbank declined much more slowly at four of the five sites (ca 20% per year) and the models predicted 95% seed loss after approximately 9 years. Seed decline was much faster at the fifth site. There were no clear differences between the four cultivars in either the numbers of seeds shed at harvest or in their subsequent persistence. The importance of the persistence of GM rape seeds, in the context of the coexistence of GM and non-GM crops and the role of good management practices that minimize seed persistence, are discussed.

  14. Persistence of seeds from crops of conventional and herbicide tolerant oilseed rape (Brassica napus)

    PubMed Central

    Lutman, Peter J.W; Berry, Kate; Payne, Roger W; Simpson, Euan; Sweet, Jeremy B; Champion, Gillian T; May, Mike J; Wightman, Pat; Walker, Kerr; Lainsbury, Martin

    2005-01-01

    A series of rotation experiments at five sites over four years has explored the environmental and agronomic implications of growing herbicide tolerant oilseed rape and sugar beet. This paper reports on the population dynamics of volunteer rape (Brassica napus). The experiments compared four winter oilseed rape (WOSR) cultivars: a conventional cultivar (Apex) and three developmental cultivars either genetically modified (GM) to be tolerant to glyphosate or glufosinate, or conventionally bred to be tolerant to herbicides of the imidazolinone group. Seed losses at harvest averaged 3575 seeds m−2 but ranged from less than 2000 up to more than 10 000 seeds m−2. There was a rapid decline in seed numbers during the first few months after harvest, resulting in a mean loss of seeds of 60%. In subsequent seasons, the seedbank declined much more slowly at four of the five sites (ca 20% per year) and the models predicted 95% seed loss after approximately 9 years. Seed decline was much faster at the fifth site. There were no clear differences between the four cultivars in either the numbers of seeds shed at harvest or in their subsequent persistence. The importance of the persistence of GM rape seeds, in the context of the coexistence of GM and non-GM crops and the role of good management practices that minimize seed persistence, are discussed. PMID:16191596

  15. Environmental stress alters genetic regulation of novelty seeking in vervet monkeys.

    PubMed

    Fairbanks, L A; Bailey, J N; Breidenthal, S E; Laudenslager, M L; Kaplan, J R; Jorgensen, M J

    2011-08-01

    Considerable attention has been paid to identifying genetic influences and gene-environment interactions that increase vulnerability to environmental stressors, with promising but inconsistent results. A nonhuman primate model is presented here that allows assessment of genetic influences in response to a stressful life event for a behavioural trait with relevance for psychopathology. Genetic and environmental influences on free-choice novelty seeking behaviour were assessed in a pedigreed colony of vervet monkeys before and after relocation from a low stress to a higher stress environment. Heritability of novelty seeking scores, and genetic correlations within and between environments were conducted using variance components analysis. The results showed that novelty seeking was markedly inhibited in the higher stress environment, with effects persisting across a 2-year period for adults but not for juveniles. There were significant genetic contributions to novelty seeking scores in each year (h(2) = 0.35-0.43), with high genetic correlations within each environment (rhoG > 0.80) and a lower genetic correlation (rhoG = 0.35, non-significant) between environments. There were also significant genetic contributions to individual change scores from before to after the move (h(2) = 0.48). These results indicate that genetic regulation of novelty seeking was modified by the level of environmental stress, and they support a role for gene-environment interactions in a behavioural trait with relevance for mental health. © 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  16. Nitric oxide-dependent killing of aerobic, anaerobic and persistent Burkholderia pseudomallei

    PubMed Central

    Jones-Carson, Jessica; Laughlin, James R.; Stewart, Amanda L.; Voskuil, Martin I.; Vázquez-Torres, Andrés

    2012-01-01

    Burkholderia pseudomallei infections are fastidious to treat with conventional antibiotic therapy, often involving a combination of drugs and long-term regimes. Bacterial genetic determinants contribute to the resistance of B. pseudomallei to many classes of antibiotics. In addition, anaerobiosis and hypoxia in abscesses typical of melioidosis select for persistent populations of B. pseudomallei refractory to a broad spectrum of antibacterials. We tested the susceptibility of B. pseudomallei to the drugs hydroxyurea, spermine NONOate and DETA NONOate that release nitric oxide (NO). Our investigations indicate that B. pseudomallei are killed by NO in a concentration and time-dependent fashion. The cytoxicity of this diatomic radical against B. pseudomallei depends on both the culture medium and growth phase of the bacteria. Rapidly growing, but not stationary phase, B. pseudomallei are readily killed upon exposure to the NO donor spermine NONOate. NO also has excellent antimicrobial activity against anaerobic B. pseudomallei. In addition, persistent bacteria highly resistant to most conventional antibiotics are remarkably susceptible to NO. Sublethal concentrations of NO inhibited the enzymatic activity of [4Fe-4S]-cofactored aconitase of aerobic and anaerobic B. pseudomallei. The strong anti-B. pseudomallei activity of NO described herein merits further studies on the application of NO-based antibiotics for the treatment of melioidosis. PMID:22521523

  17. Public Willingness to Participate in and Public Opinions About Genetic Variation Research: A Review of the Literature

    PubMed Central

    Sterling, Rene; Henderson, Gail E.; Corbie-Smith, Giselle

    2006-01-01

    Scientists are turning to genetic variation research in hopes of addressing persistent racial/ethnic disparities in health. Despite ongoing controversy, the advancement of genetic variation research is likely to produce new knowledge and technologies that will substantially change the ways in which we understand and value health. They also may affect the ways in which individuals and groups organize socially, politically, and economically. Addressing concerns that may exist in different communities is vital to the scientific and ethical advancement of genetic variation research. We review empirical studies of public willingness to participate in and opinions about genetic research with particular attention to differences in consent and opinion by racial/ethnic group membership. PMID:17018829

  18. Drought Persistence Errors in Global Climate Models

    NASA Astrophysics Data System (ADS)

    Moon, H.; Gudmundsson, L.; Seneviratne, S. I.

    2018-04-01

    The persistence of drought events largely determines the severity of socioeconomic and ecological impacts, but the capability of current global climate models (GCMs) to simulate such events is subject to large uncertainties. In this study, the representation of drought persistence in GCMs is assessed by comparing state-of-the-art GCM model simulations to observation-based data sets. For doing so, we consider dry-to-dry transition probabilities at monthly and annual scales as estimates for drought persistence, where a dry status is defined as negative precipitation anomaly. Though there is a substantial spread in the drought persistence bias, most of the simulations show systematic underestimation of drought persistence at global scale. Subsequently, we analyzed to which degree (i) inaccurate observations, (ii) differences among models, (iii) internal climate variability, and (iv) uncertainty of the employed statistical methods contribute to the spread in drought persistence errors using an analysis of variance approach. The results show that at monthly scale, model uncertainty and observational uncertainty dominate, while the contribution from internal variability is small in most cases. At annual scale, the spread of the drought persistence error is dominated by the statistical estimation error of drought persistence, indicating that the partitioning of the error is impaired by the limited number of considered time steps. These findings reveal systematic errors in the representation of drought persistence in current GCMs and suggest directions for further model improvement.

  19. Genetic Gain and Inbreeding from Genomic Selection in a Simulated Commercial Breeding Program for Perennial Ryegrass.

    PubMed

    Lin, Zibei; Cogan, Noel O I; Pembleton, Luke W; Spangenberg, German C; Forster, John W; Hayes, Ben J; Daetwyler, Hans D

    2016-03-01

    Genomic selection (GS) provides an attractive option for accelerating genetic gain in perennial ryegrass () improvement given the long cycle times of most current breeding programs. The present study used simulation to investigate the level of genetic gain and inbreeding obtained from GS breeding strategies compared with traditional breeding strategies for key traits (persistency, yield, and flowering time). Base population genomes were simulated through random mating for 60,000 generations at an effective population size of 10,000. The degree of linkage disequilibrium (LD) in the resulting population was compared with that obtained from empirical studies. Initial parental varieties were simulated to match diversity of current commercial cultivars. Genomic selection was designed to fit into a company breeding program at two selection points in the breeding cycle (spaced plants and miniplot). Genomic estimated breeding values (GEBVs) for productivity traits were trained with phenotypes and genotypes from plots. Accuracy of GEBVs was 0.24 for persistency and 0.36 for yield for single plants, while for plots it was lower (0.17 and 0.19, respectively). Higher accuracy of GEBVs was obtained for flowering time (up to 0.7), partially as a result of the larger reference population size that was available from the clonal row stage. The availability of GEBVs permit a 4-yr reduction in cycle time, which led to at least a doubling and trebling genetic gain for persistency and yield, respectively, than the traditional program. However, a higher rate of inbreeding per cycle among varieties was also observed for the GS strategy. Copyright © 2016 Crop Science Society of America.

  20. Reduced Synchronization Persistence in Neural Networks Derived from Atm-Deficient Mice

    PubMed Central

    Levine-Small, Noah; Yekutieli, Ziv; Aljadeff, Jonathan; Boccaletti, Stefano; Ben-Jacob, Eshel; Barzilai, Ari

    2011-01-01

    Many neurodegenerative diseases are characterized by malfunction of the DNA damage response. Therefore, it is important to understand the connection between system level neural network behavior and DNA. Neural networks drawn from genetically engineered animals, interfaced with micro-electrode arrays allowed us to unveil connections between networks’ system level activity properties and such genome instability. We discovered that Atm protein deficiency, which in humans leads to progressive motor impairment, leads to a reduced synchronization persistence compared to wild type synchronization, after chemically imposed DNA damage. Not only do these results suggest a role for DNA stability in neural network activity, they also establish an experimental paradigm for empirically determining the role a gene plays on the behavior of a neural network. PMID:21519382

  1. Microbial community in persistent apical periodontitis: a 16S rRNA gene clone library analysis.

    PubMed

    Zakaria, M N; Takeshita, T; Shibata, Y; Maeda, H; Wada, N; Akamine, A; Yamashita, Y

    2015-08-01

    To characterize the microbial composition of persistent periapical lesions of root filled teeth using a molecular genetics approach. Apical lesion samples were collected from 12 patients (23-80 years old) who visited the Kyushu University Hospital for apicectomy with persistent periapical lesions associated with root filled teeth. DNA was directly extracted from each sample and the microbial composition was comprehensively analysed using clone library analysis of the 16S rRNA gene. Enterococcus faecalis, Candida albicans and specific fimA genotypes of Porphyromonas gingivalis were confirmed using polymerase chain reaction (PCR) analysis with specific primers. Bacteria were detected in all samples, and the dominant findings were P. gingivalis (19.9%), Fusobacterium nucleatum (11.2%) and Propionibacterium acnes (9%). Bacterial diversity was greater in symptomatic lesions than in asymptomatic ones. In addition, the following bacteria or bacterial combinations were characteristic to symptomatic lesions: Prevotella spp., Treponema spp., Peptostreptococcaceae sp. HOT-113, Olsenella uli, Slackia exigua, Selemonas infelix, P. gingivalis with type IV fimA, and a combination of P. gingivalis, F. nucleatum, and Peptostreptococcaceae sp. HOT-113 and predominance of Streptococcus spp. On the other hand, neither Enterococcus faecalis nor C. albicans were detected in any of the samples. Whilst a diverse bacterial species were observed in the persistent apical lesions, some characteristic patterns of bacterial community were found in the symptomatic lesions. The diverse variation of community indicates that bacterial combinations as a community may cause persistent inflammation in periapical tissues rather than specific bacterial species. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  2. Seed bank dynamics govern persistence of Brassica hybrids in crop and natural habitats

    PubMed Central

    Hooftman, Danny A. P.; Bullock, James M.; Morley, Kathryn; Lamb, Caroline; Hodgson, David J.; Bell, Philippa; Thomas, Jane; Hails, Rosemary S.

    2015-01-01

    Background and Aims Gene flow from crops to their wild relatives has the potential to alter population growth rates and demography of hybrid populations, especially when a new crop has been genetically modified (GM). This study introduces a comprehensive approach to assess this potential for altered population fitness, and uses a combination of demographic data in two habitat types and mathematical (matrix) models that include crop rotations and outcrossing between parental species. Methods Full life-cycle demographic rates, including seed bank survival, of non-GM Brassica rapa × B. napus F1 hybrids and their parent species were estimated from experiments in both agricultural and semi-natural habitats. Altered fitness potential was modelled using periodic matrices including crop rotations and outcrossing between parent species. Key Results The demographic vital rates (i.e. for major stage transitions) of the hybrid population were intermediate between or lower than both parental species. The population growth rate (λ) of hybrids indicated decreases in both habitat types, and in a semi-natural habitat hybrids became extinct at two sites. Elasticity analyses indicated that seed bank survival was the greatest contributor to λ. In agricultural habitats, hybrid populations were projected to decline, but with persistence times up to 20 years. The seed bank survival rate was the main driver determining persistence. It was found that λ of the hybrids was largely determined by parental seed bank survival and subsequent replenishment of the hybrid population through outcrossing of B. rapa with B. napus. Conclusions Hybrid persistence was found to be highly dependent on the seed bank, suggesting that targeting hybrid seed survival could be an important management option in controlling hybrid persistence. For local risk mitigation, an increased focus on the wild parent is suggested. Management actions, such as control of B. rapa, could indirectly reduce hybrid

  3. Predominant Effect of Host Genetics on Levels of Lactobacillus johnsonii Bacteria in the Mouse Gut▿†

    PubMed Central

    Buhnik-Rosenblau, Keren; Danin-Poleg, Yael; Kashi, Yechezkel

    2011-01-01

    The gut microbiota is strongly associated with the well-being of the host. Its composition is affected by environmental factors, such as food and maternal inoculation, while the relative impact of the host's genetics have been recently uncovered. Here, we studied the effect of the host genetic background on the composition of intestinal bacteria in a murine model, focusing on lactic acid bacteria (LAB) as an important group that includes many probiotic strains. Based on 16S rRNA gene genotyping, variation was observed in fecal LAB populations of BALB/c and C57BL/6J mouse lines. Lactobacillus johnsonii, a potentially probiotic bacterium, appeared at significantly higher levels in C57BL/6J versus BALB/c mouse feces. In the BALB/c gut, the L. johnsonii level decreased rapidly after oral administration, suggesting that some selective force does not allow its persistence at higher levels. The genetic inheritance of L. johnsonii levels was further tested in reciprocal crosses between the two mouse lines. The resultant F1 offspring presented similar L. johnsonii levels, confirming that mouse genetics plays a major role in determining these levels compared to the smaller maternal effect. Our findings suggest that mouse genetics has a major effect on the composition of the LAB population in general and on the persistence of L. johnsonii in the gut in particular. Concentrating on a narrow spectrum of culturable LAB enables the isolation and characterization of such potentially probiotic bacterial strains, which might be specifically oriented to the genetic background of the host as part of a personalized-medicine approach. PMID:21803912

  4. Visual persistence and cinema?

    PubMed

    Galifret, Yves

    2006-01-01

    In Faraday and Plateau's days, both apparent motion and the fusion of intermittent lights, two phenomena that are hardly connected, were explained by retinal persistence. The works of Exner and of the 'Gestalt' psychologists, as well as the modern works on 'sampled' motion and smooth motion, disregarded retinal persistence. One tried, originally, to measure this persistence using intermittent stimulation, but under the pressure of practical concern, what was established in 1902 was the logarithmic relation between fusion frequency and the intensity of the stimulation. One had to wait until the 1950s for the use of harmonic analysis to finally allow a renewal in which many problems that, for decades, had only given rise to discussions that led nowhere and to groundless assertions, were correctly stated and easily solved. To cite this article: Y. Galifret, C. R. Biologies 329 (2006).

  5. Genetic Risk Prediction of Atrial Fibrillation

    PubMed Central

    Lubitz, Steven A.; Yin, Xiaoyan; Lin, Henry J.; Kolek, Matthew; Smith, J. Gustav; Trompet, Stella; Rienstra, Michiel; Rost, Natalia S.; Teixeira, Pedro L.; Almgren, Peter; Anderson, Christopher D.; Chen, Lin Y.; Engström, Gunnar; Ford, Ian; Furie, Karen L.; Guo, Xiuqing; Larson, Martin G.; Lunetta, Kathryn L.; Macfarlane, Peter W.; Psaty, Bruce M.; Soliman, Elsayed Z.; Sotoodehnia, Nona; Stott, David J.; Taylor, Kent D.; Weng, Lu-Chen; Yao, Jie; Geelhoed, Bastiaan; Verweij, Niek; Siland, Joylene E.; Kathiresan, Sekar; Roselli, Carolina; Roden, Dan; van der Harst, Pim; Darbar, Dawood; Jukema, J. Wouter; Melander, Olle; Rosand, Jonathan; Rotter, Jerome I.; Heckbert, Susan R.; Ellinor, Patrick T.; Alonso, Alvaro; Benjamin, Emelia J.

    2017-01-01

    Background Atrial fibrillation (AF) is common and has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 controls. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1×10−3 to <1×10−8 in a prior independent genetic association study. Results Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13–1.46; P=1.5×10−4) to 1.67 (25 variants; 95%CI, 1.47–1.90; P=9.3×10−15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629–0.811; maximum ΔC statistic from clinical score alone, 0.009–0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke, versus those in the lowest quartile (95%CI, 1.39–4.58; P=2.7×10−3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20–4.40; P=0.01). Conclusions Comprehensive AF genetic risk scores were associated with incident AF beyond clinical AF risk factors, with magnitudes of risk comparable to other clinical risk factors, though offered small improvements in discrimination. AF genetic risk was

  6. Variability of individual genetic load: consequences for the detection of inbreeding depression.

    PubMed

    Restoux, Gwendal; Huot de Longchamp, Priscille; Fady, Bruno; Klein, Etienne K

    2012-03-01

    Inbreeding depression is a key factor affecting the persistence of natural populations, particularly when they are fragmented. In species with mixed mating systems, inbreeding depression can be estimated at the population level by regressing the average progeny fitness by the selfing rate of their mothers. We applied this method using simulated populations to investigate how population genetic parameters can affect the detection power of inbreeding depression. We simulated individual selfing rates and genetic loads from which we computed fitness values. The regression method yielded high statistical power, inbreeding depression being detected as significant (5 % level) in 92 % of the simulations. High individual variation in selfing rate and high mean genetic load led to better detection of inbreeding depression while high among-individual variation in genetic load made it more difficult to detect inbreeding depression. For a constant sampling effort, increasing the number of progenies while decreasing the number of individuals per progeny enhanced the detection power of inbreeding depression. We discuss the implication of among-mother variability of genetic load and selfing rate on inbreeding depression studies.

  7. Genetic component of flammability variation in a Mediterranean shrub.

    PubMed

    Moreira, B; Castellanos, M C; Pausas, J G

    2014-03-01

    Recurrent fires impose a strong selection pressure in many ecosystems worldwide. In such ecosystems, plant flammability is of paramount importance because it enhances population persistence, particularly in non-resprouting species. Indeed, there is evidence of phenotypic divergence of flammability under different fire regimes. Our general hypothesis is that flammability-enhancing traits are adaptive; here, we test whether they have a genetic component. To test this hypothesis, we used the postfire obligate seeder Ulex parviflorus from sites historically exposed to different fire recurrence. We associated molecular variation in potentially adaptive loci detected with a genomic scan (using AFLP markers) with individual phenotypic variability in flammability across fire regimes. We found that at least 42% of the phenotypic variation in flammability was explained by the genetic divergence in a subset of AFLP loci. In spite of generalized gene flow, the genetic variability was structured by differences in fire recurrence. Our results provide the first field evidence supporting that traits enhancing plant flammability have a genetic component and thus can be responding to natural selection driven by fire. These results highlight the importance of flammability as an adaptive trait in fire-prone ecosystems. © 2014 John Wiley & Sons Ltd.

