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.

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.

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

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

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.

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.

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

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.

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

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.

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

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.

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.

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 = 0.651), dyslipidaemia (P = 0.328), hypertension (P = 0.507) or liver histology in these patients. Moreover, in the NASH patients, hypolactasia was an independent risk factor for insulin resistance even after adjusting for gender and age [OR = 5.0 (95%CI: 1.35-20; P = 0.017)]. CONCLUSION The LCT-13910 genotype distribution in Brazilian NAFLD patients was the same as that of the general population, but hypolactasia increased the risk of insulin resistance in the NASH patients. PMID:27648154

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

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.

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.

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

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.

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.

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.

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

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 malabsorption and osteoporosis.

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.

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.

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 criteria of IBS. Alternatively limited intestinal gut-brain responses to host microbial interactions may result in similar overlap features in both. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

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

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 ...

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.

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

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.

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.

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.

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...

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.

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...

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.

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.

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

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.

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®

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…

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.

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

[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.

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 abdominal pain, respectively. The combined administration of freeze-dried yogurt cultures and acid lactase increases lactose digestion more than either freeze-dried yogurt cultures or acid lactase alone, and more lactose malabsorbers benefited from this effect. Copyright © 2014. Published by Elsevier Ltd.

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.

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

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...

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.

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.

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.

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

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.

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.

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

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.

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.

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)

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.

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.

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

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...

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...

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.

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.

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.

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.

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…

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...

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...

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.

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.

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…

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…

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 genetic influence in dairy consumption or in metabolism of dairy foods. SNPs associated with C23:0 may reflect a role of genetic factors in the synthesis of sphingomyelin. PMID:29738550

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.

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.

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 adolescents.

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.

The gourmet ape: evolution and human food preferences.

PubMed

Krebs, John R

2009-09-01

This review explores the relation between evolution, ecology, and culture in determining human food preferences. The basic physiology and morphology of Homo sapiens sets boundaries to our eating habits, but within these boundaries human food preferences are remarkably varied, both within and between populations. This does not mean that variation is entirely cultural or learned, because genes and culture may coevolve to determine variation in dietary habits. This coevolution has been well elucidated in some cases, such as lactose tolerance (lactase persistence) in adults, but is less well understood in others, such as in favism in the Mediterranean and other regions. Genetic variation in bitter taste sensitivity has been well documented, and it affects food preferences (eg, avoidance of cruciferous vegetables). The selective advantage of this variation is not clear. In African populations, there is an association between insensitivity to bitter taste and the prevalence of malaria, which suggests that insensitivity may have been selected for in regions in which eating bitter plants would confer some protection against malaria. Another, more general, hypothesis is that variation in bitter taste sensitivity has coevolved with the use of spices in cooking, which, in turn, is thought to be a cultural tradition that reduces the dangers of microbial contamination of food. Our evolutionary heritage of food preferences and eating habits leaves us mismatched with the food environments we have created, which leads to problems such as obesity and type 2 diabetes.

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.

Early Back-to-Africa Migration into the Horn of Africa

PubMed Central

Hodgson, Jason A.; Mulligan, Connie J.; Al-Meeri, Ali; Raaum, Ryan L.

2014-01-01

Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive of earlier episodes of admixture. To investigate this further, we generated new genome-wide SNP data for a Yemeni population sample and merged these new data with published genome-wide genetic data from the HOA and a broad selection of surrounding populations. We used multidimensional scaling and ADMIXTURE methods in an exploratory data analysis to develop hypotheses on admixture and population structure in HOA populations. These analyses suggested that there might be distinct, differentiated African and non-African ancestries in the HOA. After partitioning the SNP data into African and non-African origin chromosome segments, we found support for a distinct African (Ethiopic) ancestry and a distinct non-African (Ethio-Somali) ancestry in HOA populations. The African Ethiopic ancestry is tightly restricted to HOA populations and likely represents an autochthonous HOA population. The non-African ancestry in the HOA, which is primarily attributed to a novel Ethio-Somali inferred ancestry component, is significantly differentiated from all neighboring non-African ancestries in North Africa, the Levant, and Arabia. The Ethio-Somali ancestry is found in all admixed HOA ethnic groups, shows little inter-individual variance within these ethnic groups, is estimated to have diverged from all other non-African ancestries by at least 23 ka, and does not carry the unique Arabian lactase persistence allele that arose about 4 ka. Taking into account published mitochondrial, Y chromosome, paleoclimate, and archaeological data, we find that the time of the Ethio-Somali back-to-Africa migration is most likely pre-agricultural. PMID:24921250

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.

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

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.

[Lactose intolerance].

PubMed

Rosado, Jorge L

2016-09-01

The most common problem limiting milk consumption worldwide is lactose intolerance (LI), which is defined as the experience of gastrointestinal symptoms due to the intake of lactose-containing food. When symptoms ensue the intake of milk, the condition is referred as milk intolerance, and it may or may not be due to LI. The most common cause of LI is primary lactase deficiency which occurs in 30% of Mexican adults when one glass of milk is consumed (12-18 g of lactose). LI occurs in less than 15% of adults after the intake of this dose of lactose. Another cause of lactose intolerance is due to secondary lactase deficiency, which occurs because lactase is reduced due to diseases that affect the intestinal mucosa. Lactose intolerance can be eliminated or significantly reduced by elimination or reduction of the intake of milk and milk containing products. Recent studies demonstrate that when β-casein-A1 contained in milk is hydrolyzed it produces β-casomorphine-7 which is an opioid associated with milk intolerance.

Disaccharidase Deficiencies in Children With Chronic Abdominal Pain.

PubMed

El-Chammas, Khalil; Williams, Sara E; Miranda, Adrian

2017-03-01

Carbohydrate intolerance or malabsorption has been suggested as a cause of chronic abdominal pain (CAP) in a subset of patients. We aimed to evaluate disaccharidase deficiencies in children with functional CAP and to correlate deficiencies with clinical features. Patients presenting to the gastroenterology clinic at Children's Hospital of Wisconsin with abdominal pain prospectively completed a detailed demographic, history, and symptom questionnaire. The CAP cohort included those with at least 1 month of symptoms. Data on disaccharidase activity and histology of endoscopic biopsies were collected retrospectively. Only patients with normal histology were included in the study. The association between groups with low disaccharidases and clinical features was examined. A total of 203 pediatric patients with CAP were included. The mean (SD) age was 11.5 (3.1) years, and 32.5% were male. The percentages of abnormally low disaccharidase levels using the standard laboratory cutoffs were lactase, 37%; sucrase, 21%; glucoamylase, 25%; and palatinase, 8%. Thirty-nine percent of the patients with low lactase also had low sucrase, and 67% of the patients with low sucrase had low lactase. There was no significant difference in the activities of any of the disaccharidases or sucrase/lactase ratio in relation to age. Also, no association was found between stool consistency, stool frequency, or location of pain and low disaccharidase activity. A large proportion of patients with CAP have deficiencies in disaccharidases. Bowel frequency, vomiting, or location of pain was no different between groups, suggesting that these clinical features cannot be used to predict disaccharidase deficiencies.

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.

Comparison of the quantitative dry culture methods with both conventional media and most probable number method for the enumeration of coliforms and Escherichia coli/coliforms in food.

PubMed

Teramura, H; Sota, K; Iwasaki, M; Ogihara, H

2017-07-01

Sanita-kun™ CC (coliform count) and EC (Escherichia coli/coliform count), sheet quantitative culture systems which can avoid chromogenic interference by lactase in food, were evaluated in comparison with conventional methods for these bacteria. Based on the results of inclusivity and exclusivity studies using 77 micro-organisms, sensitivity and specificity of both Sanita-kun™ met the criteria for ISO 16140. Both media were compared with deoxycholate agar, violet red bile agar, Merck Chromocult™ coliform agar (CCA), 3M Petrifilm™ CC and EC (PEC) and 3-tube MPN, as reference methods, in 100 naturally contaminated food samples. The correlation coefficients of both Sanita-kun™ for coliform detection were more than 0·95 for all comparisons. For E. coli detection, Sanita-kun™ EC was compared with CCA, PEC and MPN in 100 artificially contaminated food samples. The correlation coefficients for E. coli detection of Sanita-kun™ EC were more than 0·95 for all comparisons. There were no significant differences in all comparisons when conducting a one-way analysis of variance (anova). Both Sanita-kun™ significantly inhibited colour interference by lactase when inhibition of enzymatic staining was assessed using 40 natural cheese samples spiked with coliform. Our results demonstrated Sanita-kun™ CC and EC are suitable alternatives for the enumeration of coliforms and E. coli/coliforms, respectively, in a variety of foods, and specifically in fermented foods. Current chromogenic media for coliforms and Escherichia coli/coliforms have enzymatic coloration due to breaking down of chromogenic substrates by food lactase. The novel sheet culture media which have film layer to avoid coloration by food lactase have been developed for enumeration of coliforms and E. coli/coliforms respectively. In this study, we demonstrated these media had comparable performance with reference methods and less interference by food lactase. These media have a possibility not only to be useful alternatives but also to contribute for accurate enumeration of these bacteria in a variety of foods, and specifically in fermented foods. © 2017 The Society for Applied Microbiology.

Lactose digestion by human jejunal biopsies: the relationship between hydrolysis and absorption.

PubMed Central

Dawson, D J; Lobley, R W; Burrows, P C; Miller, V; Holmes, R

1986-01-01

The relationship between lactose hydrolysis and absorption of released glucose was investigated by determining the kinetics of lactose digestion by jejunal biopsies incubated in vitro. Lactase activity in intact biopsies correlated with conventional assay of tissue homogenates (r = 0.85, p less than 0.001), and glucose uptake from 28 mM lactose was directly proportional to lactase activity (r = 0.95, p less than 0.001) in 21 subjects with normal lactase levels, six with hypolactasia (primary or secondary to coeliac disease) and two with lactose intolerance but normal lactase activity. Kinetic analysis at 0.56-56 mM lactose in five normal subjects showed saturable kinetics for hydrolysis (app Km = 33.9 +/- 2.2 mM; app Vmax = 26.5 +/- 1.1 nmol/min/mg dry weight) but glucose uptake could be fitted to a model either of saturable uptake (app Kt = 47.2 +/- 0.3 mM; app Jmax = 14.1 +/- 0.2 nmol/min/mg) or saturable uptake plus a linear component (app Kt = 21.3 +/- 1.15; app Jmax = 4.59 +/- 0.12; app Kd = 0.093 +/- 0.010 nmol/min/mg/mM). The proportion of glucose taken into the tissue did not significantly exceed 50% of the total released at any lactose concentration suggesting the lack of an efficient capture mechanism for the released glucose. The results suggest that lactose hydrolysis is the rate limiting step in the overall absorption of glucose from lactose in vitro, and that the relationship between hydrolysis and absorption is the same in normal subjects and in hypolactasic subjects. PMID:3084346

Lactose absorption and mucosal disaccharidases in convalescent pellagra and kwashiorkor children

PubMed Central

Prinsloo, J. G.; Wittmann, W.; Kruger, H.; Freier, E.

1971-01-01

Oral lactose and glucose/galactose loading tests were done in Bantu children convalescing from kwashiorkor and pellagra. Small bowel biopsies and disaccharidase estimations were performed in all except 2 patients. Lactose absorption was more impaired and intestinal lactase levels were lower in the pellagra than in the kwashiorkor group. The fact that diarrhoea after admission to hospital was less common in pellagra than kwashiorkor was ascribed to a lesser lactose load due to the early introduction of a mixed diet in the former group, in comparison with milk feeds only in the latter group. The absence of troublesome diarrhoea while on moderate quantities of lactose in the diet, in the presence of low intestinal lactase levels, but evidence of lactose malabsorption after loading, has a bearing on preventive and therapeutic nutrition programmes in non-Caucasian children. Lactase deficiency is not necessarily synonymous with symptomatic lactose intolerance if the threshold is not exceeded. Concern is expressed that excessive caution against the use of milk may lead to a worsening of infantile malnutrition in developing countries. PMID:5109409

Lactose intolerance.

PubMed

Vandenplas, Yvan

2015-01-01

Lactose is the main carbohydrate in infant feeding, but its impact decreases as the child gets older and consumes less milk and dairy products. Congenital lactose intolerance is a very rare condition. However, lactase activity may be low and need to mature during the first weeks of life in many infants. However, the evidence that unabsorbed lactose is causing infantile crying and colic is contradictory. Unabsorbed lactose has a bifidogenic effect and improves calcium absorption. Lactose malabsorption may occur secondary and thus temporally to other etiologies such as infectious gastroenteritis, cow's milk allergy and celiac disease. One the cause is treated, lactase activity will gradually return to normal. The vast majority of Asian children will develop late onset congenital lactase deficiency. However, this entity only exceptionally causes symptoms before the age of 4-5 years. Symptoms are abdominal cramps, flatulence and watery, acid stools, and decrease the quality of life but lactose intolerance is not associated with "true disease". The diagnosis is made on clinical grounds and confirmed with a lactose breath test, if needed. These patients need to have a lifetime long reduced lactose intake to improve their quality of life.

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.

[Determination of lactose intolerance frequency in children with food allergy].

PubMed

Hutyra, Tomasz; Iwańczak, Barbara

2008-10-01

Lactose malabsorption and lactose intolerance symptoms are the most common alimentary tract disorders in children. Lactose intolerance is a result of lactase deficiency or lack of lactase and lactose malabsorption. Hypersensitivity in food allergy is connected with the presence of specific IgE (specific antibodies against some allergens) or lymphocytes. Lactose intolerance and food allergy may coexist in the same patient. The aim of this study was determination of lactose intolerance frequency in children with food allergy who were below and above 5 years of age. The number of 87 children with food allergy aged from 0.7 to 18 years were included in the study (48 boys and 39 girls). 51 patients above 5 years of age and 36 patients below 5 years of age were studied. Lactose intolerance symptoms, hydrogen breath test, activity of lactase and villous atrophy were investigated. Decreased absorption of lactose in hydrogen breath test was observed in 28% of children above 5 years of age and in 5% in younger children. Positive result of biological trial in hydrogen breath test was observed in 10% of patients who were below 5 years of age and in 26% patients above 5 years. There was no statistically significant difference in lactose intolerance frequency and in decreased activity of lactase in intestinal mucosa between these two groups. Frequent partial villous atrophy was observed in younger patients (41,38%) than in children above 5 years of age (17.86%). Lactose intolerance was observed in 10% patients who were below 5 years of age and in 26% patients above 5 years of age with food allergy. There was no statistically significant difference between these two groups.