  8. Congruent Strain Specific Intestinal Persistence of Lactobacillus plantarum in an Intestine-Mimicking In Vitro System and in Human Volunteers

    PubMed Central

    van Bokhorst-van de Veen, Hermien; van Swam, Iris; Wels, Michiel; Bron, Peter A.; Kleerebezem, Michiel

    2012-01-01

    Background An important trait of probiotics is their capability to reach their intestinal target sites alive to optimally exert their beneficial effects. Assessment of this trait in intestine-mimicking in vitro model systems has revealed differential survival of individual strains of a species. However, data on the in situ persistence characteristics of individual or mixtures of strains of the same species in the gastrointestinal tract of healthy human volunteers have not been reported to date. Methodology/Principal Findings The GI-tract survival of individual L. plantarum strains was determined using an intestine mimicking model system, revealing substantial inter-strain differences. The obtained data were correlated to genomic diversity of the strains using comparative genome hybridization (CGH) datasets, but this approach failed to discover specific genetic loci that explain the observed differences between the strains. Moreover, we developed a next-generation sequencing-based method that targets a variable intergenic region, and employed this method to assess the in vivo GI-tract persistence of different L. plantarum strains when administered in mixtures to healthy human volunteers. Remarkable consistency of the strain-specific persistence curves were observed between individual volunteers, which also correlated significantly with the GI-tract survival predicted on basis of the in vitro assay. Conclusion The survival of individual L. plantarum strains in the GI-tract could not be correlated to the absence or presence of specific genes compared to the reference strain L. plantarum WCFS1. Nevertheless, in vivo persistence analysis in the human GI-tract confirmed the strain-specific persistence, which appeared to be remarkably similar in different healthy volunteers. Moreover, the relative strain-specific persistence in vivo appeared to be accurately and significantly predicted by their relative survival in the intestine-mimicking in vitro assay, supporting the

  9. Prevalence of lactose intolerance in Chile: a double-blind placebo study.

    PubMed

    Latorre, Gonzalo; Besa, Pablo; Parodi, Carmen G; Ferrer, Verónica; Azocar, Lorena; Quirola, Marife; Villarroel, Luis; Miquel, Juan F; Agosin, Eduardo; Chianale, José

    2014-01-01

    Lactase non-persistence (LNP), or primary hypolactasia, is a genetic condition that mediates lactose malabsorption and can cause lactose intolerance. Here we report the prevalence of lactose intolerance in a double-blind placebo study. The LCT C>T-13910 variant was genotyped by RT-PCR in 121 volunteers and lactose malabsorption was assessed using the hydrogen breath test (HBT) after consuming 25 g of lactose. Lactose intolerance was assessed by scoring symptoms (SS) using a standardized questionnaire following challenge with a lactose solution or saccharose placebo. The LNP genotype was observed in 57% of the volunteers, among whom 87% were HBT⁺. In the HBT⁺ group the median SS was 9 and in the HBT⁻ group the median SS was 3 (p < 0.001). No difference was observed in the SS when both groups were challenged with the placebo. The most common symptoms included audible bowel sounds, abdominal pain and meteorism. In the ROC curve analysis, an SS ≥ 6 demonstrated 72% sensitivity and 81% specificity for predicting a positive HBT. To estimate prevalence, lactose intolerance was defined as the presence of an SS ≥ 6 points after subtracting the placebo effect and 34% of the study population met this definition. The LNP genotype was present in more than half of subjects evaluated and the observed prevalence of lactose intolerance was 34%. © 2014 S. Karger AG, Basel.

  10. Different aspects of virus persistence (review).

    PubMed

    Barnabishvili, N; Topuria, T; Gamtsemlidze, P; Topuria, M

    2012-05-01

    The article reviews different aspects of virus persistence in human organism. Persistence is a capability acquired and strengthened in the process of evolution of many viruses that is the means of maintenance of species. Viruses of measles, poliomyelitis, mite-like encephalitis, B and C hepatitis, herpes, retro and HIV viruses persist in human organism. Persistence is used by various viruses at various levels; they have different adaptive power and no different pathologic output. But in any case, the necessary condition is that virus should escape from elimination reactions of immune control system. At the same time, the important thing is not to save free virus but to save infected cell. While discussing long-term viral persistence, it is impossible to mark off distinctly the importance of biological participation of macroorganism and provoker in this process. The output of the relationship with infect cell is conditioned on the one hand by permissiveness of cell system, on the other hand by strain pathogen city. The details of attenuation mechanisms of microorganism's different reactions in cases of illness with the same strain are not known well yet. Although, it is clear that in chronic persistence the leading role still has immune system disbalance. In disbalance genesis of immunological equilibration virus-induced changes of immunocompetent cells are high.

  11. Predicting persistence to antidepressant treatment in administrative claims data: Considering the influence of refill delays and prior persistence on other medications

    PubMed Central

    Bushnell, Greta A; Stürmer, Til; White, Alice; Pate, Virginia; Swanson, Sonja A; Azrael, Deborah; Miller, Matthew

    2016-01-01

    Background Many patients with major depressive disorder (MDD) who begin antidepressant treatment discontinue use before for six months, the recommended minimum treatment length. This study sought to identify predictors of six-month antidepressant persistence including predictors utilizing patients’ electronic prescription records. Methods Commercially insured children (3–17 years) and adults (18–64 years) with MDD who initiated antidepressant treatment, 1/1/2003–2/28/2010, were assessed for six-month persistence (based on prescriptions’ days supply, allowing a 30-day grace period). Antidepressant persistence prediction models were developed separately for children and adults. Two additional measures, days without medication between the first and second antidepressant fill (children and adults) and prior persistence on other medications (adults only), were added to the models, concordance (c) statistics were compared and risk reclassification evaluated. Results Among children (n=8,837 children) and adults (n=47,495) with MDD, six-month antidepressant persistence was low and varied by age (37%, 18–24 years to 52%, 3–12 and 50–64 years, respectively). Independent baseline predictors of persistence were identified, with model c-statistics: children=0.582, adults=0.584. Patients with more days without medication between fills were less likely to be persistent (10–30 vs. 0 days, children: RR=0.72, adults: RR=0.74), as were adults not previously persistent to other medications (RR=0.73). Limitations The definition of 6-month persistence is dependent on correct days supply values and the grace period utilized; potential predictors were limited to measures available in claims data. Conclusions Six-month antidepressant persistence was low and overall prediction of persistence was poor; however, days without medication between fills and prior persistence on other medications marginally improved the ability to predict antidepressant persistence. PMID:26921866

  12. Fostering Informed Choice: Alleviating the Trauma of Genetic Abortions.

    PubMed

    Asbury, Bret D

    2015-01-01

    Each year, thousands of pregnant women learn of fetal abnormalities through prenatal genetic analysis. This discovery--made after a woman has initially declined to exercise her right to abort an unwanted pregnancy—raises the difficult and heart-wrenching question of whether to terminate on genetic grounds. Women considering a genetic abortion rely on information and support from health care providers to assist them in making their choice. Though intended to be objective and nondirective, the support women receive frequently provides them within complete and incomprehensible information having the effect of encouraging them to abort genetically anomalous fetuses. As a result, genetic terminations--which cause severe and long-standing psychological impacts such as pathological grief, depression and post-traumatic stress—are often the result of something other than a fully informed choice.Congress and eleven states have recognized the importance of better informing choice by passing legislation aimed at providing clearer and more balanced information to expectant mothers learning of fetal genetic abnormalities. But existing legislative remedies do not adequately address this problem, and this inadequacy will become more pronounced in future years as increases in access to prenatal genetic analysis further stretch the capabilities of the available support services.This Article describes the unique characteristics of terminations for a fetal abnormality, their troubling and persistent psychological impacts,and the reasons why they will become more common in future years. It then offers proposals for how to reconfigure the prenatal genetic counseling landscape in order to reduce the incidence of genetic terminations based on incomplete or misleading information, thereby alleviating their distinct psychological costs. Its overall objective is to ensure that women learning of prenatal genetic abnormalities have access to complete and comprehensible information prior to

  13. Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous in transgenic line TgN3261Rpw.

    PubMed

    Colitz, C M; Malarkey, D E; Woychik, R P; Wilkinson, J E

    2000-09-01

    Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous are congenital ocular anomalies that can lead to cataract formation. A line of insertional mutant mice, TgN3261Rpw, generated at the Oak Ridge National Laboratory in a large-scale insertional mutagenesis program was found to have a low incidence (8/243; 3.29%) of multiple developmental ocular abnormalities. The ocular abnormalities include persistent hyperplastic primary vitreous, persistent hyperplastic tunica vasculosa lentis, failure of cleavage of the anterior segment, retrolental fibrovascular membrane, posterior polar cataract, and detached retina. This transgenic mouse line provides an ontogenetic model because of the high degree of similarity of this entity in humans, dogs, and mice.

  14. A PILOT STUDY OF CHILDREN'S TOTAL EXPOSURE TO PERSISTENT PESTICIDES AND OTHER PERSISTENT ORGANIC POLLUTANTS (CTEPP)

    EPA Science Inventory

    The Pilot Study of Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) investigated the aggregate exposures of 257 preschool children and their primary adult caregivers to pollutants commonly detected in their everyday environments. ...

  15. Demographic mechanisms underpinning genetic assimilation of remnant groups of a large carnivore

    PubMed Central

    Kovach, Ryan; Kendall, Katherine C.; Macleod, Amy C.

    2016-01-01

    Current range expansions of large terrestrial carnivores are occurring following human-induced range contraction. Contractions are often incomplete, leaving small remnant groups in refugia throughout the former range. Little is known about the underlying ecological and evolutionary processes that influence how remnant groups are affected during range expansion. We used data from a spatially explicit, long-term genetic sampling effort of grizzly bears (Ursus arctos) in the Northern Continental Divide Ecosystem (NCDE), USA, to identify the demographic processes underlying spatial and temporal patterns of genetic diversity. We conducted parentage analysis to evaluate how reproductive success and dispersal contribute to spatio-temporal patterns of genetic diversity in remnant groups of grizzly bears existing in the southwestern (SW), southeastern (SE) and east-central (EC) regions of the NCDE. A few reproductively dominant individuals and local inbreeding caused low genetic diversity in peripheral regions that may have persisted for multiple generations before eroding rapidly (approx. one generation) during population expansion. Our results highlight that individual-level genetic and reproductive dynamics play critical roles during genetic assimilation, and show that spatial patterns of genetic diversity on the leading edge of an expansion may result from historical demographic patterns that are highly ephemeral. PMID:27655768

  16. GENETIC DIVERSITY AND STRUCTURE OF AN ESTUARINE FISH (FUNDULUS HETEROCLITIS) INDIGENOUS TO SITES ASSOCIATED WITH A HIGHLY CONTAMINATED URBAN HARBOR

    EPA Science Inventory

    Intense directional selection on isolated populations can result in loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that toxic pollutants, specifically, polychlor...

  17. Evidence for a genetic etiology of early-onset delinquency.

    PubMed

    Taylor, J; Iacono, W G; McGue, M

    2000-11-01

    Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

  18. The Extraction of Information From Visual Persistence

    ERIC Educational Resources Information Center

    Erwin, Donald E.

    1976-01-01

    This research sought to distinguish among three concepts of visual persistence by substituting the physical presence of the target stimulus while simultaneously inhibiting the formation of a persisting representation. Reportability of information about the stimuli was compared to a condition in which visual persistence was allowed to fully develop…

  19. Genetic health and population monitoring of two small black bear (Ursus americanus) populations in Alabama, with a regional perspective of genetic diversity and exchange

    PubMed Central

    Waits, Lisette P.; Adams, Jennifer R.; Seals, Christopher L.; Steury, Todd D.

    2017-01-01

    One of the major concerns in conservation today is the loss of genetic diversity which is a frequent consequence of population isolation and small population sizes. Fragmentation of populations and persecution of carnivores has posed a substantial threat to the persistence of free ranging carnivores in North America since the arrival of European settlers. Black bears have seen significant reductions in range size from their historic extent, which is most pronounced in the southeastern United States and even more starkly in Alabama where until recently bears were reduced to a single geographically isolated population in the Mobile River Basin. Recently a second population has naturally re-established itself in northeastern Alabama. We sought to determine size, genetic diversity and genetic connectivity for these two populations in relation to other regional populations. Both populations of black bears in Alabama had small population sizes and had moderate to low genetic diversity, but showed different levels of connectivity to surrounding populations of bears. The Mobile River Basin population had a small population size at only 86 individuals (76–124, 95% C.I.), the lowest genetic diversity of compared populations (richness = 2.33, Ho and He = 0.33), and showed near complete genetic isolation from surrounding populations across multiple tests. The newly recolonizing population in northeastern Alabama had a small but growing population doubling in 3 years (34 individuals 26–43, 95% C.I.), relatively moderate genetic diversity compared to surrounding populations (richness = 3.32, Ho = 0.53, He = 0.65), and showed a high level of genetic connectivity with surrounding populations. PMID:29117263

  20. A behavioral genetic analysis of callous-unemotional traits and Big Five personality in adolescence.

    PubMed

    Mann, Frank D; Briley, Daniel A; Tucker-Drob, Elliot M; Harden, K Paige

    2015-11-01

    Callous-unemotional (CU) traits, such as lacking empathy and emotional insensitivity, predict the onset, severity, and persistence of antisocial behavior. CU traits are heritable, and genetic influences on CU traits contribute to antisocial behavior. This study examines genetic overlap between CU traits and general domains of personality. We measured CU traits using the Inventory of Callous-Unemotional Traits (ICU) and Big Five personality using the Big Five Inventory in a sample of adolescent twins from the Texas Twin Project. Genetic influences on the Big Five personality dimensions could account for the entirety of genetic influences on CU traits. Item Response Theory results indicate that the Inventory of Callous and Unemotional Traits is better at detecting clinically relevant personality variation at lower extremes of personality trait continua, particularly low agreeableness and low conscientiousness. The proximate biological mechanisms that mediate genetic liabilities for CU traits remain an open question. The results of the current study suggest that understanding the development of normal personality may inform understanding of the genetic underpinnings of callous and unemotional behavior. (c) 2015 APA, all rights reserved).

  1. Effects of multiple founder populations on spatial genetic structure of reintroduced American martens.

    PubMed

    Williams, Bronwyn W; Scribner, Kim T

    2010-01-01

    Reintroductions and translocations are increasingly used to repatriate or increase probabilities of persistence for animal and plant species. Genetic and demographic characteristics of founding individuals and suitability of habitat at release sites are commonly believed to affect the success of these conservation programs. Genetic divergence among multiple source populations of American martens (Martes americana) and well documented introduction histories permitted analyses of post-introduction dispersion from release sites and development of genetic clusters in the Upper Peninsula (UP) of Michigan <50 years following release. Location and size of spatial genetic clusters and measures of individual-based autocorrelation were inferred using 11 microsatellite loci. We identified three genetic clusters in geographic proximity to original release locations. Estimated distances of effective gene flow based on spatial autocorrelation varied greatly among genetic clusters (30-90 km). Spatial contiguity of genetic clusters has been largely maintained with evidence for admixture primarily in localized regions, suggesting recent contact or locally retarded rates of gene flow. Data provide guidance for future studies of the effects of permeabilities of different land-cover and land-use features to dispersal and of other biotic and environmental factors that may contribute to the colonization process and development of spatial genetic associations.

  2. Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress

    PubMed Central

    Wilson, Andrew F.; Li, Xue

    2017-01-01

    ABSTRACT Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G2/M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress. PMID:28475398

  3. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Kochenderfer, James N; Dudley, Mark E; Carpenter, Robert O; Kassim, Sadik H; Rose, Jeremy J; Telford, William G; Hakim, Frances T; Halverson, David C; Fowler, Daniel H; Hardy, Nancy M; Mato, Anthony R; Hickstein, Dennis D; Gea-Banacloche, Juan C; Pavletic, Steven Z; Sportes, Claude; Maric, Irina; Feldman, Steven A; Hansen, Brenna G; Wilder, Jennifer S; Blacklock-Schuver, Bazetta; Jena, Bipulendu; Bishop, Michael R; Gress, Ronald E; Rosenberg, Steven A

    2013-12-12

    New treatments are needed for B-cell malignancies persisting after allogeneic hematopoietic stem cell transplantation (alloHSCT). We conducted a clinical trial of allogeneic T cells genetically modified to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. T cells for genetic modification were obtained from each patient's alloHSCT donor. All patients had malignancy that persisted after alloHSCT and standard donor lymphocyte infusions (DLIs). Patients did not receive chemotherapy prior to the CAR T-cell infusions and were not lymphocyte depleted at the time of the infusions. The 10 treated patients received a single infusion of allogeneic anti-CD19-CAR T cells. Three patients had regressions of their malignancies. One patient with chronic lymphocytic leukemia (CLL) obtained an ongoing complete remission after treatment with allogeneic anti-CD19-CAR T cells, another CLL patient had tumor lysis syndrome as his leukemia dramatically regressed, and a patient with mantle cell lymphoma obtained an ongoing partial remission. None of the 10 patients developed graft-versus-host disease (GVHD). Toxicities included transient hypotension and fever. We detected cells containing the anti-CD19-CAR gene in the blood of 8 of 10 patients. These results show for the first time that donor-derived allogeneic anti-CD19-CAR T cells can cause regression of B-cell malignancies resistant to standard DLIs without causing GVHD.

  4. Field performance of a genetically engineered strain of pink bollworm.

    PubMed

    Simmons, Gregory S; McKemey, Andrew R; Morrison, Neil I; O'Connell, Sinead; Tabashnik, Bruce E; Claus, John; Fu, Guoliang; Tang, Guolei; Sledge, Mickey; Walker, Adam S; Phillips, Caroline E; Miller, Ernie D; Rose, Robert I; Staten, Robert T; Donnelly, Christl A; Alphey, Luke

    2011-01-01

    Pest insects harm crops, livestock and human health, either directly or by acting as vectors of disease. The Sterile Insect Technique (SIT)--mass-release of sterile insects to mate with, and thereby control, their wild counterparts--has been used successfully for decades to control several pest species, including pink bollworm, a lepidopteran pest of cotton. Although it has been suggested that genetic engineering of pest insects provides potential improvements, there is uncertainty regarding its impact on their field performance. Discrimination between released and wild moths caught in monitoring traps is essential for estimating wild population levels. To address concerns about the reliability of current marking methods, we developed a genetically engineered strain of pink bollworm with a heritable fluorescent marker, to improve discrimination of sterile from wild moths. Here, we report the results of field trials showing that this engineered strain performed well under field conditions. Our data show that attributes critical to SIT in the field--ability to find a mate and to initiate copulation, as well as dispersal and persistence in the release area--were comparable between the genetically engineered strain and a standard strain. To our knowledge, these represent the first open-field experiments with a genetically engineered insect. The results described here provide encouragement for the genetic control of insect pests.