[Lactose intolerance in neonates with non-infectious diarrhea].

PubMed

Su, Hui-Min; Jiang, Yi; Hu, Yu-Lian; Yang, Hui; Dong, Tian-Jin

2016-04-01

To investigate the development of lactose intolerance in neonates with non-infectious diarrhea and its association with diarrhea, and to evaluate the diagnostic values of fecal pH value and urine galactose determination for neonatal lactase deficiency. Seventy hospitalized neonates who developed non-infectious diarrhea between October 2012 and June 2015 were enrolled as the diarrhea group, and 162 hospitalized neonates without non-infectious diarrhea were enrolled as the non-diarrhea group. Test paper was used to determine fecal pH value. The galactose oxidase method was used to detect urine galactose. The neonates with positive galactose oxidase were diagnosed with lactase deficiency, and those with lactase deficiency and diarrhea were diagnosed with lactose intolerance. According to the results of urine galactose detection, 69 neonates in the diarrhea group who underwent urine galactose detection were classified into lactose intolerance group (45 neonates) and lactose tolerance group (24 neonates), and their conditions after treatment were compared between the two groups. The follow-up visits were performed for neonates with diarrhea at 3 months after discharge. Fecal pH value and positive rate of urine galactose (65% vs 54%) showed no significant differences between the diarrhea and non-diarrhea groups (P>0.05). Fecal pH value showed no significant difference between the lactose intolerance and lactose tolerance groups (P>0.05), while the neonates in the lactose intolerance group had a significantly longer time to recovery of defecation than those in the lactose tolerance group (P<0.05). The incidence of lactase deficiency is high in neonates, and diarrhea due to lactose intolerance tends to occur. Determination of fecal pH value has no significance in the diagnosis of lactose intolerance in neonates with diarrhea.

Detecting and characterizing genomic signatures of positive selection in global populations.

PubMed

Liu, Xuanyao; Ong, Rick Twee-Hee; Pillai, Esakimuthu Nisha; Elzein, Abier M; Small, Kerrin S; Clark, Taane G; Kwiatkowski, Dominic P; Teo, Yik-Ying

2013-06-06

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Lack of effect of lactose digestion status on baseline fecal microflora

PubMed Central

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

2009-01-01

BACKGROUND: The genetics of intestinal lactase divide the world’s population into two phenotypes: the ability (a dominant trait) or inability (a recessive trait) to digest lactose. A prebiotic effect of lactose may impact the colonic flora of these phenotypes differently. OBJECTIVE: To detect and evaluate the effects of lactose on subjects divided according to their ability to digest lactose. METHODS: A total of 57 healthy maldigesters (n=30) and digesters (n=27) completed diet questionnaires, genetic and breath hydrogen testing, and quantitative stool analysis for species of bacteria. Log10 transformation of bacterial counts was compared with lactose intake in both groups using multiple regression analysis. RESULTS: There was a significant relationship between genetic and breath hydrogen tests. Daily lactose intake was marginally lower in lactose maldigesters (median [interquartile range] 12.2 g [31 g] versus 15 g [29.6 g], respectively). There was no relationship between lactose intake and breath hydrogen tests in either group. There were no differences in bacterial counts between the two groups, nor was there a relationship between bacterial counts and lactose intake in either group. CONCLUSION: The differential bacterial effects of lactose were not quantitatively detected in stool samples taken in the present study. PMID:19893771

The molecular basis of lactose intolerance.

PubMed

Campbell, Anthony K; Waud, Jonathan P; Matthews, Stephanie B

2009-01-01

A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.

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 patients.

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

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.

Lowering the milk lactose content in vivo: potential interests, strategies and physiological consequences.

PubMed

Vilotte, Jean-Luc

2002-01-01

Lactose is the major sugar present in milk and an important osmotic regulator of lactation. It is digested by intestinal lactase, an enzyme expressed in new-borns. Its activity declines following weaning. As a result, adult mammals are normally lactose-intolerant and more than 75% of the human adult population suffers from lactase deficiency. A reduction in milk lactose content could be beneficial for nutritional but also agricultural and industrial purposes (less volume to transport, better milk coagulation, less effluent production). Several attempts to create transgenic mice producing milk with modified carbohydrate compositions have recently been described. Depending on whether these modifications resulted from an alteration of lactose synthesis or from lactose hydrolysis, striking physiological differences are observed.

Lactose Intolerance

MedlinePlus

... tract from stool and changes it from a liquid to a solid form. In the colon, bacteria break down undigested lactose and create fluid and gas. Not all people with lactase deficiency and lactose ...

Problems Digesting Dairy Products?

MedlinePlus

... contains Bifidobacteria, they claim these microorganisms are beneficial (probiotic) and create their own lactase, which helps people ... fecal matter (animal manure) and are not considered probiotic, but instead are regarded as contaminants." Drinking raw ...

Development of small intestinal enzyme activities and their relationship with some gut regulatory peptides in grazing sheep.

PubMed

Wang, C L; Lang, X; Wu, P J; Casper, D P; Li, F D

2017-08-01

Growth depends on an animal's capacity to digest and assimilate ingested nutrients, and insufficient supply and impairment will constrain lamb growth. Eight groups of Alpine Finewool lambs were harvested on 0, 3, 7, 14, 21, 28, 42, and 56 d to measure pH and enzymatic activities in the duodenum, proximal jejunum, middle jejunum, distal jejunum, and ileum mucosa or digesta. From the duodenum to the ileum the pH of intestinal mucosa and digesta increased, whereas pH changed very little with age. The trypsin, chymotrypsin, lipase, lactase, and α-amylase activities observed at birth decreased by d 3, followed by a nonuniform enzymatic response in the small intestine. The trypsin activity increased from d 3 to peak, at d 21, followed by a decline. Chymotrypsin activity followed the same general trend but with smaller responses in activities. Trypsin demonstrated greater enzymatic activity than chymotrypsin at the same age. The lipase activity of small intestinal mucosa and digesta changed little with age. The lactase activity was high at birth, decreased by d 3, and then increased, followed by a decrease as lambs approached weaning. α-Amylase activity was similar in the small intestinal mucosa and digesta at birth but increased with age for the duodenum and proximal jejunum. Plasma concentrations of cholecystokinin (CCK), secretin, and gastrin were positively correlated ( < 0.05) with ileal mucosa lipase activity. Plasma concentration of CCK, secretin, gastrin, and gastric inhibitory polypeptide (GIP) were positively correlated ( < 0.05) with ileal mucosa lactase activity. Plasma concentration of pancreatic polypeptide (PP) was negatively correlated ( < 0.05) with lactase activity in the middle jejunum and ileal mucosa. Plasma concentrations of CCK, secretin, gastrin, and GIP were positively correlated ( < 0.05) with α-amylase activity in the ileal mucosa but negatively correlated ( < 0.05) with duodenum, prejejunum, and middle jejunum. Plasma PP concentrations were positively correlated ( < 0.01) with α-amylase activity of duodenum, middle jejunum, and postjejunum mucosa but not with the enzyme activity of postjejunum and ileal mucosa ( > 0.05). Small intestinal enzymatic activities exist and may be sufficient to enhance lamb growth via appropriate nutrient supplementation.

21 CFR 184.1388 - Lactase enzyme preparation from Kluyveromyces lactis.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) This enzyme preparation is derived from the nonpathogenic, nontoxicogenic yeast Kluyveromyces lactis... 683), which converts lactose to glucose and galactose. It is prepared from yeast that has been grown...

21 CFR 184.1388 - Lactase enzyme preparation from Kluyveromyces lactis.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., nontoxicogenic yeast Kluyveromyces lactis (previously named Saccharomyces lactis). It contains the enzyme β... prepared from yeast that has been grown in a pure culture fermentation and by using materials that are...

21 CFR 184.1388 - Lactase enzyme preparation from Kluyveromyces lactis.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., nontoxicogenic yeast Kluyveromyces lactis (previously named Saccharomyces lactis). It contains the enzyme β... prepared from yeast that has been grown in a pure culture fermentation and by using materials that are...

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.

Modifications of allergenicity linked to food technologies.

PubMed

Moneret-Vautrin, D A

1998-01-01

The prevalence of food allergies (FA) has increased over the past fifteen years. The reasons suggested are changes in dietary behaviour and the evolution of food technologies. New cases of FA have been described with chayote, rambutan, arguta, pumpkin seeds, custard apple, and with mycoproteins from Fusarium.... Additives using food proteins are at high risk: caseinates, lysozyme, cochineal red, papaïn, alpha-amylase, lactase etc. Heating can reduce allergenicity or create neo-allergens, as well as storage, inducing the synthesis of allergenic stress or PR proteins. Aeroallergens (miles, moulds) contaminate foods and can induce allergic reactions. Involuntary contamination by peanut proteins on production lines is a problem which is not yet solved. Genetically modified plants are at risk of allergenicity, requiring methodological steps of investigations: the comparison of the amino-acid sequence of the transferred protein with the sequence of known allergens, the evaluation of thermo degradability and of the denaturation by pepsin and trypsin are required, as well as the study with sera from patients allergic to the plant producing the gene. The combination of enzymatic hydrolysis, heating, or the development of genetically modified plants may offer new alternatives towards hypoallergenic foods (57 references).

Lactose Intolerance

MedlinePlus

... a necessity for infants, who get all their nutrition from milk. As children replace milk with other foods, their lactase production normally decreases, but remains high enough to digest the amount of dairy in a typical adult diet. In primary lactose ...

Lactose intolerance

MedlinePlus

... age 5. This is the age when our bodies may stop making lactase. In African Americans, the problem can occur as early as age 2. The condition is very common among adults with Asian, African, or Native American heritage. It is less ...

Variable Use of Disaccharidase Assays When Evaluating Abdominal Pain

PubMed Central

Oloyede, Hannah

2018-01-01

Background and Aims: Patients with a disaccharidase deficiency typically present with abdominal discomfort and often with diarrhea. However, disaccharidase deficiency is often overlooked as a cause of these complaints. Therefore, we sought to determine the prevalence of lactase and sucrase deficiencies in a pediatric population undergoing diagnostic esophagogastroduodenoscopy (EGD) and to describe disaccharidase testing practices among pediatric gastroenterologists. Methods: Endoscopic records from patients undergoing diagnostic EGD and disaccharidase analysis (DA) were retrospectively reviewed. Diagnostic EGDs performed over a 5-year period (2010 through 2014) at a freestanding endoscopy center serving 13 pediatric gastroenterologists were assessed. Demographic and clinical data on patients were collected and grouped; patients with primary sucrase-isomaltase deficiency (SID) were the main focus. The data were stratified by the physician performing the procedures. Results: Over the 5-year study period, 5368 EGDs were performed, with abdominal pain as the primary indication in 3235 cases (60.2%). DAs were performed on 963 patients (17.9% of the total cohort; 29.8% of those with abdominal pain). Lactase deficiencies, sucrase deficiencies, and primary SID were found in 44.7%, 7.6%, and 3.5% of DAs, respectively. The number of DAs performed varied widely among physicians, ranging from 1.6% to 64.5% of EGDs evaluating patients with abdominal pain. Univariate regression analysis revealed significant correlations between the number of DAs performed and the number of SID and lactase deficiencies found (P<.001 for both). Conclusion: Rates of DAs vary widely among pediatric gastroenterologists performing diagnostic EGDs in children with abdominal pain. Physician education and clinical practice guidelines regarding the use of DAs are warranted. PMID:29491758

What People with Lactose Intolerance Need to Know about Osteoporosis

MedlinePlus

... intestine. Lactase is necessary to digest lactose—the natural sugar found in milk and other dairy products. In the intestines, undigested lactose leads to the buildup of gas. Within 30 minutes to 2 hours after eating ...

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.

Study of enzyme activities in the descending part of the duodenum in patients of duodenal ulcer.

PubMed

Fernandes, V L C; Bhasin, D K; Rana, S V

2006-03-01

The aim of this study was to measure the levels of lactase, sucrase, maltase, leucine amino peptidase and gamma-glutamyl transpeptidase in duodenum of Indian patients with duodenal ulcer. The effect of duodenum inflammation on these brush border enzymes has also been analysed in this study. Levels of lactase, sucrase, maltase, leucine amino peptidase and gamma-glutamyl transpeptidase were assessed in duodenal biopsies of 20 patients of duodenal ulcer and 20 non-ulcer dyspepsia. The duodenal biopsy specimens were also examined histopathologically for presence or absence of inflammation. There was no significant difference (p>0.05) in the activity of above mentioned enzyme levels in both the groups. Only levels of gamma-glutamyl transpeptidase were significantly decreased in patients of duodenal ulcer with duodenal inflammation. This study shows that only the levels of gamma-glutamyl transpeptidase were significantly decreased in patients of duodenal ulcer with inflammation but no change in duodenal enzymes due to duodenal ulcer as compared to non-ulcer dyspepsia.

[Lactose intolerance: past and present. Part II].

PubMed

Buzás, György Miklós

2015-10-25

The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10-750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied.

Working with Enzymes - Where Is Lactose Digested? An Enzyme Assay for Nutritional Biochemistry Laboratories

NASA Astrophysics Data System (ADS)

Pope, Sandi R.; Tolleson, Tonya D.; Williams, R. Jill; Underhill, Russell D.; Deal, S. Todd

1998-06-01

At Georgia Southern University, we offer a sophomore-level introductory biochemistry course that is aimed at nutrition and chemistry education majors. The laboratory portion of this course has long lacked an experimental introduction to enzymes. We have developed a simple enzyme assay utilizing lactase enzyme from crushed LactAid tablets and a 5% lactose solution ("synthetic milk"). In the experiment, the students assay the activity of the enzyme on the "synthetic milk" at pHs of approximately 1, 6, and 8 with the stated goal of determining where lactose functions in the digestive tract. The activity of the lactase may be followed chromatographically or spectrophotometrically. The experiment, which is actually a simple pH assay, is easily implemented in allied health chemistry laboratory courses and readily lends itself to adaptation for more complex kinetic assays in upper-level biochemistry laboratory courses. The experimental details, including a list of required supplies and hints for implementation, are provided.

Direct evidence of milk consumption from ancient human dental calculus.