  5. Persistence. Snapshot Report, Fall 2011

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2011

    2011-01-01

    Today's college student is not your '60s drop-out. In 2010, college students tended to stay enrolled (i.e., persist), even if it was in a different school, according to the National Student Clearinghouse Research Center. For a student enrolled in the fall, persistence is defined as either continued enrollment during the next term after the fall or…

  6. Exploring Non-Traditional Adult Undergraduate Student Persistence and Non-Persistence in Higher Education: A Stress and Coping Model Approach

    ERIC Educational Resources Information Center

    Maroney, Barbara R.

    2010-01-01

    This study explores persistence and non-persistence among adult undergraduate students with particular focus on these students' lives, their stressors, their coping resources including academic supports, and their styles of coping. The study approaches the issue of non-persistence not as a personal failure but rather as a consequence of multiple…

  7. Genetic signals of past demographic changes and the history of oak populations in California

    NASA Astrophysics Data System (ADS)

    Dodd, R. S.

    2009-04-01

    A retrospective view of species' demographic changes can inform on population stability through times of climatic change and the origins and spatial structure of genetic diversity in contemporary populations. The former provides the means to predict responses to future climatic change, while the latter allows us to infer the ability of populations to buffer the effects of reductions in population size and fragmentation. The approximately 1.8 my of the Pleistocene is believed to have had a significant impact on diversity through high rates of extinction during early glacial cycles and population expansions and contractions during the later cycles. In the Mediterranean basin, early emphasis on taxa with wide latitudinal ranges led to models of refugial sites and subsequent recolonization routes that could explain geographic patterns in genetic diversity, with a trend towards reduced genetic diversity in the north. More recently, the study of strictly Mediterranean taxa has revealed relictual sites that have persisted over very long periods of time, commonly relatively poor in diversity, but populations well differentiated from one site to another. In California, relatively little is known of the population dynamics of plant taxa during the Pleistocene glacial cycles, or to what extent differentiation today is a result of pre-Pleistocene events. For several animal taxa, differentiation between Coastal and Sierran taxa are believed to date to the Pliocene. Major demographic changes resulting in population isolation, bottlenecks, founder events and population expansions leave a genetic signal that can be detected through appropriate genetic markers and analyses. Such signals help to infer whether past climate fluctuations have had important effects on population demographics. Here, I will focus on key oak species of the California mediterranean climate zone. I will explore the likely effects of the last glacial maximum on oak populations using palaeoclimate and niche

  8. MOOCs and Persistence: Definitions and Predictors

    ERIC Educational Resources Information Center

    Evans, Brent J.; Baker, Rachel B.

    2016-01-01

    The chapter argues for redefining the term "persistence" as it relates to MOOCs and considers how different measures produce different results in the research; it closes with a review of research on persistence in MOOCs.

  9. Persistence at distributional edges: Columbia spotted frog habitat in the arid Great Basin, USA

    PubMed Central

    Arkle, Robert S; Pilliod, David S

    2015-01-01

    A common challenge in the conservation of broadly distributed, yet imperiled species is understanding which factors facilitate persistence at distributional edges, locations where populations are often vulnerable to extirpation due to changes in climate, land use, or distributions of other species. For Columbia spotted frogs (Rana luteiventris) in the Great Basin (USA), a genetically distinct population segment of conservation concern, we approached this problem by examining (1) landscape-scale habitat availability and distribution, (2) water body-scale habitat associations, and (3) resource management-identified threats to persistence. We found that areas with perennial aquatic habitat and suitable climate are extremely limited in the southern portion of the species’ range. Within these suitable areas, native and non-native predators (trout and American bullfrogs [Lithobates catesbeianus]) are widespread and may further limit habitat availability in upper- and lower-elevation areas, respectively. At the water body scale, spotted frog occupancy was associated with deeper sites containing abundant emergent vegetation and nontrout fish species. Streams with American beaver (Castor canadensis) frequently had these structural characteristics and were significantly more likely to be occupied than ponds, lakes, streams without beaver, or streams with inactive beaver ponds, highlighting the importance of active manipulation of stream environments by beaver. Native and non-native trout reduced the likelihood of spotted frog occupancy, especially where emergent vegetation cover was sparse. Intensive livestock grazing, low aquatic connectivity, and ephemeral hydroperiods were also negatively associated with spotted frog occupancy. We conclude that persistence of this species at the arid end of its range has been largely facilitated by habitat stability (i.e., permanent hydroperiod), connectivity, predator-free refugia, and a commensalistic interaction with an ecosystem

  10. Persistence at distributional edges: Columbia spotted frog habitat in the arid Great Basin, USA.

    PubMed

    Arkle, Robert S; Pilliod, David S

    2015-09-01

    A common challenge in the conservation of broadly distributed, yet imperiled species is understanding which factors facilitate persistence at distributional edges, locations where populations are often vulnerable to extirpation due to changes in climate, land use, or distributions of other species. For Columbia spotted frogs (Rana luteiventris) in the Great Basin (USA), a genetically distinct population segment of conservation concern, we approached this problem by examining (1) landscape-scale habitat availability and distribution, (2) water body-scale habitat associations, and (3) resource management-identified threats to persistence. We found that areas with perennial aquatic habitat and suitable climate are extremely limited in the southern portion of the species' range. Within these suitable areas, native and non-native predators (trout and American bullfrogs [Lithobates catesbeianus]) are widespread and may further limit habitat availability in upper- and lower-elevation areas, respectively. At the water body scale, spotted frog occupancy was associated with deeper sites containing abundant emergent vegetation and nontrout fish species. Streams with American beaver (Castor canadensis) frequently had these structural characteristics and were significantly more likely to be occupied than ponds, lakes, streams without beaver, or streams with inactive beaver ponds, highlighting the importance of active manipulation of stream environments by beaver. Native and non-native trout reduced the likelihood of spotted frog occupancy, especially where emergent vegetation cover was sparse. Intensive livestock grazing, low aquatic connectivity, and ephemeral hydroperiods were also negatively associated with spotted frog occupancy. We conclude that persistence of this species at the arid end of its range has been largely facilitated by habitat stability (i.e., permanent hydroperiod), connectivity, predator-free refugia, and a commensalistic interaction with an ecosystem

  11. Persistence at distributional edges: Columbia spotted frog habitat in the arid Great Basin, USA

    USGS Publications Warehouse

    Arkle, Robert S.; Pilliod, David S.

    2015-01-01

    A common challenge in the conservation of broadly distributed, yet imperiled species is understanding which factors facilitate persistence at distributional edges, locations where populations are often vulnerable to extirpation due to changes in climate, land use, or distributions of other species. For Columbia spotted frogs (Rana luteiventris) in the Great Basin (USA), a genetically distinct population segment of conservation concern, we approached this problem by examining (1) landscape-scale habitat availability and distribution, (2) water body-scale habitat associations, and (3) resource management-identified threats to persistence. We found that areas with perennial aquatic habitat and suitable climate are extremely limited in the southern portion of the species’ range. Within these suitable areas, native and non-native predators (trout and American bullfrogs [Lithobates catesbeianus]) are widespread and may further limit habitat availability in upper- and lower-elevation areas, respectively. At the water body scale, spotted frog occupancy was associated with deeper sites containing abundant emergent vegetation and nontrout fish species. Streams with American beaver (Castor canadensis) frequently had these structural characteristics and were significantly more likely to be occupied than ponds, lakes, streams without beaver, or streams with inactive beaver ponds, highlighting the importance of active manipulation of stream environments by beaver. Native and non-native trout reduced the likelihood of spotted frog occupancy, especially where emergent vegetation cover was sparse. Intensive livestock grazing, low aquatic connectivity, and ephemeral hydroperiods were also negatively associated with spotted frog occupancy. We conclude that persistence of this species at the arid end of its range has been largely facilitated by habitat stability (i.e., permanent hydroperiod), connectivity, predator-free refugia, and a commensalistic interaction with an ecosystem

  12. Population structure, persistence, and seasonality of autochthonous Escherichia coli in temperate, coastal forest soil from a Great Lakes watershed

    USGS Publications Warehouse

    Byappanahalli, M.N.; Whitman, R.L.; Shively, D.A.; Sadowsky, M.J.; Ishii, S.

    2006-01-01

    The common occurrence of Escherichia coli in temperate soils has previously been reported, however, there are few studies to date to characterize its source, distribution, persistent capability and genetic diversity. In this study, undisturbed, forest soils within six randomly selected 0.5 m2 exclosure plots (covered by netting of 2.3 mm2 mesh size) were monitored from March to October 2003 for E. coli in order to describe its numerical and population characteristics. Culturable E. coli occurred in 88% of the samples collected, with overall mean counts of 16 MPN g-1, ranging from <1 to 1657 (n = 66). Escherichia coli counts did not correlate with substrate moisture content, air, or soil temperatures, suggesting that seasonality were not a strong factor in population density control. Mean E. coli counts in soil samples (n = 60) were significantly higher inside than immediately outside the exclosures; E. coli distribution within the exclosures was patchy. Repetitive extragenic palindromic polymerase chain reaction (Rep-PCR) demonstrated genetic heterogeneity of E. coli within and among exclosure sites, and the soil strains were genetically distinct from animal (E. coli) strains tested (i.e. gulls, terns, deer and most geese). These results suggest that E. coli can occur and persist for extended periods in undisturbed temperate forest soils independent of recent allochthonous input and season, and that the soil E. coli populations formed a cohesive phylogenetic group in comparison to the set of fecal strains with which they were compared. Thus, in assessing E. coli sources within a stream, it is important to differentiate background soil loadings from inputs derived from animal and human fecal contamination. ?? 2005 Society for Applied Microbiology and Blackwell Publishing Ltd.

  13. Identification of genetically and oceanographically distinct blooms of jellyfish

    PubMed Central

    Lee, Patricia L. M.; Dawson, Michael N; Neill, Simon P.; Robins, Peter E.; Houghton, Jonathan D. R.; Doyle, Thomas K.; Hays, Graeme C.

    2013-01-01

    Reports of nuisance jellyfish blooms have increased worldwide during the last half-century, but the possible causes remain unclear. A persistent difficulty lies in identifying whether blooms occur owing to local or regional processes. This issue can be resolved, in part, by establishing the geographical scales of connectivity among locations, which may be addressed using genetic analyses and oceanographic modelling. We used landscape genetics and Lagrangian modelling of oceanographic dispersal to explore patterns of connectivity in the scyphozoan jellyfish Rhizostoma octopus, which occurs en masse at locations in the Irish Sea and northeastern Atlantic. We found significant genetic structure distinguishing three populations, with both consistencies and inconsistencies with prevailing physical oceanographic patterns. Our analyses identify locations where blooms occur in apparently geographically isolated populations, locations where blooms may be the source or result of migrants, and a location where blooms do not occur consistently and jellyfish are mostly immigrant. Our interdisciplinary approach thus provides a means to ascertain the geographical origins of jellyfish in outbreaks, which may have wide utility as increased international efforts investigate jellyfish blooms. PMID:23287405

  14. Population genetics of the olive-winged bulbul (Pycnonotus plumosus) in a tropical urban-fragmented landscape.

    PubMed

    Tang, Grace S Y; Sadanandan, Keren R; Rheindt, Frank E

    2016-01-01

    With increasing urbanization, urban-fragmented landscapes are becoming more and more prevalent worldwide. Such fragmentation may lead to small, isolated populations that face great threats from genetic factors that affect even avian species with high dispersal propensities. Yet few studies have investigated the population genetics of species living within urban-fragmented landscapes in the Old World tropics, in spite of the high levels of deforestation and fragmentation within this region. We investigated the evolutionary history and population genetics of the olive-winged bulbul (Pycnonotus plumosus) in Singapore, a highly urbanized island which retains <5% of its original forest cover in fragments. Combining our own collected and sequenced samples with those from the literature, we conducted phylogenetic and population genetic analyses. We revealed high genetic diversity, evidence for population expansion, and potential presence of pronounced gene flow across the population in Singapore. This suggests increased chances of long-term persistence for the olive-winged bulbul and the ecosystem services it provides within this landscape.

  15. Population status and population genetics of northern leopard frogs in Arizona

    USGS Publications Warehouse

    Theimer, Tad C.; Drost, Charles A.; O'Donnell, Ryan P.; Mock, Karen E.

    2011-01-01

    Increasing isolation of populations by habitat fragmentation threatens the persistence of many species, both from stochastic loss of small isolated populations, and from inbreeding effects in populations that have become genetically isolated. In the southwestern United States, amphibian habitat is naturally patchy in occurrence because of the prevailing aridity of the region. Streams, rivers, and other wetlands are important both as habitat and as corridors that connect populations. However, populations of some species have become more fragmented and isolated by habitat degradation and loss. Northern leopard frogs (Rana pipiens) have experienced serious declines in the Southwest. We conducted an extensive survey across the known range of northern leopard frogs in Arizona to determine the current distribution and abundance of the species. From a range that once spanned much of the northern and central part of the State, northern leopard frogs have been reduced to three or four widely separated populations, near Lyman Lake in east-central Arizona, in the Stoneman Lake area south of Flagstaff, along Truxton Wash near Peach Springs, and a population of uncertain extent on Navajo Nation lands. The Lyman Lake and Truxton Wash populations are small and extremely isolated. The Stoneman Lake population, however, is an extensive metapopulation spread across several stream drainages, including numerous ponds, wetlands, and artificial tanks. This is the only population in Arizona that is increasing in extent and numbers, but there is concern about the apparent introduction of nonnative genetic stock from eastern North America into this area. We analyzed genetic diversity within and genetic divergence among populations of northern leopard frogs, across both extant and recently extirpated populations in Arizona. We also analyzed mitochondrial DNA to place these populations into a larger phylogenetic framework and to determine whether any populations contained genetic material

  16. Personality and intelligence: persistence, not self-directedness, cooperativeness or self-transcendence, is related to twins' cognitive abilities.

    PubMed

    Mousavi, Fariba; Rozsa, Sandor; Nilsson, Thomas; Archer, Trevor; Anckarsäter, Henrik; Garcia, Danilo

    2015-01-01

    Background. A person-centered approach focusing on the interaction of an individual's temperament-character-life events is essential in the path of individuals' well-being. In this context, three character traits, Self-directedness (e.g., self-acceptance, self-control, goal-directed behavior), Cooperativeness (e.g., social affiliation, social tolerance, empathy and helpfulness) and Self-transcendence (e.g., spiritual acceptance, transpersonal identification), measured using Cloninger's model of personality are suggested to help the individual to regulate and resolve the conflicts derived from her/his temperament combinations as a reaction to life events. However, if character is related to the individual's cognitive ability, then this association might limit any intervention that focuses on character development. We used data from the Child and Adolescent Twin Study in Sweden (CATSS) to investigate the relationship between personality and cognitive ability. Method. The sample consisted of 370 15-year-old twins (159 girls/211 boys), 192 of whom screen-positive with various types of mental health problems. We used the Temperament and Character Inventory to measure personality and the Wechsler Intelligence Scales for Children (WISC-IV) to measure intelligence. The relationship was investigated using correlation analyses using random-selected twins from each dyad and separately for monozygotic and dizygotic twins. Additional analyses investigated the genetic and environmental effects on personality and cognitive ability in this specific sample. Results. There were no significant correlations between the WISC-IV indices and any of the character traits (i.e., Self-directedness, Cooperativeness, and Self-transcendence). Persistence was significantly related, if weak, to four WISC-IV indices: Verbal Comprehension, Perceptual Reasoning, Working Memory, and the Full WISC-IV Scale. Post-hoc cross-twin/cross-trait analyses showed that the Persistence-cognitive ability

  17. Personality and intelligence: persistence, not self-directedness, cooperativeness or self-transcendence, is related to twins’ cognitive abilities

    PubMed Central

    Mousavi, Fariba; Rozsa, Sandor; Nilsson, Thomas; Archer, Trevor; Anckarsäter, Henrik

    2015-01-01

    Background. A person-centered approach focusing on the interaction of an individual’s temperament-character-life events is essential in the path of individuals’ well-being. In this context, three character traits, Self-directedness (e.g., self-acceptance, self-control, goal-directed behavior), Cooperativeness (e.g., social affiliation, social tolerance, empathy and helpfulness) and Self-transcendence (e.g., spiritual acceptance, transpersonal identification), measured using Cloninger’s model of personality are suggested to help the individual to regulate and resolve the conflicts derived from her/his temperament combinations as a reaction to life events. However, if character is related to the individual’s cognitive ability, then this association might limit any intervention that focuses on character development. We used data from the Child and Adolescent Twin Study in Sweden (CATSS) to investigate the relationship between personality and cognitive ability. Method. The sample consisted of 370 15-year-old twins (159 girls/211 boys), 192 of whom screen-positive with various types of mental health problems. We used the Temperament and Character Inventory to measure personality and the Wechsler Intelligence Scales for Children (WISC-IV) to measure intelligence. The relationship was investigated using correlation analyses using random-selected twins from each dyad and separately for monozygotic and dizygotic twins. Additional analyses investigated the genetic and environmental effects on personality and cognitive ability in this specific sample. Results. There were no significant correlations between the WISC-IV indices and any of the character traits (i.e., Self-directedness, Cooperativeness, and Self-transcendence). Persistence was significantly related, if weak, to four WISC-IV indices: Verbal Comprehension, Perceptual Reasoning, Working Memory, and the Full WISC-IV Scale. Post-hoc cross-twin/cross-trait analyses showed that the Persistence-cognitive ability

  18. Persistence. Snapshot™ Report, Spring 2016

    ERIC Educational Resources Information Center

    National Student Clearinghouse, 2016

    2016-01-01

    Of all students who started college in fall 2014, 72.1 percent persisted at any U.S. institution in fall 2015, while 60.6 percent were retained at their starting institution. The persistence rate is the percentage of students who return to college at any institution for their second year, while the retention rate is the percentage of students who…

  19. Smoking and caffeine consumption: a genetic analysis of their association

    PubMed Central

    Taylor, Amy E.; Ware, Jennifer J.; Nivard, Michel G.; Neale, Michael C.; McMahon, George; Hottenga, Jouke‐Jan; Baselmans, Bart M. L.; Boomsma, Dorret I.; Munafò, Marcus R.; Vink, Jacqueline M.

    2016-01-01

    Abstract Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta‐analyses of genome‐wide association studies on smoking and caffeine, the genetic correlation was calculated by LD‐score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD‐score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. PMID:27027469

  20. Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer.

    PubMed

    Wang, Sophia S; Bratti, M Concepcion; Rodríguez, Ana Cecilia; Herrero, Rolando; Burk, Robert D; Porras, Carolina; González, Paula; Sherman, Mark E; Wacholder, Sholom; Lan, Z Elizabeth; Schiffman, Mark; Chanock, Stephen J; Hildesheim, Allan

    2009-01-01

    We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95-1.8-fold) and 1.7-fold (95% CI, 1.1-2.6-fold) increased risk for CIN3 or cancer, respectively (P(trend) = .008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (P(trend) = .009). Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence.

  1. A rare genetic disorder causing persistent severe neonatal hypoglycaemia the diagnostic workup.

    PubMed

    Francescato, Gaia; Salvatoni, Alessandro; Persani, Luca; Agosti, Massimo

    2012-07-19

    We report a case of familial glucocorticoid deficiency (FGD), a rare genetic autosomal-recessive disorder with typical hyperpigmentation of the skin and mucous membranes, severe hypoglycaemia, occasionally leading to seizures and coma, feeding difficulties, failure to thrive and infections. A newborn child was admitted, on his second day of life, to our neonatal intensive care unit because of seizures and respiratory insufficiency. Hyperpigmentation was not evident due to his Senegalese origin. The clinical presentation led us to consider a wide range of diagnostic hypothesis. Laboratory findings brought us to the diagnosis of FGD that was confirmed by molecular analysis showing an MC2R:p.Y254C mutation previously reported as causative of type 1 FGD and two novel heterozygous non-synonymous single-nucleotide polymorphisms in exon 2 and 3 of melanocortin 2 receptor accessory protein-α, whose role in the disease is currently unknown. The importance of an early collection and storage of blood samples during hypoglycaemic event is emphasised.

  2. Nitric oxide-dependent killing of aerobic, anaerobic and persistent Burkholderia pseudomallei.

    PubMed

    Jones-Carson, Jessica; Laughlin, James R; Stewart, Amanda L; Voskuil, Martin I; Vázquez-Torres, Andrés

    2012-06-30

    Burkholderia pseudomallei infections are fastidious to treat with conventional antibiotic therapy, often involving a combination of drugs and long-term regimes. Bacterial genetic determinants contribute to the resistance of B. pseudomallei to many classes of antibiotics. In addition, anaerobiosis and hypoxia in abscesses typical of melioidosis select for persistent populations of B. pseudomallei refractory to a broad spectrum of antibacterials. We tested the susceptibility of B. pseudomallei to the drugs hydroxyurea, spermine NONOate and DETA NONOate that release nitric oxide (NO). Our investigations indicate that B. pseudomallei are killed by NO in a concentration and time-dependent fashion. The cytoxicity of this diatomic radical against B. pseudomallei depends on both the culture medium and growth phase of the bacteria. Rapidly growing, but not stationary phase, B. pseudomallei are readily killed upon exposure to the NO donor spermine NONOate. NO also has excellent antimicrobial activity against anaerobic B. pseudomallei. In addition, persistent bacteria highly resistant to most conventional antibiotics are remarkably susceptible to NO. Sublethal concentrations of NO inhibited the enzymatic activity of [4Fe-4S]-cofactored aconitase of aerobic and anaerobic B. pseudomallei. The strong anti-B. pseudomallei activity of NO described herein merits further studies on the application of NO-based antibiotics for the treatment of melioidosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. The genetic prehistory of the Baltic Sea region.

    PubMed

    Mittnik, Alissa; Wang, Chuan-Chao; Pfrengle, Saskia; Daubaras, Mantas; Zariņa, Gunita; Hallgren, Fredrik; Allmäe, Raili; Khartanovich, Valery; Moiseyev, Vyacheslav; Tõrv, Mari; Furtwängler, Anja; Andrades Valtueña, Aida; Feldman, Michal; Economou, Christos; Oinonen, Markku; Vasks, Andrejs; Balanovska, Elena; Reich, David; Jankauskas, Rimantas; Haak, Wolfgang; Schiffels, Stephan; Krause, Johannes

    2018-01-30

    While the series of events that shaped the transition between foraging societies and food producers are well described for Central and Southern Europe, genetic evidence from Northern Europe surrounding the Baltic Sea is still sparse. Here, we report genome-wide DNA data from 38 ancient North Europeans ranging from ~9500 to 2200 years before present. Our analysis provides genetic evidence that hunter-gatherers settled Scandinavia via two routes. We reveal that the first Scandinavian farmers derive their ancestry from Anatolia 1000 years earlier than previously demonstrated. The range of Mesolithic Western hunter-gatherers extended to the east of the Baltic Sea, where these populations persisted without gene-flow from Central European farmers during the Early and Middle Neolithic. The arrival of steppe pastoralists in the Late Neolithic introduced a major shift in economy and mediated the spread of a new ancestry associated with the Corded Ware Complex in Northern Europe.

  4. PERSISTENT CONTAMINANTS: NEW PRIORITIES, NEW CONCERNS

    EPA Science Inventory


    The Stockholm Convention on persistent organic pollutants (POPs) was adopted in 2001 to protect human health and the environment from chemicals that are highly toxic, persistent, bioaccumulative, and undergo long range transport. These POPs include 9 pesticides, polychlorin...

  5. Persistent and Newly Developed Chronic Bronchitis Are Associated with Worse Outcomes in Chronic Obstructive Pulmonary Disease.

    PubMed

    Kim, Victor; Zhao, Huaqing; Boriek, Aladin M; Anzueto, Antonio; Soler, Xavier; Bhatt, Surya P; Rennard, Stephen I; Wise, Robert; Comellas, Alejandro; Ramsdell, Joe W; Kinney, Gregory L; Han, MeiLan K; Martinez, Carlos H; Yen, Andrew; Black-Shinn, Jennifer; Porszasz, Janos; Criner, Gerard J; Hanania, Nicola A; Sharafkhaneh, Amir; Crapo, James D; Make, Barry J; Silverman, Edwin K; Curtis, Jeffrey L

    2016-07-01

    Chronic bronchitis is, by definition, a chronic condition, but the development and remission of this condition in cigarette smokers with or without chronic obstructive pulmonary disease (COPD) are poorly understood. Also, it is unclear how the persistence or new development of chronic bronchitis affects symptoms and outcomes. To ascertain the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes. We analyzed 1,775 current or ex-smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0-IV COPD in phase 2 of the Genetic Epidemiology of COPD (COPDGene) Study, which included subjects after 5 years of follow-up from phase 1. We asked subjects at enrollment and at 5 years of follow-up about symptoms consistent with chronic bronchitis. We divided subjects into four groups: persistent chronic bronchitis- (negative at phase 1/negative at phase 2), resolved chronic bronchitis (positive/negative), new chronic bronchitis (negative/positive), and persistent chronic bronchitis+ (positive/positive). We analyzed respiratory symptoms, health-related quality of life, lung function, exacerbation frequency, and 6-minute walk distance. Compared with the persistent chronic bronchitis- group, members of the persistent chronic bronchitis+ group were more likely to have continued smoking (53.4%). Subjects with new chronic bronchitis were more likely to have resumed (6.6%) or continued smoking (45.6%), whereas subjects with resolved chronic bronchitis were more likely to have quit smoking (23.5%). Compared with the persistent chronic bronchitis- group, the other groups had a shorter 6-minute walk distance, worse lung function, greater exacerbation frequency, and worse respiratory symptoms. Modified Medical Research Council dyspnea and St. George's Respiratory Questionnaire scores worsened between phase 1 and phase 2 in subjects with new chronic bronchitis but improved in the resolved

  6. Organizing and Typing Persistent Objects Within an Object-Oriented Framework

    NASA Technical Reports Server (NTRS)

    Madany, Peter W.; Campbell, Roy H.

    1991-01-01

    Conventional operating systems provide little or no direct support for the services required for an efficient persistent object system implementation. We have built a persistent object scheme using a customization and extension of an object-oriented operating system called Choices. Choices includes a framework for the storage of persistent data that is suited to the construction of both conventional file system and persistent object system. In this paper we describe three areas in which persistent object support differs from file system support: storage organization, storage management, and typing. Persistent object systems must support various sizes of objects efficiently. Customizable containers, which are themselves persistent objects and can be nested, support a wide range of object sizes in Choices. Collections of persistent objects that are accessed as an aggregate and collections of light-weight persistent objects can be clustered in containers that are nested within containers for larger objects. Automated garbage collection schemes are added to storage management and have a major impact on persistent object applications. The Choices persistent object store provides extensible sets of persistent object types. The store contains not only the data for persistent objects but also the names of the classes to which they belong and the code for the operation of the classes. Besides presenting persistent object storage organization, storage management, and typing, this paper discusses how persistent objects are named and used within the Choices persistent data/file system framework.

  7. Neisseria infection of rhesus macaques as a model to study colonization, transmission, persistence, and horizontal gene transfer.

    PubMed

    Weyand, Nathan J; Wertheimer, Anne M; Hobbs, Theodore R; Sisko, Jennifer L; Taku, Nyiawung A; Gregston, Lindsay D; Clary, Susan; Higashi, Dustin L; Biais, Nicolas; Brown, Lewis M; Planer, Shannon L; Legasse, Alfred W; Axthelm, Michael K; Wong, Scott W; So, Magdalene

    2013-02-19

    The strict tropism of many pathogens for man hampers the development of animal models that recapitulate important microbe-host interactions. We developed a rhesus macaque model for studying Neisseria-host interactions using Neisseria species indigenous to the animal. We report that Neisseria are common inhabitants of the rhesus macaque. Neisseria isolated from the rhesus macaque recolonize animals after laboratory passage, persist in the animals for at least 72 d, and are transmitted between animals. Neisseria are naturally competent and acquire genetic markers from each other in vivo, in the absence of selection, within 44 d after colonization. Neisseria macacae encodes orthologs of known or presumed virulence factors of human-adapted Neisseria, as well as current or candidate vaccine antigens. We conclude that the rhesus macaque model will allow studies of the molecular mechanisms of Neisseria colonization, transmission, persistence, and horizontal gene transfer. The model can potentially be developed further for preclinical testing of vaccine candidates.

  8. Neisseria infection of rhesus macaques as a model to study colonization, transmission, persistence, and horizontal gene transfer

    PubMed Central

    Weyand, Nathan J.; Wertheimer, Anne M.; Hobbs, Theodore R.; Sisko, Jennifer L.; Taku, Nyiawung A.; Gregston, Lindsay D.; Clary, Susan; Higashi, Dustin L.; Biais, Nicolas; Brown, Lewis M.; Planer, Shannon L.; Legasse, Alfred W.; Axthelm, Michael K.; Wong, Scott W.; So, Magdalene

    2013-01-01

    The strict tropism of many pathogens for man hampers the development of animal models that recapitulate important microbe–host interactions. We developed a rhesus macaque model for studying Neisseria–host interactions using Neisseria species indigenous to the animal. We report that Neisseria are common inhabitants of the rhesus macaque. Neisseria isolated from the rhesus macaque recolonize animals after laboratory passage, persist in the animals for at least 72 d, and are transmitted between animals. Neisseria are naturally competent and acquire genetic markers from each other in vivo, in the absence of selection, within 44 d after colonization. Neisseria macacae encodes orthologs of known or presumed virulence factors of human-adapted Neisseria, as well as current or candidate vaccine antigens. We conclude that the rhesus macaque model will allow studies of the molecular mechanisms of Neisseria colonization, transmission, persistence, and horizontal gene transfer. The model can potentially be developed further for preclinical testing of vaccine candidates. PMID:23382234

  9. On species persistence-time distributions.

    PubMed

    Suweis, S; Bertuzzo, E; Mari, L; Rodriguez-Iturbe, I; Maritan, A; Rinaldo, A

    2012-06-21

    We present new theoretical and empirical results on the probability distributions of species persistence times in natural ecosystems. Persistence times, defined as the timespans occurring between species' colonization and local extinction in a given geographic region, are empirically estimated from local observations of species' presence/absence. A connected sampling problem is presented, generalized and solved analytically. Species persistence is shown to provide a direct connection with key spatial macroecological patterns like species-area and endemics-area relationships. Our empirical analysis pertains to two different ecosystems and taxa: a herbaceous plant community and a estuarine fish database. Despite the substantial differences in ecological interactions and spatial scales, we confirm earlier evidence on the general properties of the scaling of persistence times, including the predicted effects of the structure of the spatial interaction network. The framework tested here allows to investigate directly nature and extent of spatial effects in the context of ecosystem dynamics. The notable coherence between spatial and temporal macroecological patterns, theoretically derived and empirically verified, is suggested to underlie general features of the dynamic evolution of ecosystems. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Genome-wide association meta-analysis of circulating odd-numbered chain saturated fatty acids: Results from the CHARGE Consortium

    PubMed Central

    King, Irena B.; Wu, Jason H. Y.; Manichaikul, Ani; Rich, Stephen S.; Tsai, Michael Y.; Chen, Y. D.; Fornage, Myriam; Weihua, Guan; Aslibekyan, Stella; Irvin, Marguerite R.; Kabagambe, Edmond K.; Arnett, Donna K.; Jensen, Majken K.; McKnight, Barbara; Psaty, Bruce M.; Steffen, Lyn M.; Smith, Caren E.; Risérus, Ulf; Lind, Lars; Hu, Frank B.; Rimm, Eric B.; Siscovick, David S.; Mozaffarian, Dariush

    2018-01-01

    Background Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established. Objective To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA. Design We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European descent. We also investigated relationships between specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, associated with adult-onset lactase intolerance, with circulating levels of dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes with C23:0 levels. Results We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10−8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10−9). In contrast, when using a candidate-gene approach, we found evidence that three SNPs in LCT (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 level (adjusted P = 4×10−2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P<5×10−2). Conclusions Our findings suggest that circulating levels of OCSFA may be predominantly influenced by non-genetic factors. SNPs associated with C17:0 level in the LCT gene may reflect

  11. Genetic variation in westslope cutthroat trout Oncorhynchus clarkii lewisi: Implications for conservation

    USGS Publications Warehouse

    Drinan, D.P.; Kalinowski, S.T.; Vu, N.V.; Shepard, B.B.; Muhlfeld, C.C.; Campbell, M.R.

    2011-01-01

    Twenty-five populations of westslope cutthroat trout from throughout their native range were genotyped at 20 microsatellite loci to describe the genetic structure of westslope cutthroat trout. The most genetic diversity (heterozygosity, allelic richness, and private alleles) existed in populations from the Snake River drainage, while populations from the Missouri River drainage had the least. Neighbor-joining trees grouped populations according to major river drainages. A great amount of genetic differentiation was present among and within all drainages. Based on Nei's DS, populations in the Snake River were the most differentiated, while populations in the Missouri River were the least. This pattern of differentiation is consistent with a history of sequential founding events through which westslope cutthroat trout may have experienced a genetic bottleneck as they colonized each river basin from the Snake to the Clark Fork to the Missouri river. These data should serve as a starting point for a discussion on management units and possible distinct population segments. Given the current threats to the persistence of westslope cutthroat trout, and the substantial genetic differentiation between populations, these topics warrant attention. ?? 2011 Springer Science+Business Media B.V.

  12. Can sexual selection theory inform genetic management of captive populations? A review

    PubMed Central

    Chargé, Rémi; Teplitsky, Céline; Sorci, Gabriele; Low, Matthew

    2014-01-01

    Captive breeding for conservation purposes presents a serious practical challenge because several conflicting genetic processes (i.e., inbreeding depression, random genetic drift and genetic adaptation to captivity) need to be managed in concert to maximize captive population persistence and reintroduction success probability. Because current genetic management is often only partly successful in achieving these goals, it has been suggested that management insights may be found in sexual selection theory (in particular, female mate choice). We review the theoretical and empirical literature and consider how female mate choice might influence captive breeding in the context of current genetic guidelines for different sexual selection theories (i.e., direct benefits, good genes, compatible genes, sexy sons). We show that while mate choice shows promise as a tool in captive breeding under certain conditions, for most species, there is currently too little theoretical and empirical evidence to provide any clear guidelines that would guarantee positive fitness outcomes and avoid conflicts with other genetic goals. The application of female mate choice to captive breeding is in its infancy and requires a goal-oriented framework based on the needs of captive species management, so researchers can make honest assessments of the costs and benefits of such an approach, using simulations, model species and captive animal data. PMID:25553072

  13. Predicting Acute and Persistent Neuropathy Associated with Oxaliplatin

    PubMed Central

    Alejandro, Linh; Behrendt, Carolyn E.; Chen, Kim; Openshaw, Harry; Shibata, Stephen

    2014-01-01

    Objectives We sought to predict oxaliplatin-associated peripheral neuropathy during modified FOLFOX6 (mFOLFOX6) therapy. Methods In a 50% female sample, patients with previously untreated, primary or recurrent colorectal cancer were followed through a first course of mFOLFOX6 with oxaliplatin 85 mg/m2 every 2 weeks. Accounting for correlation among a subject's cycles, logistic regression estimated per-cycle risk of acute (under 14 days) and persistent (14 days or more) neuropathy. Proportional hazards regression predicted time to persistent neuropathy. Results Among mFOLFOX6 recipients (n=50, age 58.9 +10.1 years), 36% received concomitant bevacizumab. Of total cycles, 94.2% (422/448) were evaluable. Most (84%) subjects reported neuropathy at least once: 74% reported acute and 48% reported persistent symptoms. On multivariate analysis, risk factors shared by acute and persistent neuropathy were body-surface area >2.0, acute neuropathy in a past cycle, and lower body weight. In addition, risk of acute neuropathy decreased with age (adjusted for renal function and winter season), while risk of persistent neuropathy increased with cumulative dose of oxaliplatin and persistent neuropathy in a past cycle. Concomitant bevacizumab was not a risk factor when administered in Stage IV disease but was associated with persistent neuropathy when administered experimentally in Stage III. Females had no increased risk of either form of neuropathy. After 3 cycles, weight, body-surface area, and prior acute neuropathy predicted time to persistent neuropathy. Conclusions Routinely available clinical factors predict acute and persistent neuropathy associated with oxaliplatin. When validated, the proposed prognostic score for persistent neuropathy can help clinicians counsel patients about chemotherapy. PMID:22547012

  14. The role of viral persistence in flavivirus biology

    PubMed Central

    Mlera, Luwanika; Melik, Wessam; Bloom, Marshall E.

    2014-01-01

    In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. These viruses account for considerable human morbidity and mortality worldwide. Increasing and substantial evidence of viral persistence in humans, which includes the isolation of RNA by RT-PCR and infectious virus by culture, continues to be reported. Viral persistence can also be established in vitro in various human, animal, arachnid and insect cell lines in culture. Although some research has focused on the potential roles of defective virus particles, evasion of the immune response through the manipulation of autophagy and/or apoptosis, the precise mechanism of flavivirus persistence is still not well understood. We propose additional research for further understanding of how viral persistence is established in different systems. Avenues for additional studies include determining if the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence as well as investigating the host responses that allow vector borne flavivirus replication without detrimental effects on infected cells. Such studies might shed more light on the viral-host relationships, and could be used to unravel the mechanisms for establishment of persistence. PMID:24737600

  15. CTEPP OVERVIEW: A PILOT STUDY OF CHILDREN'S TOTAL EXPOSURE TO PERSISTENT PESTICIDES AND OTHER PERSISTENT ORGANIC POLLUTANTS

    EPA Science Inventory

    The research study, "Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants," (CTEPP) is a pilot-scale project involving about 260 children in their everyday surroundings. The objectives of CTEPP are twofold: (1) To measure the agg...