PubMed

Warinner, C; Hendy, J; Speller, C; Cappellini, E; Fischer, R; Trachsel, C; Arneborg, J; Lynnerup, N; Craig, O E; Swallow, D M; Fotakis, A; Christensen, R J; Olsen, J V; Liebert, A; Montalva, N; Fiddyment, S; Charlton, S; Mackie, M; Canci, A; Bouwman, A; Rühli, F; Gilbert, M T P; Collins, M J

2014-11-27

Milk is a major food of global economic importance, and its consumption is regarded as a classic example of gene-culture evolution. Humans have exploited animal milk as a food resource for at least 8500 years, but the origins, spread, and scale of dairying remain poorly understood. Indirect lines of evidence, such as lipid isotopic ratios of pottery residues, faunal mortality profiles, and lactase persistence allele frequencies, provide a partial picture of this process; however, in order to understand how, where, and when humans consumed milk products, it is necessary to link evidence of consumption directly to individuals and their dairy livestock. Here we report the first direct evidence of milk consumption, the whey protein β-lactoglobulin (BLG), preserved in human dental calculus from the Bronze Age (ca. 3000 BCE) to the present day. Using protein tandem mass spectrometry, we demonstrate that BLG is a species-specific biomarker of dairy consumption, and we identify individuals consuming cattle, sheep, and goat milk products in the archaeological record. We then apply this method to human dental calculus from Greenland's medieval Norse colonies, and report a decline of this biomarker leading up to the abandonment of the Norse Greenland colonies in the 15(th) century CE.

Direct evidence of milk consumption from ancient human dental calculus

PubMed Central

Warinner, C.; Hendy, J.; Speller, C.; Cappellini, E.; Fischer, R.; Trachsel, C.; Arneborg, J.; Lynnerup, N.; Craig, O. E.; Swallow, D. M.; Fotakis, A.; Christensen, R. J.; Olsen, J. V.; Liebert, A.; Montalva, N.; Fiddyment, S.; Charlton, S.; Mackie, M.; Canci, A.; Bouwman, A.; Rühli, F.; Gilbert, M. T. P.; Collins, M. J.

2014-01-01

Milk is a major food of global economic importance, and its consumption is regarded as a classic example of gene-culture evolution. Humans have exploited animal milk as a food resource for at least 8500 years, but the origins, spread, and scale of dairying remain poorly understood. Indirect lines of evidence, such as lipid isotopic ratios of pottery residues, faunal mortality profiles, and lactase persistence allele frequencies, provide a partial picture of this process; however, in order to understand how, where, and when humans consumed milk products, it is necessary to link evidence of consumption directly to individuals and their dairy livestock. Here we report the first direct evidence of milk consumption, the whey protein β-lactoglobulin (BLG), preserved in human dental calculus from the Bronze Age (ca. 3000 BCE) to the present day. Using protein tandem mass spectrometry, we demonstrate that BLG is a species-specific biomarker of dairy consumption, and we identify individuals consuming cattle, sheep, and goat milk products in the archaeological record. We then apply this method to human dental calculus from Greenland's medieval Norse colonies, and report a decline of this biomarker leading up to the abandonment of the Norse Greenland colonies in the 15th century CE. PMID:25429530

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 values for persistency. However, if the breeding goal is to improve only milk yield, the traditional selection index is indicated. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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,…

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

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

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.

Climate-driven range shifts explain the distribution of extant gene pools and predict future loss of unique lineages in a marine brown alga.

PubMed

Assis, J; Serrão, E A; Claro, B; Perrin, C; Pearson, G A

2014-06-01

The climate-driven dynamics of species ranges is a critical research question in evolutionary ecology. We ask whether present intraspecific diversity is determined by the imprint of past climate. This is an ongoing debate requiring interdisciplinary examination of population genetic pools and persistence patterns across global ranges. Previously, contrasting inferences and predictions have resulted from distinct genomic coverage and/or geographical information. We aim to describe and explain the causes of geographical contrasts in genetic diversity and their consequences for the future baseline of the global genetic pool, by comparing present geographical distribution of genetic diversity and differentiation with predictive species distribution modelling (SDM) during past extremes, present time and future climate scenarios for a brown alga, Fucus vesiculosus. SDM showed that both atmospheric and oceanic variables shape the global distribution of intertidal species, revealing regions of persistence, extinction and expansion during glacial and postglacial periods. These explained the distribution and structure of present genetic diversity, consisting of differentiated genetic pools with maximal diversity in areas of long-term persistence. Most of the present species range comprises postglacial expansion zones and, in contrast to highly dispersive marine organisms, expansions involved only local fronts, leaving distinct genetic pools at rear edges. Besides unravelling a complex phylogeographical history and showing congruence between genetic diversity and persistent distribution zones, supporting the hypothesis of niche conservatism, range shifts and loss of unique genetic diversity at the rear edge were predicted for future climate scenarios, impoverishing the global gene pool. © 2014 John Wiley & Sons Ltd.

21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

Code of Federal Regulations, 2010 CFR

2010-04-01

....2.1.23), which converts lactose to glucose and galactose. It is prepared from yeast that has been... defined in § 170.3(o)(9) of this chapter, to convert lactose to glucose and galactose. (2) The ingredient... manufacturing practice is limited to use of this ingredient to reduce the lactose content in milk and milk...

21 CFR 184.1387 - Lactase enzyme preparation from Candida pseudotropicalis.

Code of Federal Regulations, 2011 CFR

2011-04-01

....2.1.23), which converts lactose to glucose and galactose. It is prepared from yeast that has been... defined in § 170.3(o)(9) of this chapter, to convert lactose to glucose and galactose. (2) The ingredient... manufacturing practice is limited to use of this ingredient to reduce the lactose content in milk and milk...

Characterizations of substrate and enzyme specificity of glucoamylase assays of mucosal starch digestion with determinations of group and single biopsy reference values

USDA-ARS?s Scientific Manuscript database

Carbohydrate digesting enzyme activities are measured in duodenal biopsies to detect deficiencies of lactase and sucrase activities, however glucoamylase (GA) assays for starch digestion are not included. Because food starch represents half of energy intake in the human diet, assays for starch diges...

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.

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.

New radiocarbon dates and the herder occupation at Kasteelberg B, South Africa [NEW RADIOCARBON DATES SHED LIGHT ON THE HERDER OCCUPATION SEQUENCE AT KASTEELBERG B, SOUTH AFRICA

DOE PAGES

Sadr, Karim; Bousman, C. Britt; Brown, Thomas A.; ...

2017-09-20

In this paper, we present that five centuries ago, the first European mariners rounding the Cape of Good Hope encountered Khoekhoe-speaking people who occasionally supplied beef and mutton in return for iron, tobacco, alcohol and other exotic goods. The origin of their livestock, as well as of the Khoekhoen themselves, continues to intrigue academics. We now know the first livestock were introduced from the north and that they reached southern Africa over 2000 years ago (Robbins et al. 2005; Pleurdeau et al. 2012). Y-chromosome E3b1f-M293 (Henn et al. 2008) and lactase persistence allele -14010*C (Macholdt et al. 2014) indicate thatmore » some Khoe-speakers are distantly related through the male lineage to pastoralists in East Africa (Barbieri et al. 2014); a conclusion that is supported by linguists who locate the origins of proto-Khoe languages in that part of the continent (e.g., Güldemann 2008). But it remains unclear whether the earliest livestock in southern Africa arrived with immigrant Khoespeakers, or whether the Khoe-speakers arrived later: the first livestock may have been traded down the line or infiltrated among southern African San hunter-gatherers (e.g., Sadr 2015).« less

New radiocarbon dates and the herder occupation at Kasteelberg B, South Africa [NEW RADIOCARBON DATES SHED LIGHT ON THE HERDER OCCUPATION SEQUENCE AT KASTEELBERG B, SOUTH AFRICA

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

Sadr, Karim; Bousman, C. Britt; Brown, Thomas A.