  16. Genetic Modeling of Radiation Injury in Prostate Cancer Patients Treated with Radiotherapy

    DTIC Science & Technology

    2016-10-01

    2/wk OR Occasional transfusion Severe; blood transfusion or surgery OR Persistent; daily OR Frequent transfusions Gross hemorrhage OR...physicians in practice and/or genetic testing laboratories. (Months 24-36) This represents a major goal for the final six months of the project...used to test for the association of each SNP with each toxicity outcome. We also completed data imputation for the genome-wide SNP datasets so that we

  17. In Vivo Persistence of Human Rhinoviruses in Immunosuppressed Patients

    PubMed Central

    Engelmann, Ilka; Dewilde, Anny; Lazrek, Mouna; Batteux, Mathilde; Hamissi, Aminati; Yakoub-Agha, Ibrahim; Hober, Didier

    2017-01-01

    Several species of the genus Enterovirus cause persistent infections in humans. Human rhinovirus (HRV) infections are generally self-limiting but occasionally persistent infections have been described. This study aimed to identify persistent HRV infections and investigate the clinical and virologic characteristics of patients with persistent infections. From January 2012 to March 2015, 3714 respiratory specimens from 2608 patients were tested for respiratory viruses by using a multiplex reverse transcription–polymerase chain reaction. A retrospective study was performed. Patients with at least two specimens positive for HRV/enterovirus taken 45 days or longer apart were identified and the HRV/enteroviruses were typed. Patients with persistent infection were compared to patients with reinfection and patients with cleared infection. Phylogenetic analysis of the viral protein(VP)4/VP2 region was performed. 18 patients with persistent HRV/enterovirus infection were identified. Minimum median duration of persistence was 92 days (range 50–455 days). All but one patients with persistence were immunosuppressed. Immunosuppression and hematologic disorders were more frequent in patients with persistence (n = 18) than in patients with reinfection (n = 33) and with cleared infection (n = 25) (p = 0.003 and p = 0.001, respectively). In conclusion, this retrospective study identified HRV persistence in vivo which occurred mainly in immunosuppressed patients. PMID:28151988

  18. Unraveling the covariation of low self-control and victimization: a behavior genetic approach.

    PubMed

    Boutwell, Brian B; Franklin, Cortney A; Barnes, J C; Tamplin, Amanda K; Beaver, Kevin M; Petkovsek, Melissa

    2013-08-01

    A growing body of literature examining the antecedents of victimization experiences has suggested that personality constructs play a role in the origins of victimization. Low self-control, in particular, represents a trait thought to directly increase the risk of victimization. At the same time, different lines of evidence suggest that genetic factors account for portions of the variance in both self-control and victimization. These findings leave open the possibility that the two traits might covary because of previously unmeasured genetic factors. The current analysis seeks to test this possibility. Additionally, we examine whether the covariation between self-control and victimization persists once genetic effects are held constant. Our findings suggest a nuanced explanation for the relationship between self-control and experiences of victimization. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  19. Genetic continuity across a deeply divergent linguistic contact zone in North Maluku, Indonesia

    PubMed Central

    2011-01-01

    Background The islands of North Maluku, Indonesia occupy a central position in the major prehistoric dispersal streams that shaped the peoples of Island Southeast Asia and the Pacific. Within this region a linguistic contact zone exists where speakers of Papuan and Austronesian languages reside in close proximity. Here we use population genetic data to assess the extent to which North Maluku populations experienced admixture of Asian genetic material, and whether linguistic boundaries reflect genetic differentiation today. Results Autosomal and X-linked markers reveal overall Asian admixture of 67% in North Maluku, demonstrating a substantial contribution of genetic material into the region from Asia. We observe no evidence of population structure associated with ethnicity or language affiliation. Conclusions Our data support a model of widespread Asian admixture in North Maluku, likely mediated by the expansion of Austronesian-speaking peoples into the region during the mid Holocene. In North Maluku there is no genetic differentiation in terms of Austronesian- versus Papuan-speakers, suggesting extensive gene flow across linguistic boundaries. In a regional context, our results illuminate a major genetic divide at the Molucca Sea, between the islands of Sulawesi and North Maluku. West of this divide, populations exhibit predominantly Asian ancestry, with very little contribution of Papuan genetic material. East of the Molucca Sea, populations show diminished rates of Asian admixture and substantial persistence of Papuan genetic diversity. PMID:22098696

  20. Genetic continuity across a deeply divergent linguistic contact zone in North Maluku, Indonesia.

    PubMed

    Wilder, Jason A; Cox, Murray P; Paquette, Andrew M; Alford, Regan; Satyagraha, Ari W; Harahap, Alida; Sudoyo, Herawati

    2011-11-18

    The islands of North Maluku, Indonesia occupy a central position in the major prehistoric dispersal streams that shaped the peoples of Island Southeast Asia and the Pacific. Within this region a linguistic contact zone exists where speakers of Papuan and Austronesian languages reside in close proximity. Here we use population genetic data to assess the extent to which North Maluku populations experienced admixture of Asian genetic material, and whether linguistic boundaries reflect genetic differentiation today. Autosomal and X-linked markers reveal overall Asian admixture of 67% in North Maluku, demonstrating a substantial contribution of genetic material into the region from Asia. We observe no evidence of population structure associated with ethnicity or language affiliation. Our data support a model of widespread Asian admixture in North Maluku, likely mediated by the expansion of Austronesian-speaking peoples into the region during the mid Holocene. In North Maluku there is no genetic differentiation in terms of Austronesian- versus Papuan-speakers, suggesting extensive gene flow across linguistic boundaries. In a regional context, our results illuminate a major genetic divide at the Molucca Sea, between the islands of Sulawesi and North Maluku. West of this divide, populations exhibit predominantly Asian ancestry, with very little contribution of Papuan genetic material. East of the Molucca Sea, populations show diminished rates of Asian admixture and substantial persistence of Papuan genetic diversity.

  1. Differences in Meteorological Conditions between Days with Persistent and Non-Persistent Pollution in Beijing, China

    NASA Astrophysics Data System (ADS)

    You, Ting; Wu, Renguang; Huang, Gang

    2018-02-01

    We compared the regional synoptic patterns and local meteorological conditions during persistent and non-persistent pollution events in Beijing using US NCEP-Department of Energy reanalysis outputs and observations from meteorological stations. The analysis focused on the impacts of high-frequency (period < 90 days) variations in meteorological conditions on persistent pollution events (those lasting for at least 3 days). Persistent pollution events tended to occur in association with slow-moving weather systems producing stagnant weather conditions, whereas rapidly moving weather systems caused a dramatic change in the local weather conditions so that the pollution event was short-lived. Although Beijing was under the influence of anomalous southerly winds in all four seasons during pollution events, notable differences were identified in the regional patterns of sea-level pressure and local anomalies in relative humidity among persistent pollution events in different seasons. A region of lower pressure was present to the north of Beijing in spring, fall, and winter, whereas regions of lower and higher pressures were observed northwest and southeast of Beijing, respectively, in summer. The relative humidity near Beijing was higher in fall and winter, but lower in spring and summer. These differences may explain the seasonal dependence of the relationship between air pollution and the local meteorological variables. Our analysis showed that the temperature inversion in the lower troposphere played an important part in the occurrence of air pollution under stagnant weather conditions. Some results from this study are based on a limited number of events and thus require validation using more data.

  2. Measuring persistence: A literature review focusing on methodological issues

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wolfe, A.K.; Brown, M.A.; Trumble, D.

    1995-03-01

    This literature review was conducted as part of a larger project to produce a handbook on the measurement of persistence. The past decade has marked the development of the concept of persistence and a growing recognition that the long-term impacts of demand-side management (DSM) programs warrant careful assessment. Although Increasing attention has been paid to the topic of persistence, no clear consensus has emerged either about its definition or about the methods most appropriate for its measurement and analysis. This project strives to fill that gap by reviewing the goals, terminology, and methods of past persistence studies. It was conductedmore » from the perspective of a utility that seeks to acquire demand-side resources and is interested in their long-term durability; it was not conducted from the perspective of the individual consumer. Over 30 persistence studies, articles, and protocols were examined for this report. The review begins by discussing the underpinnings of persistence studies: namely, the definitions of persistence and the purposes of persistence studies. Then. it describes issues relevant to both the collection and analysis of data on the persistence of energy and demand savings. Findings from persistence studies also are summarized. Throughout the review, four studies are used repeatedly to illustrate different methodological and analytical approaches to persistence so that readers can track the data collection. data analysis, and findings of a set of comprehensive studies that represent alternative approaches.« less

  3. DNA-crosslinker cisplatin eradicates bacterial persister cells.

    PubMed

    Chowdhury, Nityananda; Wood, Thammajun L; Martínez-Vázquez, Mariano; García-Contreras, Rodolfo; Wood, Thomas K

    2016-09-01

    For all bacteria, nearly every antimicrobial fails since a subpopulation of the bacteria enter a dormant state known as persistence, in which the antimicrobials are rendered ineffective due to the lack of metabolism. This tolerance to antibiotics makes microbial infections the leading cause of death worldwide and makes treating chronic infections, including those of wounds problematic. Here, we show that the FDA-approved anti-cancer drug cisplatin [cis-diamminodichloroplatinum(II)], which mainly forms intra-strand DNA crosslinks, eradicates Escherichia coli K-12 persister cells through a growth-independent mechanism. Additionally, cisplatin is more effective at killing Pseudomonas aeruginosa persister cells than mitomycin C, which forms inter-strand DNA crosslinks, and cisplatin eradicates the persister cells of several pathogens including enterohemorrhagic E. coli, Staphylococcus aureus, and P. aeruginosa. Cisplatin was also highly effective against clinical isolates of S. aureus and P. aeruginosa. Therefore, cisplatin has broad spectrum activity against persister cells. Biotechnol. Bioeng. 2016;113: 1984-1992. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Analysis of a SNP Linked to Lactase Persistence: An Exercise for Teaching Molecular Biology Techniques to Undergraduates

    ERIC Educational Resources Information Center

    Schultheis, Patrick J.; Bowling, Bethany V.

    2011-01-01

    Recent experimental evidence indicates that the ability of adults to tolerate milk, cheese, and other lactose-containing dairy products is an autosomal dominant trait that co-evolved with dairy farming in Central Europe about 7,500 years ago. Among persons of European descent, this trait is strongly associated with a C to T substitution at a…

  5. Elevational patterns of genetic variation in the cosmopolitan moss Bryum argenteum (Bryaceae).

    PubMed

    Pisa, Sergio; Werner, Olaf; Vanderpoorten, Alain; Magdy, Mahmoud; Ros, Rosa M

    2013-10-01

    The Baas Becking tenet posits that 'everything is everywhere, but the environment selects' to explain cosmopolitan distributions in highly vagile taxa. Bryophyte species show wider distributions than vascular plants and include examples of truly cosmopolitan ranges, which have been interpreted as a result of high dispersal capacities and ecological plasticity. In the current study, we documented patterns of genetic structure and diversity in the cosmopolitan moss Bryum argenteum along an elevational gradient to determine if genetic diversity and structure is homogenized by intense migrations in the lack of ecological differentiation. • 60 specimens were collected in the Sierra Nevada Mountains (Spain) between 100 and 2870 m and sequenced for ITS and rps4. Comparative analyses, genetic diversity estimators, and Mantel's tests were employed to determine the relationship between genetic variation, elevation, and geographic distance and to look for signs of demographic shifts. • Genetic diversity peaked above 1900 m and no signs of demographic shifts were detected at any elevation. There was a strong phylogenetic component in elevational variation. Genetic variation was significantly correlated with elevation, but not with geographic distance. • The results point to the long-term persistence of Bryum argenteum in a range that was glaciated during the Late Pleistocene. Evidence for an environmentally driven pattern of genetic differentiation suggests adaptive divergence. This supports the Baas Becking tenet and indicates that ecological specialization might play a key role in explaining patterns of genetic structure in cosmopolitan mosses.

  6. Fundamental bound on the persistence and capacity of short-term memory stored as graded persistent activity.

    PubMed

    Koyluoglu, Onur Ozan; Pertzov, Yoni; Manohar, Sanjay; Husain, Masud; Fiete, Ila R

    2017-09-07

    It is widely believed that persistent neural activity underlies short-term memory. Yet, as we show, the degradation of information stored directly in such networks behaves differently from human short-term memory performance. We build a more general framework where memory is viewed as a problem of passing information through noisy channels whose degradation characteristics resemble those of persistent activity networks. If the brain first encoded the information appropriately before passing the information into such networks, the information can be stored substantially more faithfully. Within this framework, we derive a fundamental lower-bound on recall precision, which declines with storage duration and number of stored items. We show that human performance, though inconsistent with models involving direct (uncoded) storage in persistent activity networks, can be well-fit by the theoretical bound. This finding is consistent with the view that if the brain stores information in patterns of persistent activity, it might use codes that minimize the effects of noise, motivating the search for such codes in the brain.

  7. Fundamental bound on the persistence and capacity of short-term memory stored as graded persistent activity

    PubMed Central

    Pertzov, Yoni; Manohar, Sanjay; Husain, Masud; Fiete, Ila R

    2017-01-01

    It is widely believed that persistent neural activity underlies short-term memory. Yet, as we show, the degradation of information stored directly in such networks behaves differently from human short-term memory performance. We build a more general framework where memory is viewed as a problem of passing information through noisy channels whose degradation characteristics resemble those of persistent activity networks. If the brain first encoded the information appropriately before passing the information into such networks, the information can be stored substantially more faithfully. Within this framework, we derive a fundamental lower-bound on recall precision, which declines with storage duration and number of stored items. We show that human performance, though inconsistent with models involving direct (uncoded) storage in persistent activity networks, can be well-fit by the theoretical bound. This finding is consistent with the view that if the brain stores information in patterns of persistent activity, it might use codes that minimize the effects of noise, motivating the search for such codes in the brain. PMID:28879851

  8. Lactose malabsorption and intolerance: What should be the best clinical management?

    PubMed

    Usai-Satta, Paolo; Scarpa, Mariella; Oppia, Francesco; Cabras, Francesco

    2012-06-06

    Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase deficiency, which may occur as a primary disorder or secondary to other intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive condition resulting from the physiological decline of lactase activity. Different methods have been used to diagnose LM. Lactose breath test represents the most reliable technique. A recent consensus conference has proposed the more physiological dosage of 25 g of lactose and a standardized procedure for breath testing. Recently a new genetic test, based on C/T13910 polymorphism, has been proposed for the diagnosis of adult-type hypolactasia, complementing the role of breath testing. LM represents a well-known cause of abdominal symptoms although only some lactose malabsorbers are also intolerants. Diagnosing lactose intolerance is not straightforward. Many non-malabsorber subjects diagnose themselves as being lactose intolerant. Blind lactose challenge studies should be recommended to obtain objective results. Besides several studies indicate that subjects with lactose intolerance can ingest up to 15 g of lactose with no or minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted diet avoiding the nutritional disadvantages of reduced calcium and vitamin intake.Various pharmacological options are also available. Unfortunately there is insufficient evidence that these therapies are effective. Further double-blind studies are needed to demonstrate treatment effectiveness in lactose intolerance.

  9. Lactose malabsorption and intolerance: What should be the best clinical management?

    PubMed Central

    Usai-Satta, Paolo; Scarpa, Mariella; Oppia, Francesco; Cabras, Francesco

    2012-01-01

    Lactose malabsorption (LM) is the incomplete hydrolysis of lactose due to lactase deficiency, which may occur as a primary disorder or secondary to other intestinal diseases. Primary adult-type hypolactasia is an autosomal recessive condition resulting from the physiological decline of lactase activity. Different methods have been used to diagnose LM. Lactose breath test represents the most reliable technique. A recent consensus conference has proposed the more physiological dosage of 25 g of lactose and a standardized procedure for breath testing. Recently a new genetic test, based on C/T13910 polymorphism, has been proposed for the diagnosis of adult-type hypolactasia, complementing the role of breath testing. LM represents a well-known cause of abdominal symptoms although only some lactose malabsorbers are also intolerants. Diagnosing lactose intolerance is not straightforward. Many non-malabsorber subjects diagnose themselves as being lactose intolerant. Blind lactose challenge studies should be recommended to obtain objective results. Besides several studies indicate that subjects with lactose intolerance can ingest up to 15 g of lactose with no or minor symptoms. Therefore a therapeutic strategy consists of a lactose restricted diet avoiding the nutritional disadvantages of reduced calcium and vitamin intake.Various pharmacological options are also available. Unfortunately there is insufficient evidence that these therapies are effective. Further double-blind studies are needed to demonstrate treatment effectiveness in lactose intolerance. PMID:22966480

  10. Genetic diversity of symbiotic Bradyrhizobium elkanii populations recovered from inoculated and non-inoculated Acacia mangium field trials in Brazil.

    PubMed

    Perrineau, M M; Le Roux, C; de Faria, S M; de Carvalho Balieiro, F; Galiana, A; Prin, Y; Béna, G

    2011-07-01

    Acacia mangium is a legume tree native to Australasia. Since the eighties, it has been introduced into many tropical countries, especially in a context of industrial plantations. Many field trials have been set up to test the effects of controlled inoculation with selected symbiotic bacteria versus natural colonization with indigenous strains. In the introduction areas, A. mangium trees spontaneously nodulate with local and often ineffective bacteria. When inoculated, the persistence of inoculants and possible genetic recombination with local strains remain to be explored. The aim of this study was to describe the genetic diversity of bacteria spontaneously nodulating A. mangium in Brazil and to evaluate the persistence of selected strains used as inoculants. Three different sites, several hundred kilometers apart, were studied, with inoculated and non-inoculated plots in two of them. Seventy-nine strains were isolated from nodules and sequenced on three housekeeping genes (glnII, dnaK and recA) and one symbiotic gene (nodA). All but one of the strains belonged to the Bradyrhizobium elkanii species. A single case of housekeeping gene transfer was detected among the 79 strains, suggesting an extremely low rate of recombination within B. elkanii, whereas the nodulation gene nodA was found to be frequently transferred. The fate of the inoculant strains varied depending on the site, with a complete disappearance in one case, and persistence in another. We compared our results with the sister species Bradyrhizobium japonicum, both in terms of population genetics and inoculant strain destiny. Copyright © 2011 Elsevier GmbH. All rights reserved.

  11. Seed bank dynamics govern persistence of Brassica hybrids in crop and natural habitats.

    PubMed

    Hooftman, Danny A P; Bullock, James M; Morley, Kathryn; Lamb, Caroline; Hodgson, David J; Bell, Philippa; Thomas, Jane; Hails, Rosemary S

    2015-01-01

    Gene flow from crops to their wild relatives has the potential to alter population growth rates and demography of hybrid populations, especially when a new crop has been genetically modified (GM). This study introduces a comprehensive approach to assess this potential for altered population fitness, and uses a combination of demographic data in two habitat types and mathematical (matrix) models that include crop rotations and outcrossing between parental species. Full life-cycle demographic rates, including seed bank survival, of non-GM Brassica rapa × B. napus F1 hybrids and their parent species were estimated from experiments in both agricultural and semi-natural habitats. Altered fitness potential was modelled using periodic matrices including crop rotations and outcrossing between parent species. The demographic vital rates (i.e. for major stage transitions) of the hybrid population were intermediate between or lower than both parental species. The population growth rate (λ) of hybrids indicated decreases in both habitat types, and in a semi-natural habitat hybrids became extinct at two sites. Elasticity analyses indicated that seed bank survival was the greatest contributor to λ. In agricultural habitats, hybrid populations were projected to decline, but with persistence times up to 20 years. The seed bank survival rate was the main driver determining persistence. It was found that λ of the hybrids was largely determined by parental seed bank survival and subsequent replenishment of the hybrid population through outcrossing of B. rapa with B. napus. Hybrid persistence was found to be highly dependent on the seed bank, suggesting that targeting hybrid seed survival could be an important management option in controlling hybrid persistence. For local risk mitigation, an increased focus on the wild parent is suggested. Management actions, such as control of B. rapa, could indirectly reduce hybrid populations by blocking hybrid replenishment. © The Author

  12. Herbicide Persistence in Seawater Simulation Experiments

    PubMed Central

    Mercurio, Philip; Mueller, Jochen F.; Eaglesham, Geoff; Flores, Florita; Negri, Andrew P.

    2015-01-01

    Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR). The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities). Very little degradation was recorded over the standard 60 d period (Experiment 1) so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated flood plumes

  13. Herbicide Persistence in Seawater Simulation Experiments.

    PubMed

    Mercurio, Philip; Mueller, Jochen F; Eaglesham, Geoff; Flores, Florita; Negri, Andrew P

    2015-01-01

    Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR). The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities). Very little degradation was recorded over the standard 60 d period (Experiment 1) so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated flood plumes

  14. Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy

    PubMed Central

    Nishizawa, Masako; Matsuda, Masakazu; Hattori, Junko; Shiino, Teiichiro; Matano, Tetsuro; Heneine, Walid; Johnson, Jeffrey A.; Sugiura, Wataru

    2015-01-01

    Background Drug-resistant HIV are more prevalent and persist longer than previously demonstrated by bulk sequencing due to the ability to detect low-frequency variants. To clarify a clinical benefit to monitoring minority-level drug resistance populations as a guide to select active drugs for salvage therapy, we retrospectively analyzed the dynamics of low-frequency drug-resistant population in antiretroviral (ARV)-exposed drug resistant individuals. Materials and Methods Six HIV-infected individuals treated with ARV for more than five years were analyzed. These individuals had difficulty in controlling viremia, and treatment regimens were switched multiple times guided by standard drug resistance testing using bulk sequencing. To detect minority variant populations with drug resistance, we used a highly sensitive allele-specific PCR (AS-PCR) with detection thresholds of 0.3–2%. According to ARV used in these individuals, we focused on the following seven reverse transcriptase inhibitor-resistant mutations: M41L, K65R, K70R, K103N, Y181C, M184V, and T215F/Y. Results of AS-PCR were compared with bulk sequencing data for concordance and presence of additional mutations. To clarify the genetic relationship between low-frequency and high-frequency populations, AS-PCR amplicon sequences were compared with bulk sequences in phylogenetic analysis. Results The use of AS-PCR enabled detection of the drug-resistant mutations, M41L, K103N, Y181C, M184V and T215Y, present as low-frequency populations in five of the six individuals. These drug resistant variants persisted for several years without ARV pressure. Phylogenetic analysis indicated that pre-existing K103N and T215I variants had close genetic relationships with high-frequency K103N and T215I observed during treatment. Discussion and Conclusion Our results demonstrate the long-term persistence of drug-resistant viruses in the absence of drug pressure. The rapid virologic failures with pre-existing mutant viruses

  15. Genome Sequencing Identifies Two Nearly Unchanged Strains of Persistent Listeria monocytogenes Isolated at Two Different Fish Processing Plants Sampled 6 Years Apart

    PubMed Central

    Holch, Anne; Webb, Kristen; Lukjancenko, Oksana; Ussery, David; Rosenthal, Benjamin M.

    2013-01-01

    phenotype, the remarkable similarity between the two strains indicates that subtypes with specific traits are selected for in the food processing environment and that particular genetic and physiological factors are responsible for the persistent phenotype. PMID:23435887

  16. Characterization and Transcriptome Analysis of Acinetobacter baumannii Persister Cells.

    PubMed

    Alkasir, Rashad; Ma, Yanan; Liu, Fei; Li, Jing; Lv, Na; Xue, Yong; Hu, Yongfei; Zhu, Baoli

    2018-06-14

    Acinetobacter baumannii is a nonfermenting Gram-negative bacillus. A. baumannii resistance is a significant obstacle to clinical infection treatment. The existence of persister cells (persisters) might represent the reason for therapy failure and relapse, and such cells may be the driving force behind rising resistance rates. In this study, A. baumannii ATCC 19606 was used as a target to explore the essential features of A. baumannii persisters. Antibiotic treatment of A. baumannii cultures at 50-fold the minimum inhibitory concentration resulted in a distinct plateau of surviving drug-tolerant persisters. The sensitive bacteria were lysed with ceftazidime, and the nonreplicating bacteria were isolated for transcriptome analysis using RNA sequencing. We analyzed the transcriptome of A. baumannii persisters and identified significantly differentially expressed genes, as well as their enriched pathways. The results showed that both the GP49 (HigB)/Cro (HigA) and DUF1044/RelB toxin/antitoxin systems were significantly increased during the persister incubation period. In addition, the activities of certain metabolic pathways (such as electron transport, adenosine triphosphate [ATP], and the citrate cycle) decreased sharply after antibiotic treatment and remained low during the persister period, while aromatic compound degradation genes were only upregulated in persisters. These results suggest the involvement of aromatic compound degradation genes in persister formation and maintenance. They further provide the first insight into the mechanism of persister formation in A. baumannii.

  17. The comparative phylogeography of east coast estuarine fishes in formerly glaciated sites: Persistence versus recolonization in Cyprinodon variegatus ovinus and Fundulus heteroclitus macrolepidotus.

    PubMed

    Haney, Robert A; Dionne, Michelle; Puritz, Jon; Rand, David M

    2009-01-01

    Species distributions may be dramatically affected by climatic variability, such as occurred during Pleistocene glaciation. Populations of coastal organisms could have been affected directly by ice movement or through sea level change. Response could involve shifts in distribution southwards or persistence through the full range or in limited high-latitude refugia. Comparative studies of the response of ecologically similar species can provide a useful complement to those examining response across disparate species in defining what parameters influence persistence. Patterns of mitochondrial genetic variation in 2 estuarine fish subspecies from the Northwest Atlantic, Fundulus heteroclitus macrolepidotus and Cyprinodon variegatus ovinus, indicate that ecological similarity does not necessarily predict propensity for glacial persistence. Fundulus heteroclitus macrolepidotus is highly diverse in glaciated regions, with isolated populations whose origins predate the last glacial maximum and may have recently expanded it's range to the south from New England. However, within glaciated regions, signals of population growth and distributional shifts indicate a dynamic Pleistocene history for F. h. macrolepidotus, in contrast with recent studies involving microsatellites. A different pattern is found in C. v. ovinus, which is depauperate in formerly glaciated sites, with a clear signal of recent recolonization of glaciated regions from the south. Genetic differentiation in glaciated areas is consistent with isolation after glacial withdrawal. In C. v. ovinus, rapidly evolving microsatellite loci show a similar pattern to mitochondrial DNA but may be reaching equilibrium on small spatial scales. These contrasting patterns of variation illustrate how ecologically similar species can respond to large-scale environmental change in distinct ways.

  18. Rhinophototherapy in persistent allergic rhinitis.

    PubMed

    Bella, Zsolt; Kiricsi, Ágnes; Viharosné, Éva Dósa-Rácz; Dallos, Attila; Perényi, Ádám; Kiss, Mária; Koreck, Andrea; Kemény, Lajos; Jóri, József; Rovó, László; Kadocsa, Edit

    2017-03-01

    Previous published results have revealed that Rhinolight ® intranasal phototherapy is safe and effective in intermittent allergic rhinitis. The present objective was to assess whether phototherapy is also safe and effective in persistent allergic rhinitis. Thirty-four patients with persistent allergic rhinitis were randomized into two groups; twenty-five subjects completed the study. The Rhinolight ® group was treated with a combination of UV-B, UV-A, and high-intensity visible light, while the placebo group received low-intensity visible white light intranasal phototherapy on a total of 13 occasions in 6 weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak flow, quantitative smell threshold, mucociliary transport function, and ICAM-1 expression of the epithelial cells. All nasal symptom scores and nasal inspiratory peak flow measurements improved significantly in the Rhinolight ® group relative to the placebo group and this finding persisted after 4 weeks of follow-up. The smell and mucociliary functions did not change significantly in either group. The number of ICAM-1 positive cells decreased non-significantly in the Rhinolight ® group. No severe side-effects were reported during the treatment period. These results suggest that Rhinolight ® treatment is safe and effective in persistent allergic rhinitis.

  19. Persistent depressive disorder

    MedlinePlus

    ... But, symptoms are not as severe as with major depression . Persistent depressive disorder used to be called dysthymia. ... with PDD will also have an episode of major depression at some point in their lives. Older people ...

  20. Survival and persistence of fecal host-specific Bacteroidales cells and their DNA assessed by PMA-qPCR

    NASA Astrophysics Data System (ADS)

    Bae, S.; Bombardelli, F.; Wuertz, S.

    2008-12-01

    Understanding and managing microbial pollutions in water is one of the foremost challenges of establishing effective managements and remediation strategies to impaired water bodies polluted by uncharacterized fecal sources. Quantitative microbial source tracking (MST) approaches using fecal Bacteroidales and quantitative PCR (qPCR) assays to measure gene copies of host-specific 16S rRNA genetic markers are promising because they can allow for identifying and quantifying fecal loadings from a particular animal host and understanding the fate and transport of host-specific Bacteroidales over a range of conditions in water bodies. Similar to the case of traditional fecal indicator bacteria, a relatively long persistence of target DNA may hamper applied MST studies, if genetic markers cannot be linked to recent fecal pollution in water. We report a successful approach to removing the qPCR signal derived from free DNA and dead host-specific Bacteroidales cells by selectively binding the DNA and consequently inhibiting PCR amplification using light- activated propidium monoazide (PMA). Optimal PMA-qPCR conditions were determined as 100 µM of PMA concentration and a 10-min light exposure time at different solids concentrations in order to mimic a range of water samples. Under these conditions, PMA-qPCR resulted in the selective exclusion of DNA from heat- treated cells of non-culturable Bacteroidales in human feces and wastewater influent and effluent samples. Also, the persistence of feces-derived host-specific Bacteroidales DNA and their cells (determined by universal, human-, cow- and dog-specific Bacteroidales qPCR assays) in seawater was investigated in microcosms at environmental conditions. The average T99 (two log reduction) value for host-specific viable Bacteroidales cells was 28 h, whereas that for total host-specific Bacteroidales DNA was 177 h. Natural sunlight did not have a strong influence on the fate of fecal Bacteroidales cells and their DNA, presumably

  1. Smoking and caffeine consumption: a genetic analysis of their association.

    PubMed

    Treur, Jorien L; Taylor, Amy E; Ware, Jennifer J; Nivard, Michel G; Neale, Michael C; McMahon, George; Hottenga, Jouke-Jan; Baselmans, Bart M L; Boomsma, Dorret I; Munafò, Marcus R; Vink, Jacqueline M

    2017-07-01

    Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta-analyses of genome-wide association studies on smoking and caffeine, the genetic correlation was calculated by LD-score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. © 2016 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  2. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Dudley, Mark E.; Carpenter, Robert O.; Kassim, Sadik H.; Rose, Jeremy J.; Telford, William G.; Hakim, Frances T.; Halverson, David C.; Fowler, Daniel H.; Hardy, Nancy M.; Mato, Anthony R.; Hickstein, Dennis D.; Gea-Banacloche, Juan C.; Pavletic, Steven Z.; Sportes, Claude; Maric, Irina; Feldman, Steven A.; Hansen, Brenna G.; Wilder, Jennifer S.; Blacklock-Schuver, Bazetta; Jena, Bipulendu; Bishop, Michael R.; Gress, Ronald E.; Rosenberg, Steven A.

    2013-01-01

    New treatments are needed for B-cell malignancies persisting after allogeneic hematopoietic stem cell transplantation (alloHSCT). We conducted a clinical trial of allogeneic T cells genetically modified to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. T cells for genetic modification were obtained from each patient’s alloHSCT donor. All patients had malignancy that persisted after alloHSCT and standard donor lymphocyte infusions (DLIs). Patients did not receive chemotherapy prior to the CAR T-cell infusions and were not lymphocyte depleted at the time of the infusions. The 10 treated patients received a single infusion of allogeneic anti-CD19-CAR T cells. Three patients had regressions of their malignancies. One patient with chronic lymphocytic leukemia (CLL) obtained an ongoing complete remission after treatment with allogeneic anti-CD19-CAR T cells, another CLL patient had tumor lysis syndrome as his leukemia dramatically regressed, and a patient with mantle cell lymphoma obtained an ongoing partial remission. None of the 10 patients developed graft-versus-host disease (GVHD). Toxicities included transient hypotension and fever. We detected cells containing the anti-CD19-CAR gene in the blood of 8 of 10 patients. These results show for the first time that donor-derived allogeneic anti-CD19-CAR T cells can cause regression of B-cell malignancies resistant to standard DLIs without causing GVHD. This trial was registered at www.clinicaltrials.gov as #NCT01087294. PMID:24055823

  3. Genetic architecture and balancing selection: the life and death of differentiated variants.

    PubMed

    Llaurens, Violaine; Whibley, Annabel; Joron, Mathieu

    2017-05-01

    Balancing selection describes any form of natural selection, which results in the persistence of multiple variants of a trait at intermediate frequencies within populations. By offering up a snapshot of multiple co-occurring functional variants and their interactions, systems under balancing selection can reveal the evolutionary mechanisms favouring the emergence and persistence of adaptive variation in natural populations. We here focus on the mechanisms by which several functional variants for a given trait can arise, a process typically requiring multiple epistatic mutations. We highlight how balancing selection can favour specific features in the genetic architecture and review the evolutionary and molecular mechanisms shaping this architecture. First, balancing selection affects the number of loci underlying differentiated traits and their respective effects. Control by one or few loci favours the persistence of differentiated functional variants by limiting intergenic recombination, or its impact, and may sometimes lead to the evolution of supergenes. Chromosomal rearrangements, particularly inversions, preventing adaptive combinations from being dissociated are increasingly being noted as features of such systems. Similarly, due to the frequency of heterozygotes maintained by balancing selection, dominance may be a key property of adaptive variants. High heterozygosity and limited recombination also influence associated genetic load, as linked recessive deleterious mutations may be sheltered. The capture of deleterious elements in a locus under balancing selection may reinforce polymorphism by further promoting heterozygotes. Finally, according to recent genomewide scans, balanced polymorphism might be more pervasive than generally thought. We stress the need for both functional and ecological studies to characterize the evolutionary mechanisms operating in these systems. © 2017 John Wiley & Sons Ltd.

  4. Short communication: Effect of active food packaging materials on fluid milk quality and shelf life.

    PubMed

    Wong, Dana E; Goddard, Julie M

    2014-01-01

    Active packaging, in which active agents are embedded into or on the surface of food packaging materials, can enhance the nutritive value, economics, and stability of food, as well as enable in-package processing. In one embodiment of active food packaging, lactase was covalently immobilized onto packaging films for in-package lactose hydrolysis. In prior work, lactase was covalently bound to low-density polyethylene using polyethyleneimine and glutaraldehyde cross-linkers to form the packaging film. Because of the potential contaminants of proteases, lipases, and spoilage organisms in typical enzyme preparations, the goal of the current work was to determine the effect of immobilized-lactase active packaging technology on unanticipated side effects, such as shortened shelf-life and reduced product quality. Results suggested no evidence of lipase or protease activity on the active packaging films, indicating that such active packaging films could enable in-package lactose hydrolysis without adversely affecting product quality in terms of dairy protein or lipid stability. Storage stability studies indicated that lactase did not migrate from the film over a 49-d period, and that dry storage resulted in 13.41% retained activity, whereas wet storage conditions enabled retention of 62.52% activity. Results of a standard plate count indicated that the film modification reagents introduced minor microbial contamination; however, the microbial population remained under the 20,000 cfu/mL limit through the manufacturer's suggested 14-d storage period for all film samples. This suggests that commercially produced immobilized lactase active packaging should use purified cross-linkers and enzymes. Characterization of unanticipated effects of active packaging on food quality reported here is important in demonstrating the commercial potential of such technologies. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Persistence in the WFC3 IR Detector: Intrinsic Variability

    NASA Astrophysics Data System (ADS)

    Long, Knox S.; Baggett, Sylvia M.

    2018-03-01

    When the WFC3 IR detector is exposed to a bright source or sources, the sources can appear as afterimages in subsequent exposures, a phenomenon known as persistence. This can affect the science obtained with the IR channel. We have been involved in an effort to predict the brightness of the afterimages so that users can (at a minimum) flag the affected pixels and remove them from their analysis or (even better) subtract the afterimages from their science images to salvage the data. The ability of any model to remove afterimages depends on the degree to which persistence is the same for identical sets of exposures. We investigate possible time variability of persistence in the WFC3 detector using sets of (almost) identical visits comprised of single exposures of Omega Cen followed by a series of darks in which persistence is measured. We analyze 8 data sets, each consisting of two or three identical visits, with stimulus exposures between 49 and 1199 s, and find clear evidence of variability in several of the datasets in darks taken within 1000 s of the stimulus exposure. In most of the datasets, the difference in persistence for saturated pixels in the stimulus exposure is < 0.01 e-/s for darks taken 1000 s after the initial exposure. One of three 274-second visits has significantly more persistence than its two identical visits. Persistence in this visit was higher in all 4 detector quadrants. The persistence in all three visits is well modeled as a power law decay; the visit with higher persistence has a higher power law amplitude. There was nothing unusual about the observing conditions preceding and during each of these visits that can explain the discrepancy in persistence levels. Variation in persistence implies that: (1) Unless and until the source of the variability is understood, any persistence model for the WFC3 array will be limited in its ability to predict persistence in a single observation, and, (2) as a consequence, users should always carefully

  6. Sequence-Dependent Persistence Length of Long DNA

    NASA Astrophysics Data System (ADS)

    Chuang, Hui-Min; Reifenberger, Jeffrey G.; Cao, Han; Dorfman, Kevin D.

    2017-12-01

    Using a high-throughput genome-mapping approach, we obtained circa 50 million measurements of the extension of internal human DNA segments in a 41 nm ×41 nm nanochannel. The underlying DNA sequences, obtained by mapping to the reference human genome, are 2.5-393 kilobase pairs long and contain percent GC contents between 32.5% and 60%. Using Odijk's theory for a channel-confined wormlike chain, these data reveal that the DNA persistence length increases by almost 20% as the percent GC content increases. The increased persistence length is rationalized by a model, containing no adjustable parameters, that treats the DNA as a statistical terpolymer with a sequence-dependent intrinsic persistence length and a sequence-independent electrostatic persistence length.