In this paper, we present that five centuries ago, the first European mariners rounding the Cape of Good Hope encountered Khoekhoe-speaking people who occasionally supplied beef and mutton in return for iron, tobacco, alcohol and other exotic goods. The origin of their livestock, as well as of the Khoekhoen themselves, continues to intrigue academics. We now know the first livestock were introduced from the north and that they reached southern Africa over 2000 years ago (Robbins et al. 2005; Pleurdeau et al. 2012). Y-chromosome E3b1f-M293 (Henn et al. 2008) and lactase persistence allele -14010*C (Macholdt et al. 2014) indicate thatmore » some Khoe-speakers are distantly related through the male lineage to pastoralists in East Africa (Barbieri et al. 2014); a conclusion that is supported by linguists who locate the origins of proto-Khoe languages in that part of the continent (e.g., Güldemann 2008). But it remains unclear whether the earliest livestock in southern Africa arrived with immigrant Khoespeakers, or whether the Khoe-speakers arrived later: the first livestock may have been traded down the line or infiltrated among southern African San hunter-gatherers (e.g., Sadr 2015).« less

Population genomics reveals seahorses (Hippocampus erectus) of the western mid-Atlantic coast to be residents rather than vagrants.

PubMed

Boehm, J T; Waldman, John; Robinson, John D; Hickerson, Michael J

2015-01-01

Understanding population structure and areas of demographic persistence and transients is critical for effective species management. However, direct observational evidence to address the geographic scale and delineation of ephemeral or persistent populations for many marine fishes is limited. The Lined seahorse (Hippocampus erectus) can be commonly found in three western Atlantic zoogeographic provinces, though inhabitants of the temperate northern Virginia Province are often considered tropical vagrants that only arrive during warm seasons from the southern provinces and perish as temperatures decline. Although genetics can locate regions of historical population persistence and isolation, previous evidence of Virginia Province persistence is only provisional due to limited genetic sampling (i.e., mitochondrial DNA and five nuclear loci). To test alternative hypotheses of historical persistence versus the ephemerality of a northern Virginia Province population we used a RADseq generated dataset consisting of 11,708 single nucleotide polymorphisms (SNP) sampled from individuals collected from the eastern Gulf of Mexico to Long Island, NY. Concordant results from genomic analyses all infer three genetically divergent subpopulations, and strongly support Virginia Province inhabitants as a genetically diverged and a historically persistent ancestral gene pool. These results suggest that individuals that emerge in coastal areas during the warm season can be considered "local" and supports offshore migration during the colder months. This research demonstrates how a large number of genes sampled across a geographical range can capture the diversity of coalescent histories (across loci) while inferring population history. Moreover, these results clearly demonstrate the utility of population genomic data to infer peripheral subpopulation persistence in difficult-to-observe species.

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...

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

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.

The role of hybridization in the origin and spread of asexuality in Daphnia

PubMed Central

Xu, Sen; Innes, David J.; Lynch, Michael; Cristescu, Melania E.

2014-01-01

The molecular mechanisms leading to asexuality remain little understood despite their substantial bearing on why sexual reproduction is dominant in nature. Here we examine the role of hybridization in the origin and spread of obligate asexuality in Daphnia pulex, arguably the best-documented case of contagious asexuality. Obligately parthenogenetic (OP) clones of D. pulex have traditionally been separated into “hybrid” (Ldh SF) and “non-hybrid” (Ldh SS) forms because the lactase dehydrogenase (Ldh) locus distinguishes the cyclically parthenogenetic (CP) lake dwelling Daphnia pulicaria (Ldh FF) from its ephemeral pond dwelling sister species D. pulex (Ldh SS). The results of our population genetic analyses based on microsatellite loci suggest that both Ldh SS and SF OP individuals can originate from the crossing of CP female F1 (D. pulex × D. pulicaria) and backcrosses with males from OP lineages carrying genes that suppress meiosis specifically in female offspring. In previous studies, a suite of diagnostic markers was found to be associated with OP in Ldh SS D. pulex lineages. Our association mapping supports a similar genetic mechanism for the spread of obligate parthenogenesis in Ldh SF OP individuals. Interestingly, our study shows that CP D. pulicaria carry many of the diagnostic microsatellite alleles associated with obligate parthenogenesis. We argue that the assemblage of mutations that suppress meiosis and underlie obligate parthenogenesis in D. pulex originated due to a unique historical hybridization and introgression event between D. pulex and D. pulicaria. PMID:23879327

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.

First-pass uptake and oxidation of glucose by the splanchnic tissue in young goats fed soy protein-based milk diets with or without amino acid supplementation: glucose metabolism in goat kids after soy feeding.

PubMed

Schönhusen, U; Junghans, P; Flöter, A; Steinhoff-Wagner, J; Görs, S; Schneider, F; Metges, C C; Hammon, H M

2013-04-01

The study was designed to examine whether feeding soy protein isolate as partial replacement of casein (CN) affects glucose metabolism in young goats and whether effects may be ameliorated by supplementation of those AA known to be lower concentrated in soy than in CN. Goat kids (d 20 of age) were fed comparable milk protein diets, in which 50% of the crude protein was either CN (control, CON), soy protein isolate (SPI), or soy protein isolate supplemented with AA (SPIA) for 43 d (n=8 per group). On d 62 of age, a single bolus dose of d-[(13)C6]glucose (10mg/kg of BW) was given with the morning diet, and simultaneously, a single bolus dose of d-[6,6-(2)H2]glucose (5mg/kg of BW) was injected into a jugular vein. Blood samples were collected between -30 and +420 min relative to the tracer administration to measure the (13)C and (2)H enrichments of plasma glucose and the (13)C enrichment of blood CO2. Glucose first-pass uptake by the splanchnic tissues was calculated from the rate of appearance of differentially labeled glucose tracer in plasma. Glucose oxidation was calculated from (13)C enrichment in blood CO2. In addition, plasma concentrations of triglycerides, nonesterified fatty acids, glucose, insulin, and glucagon were measured. On d 63 of age, kids were killed and jejunal mucosa and liver samples were collected to measure lactase mRNA levels and lactase and maltase activities in the jejunum and activities of pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK) in the liver. Basal plasma glucose concentration tended to be higher in the CON than the SPIA group, whereas basal insulin was higher in the CON group than the SPI and SPIA groups, and glucagon was higher in the CON than the SPIA group. Plasma glucose and insulin concentrations increased during the first hour after feeding, whereas plasma glucagon increased immediately after feeding and after 1h of feeding. First-pass uptake and glucose oxidation were not affected by diet. Maltase activities in proximal and mid jejunum and lactase activities in mid jejunum were lower in the CON than in the SPIA group. Activities of PEPCK were higher in the SPIA than in the SPI group. In conclusion, feeding milk diets with soy protein isolate seems to affect glucose status in kids, but has no effect on first-pass uptake and oxidation of glucose. The highest activities of lactase and maltase were observed after supplementation with AA. Higher PEPCK activities in the liver may point at elevated gluconeogenic activities after AA supplementation in soy-fed kids. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Population Genomics Reveals Seahorses (Hippocampus erectus) of the Western Mid-Atlantic Coast to Be Residents Rather than Vagrants

PubMed Central

Boehm, J. T.; Waldman, John; Robinson, John D.; Hickerson, Michael J.