  7. Persistence with treatment for hypertension in actual practice

    PubMed Central

    Caro, J J; Salas, M; Speckman, J L; Raggio, G; Jackson, J D

    1999-01-01

    BACKGROUND: Despite the existence of efficacious medications, many patients in actual practice remain with uncontrolled hypertension. Randomized clinical trials, cannot address this issue well given their highly restricted environment. This paper examines persistence with antihypertensive therapy among patients in actual practice. METHODS: Cohort study of patients who received a diagnosis of hypertension and were treated between 1989 and 1994 identified through the Saskatchewan Health databases. Patients with concurrent diagnoses likely to affect initial treatment choice were excluded. The resulting population of 79,591 subjects was grouped into those with established hypertension (52,227 [66%]) and those with newly diagnosed hypertension (27,364 [34%]). The initial antihypertensive prescription, subsequent changes in treatment and persistence with antihypertensive therapy were analysed. RESULTS: Persistence with antihypertensive therapy decreased in the first 6 months after treatment was started and continued to decline over the next 4 years. Of the patients with newly diagnosed hypertension, only 78% persisted with therapy at the end of 1 year, as compared with 97% of the patients with established hypertension (p < 0.001). Among those with newly diagnosed hypertension, older patients were more likely than younger ones to persist, and women were more likely than men to persist (p < 0.001). INTERPRETATION: This analysis of actual practice data indicates that barriers to persistence occur early in the therapeutic course and that achieving successful therapy when treatment is started is important to maintaining long-term persistence. PMID:9934341

  8. Genomic and Biological Characterization of Aggressive and Docile Strains of LCMV Rescued from a Plasmid-Based Reverse Genetics System

    PubMed Central

    Chen, Minjie; Lan, Shuiyun; Ou, Rong; Price, Graeme E.; Jiang, Hong; de la Torre, Juan Carlos; Moskophidis, Demetrius

    2008-01-01

    Arenaviruses include several causative agents of hemorrhagic fever disease in humans. In addition, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a superb model for the study of virus-host interactions, including the basis of viral persistence and associated diseases. The molecular mechanisms concerning the regulation and specific role of viral proteins in modulating arenavirus-host cell interactions associated either with an acute or persistent infection and associated disease remain little understood. Here we report the genomic and biological characterization of LCMV strains Docile (persistent) and Aggressive (not persistent) recovered from cloned cDNA via reverse genetics. Our results confirmed that the cloned viruses accurately recreated the in vivo phenotypes associated with the corresponding natural Docile and Aggressive viral isolates. In addition, we provide evidence that the ability of the Docile strain to persist is determined by the nature of both S and L RNA segments. Thus, our findings provide the foundation for studies aimed at gaining a detailed understanding of viral determinants of LCMV persistence in its natural host that may aid in the development of vaccines to prevent or treat the diseases caused by arenaviruses in humans. PMID:18474558

  9. Persistent agents in Axelrod's social dynamics model

    NASA Astrophysics Data System (ADS)

    Reia, Sandro M.; Neves, Ubiraci P. C.

    2016-01-01

    Axelrod's model of social dynamics has been studied under the effect of external media. Here we study the formation of cultural domains in the model by introducing persistent agents. These are agents whose cultural traits are not allowed to change but may be spread through local neighborhood. In the absence of persistent agents, the system is known to present a transition from a monocultural to a multicultural regime at some critical Q (number of traits). Our results reveal a dependence of critical Q on the occupation probability p of persistent agents and we obtain the phase diagram of the model in the (p,Q) -plane. The critical locus is explained by the competition of two opposite forces named here barrier and bonding effects. Such forces are verified to be caused by non-persistent agents which adhere (adherent agents) to the set of traits of persistent ones. The adherence (concentration of adherent agents) as a function of p is found to decay for constant Q. Furthermore, adherence as a function of Q is found to decay as a power law with constant p.

  10. Long Persistent Light Emitting Diode Indicators

    ERIC Educational Resources Information Center

    Jia, Dongdong; Ma, Yiwei; Hunter, D. N.

    2007-01-01

    An undergraduate laboratory was designed for undergraduate students to make long persistent light emitting diode (LED) indicators using phosphors. Blue LEDs, which emit at 465 nm, were characterized and used as an excitation source. Long persistent phosphors, SrAl[subscript 2]O[subscript 4]:Eu[superscript 2+],Dy[superscript 3+] (green) and…

  11. Cutaneous human papillomaviruses persist on healthy skin.

    PubMed

    Hazard, Kristina; Karlsson, Anna; Andersson, Kristin; Ekberg, Henrik; Dillner, Joakim; Forslund, Ola

    2007-01-01

    Cutaneous human papillomaviruses (HPVs) are frequently found in healthy skin and have also been implicated in non-melanoma skin cancer. For genital HPV types, a persistent infection with one of the high-risk types is a prerequisite for the development of cervical cancer. However, there is only limited data on whether infections with cutaneous HPV types persist over time. Serial forehead swab samples collected from 63 volunteers (42 healthy individuals and 31 renal transplant recipients (RTRs)), sampled 6.3 years (range: 5.0-7.0 years) apart, were analyzed for HPV using general primer PCR, cloning, and sequencing. Among the healthy individuals, the prevalences of HPV were 69% (29/42) at enrolment and 71% (30/42) at follow-up. Among the individuals positive at baseline, 48% (14/29) had a persistent infection. Among the RTRs, 71% (15/21) were positive for HPV at enrolment and 90% (19/21) at follow-up. A persistent infection was detected in 33% (5/15). In total, HPV was detected in 44 of the samples collected at baseline and the same virus was found at follow-up in 43% (19/44). Persistence was not significantly associated with age, sex, immunosuppressive treatment, history of warts, or genus of HPV. We conclude that cutaneous HPV infections commonly persist over several years on healthy skin.

  12. Lactose intolerance: from diagnosis to correct management.

    PubMed

    Di Rienzo, T; D'Angelo, G; D'Aversa, F; Campanale, M C; Cesario, V; Montalto, M; Gasbarrini, A; Ojetti, V

    2013-01-01

    This review discusses one of the most relevant problems in gastrointestinal clinical practice: lactose intolerance. The role of lactase-persistence alleles the diagnosis of lactose malabsorption the development of lactose intolerance symptoms and its management. Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately, 75% of the world's population loses this ability at some point, while others can digest lactose into adulthood. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhea with a considerable intraindividual and interindividual variability in the severity. Diagnosis is most commonly performed by the non invasive lactose hydrogen breath test. Management of lactose intolerance consists of two possible clinical choice not mutually exclusive: alimentary restriction and drug therapy.

  13. Treatment of acral persistent papular mucinosis with electrocoagulation.

    PubMed

    André Jorge, Flávia; Mimura Cortez, Tatiana; Guadalini Mendes, Fabiana; Esther Alencar Marques, Mariângela; Amante Miot, Hélio

    2011-01-01

    Acral persistent papular mucinosis is a rare localized form of lichen myxedematosus with few case reports and no documented therapeutic options. To report full resolution of acral persistent papular mucinosis after electrocoagulation. Case report of a 51-year-old white female diagnosed with an acral persistent papular mucinosis. The clinical and histopathologic features, treatment provided, and response to treatment are detailed. Acral persistent papular mucinosis presented as multiple asymptomatic normochromic papules on the wrists. Treatment with topical and intralesional steroids was unsatisfactory. Gentle electrocoagulation led to complete resolution of the lesions and negligible scarring. The favorable results remained for 6 months of follow-up, and no new lesions have emerged. Our case of acral persistent papular mucinosis was successfully treated with electrocoagulation and long-lasting, excellent cosmetic results.

  14. Conservation genetics of the rare Pyreneo-Cantabrian endemic Aster pyrenaeus (Asteraceae)

    PubMed Central

    Escaravage, Nathalie; Cambecèdes, Jocelyne; Largier, Gérard; Pornon, André

    2011-01-01

    Background and aims Aster pyrenaeus (Asteraceae) is an endangered species, endemic to the Pyrenees and Cantabrian Mountain ranges (Spain). For its long-term persistence, this taxon needs an appropriate conservation strategy to be implemented. In this context, we studied the genetic structure over the entire geographical range of the species and then inferred the genetic relationships between populations. Methodology Molecular diversity was analysed for 290 individuals from 12 populations in the Pyrenees and the Cantabrian Mountains using inter simple sequence repeats (ISSRs). Bayesian-based analysis was applied to examine population structure. Principal results Analysis of genetic similarity and diversity, based on 87 polymorphic ISSR markers, suggests that despite being small and isolated, populations have an intermediate genetic diversity level (P % = 52.8 %, HE = 0.21 ± 0.01, genetic similarity between individuals = 49.6 %). Genetic variation was mainly found within populations (80–84 %), independently of mountain ranges, whereas 16–18 % was found between populations and <5 % between mountain ranges. Analyses of molecular variance indicated that population differentiation was highly significant. However, no significant correlation was found between the genetic and geographical distances among populations (Rs = 0.359, P = 0.140). Geographical structure based on assignment tests identified five different gene pools that were independent of any particular structure in the landscape. Conclusions The results suggest that population isolation is probably relatively recent, and that the outbreeding behaviour of the species maintains a high within-population genetic diversity. We assume that some long-distance dispersal, even among topographically remote populations, may be determinant for the pattern of genetic variation found in populations. Based on these findings, strategies are proposed for genetic conservation and management of the species. PMID:22476499

  15. Evolutionary and demographic processes shaping geographic patterns of genetic diversity in a keystone species, the African forest elephant (Loxodonta cyclotis).

    PubMed

    Ishida, Yasuko; Gugala, Natalie A; Georgiadis, Nicholas J; Roca, Alfred L

    2018-05-01

    The past processes that have shaped geographic patterns of genetic diversity may be difficult to infer from current patterns. However, in species with sex differences in dispersal, differing phylogeographic patterns between mitochondrial (mt) and nuclear (nu) DNA may provide contrasting insights into past events. Forest elephants ( Loxodonta cyclotis ) were impacted by climate and habitat change during the Pleistocene, which likely shaped phylogeographic patterns in mitochondrial (mt) DNA that have persisted due to limited female dispersal. By contrast, the nuclear (nu) DNA phylogeography of forest elephants in Central Africa has not been determined. We therefore examined the population structure of Central African forest elephants by genotyping 94 individuals from six localities at 21 microsatellite loci. Between forest elephants in western and eastern Congolian forests, there was only modest genetic differentiation, a pattern highly discordant with that of mtDNA. Nuclear genetic patterns are consistent with isolation by distance. Alternatively, male-mediated gene flow may have reduced the previous regional differentiation in Central Africa suggested by mtDNA patterns, which likely reflect forest fragmentation during the Pleistocene. In species like elephants, male-mediated gene flow erases the nuclear genetic signatures of past climate and habitat changes, but these continue to persist as patterns in mtDNA because females do not disperse. Conservation implications of these results are discussed.

  16. Genetic and epigenetic variation in Spartina alterniflora following the Deepwater Horizon oil spill.

    PubMed

    Robertson, Marta; Schrey, Aaron; Shayter, Ashley; Moss, Christina J; Richards, Christina

    2017-09-01

    Catastrophic events offer unique opportunities to study rapid population response to stress in natural settings. In concert with genetic variation, epigenetic mechanisms may allow populations to persist through severe environmental challenges. In 2010, the Deepwater Horizon oil spill devastated large portions of the coastline along the Gulf of Mexico. However, the foundational salt marsh grass, Spartina alterniflora , showed high resilience to this strong environmental disturbance. Following the spill, we simultaneously examined the genetic and epigenetic structure of recovering populations of S. alterniflora to oil exposure. We quantified genetic and DNA methylation variation using amplified fragment length polymorphism and methylation sensitive fragment length polymorphism (MS-AFLP) to test the hypothesis that response to oil exposure in S. alterniflora resulted in genetically and epigenetically based population differentiation. We found high genetic and epigenetic variation within and among sites and found significant genetic differentiation between contaminated and uncontaminated sites, which may reflect nonrandom mortality in response to oil exposure. Additionally, despite a lack of genomewide patterns in DNA methylation between contaminated and uncontaminated sites, we found five MS-AFLP loci (12% of polymorphic MS-AFLP loci) that were correlated with oil exposure. Overall, our findings support genetically based differentiation correlated with exposure to the oil spill in this system, but also suggest a potential role for epigenetic mechanisms in population differentiation.

  17. Persistent and Newly Developed Chronic Bronchitis Are Associated with Worse Outcomes in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Zhao, Huaqing; Boriek, Aladin M.; Anzueto, Antonio; Soler, Xavier; Bhatt, Surya P.; Rennard, Stephen I.; Wise, Robert; Comellas, Alejandro; Ramsdell, Joe W.; Kinney, Gregory L.; Han, MeiLan K.; Martinez, Carlos H.; Yen, Andrew; Black-Shinn, Jennifer; Porszasz, Janos; Criner, Gerard J.; Hanania, Nicola A.; Sharafkhaneh, Amir; Crapo, James D.; Make, Barry J.; Silverman, Edwin K.; Curtis, Jeffrey L.

    2016-01-01

    Rationale: Chronic bronchitis is, by definition, a chronic condition, but the development and remission of this condition in cigarette smokers with or without chronic obstructive pulmonary disease (COPD) are poorly understood. Also, it is unclear how the persistence or new development of chronic bronchitis affects symptoms and outcomes. Objectives: To ascertain the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes. Methods: We analyzed 1,775 current or ex-smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0–IV COPD in phase 2 of the Genetic Epidemiology of COPD (COPDGene) Study, which included subjects after 5 years of follow-up from phase 1. We asked subjects at enrollment and at 5 years of follow-up about symptoms consistent with chronic bronchitis. We divided subjects into four groups: persistent chronic bronchitis– (negative at phase 1/negative at phase 2), resolved chronic bronchitis (positive/negative), new chronic bronchitis (negative/positive), and persistent chronic bronchitis+ (positive/positive). We analyzed respiratory symptoms, health-related quality of life, lung function, exacerbation frequency, and 6-minute walk distance. Measurements and Main Results: Compared with the persistent chronic bronchitis– group, members of the persistent chronic bronchitis+ group were more likely to have continued smoking (53.4%). Subjects with new chronic bronchitis were more likely to have resumed (6.6%) or continued smoking (45.6%), whereas subjects with resolved chronic bronchitis were more likely to have quit smoking (23.5%). Compared with the persistent chronic bronchitis– group, the other groups had a shorter 6-minute walk distance, worse lung function, greater exacerbation frequency, and worse respiratory symptoms. Modified Medical Research Council dyspnea and St. George’s Respiratory Questionnaire scores worsened between phase 1 and

  18. Quantification of temperature persistence over the Northern Hemisphere land-area

    NASA Astrophysics Data System (ADS)

    Pfleiderer, Peter; Coumou, Dim

    2017-10-01

    Extreme weather events such as heat waves and floods are damaging to society and their contribution to future climate impacts is expected to be large. Such extremes are often related to persistent local weather conditions. Weather persistence is linked to sea surface temperatures, soil-moisture (especially in summer) and large-scale circulation patterns and these factors can alter under past and future climate change. Though persistence is a key characteristic for extreme weather events, to date the climatology and potential changes in persistence have only been poorly documented. Here, we present a systematic analysis of temperature persistence for the northern hemisphere land area. We define persistence as the length of consecutive warm or cold days and use spatial clustering techniques to create regional persistence distributions. We find that persistence is longest in the Arctic and shortest in the mid-latitudes. Parameterizations of the regional persistence distributions show that they are characterized by an exponential decay with a drop in the decay rate for very persistent events, implying that feedback mechanisms are important in prolonging these events. For the mid-latitudes, we find that persistence in summer has increased over the past 60 years. The changes are particularly pronounced for prolonged events suggesting a lengthening in the duration of heat waves.

  19. Genetic disruptions of Drosophila Pavlovian learning leave extinction learning intact.

    PubMed

    Qin, H; Dubnau, J

    2010-03-01

    Individuals who experience traumatic events may develop persistent posttraumatic stress disorder. Patients with this disorder are commonly treated with exposure therapy, which has had limited long-term success. In experimental neurobiology, fear extinction is a model for exposure therapy. In this behavioral paradigm, animals are repeatedly exposed in a safe environment to the fearful stimulus, which leads to greatly reduced fear. Studying animal models of extinction already has lead to better therapeutic strategies and development of new candidate drugs. Lack of a powerful genetic model of extinction, however, has limited progress in identifying underlying molecular and genetic factors. In this study, we established a robust behavioral paradigm to study the short-term effect (acquisition) of extinction in Drosophila melanogaster. We focused on the extinction of olfactory aversive 1-day memory with a task that has been the main workhorse for genetics of memory in flies. Using this paradigm, we show that extinction can inhibit each of two genetically distinct forms of consolidated memory. We then used a series of single-gene mutants with known impact on associative learning to examine the effects on extinction. We find that extinction is intact in each of these mutants, suggesting that extinction learning relies on different molecular mechanisms than does Pavlovian learning.

  20. Genetic variation within and between strains of outbred Swiss mice.

    PubMed

    Cui, S; Chesson, C; Hope, R

    1993-04-01

    The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. Ten to 15 animals from each strain (NIH, Q(S), ARC, IMVS and STUD) were typed, using allozyme electrophoresis, at 10 gene loci: Mod-1, Idh-1, Gpi-I, Es-1, Es-3, Hbb, Pep-3, Gr-1, Got-2 and Pgm-1. Polymorphic variation in at least one of the 5 strains was detected at all 10 loci. The proportion of polymorphic loci ranged from 0.3 (NIH) to 0.8 (IMVS) with a mean of 0.52. Average expected heterozygosities ranged from 0.08 (NIH) to 0.37 (IMVS) with a mean of 0.21. The inbred strain SWR was, as expected, homozygous at all 10 loci. The amount of allelic substitution between pairs of strains was quantified using Nei's genetic distance, and a dendrogram based on these genetic distances showed a close overall similarity in its branching pattern to the known genealogy of the strains. This survey showed that a considerable degree of genetic variation persists in the 5 strains examined, a level of variation similar to that previously detected by Rice and O'Brien (1980) in 3 other outbred Swiss strains.

  1. Nuclear and plastid markers reveal the persistence of genetic identity: a new perspective on the evolutionary history of Petunia exserta.

    PubMed

    Segatto, Ana Lúcia Anversa; Cazé, Ana Luíza Ramos; Turchetto, Caroline; Klahre, Ulrich; Kuhlemeier, Cris; Bonatto, Sandro Luis; Freitas, Loreta Brandão

    2014-01-01

    Recently divergent species that can hybridize are ideal models for investigating the genetic exchanges that can occur while preserving the species boundaries. Petunia exserta is an endemic species from a very limited and specific area that grows exclusively in rocky shelters. These shaded spots are an inhospitable habitat for all other Petunia species, including the closely related and widely distributed species P. axillaris. Individuals with intermediate morphologic characteristics have been found near the rocky shelters and were believed to be putative hybrids between P. exserta and P. axillaris, suggesting a situation where Petunia exserta is losing its genetic identity. In the current study, we analyzed the plastid intergenic spacers trnS/trnG and trnH/psbA and six nuclear CAPS markers in a large sampling design of both species to understand the evolutionary process occurring in this biological system. Bayesian clustering methods, cpDNA haplotype networks, genetic diversity statistics, and coalescence-based analyses support a scenario where hybridization occurs while two genetic clusters corresponding to two species are maintained. Our results reinforce the importance of coupling differentially inherited markers with an extensive geographic sample to assess the evolutionary dynamics of recently diverged species that can hybridize. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Awareness of Cancer Susceptibility Genetic Testing

    PubMed Central

    Mai, Phuong L.; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S.; Wideroff, Louise; Graubard, Barry I.