2015-01-01

Understanding population structure and areas of demographic persistence and transients is critical for effective species management. However, direct observational evidence to address the geographic scale and delineation of ephemeral or persistent populations for many marine fishes is limited. The Lined seahorse (Hippocampus erectus) can be commonly found in three western Atlantic zoogeographic provinces, though inhabitants of the temperate northern Virginia Province are often considered tropical vagrants that only arrive during warm seasons from the southern provinces and perish as temperatures decline. Although genetics can locate regions of historical population persistence and isolation, previous evidence of Virginia Province persistence is only provisional due to limited genetic sampling (i.e., mitochondrial DNA and five nuclear loci). To test alternative hypotheses of historical persistence versus the ephemerality of a northern Virginia Province population we used a RADseq generated dataset consisting of 11,708 single nucleotide polymorphisms (SNP) sampled from individuals collected from the eastern Gulf of Mexico to Long Island, NY. Concordant results from genomic analyses all infer three genetically divergent subpopulations, and strongly support Virginia Province inhabitants as a genetically diverged and a historically persistent ancestral gene pool. These results suggest that individuals that emerge in coastal areas during the warm season can be considered “local” and supports offshore migration during the colder months. This research demonstrates how a large number of genes sampled across a geographical range can capture the diversity of coalescent histories (across loci) while inferring population history. Moreover, these results clearly demonstrate the utility of population genomic data to infer peripheral subpopulation persistence in difficult-to-observe species. PMID:25629166

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.

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

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.

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

Longevity of clonal plants: why it matters and how to measure it

PubMed Central

de Witte, Lucienne C.; Stöcklin, Jürg

2010-01-01

Background Species' life-history and population dynamics are strongly shaped by the longevity of individuals, but life span is one of the least accessible demographic traits, particularly in clonal plants. Continuous vegetative reproduction of genets enables persistence despite low or no sexual reproduction, affecting genet turnover rates and population stability. Therefore, the longevity of clonal plants is of considerable biological interest, but remains relatively poorly known. Scope Here, we critically review the present knowledge on the longevity of clonal plants and discuss its importance for population persistence. Direct life-span measurements such as growth-ring analysis in woody plants are relatively easy to take, although, for many clonal plants, these methods are not adequate due to the variable growth pattern of ramets and difficult genet identification. Recently, indirect methods have been introduced in which genet size and annual shoot increments are used to estimate genet age. These methods, often based on molecular techniques, allow the investigation of genet size and age structure of whole populations, a crucial issue for understanding their viability and persistence. However, indirect estimates of clonal longevity are impeded because the process of ageing in clonal plants is still poorly understood and because their size and age are not always well correlated. Alternative estimators for genet life span such as somatic mutations have recently been suggested. Conclusions Empirical knowledge on the longevity of clonal species has increased considerably in the last few years. Maximum age estimates are an indicator of population persistence, but are not sufficient to evaluate turnover rates and the ability of long-lived clonal plants to enhance community stability and ecosystem resilience. In order to understand the dynamics of populations it will be necessary to measure genet size and age structure, not only life spans of single individuals, and to use such data for modelling of genet dynamics. PMID:20880935

Heritability of Respiratory Infection with Pseudomonas aeruginosa in Cystic Fibrosis

PubMed Central

Green, Deanna M.; Collaco, J. Michael; McDougal, Kathryn E.; Naughton, Kathleen M.; Blackman, Scott M.; Cutting, Garry R.

2013-01-01

Objective To quantify the relative contribution of factors other than cystic fibrosis transmembrane conductance regulator genotype and environment on the acquisition of Pseudomonas aeruginosa (Pa) by patients with cystic fibrosis. Study design Lung infection with Pa and mucoid Pa was assessed using a co-twin study design of 44 monozygous (MZ) and 17 dizygous (DZ) twin pairs. Two definitions were used to establish infection: first positive culture and persistent positive culture. Genetic contribution to infection (ie, heritability) was estimated based on concordance analysis, logistic regression, and age at onset of infection through comparison of intraclass correlation coefficients. Results Concordance for persistent Pa infection was higher in MZ (0.83; 25 of 30 pairs) than DZ twins (0.45; 5 of 11 pairs), generating a heritability of 0.76. Logistic regression adjusted for age corroborated genetic control of persistent Pa infection. The correlation for age at persistent Pa infection was higher in MZ twins (0.589; 95% CI, 0.222-0.704) than in DZ twins (0.162; 95% CI, −0.352 to 0.607), generating a heritability of 0.85. Conclusion Genetic modifiers play a significant role in the establishment and timing of persistent Pa infection in individuals with cystic fibrosis. PMID:22364820

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

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.

[Lactose-containing tablets for patients with lactose intolerance?].

PubMed

Picksak, Gesine; Stichtenoth, Dirk O

2009-01-01

Lactose is often used as an excipient in tablets because of its ideal characteristics. Most patients with lactose intolerance tolerate small amounts of lactose. However, the nocebo effect must be considered. Thus, patients should be informed about the very small amounts of lactose in the medication. If the patient is still suffering from gastrointestinal symptoms and there is no lactose-free alternative, the enzyme lactase can be substituted individually.

Proceedings of the Natick Science Symposium (4th) Held in Natick, Massachusetts on 9-10 June 1992

DTIC Science & Technology

1992-09-01

HQ - hydroquinone; MG - methyl gallate; CA - caffeic acid ; CHIA - chlorogenic acid ; GA - gallic acid ; FOLY - polymeric antioxidant. Values shown...examples 268 FQRrER & BIACK (qu~tin, hydroquinone, caffeic acid , chlorogenic acid and gallic acid ) , these are relatively ineffective in HSV...unless covalently bonded to the membrane. 279 SENECAL & RAND A membrane lactase reactor, modelled after the mammalian small intestine, has been

Immunological implications of pregnancy-induced microchimerism

PubMed Central

Kinder, Jeremy M.; Stelzer, Ina A.; Arck, Petra C.; Way, Sing Sing

2017-01-01

Immunological identity is traditionally defined by genetically encoded antigens, with equal maternal and paternal contributions as a result of Mendelian inheritance. However, vertically transferred maternal cells also persist in individuals at very low levels throughout postnatal development. Reciprocally, mothers are seeded during pregnancy with genetically foreign fetal cells that persist long after parturition. Recent findings suggest that these microchimeric cells expressing noninherited familially relevant antigenic traits are not accidental souvenirs of pregnancy, but are purposefully retained within mothers and their offspring to promote genetic fitness by improving the outcome of future pregnancies. Here, we discuss the immunological implications, benefits and potential consequences of individuals being constitutively chimeric with a biologically active ‘microchiome’ of genetically foreign cells. PMID:28480895

Novel epoxy activated hydrogels for solving lactose intolerance.