    2014-01-01

    Background Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. Purpose To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. Methods The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000–2005 and 2005–2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Results Awareness decreased from 44.4% to 41.5% (p<0.001) between 2000 and 2005, and increased to 47.0% (p<0.001) in 2010. Awareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (p-interaction=0.03) or with a usual place of care (p-interaction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25–39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Conclusions Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. PMID:24745633

  3. Mortality, Disenrollment, and Spending Persistence in Medicaid and CHIP.

    PubMed

    DeLia, Derek

    2017-03-01

    Research on spending persistence has not focused on Medicaid and the Children's Health Insurance Program (Medicaid/CHIP), which includes a complex and growing population. The objective of the study was to describe patterns of expenditure persistence, mortality, and disenrollment among nondually eligible Medicaid/CHIP enrollees and identify factors predicting these outcomes. The study is based on New Jersey Medicaid/CHIP claims data from 2011 to 2014. Descriptive and multinomial regression methods were used to characterize persistently extreme spenders, defined as those appearing in the top 1% of statewide spending every year, according to demographics, Medicaid/CHIP eligibility, nursing facility residence, patient risk scores, and clinical diagnostic categories measured in 2011. Similar analyses were done for persistently high spenders (ie, always in the top 10% but not always top 1%) as well as decedents, disenrollees, and moderate spenders (ie, at least 1 year outside of the top 10%). Nondually eligible NJ Medicaid/CHIP enrollees in 2011. One fourth of extreme spenders in 2011 remained in that category throughout 2011-2014. Almost all (89.3%) of the persistently extreme spenders were aged, blind, or disabled. Within the aged, blind, or disabled population, the strongest predictors of persistently extreme spending were diagnoses involving developmental disability, HIV/AIDS, central nervous system conditions, psychiatric disorders, type 1 diabetes, and renal conditions. Individuals in nursing facilities and those with very high risk scores were more likely to die or have persistently high spending than to have persistently extreme spending. The study highlights unique features of spending persistence within Medicaid/CHIP and provides methodological contributions to the broader persistence literature.

  4. ANALYTICAL METHODS DEVELOPED FOR THE CHILDREN'S TOTAL EXPOSURES TO PERSISTENT PESTICIDES AND OTHER PERSISTENT ORGANIC POLLUTANTS (CTEPP) STUDY

    EPA Science Inventory

    The Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) study was designed by the U.S. EPA to collect data on young children's exposures to pesticides and other pollutants in their everyday environments in support of the Food Quality...

  5. Spatial patterns of drought persistence in East China

    NASA Astrophysics Data System (ADS)

    Meng, L.; Ford, T.

    2017-12-01

    East China has experienced a number of severe droughts in recent decades. Understanding the characteristics of droughts and their persistence will provide operational guidelines for water resource management and agricultural production. This study uses a logistic regression model to measure the probability of drought occurrence in the current season given the previous season's Standardized Precipitation Index (SPI) and Southern Oscillation Index (SOI) as well as drought persistence. Results reveal large spatial and seasonal variations in the relationship between the previous season's SPI and the drought occurrence probability in a given season. The drought persistence averaged over the entire study area for all the four seasons is approximately 34% with large variations from season to season and from region to region. The East and Northeast regions have the largest summer drought persistence ( 40%) and lowest fall drought persistence ( 28%). The spatial pattern in winter and spring drought persistence is dissimilar with stronger winter and weaker spring drought persistence in the Southwest and Northeast relative to other regions. Logistic regression analysis indicates a stronger negative relationship in summer-to-fall (or between fall drought occurrence and summer SPI) than other inter-season relationships. This study demonstrates that the impact of previous season SPI and SOI on current season drought varies substantially from region to region and from season to season. This study also shows stronger drought persistence in summer than in other seasons. In other words, the probability of fall drought occurrence is closely related to summer moisture conditions in the East China.

  6. Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio

    PubMed Central

    Amory, Colum F.; Levine, Steve R.; Brey, Robin L.; Gebregziabher, Mulugeta; Tuhrim, Stanley; Tilley, Barbara C.; Simpson, Ann-Catherin N.; Sacco, Ralph L.; Mohr, J.P.

    2015-01-01

    Background There are very limited prospective data on the significance of persistent of antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) two newer aPL assays, (2) an aPL portfolio, and (3) persistent aPL positivity following stroke. Methods 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and β2-glycoprotein-I (anti-β2GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, MI, TIA, DVT, PE, or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. Results Persistent anti-β2GPI decreased the time to TOE/death after adjustment for potential confounders (HR=2.86, CI 1.21-6.76, p=0.017). When persistent anti-β2GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR=3.79, CI 1.18-12.14, p=0.025). Neither persistent aCL, persistent aPS alone, nor a single positive anti-β2GPI or aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL, or any persistent aPL increased the rate of TOE/death. Conclusions Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-β2GPI alone and with persistent second aPL were independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio, and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs. PMID:26513489

  7. You want to do what? My mother's choice to have direct-to-consumer genetic testing.

    PubMed

    Varga, Elizabeth A

    2012-06-01

    As a genetic counselor, I had mixed opinions when my mother told me of her intent to undergo genomewide, SNP-based direct-to-consumer (DTC) genetic testing. I cautioned her that results could be misleading, could increase anxiety and were often of limited clinical validity or utility. I warned of the possibility of learning unintended health information and expressed concerns about how the information might be used by a private company. I told her about the variability in results among companies. Yet, she persisted in her desire, reminding me that she was an informed consumer. After reviewing her goals and understanding of the information she might receive, she elected to proceed. Despite my insistence that I would not be her personal genetic counselor, when the results came back, I found myself immersed in her genetic data. In this manuscript, I will examine how this personal experience challenged my perceptions of DTC testing.

  8. Clinical Characteristics of Disaccharidase Deficiencies Among Children Undergoing Upper Endoscopy.

    PubMed

    Cohen, Stanley A; Oloyede, Hannah; Gold, Benjamin D; Mohammed, Aminu; Elser, Heather E

    2018-06-01

    The epidemiology and clinical significance of disaccharidase deficiencies have not been thoroughly characterized. Recent work suggests at least genetic sucrase-isomaltase deficiency is more prevalent than previously believed. Because lactase deficiency (LD) is well described, the present study focuses on the clinical characteristics of children with disaccharidase deficiencies determined by esophagogastroduodenoscopy. Endoscopic records were reviewed from patients undergoing esophagogastroduodenoscopies with biopsies assayed for disaccharidase activity performed by 13 pediatric gastroenterologists during 5 years (2010-2014). Presenting symptoms, clinical and histological diagnosis, treatment, disaccharidase results, and demographic variables were obtained from medical and endoscopic records of those with maltase and sucrase deficiency (SD). Among 963 patients undergoing intestinal disaccharidase testing, 73 (7.6%) had SD on biopsy (enzyme activity <25 μmol · min · g). Thirty-four (34/73; 47%) had normal duodenal histology and are the focus of this report. Four patients had SD without LD. Pan-disaccharidase deficiency was observed in 24 patients when maltase and palatinase assays were obtained (n = 646), and 11 had SD + LD when just those 2 enzymes were analyzed (n = 317). Those with SD without LD were younger 4.6 ± 6.1 versus 14.1 ± 3.6 years and uniformly presented with diarrhea. Patients with pan-disaccharidase deficiency or SD + LD primarily reported abdominal pain (33/35; 94%), diarrhea (16/35; 46%), nausea (14/35; 40%); and poor weight gain/weight loss (10/35; 29%); constipation, flatulence, and bloating were also noted. Maltase deficiency is less common (8/963; 0.8%), presenting with similar symptoms. Genetic sucrase-isomaltase deficiency often occurs together with lactase or pan-disaccharide deficiency. Disaccharidase deficiency should be considered a potential cause of abdominal pain and/or diarrhea in children and

  9. [Persistent diarrhea in the returned traveler].

    PubMed

    de Saussure, P; Hadengue, A

    2006-05-10

    Persistent diarrhea in a returned traveler is a frequent presenting complaint and may result from three etiologic groups: persistant infections, non-infectious post-gastroenteritis processes (in particular postinfectious irritable bowel syndrome) and appearance of an unrelated cause of chronic diarrhea. This article reviews the most frequent diseases involved and provides management guidelines for primary care physicians.

  10. Genetic diversity and population structure of a protected species: Polygala tenuifolia Willd.

    PubMed

    Peng, Yan Qun; Fan, Ling Ling; Mao, Fu Ying; Zhao, Yun Sheng; Xu, Rui; Yin, Yu Jie; Chen, Xin; Wan, De Guang; Zhang, Xin Hui

    2018-03-01

    Polygala tenuifolia Willd. is an important protected species used in traditional Chinese medicine. In the present study, amplified fragment length polymorphism (AFLP) markers were employed to characterize the genetic diversity in wild and cultivated P. tenuifolia populations. Twelve primer combinations of AFLP produced 310 unambiguous and repetitious bands. Among these bands, 261 (84.2%) were polymorphic. The genetic diversity was high at the species level: percentage of polymorphic loci (PPL)=84.2%, Nei's gene diversity (h)=0.3296 and Shannon's information index (I)=0.4822. Between the two populations, the genetic differentiation of 0.1250 was low and the gene flow was relatively high, at 3.4989. The wild population (PPL=81.9%, h=0.3154, I=0.4635) showed a higher genetic diversity level than the cultivated population (PPL=63.9%, h=0.2507, I=0.3688). The results suggest that the major factors threatening the persistence of P. tenuifolia resources are ecological and human factors rather than genetic. These results will assist with the design of conservation and management programs, such as in natural habitat conservation, setting the excavation time interval for resource regeneration and the substitution of cultivated for wild plants. Copyright © 2018 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  11. Non-persistent pesticides removal in constructed wetlands

    NASA Astrophysics Data System (ADS)

    Tu, Yue; Jiang, Lei; Li, Haixiang

    2018-03-01

    The heavy use of non-persistent pesticides, resulting in the accumulation of environment and destroy the aquatic environment. This paper presents the research status of using CWs to treat non-persistent pesticides in water. The removal mechanisms are mainly physical deposition, chemical hydrolysis and plant absorption. Analysis of the factors that affect the removal effect are mainly the nature of pesticides, HRT, plants. Some scholars have proposed that secondary products of non-persistent pesticides may be more harmful to the environment, However, the relevant reports are scarce.

  12. Community College Students' Self-Reports of Persistence: Looking beyond Student Satisfaction Ratings of Persisters and Nonpersisters

    ERIC Educational Resources Information Center

    Cole, Marsha Dee

    2013-01-01

    Approximately 30% of students who persist to the end of their courses at two-year colleges do not do so with a passing grade, yet research on the educational experiences of these unsuccessful community college persisters remains limited. The purpose of this explanatory mixed-methods study was threefold. First, this study attempted to identify…

  13. Allergic inflammation induces a persistent mechanistic switch in thromboxane-mediated airway constriction in the mouse

    PubMed Central

    Cyphert, Jaime M.; Allen, Irving C.; Church, Rachel J.; Latour, Anne M.; Snouwaert, John N.; Coffman, Thomas M.

    2012-01-01

    Actions of thromboxane (TXA2) to alter airway resistance were first identified over 25 years ago. However, the mechanism underlying this physiological response has remained largely undefined. Here we address this question using a novel panel of mice in which expression of the thromboxane receptor (TP) has been genetically manipulated. We show that the response of the airways to TXA2 is complex: it depends on expression of other G protein-coupled receptors but also on the physiological context of the signal. In the healthy airway, TXA2-mediated airway constriction depends on expression of TP receptors by smooth muscle cells. In contrast, in the inflamed lung, the direct actions of TXA2 on smooth muscle cell TP receptors no longer contribute to bronchoconstriction. Instead, in allergic lung disease, TXA2-mediated airway constriction depends on neuronal TP receptors. Furthermore, this mechanistic switch persists long after resolution of pulmonary inflammation. Our findings demonstrate the powerful ability of lung inflammation to modify pathways leading to airway constriction, resulting in persistent changes in mechanisms of airway reactivity to key bronchoconstrictors. Such alterations are likely to shape the pathogenesis of asthmatic lung disease. PMID:21984570

  14. Spatial and temporal genetic analysis of Walleyes in the Ohio River

    USGS Publications Warehouse

    Page, Kevin S.; Zweifela, Richard D.; Stott, Wendylee

    2017-01-01

    Previous genetic analyses have shown that Walleyes Sander vitreus in the upper Ohio River comprise two distinct genetic strains: (1) fish of Great Lakes origin that were stocked into the Ohio River basin and (2) a remnant native strain (Highlands strain). Resource agencies are developing management strategies to conserve and restore the native strain within the upper reaches of the Ohio River. Hybridization between strains has impacted the genetic integrity of the native strain. To better understand the extent and effects of hybridization on the native strain, we used mitochondrial DNA and microsatellite markers to evaluate the spatial (river sections) and temporal (pre- and poststocking) genetic diversity of Ohio River Walleyes. Contemporary Lake Erie Walleyes and archival museum specimens collected from the Ohio River basin were used for comparison to contemporary Ohio River samples. Although there was evidence of hybridization between strains, most of the genetic diversity within the Ohio River was partitioned by basin of origin (Great Lakes versus the Ohio River), with greater similarity among river sections than between strains within the same section. Results also suggested that the native strain has diverged from historical populations. Furthermore, notable decreases in measures of genetic diversity and increased relatedness among native-strain Walleyes within two sections of the Ohio River may be related to stocking aimed at restoration of the Highlands strain. Our results suggest that although the Highlands strain persists within the Ohio River, it has diverged over time, and managers should consider the potential impacts of future management practices on the genetic diversity of this native strain.

  15. Genetic concepts and uncertainties in restoring fish populations and species

    USGS Publications Warehouse

    Reisenbichler, R.R.; Utter, F.M.; Krueger, C.C.

    2003-01-01

    Genetic considerations can be crucially important to the success of reintroductions of lotic species. Current paradigms for conservation and population genetics provide guidance for reducing uncertainties in genetic issues and for increasing the likelihood of achieving restoration. Effective restoration is facilitated through specific goals and objectives developed from the definition that a restored or healthy population is (i) genetically adapted to the local environment, (ii) self-sustaining at abundances consistent with the carrying capacity of the river system, (iii) genetically compatible with neighboring populations so that substantial outbreeding depression does not result from straying and interbreeding between populations, and (iv) sufficiently diverse genetically to accommodate environmental variability over many decades. Genetic principles reveal the importance of describing and adhering to the ancestral lineages for the species to be restored and enabling genetic processes to maintain diversity and fitness in the populations under restoration. Newly established populations should be protected from unnecessary human sources of mortality, gene flow from maladapted (e.g., hatchery) or exotic populations, and inadvertent selection by fisheries or other human activities. Such protection facilitates initial, rapid adaptation of the population to its environment and should enhance the chances for persistence. Various uncertainties about specific restoration actions must be addressed on a case-by-case basis. Such uncertainties include whether to allow natural colonization or to introduce fish, which populations are suitable as sources for reintroduction, appropriate levels of gene flow from other populations, appropriate levels of artificial production, appropriate minimum numbers of individuals released or maintained in the population, and the best developmental stages for releasing fish into the restored stream. Rigorous evaluation or

  16. Using emergency department-based inception cohorts to determine genetic characteristics associated with long term patient outcomes after motor vehicle collision: methodology of the CRASH study.

    PubMed

    Platts-Mills, Timothy F; Ballina, Lauren; Bortsov, Andrey V; Soward, April; Swor, Robert A; Jones, Jeffrey S; Lee, David C; Peak, David A; Domeier, Robert M; Rathlev, Niels K; Hendry, Phyllis L; McLean, Samuel A

    2011-09-26

    Persistent musculoskeletal pain and psychological sequelae following minor motor vehicle collision (MVC) are common problems with a large economic cost. Prospective studies of pain following MVC have demonstrated that demographic characteristics, including female gender and low education level, and psychological characteristics, including high pre-collision anxiety, are independent predictors of persistent pain. These results have contributed to the psychological and social components of a biopsychosocial model of post-MVC pain pathogenesis, but the biological contributors to the model remain poorly defined. Recent experimental studies indicate that genetic variations in adrenergic system function influence the vulnerability to post-traumatic pain, but no studies have examined the contribution of genetic factors to existing predictive models of vulnerability to persistent pain. The Project CRASH study is a federally supported, multicenter, prospective study designed to determine whether variations in genes affecting synaptic catecholamine levels and alpha and beta adrenergic receptor function augment social and psychological factors in a predictive model of persistent musculoskeletal pain and posttraumatic stress disorder (PTSD) following minor MVC. The Project CRASH study will assess pain, pain interference and PTSD symptoms at 6 weeks, 6 months, and 1 year in approximately 1,000 patients enrolled from 8 Emergency Departments in four states with no-fault accident laws. The results from this study will provide insights into the pathophysiology of persistent pain and PTSD following MVC and may serve to improve the ability of clinicians and researchers to identify individuals at high risk for adverse outcomes following minor MVC.

  17. Low genetic diversity in pygmy blue whales is due to climate-induced diversification rather than anthropogenic impacts.

    PubMed

    Attard, Catherine R M; Beheregaray, Luciano B; Jenner, K Curt S; Gill, Peter C; Jenner, Micheline-Nicole M; Morrice, Margaret G; Teske, Peter R; Möller, Luciana M

    2015-05-01

    Unusually low genetic diversity can be a warning of an urgent need to mitigate causative anthropogenic activities. However, current low levels of genetic diversity in a population could also be due to natural historical events, including recent evolutionary divergence, or long-term persistence at a small population size. Here, we determine whether the relatively low genetic diversity of pygmy blue whales (Balaenoptera musculus brevicauda) in Australia is due to natural causes or overexploitation. We apply recently developed analytical approaches in the largest genetic dataset ever compiled to study blue whales (297 samples collected after whaling and representing lineages from Australia, Antarctica and Chile). We find that low levels of genetic diversity in Australia are due to a natural founder event from Antarctic blue whales (Balaenoptera musculus intermedia) that occurred around the Last Glacial Maximum, followed by evolutionary divergence. Historical climate change has therefore driven the evolution of blue whales into genetically, phenotypically and behaviourally distinct lineages that will likely be influenced by future climate change. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  18. Hemiclonal analysis reveals significant genetic, environmental and genotype x environment effects on sperm size in Drosophila melanogaster.

    PubMed

    Morrow, E H; Leijon, A; Meerupati, A

    2008-11-01

    Spermatozoa are the most diverse of all animal cells. Variation in size alone is enormous and yet there are still no clear evolutionary explanations that can account for such diversity. The basic genetics of sperm form is also poorly understood, although sperm size is known to have a strong genetic component. Here, using hemiclonal analysis of Drosophila melanogaster, we demonstrate that there is not only a significant additive genetic component contributing to phenotypic variation in sperm length but also a significant environmental effect. Furthermore, the plasticity of sperm size has a significant genetic component to it (a genotype x environment interaction). A genotype x environment interaction could contribute to the maintenance of the substantial genetic variation in this trait and thereby explain the persistent inter-male differences in sperm size seen in numerous taxa. We suggest that the low conditional dependence and high heritability but low evolvability (the coefficient of additive genetic variation) of sperm length is more consistent with a history of stabilizing selection rather than either sexual selection or strong directional selection.

  19. Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

    PubMed Central

    Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

    2013-01-01

    The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attem