PubMed

Elnashar, Magdy M M; Hassan, Mohamed E

2014-01-01

"Lactose intolerance" is a medical problem for almost 70% of the world population. Milk and dairy products contain 5-10% w/v lactose. Hydrolysis of lactose by immobilized lactase is an industrial solution. In this work, we succeeded to increase the lactase loading capacity to more than 3-fold to 36.3 U/g gel using epoxy activated hydrogels compared to 11 U/g gel using aldehyde activated carrageenan. The hydrogel's mode of interaction was proven by FTIR, DSC, and TGA. The high activity of the epoxy group was regarded to its ability to attach to the enzyme's -SH, -NH, and -OH groups, whereas the aldehyde group could only bind to the enzyme's -NH2 group. The optimum conditions for immobilization such as epoxy chain length and enzyme concentration have been studied. Furthermore, the optimum enzyme conditions were also deliberated and showed better stability for the immobilized enzyme and the Michaelis constants, K m and V max, were doubled. Results revealed also that both free and immobilized enzymes reached their maximum rate of lactose conversion after 2 h, albeit, the aldehyde activated hydrogel could only reach 63% of the free enzyme. In brief, the epoxy activated hydrogels are more efficient in immobilizing more enzymes than the aldehyde activated hydrogel.

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 regression of both 305-d yield and 305-d yield and lactation persistency on 400-d yield. Goodness-of-fit was very good for both models, but the addition of lactation persistency to the model significantly improved fit in all cases. Routine genetic evaluations for lactation persistency, as well as the development of prediction equations for several lactation end-points, may provide producers with tools to better manage their herds.

The evolution of dual meat and milk cattle husbandry in Linearbandkeramik societies

PubMed Central

Kovačiková, Lenka; Bréhard, Stéphanie; Guthmann, Emilie; Vostrovská, Ivana; Nohálová, Hana; Arbogast, Rose-Marie; Domboróczki, László; Pechtl, Joachim; Anders, Alexander; Marciniak, Arkadiusz; Tresset, Anne; Vigne, Jean-Denis

2017-01-01

Cattle dominate archaeozoological assemblages from the north-central Europe between the sixth and fifth millennium BC and are frequently considered as exclusively used for their meat. Dairy products may have played a greater role than previously believed. Selective pressure on the lactase persistence mutation has been modelled to have begun between 6000 and 4000 years ago in central Europe. The discovery of milk lipids in late sixth millennium ceramic sieves in Poland may reflect an isolated regional peculiarity for cheese making or may signify more generalized milk exploitation in north-central Europe during the Early Neolithic. To investigate these issues, we analysed the mortality profiles based on age-at-death analysis of cattle tooth eruption, wear and replacement from 19 archaeological sites of the Linearbandkeramik (LBK) culture (sixth to fifth millennium BC). The results indicate that cattle husbandry was similar across time and space in the LBK culture with a degree of specialization for meat exploitation in some areas. Statistical comparison with reference age-at-death profiles indicate that mixed husbandry (milk and meat) was practised, with mature animals being kept. The analysis provides a unique insight into LBK cattle husbandry and how it evolved in later cultures in central and western Europe. It also opens a new perspective on how and why the Neolithic way of life developed through continental Europe and how dairy products became a part of the human diet. PMID:28768891

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.

[Lactose malabsorption and -intolerance - who will benefit from a lactose-reduced diet?

PubMed

Malham, Mikkel; Olin, Anne Bille; Pærregaard, Anders

2017-02-06

During the last decade, lactose-free diets have become increasingly popular in the general population, either isolated or as a part of a cow's milk-free diet. However, health-related benefits from a lactose-free diet are only documented for individuals with clinical lactose intolerance due to decreased intestinal lactase activity and subsequent lactose malabsorption. In this paper we summarize the current knowledge of lactose intolerance regarding diagnostic procedures and treatment.

AFLP markers reveal high clonal diversity and extreme longevity in four key arctic-alpine species.

PubMed

de Witte, Lucienne C; Armbruster, Georg F J; Gielly, Ludovic; Taberlet, Pierre; Stöcklin, Jürg

2012-03-01

We investigated clonal diversity, genet size structure and genet longevity in populations of four arctic-alpine plants (Carex curvula, Dryas octopetala, Salix herbacea and Vaccinium uliginosum) to evaluate their persistence under past climatic oscillations and their potential resistance to future climate change. The size and number of genets were determined by an analysis of amplified fragment length polymorphisms and a standardized sampling design in several European arctic-alpine populations, where these species are dominant in the vegetation. Genet age was estimated by dividing the size by the annual horizontal size increment from in situ growth measurements. Clonal diversity was generally high but differed among species, and the frequency distribution of genet size was strongly left-skewed. The largest C. curvula genet had an estimated minimum age of c. 4100 years and a maximum age of c. 5000 years, although 84.8% of the genets in this species were <200 years old. The oldest genets of D. octopetala, S. herbacea and V. uliginosum were found to be at least 500, 450 and 1400 years old, respectively. These results indicate that individuals in the studied populations have survived pronounced climatic oscillations, including the Little Ice Age and the postindustrial warming. The presence of genets in all size classes and the dominance of presumably young individuals suggest repeated recruitment over time, a precondition for adaptation to changing environmental conditions. Together, persistence and continuous genet turnover may ensure maximum ecosystem resilience. Thus, our results indicate that long-lived clonal plants in arctic-alpine ecosystems can persist, despite considerable climatic change. © 2011 Blackwell Publishing Ltd.

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

PHENOTYPIC DIFFERENTIATION AT SOUTHERN LIMIT BORDERS: THE CASE STUDY OF TWO FUCOID MACROALGAL SPECIES WITH DIFFERENT LIFE-HISTORY TRAITS1.

PubMed

Araújo, Rita; Serrão, Ester A; Sousa-Pinto, Isabel; Åberg, Per

2011-06-01

Marginal populations are often geographically isolated, smaller, and more fragmented than central populations and may frequently have to face suboptimal local environmental conditions. Persistence of these populations frequently involves the development of adaptive traits at phenotypic and genetic levels. We compared population structure and demographic variables in two fucoid macroalgal species contrasting in patterns of genetic diversity and phenotypic plasticity at their southern distribution limit with a more central location. Models were Ascophyllum nodosum (L.) Le Jol. (whose extreme longevity and generation overlap may buffer genetic loss by drift) and Fucus serratus L. (with low genetic diversity at southern margins). At edge locations, both species exhibited trends in life-history traits compatible with population persistence but by using different mechanisms. Marginal populations of A. nodosum had higher reproductive output in spite of similar mortality rates at all life stages, making edge populations denser and with smaller individuals. In F. serratus, rather than demographic changes, marginal populations differed in habitat, occurring restricted to a narrower vertical habitat range. We conclude that persistence of both A. nodosum and F. serratus at the southern-edge locations depends on different strategies. Marginal population persistence in A. nodosum relies on a differentiation in life-history traits, whereas F. serratus, putatively poorer in evolvability potential, is restricted to a narrower vertical range at border locations. These results contribute to the general understanding of mechanisms that lead to population persistence at distributional limits and to predict population resilience under a scenario of environmental change. © 2011 Phycological Society of America.

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…

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.

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

Age of onset and the subclassification of conduct/dissocial disorder

PubMed Central

Silberg, Judy; Moore, Ashlee A.; Rutter, Michael

2015-01-01

Background Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. Methods The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Results Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Conclusions Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood. PMID:25359313

Age of onset and the subclassification of conduct/dissocial disorder.

PubMed

Silberg, Judy; Moore, Ashlee A; Rutter, Michael

2015-07-01

Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurrence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood. © 2014 Association for Child and Adolescent Mental Health.

Testing Models for the Contributions of Genes and Environment to Developmental Change in Adolescent Depression

PubMed Central

Eaves, Lindon J.; Maes, Hermine; Silberg, Judy L.

2015-01-01

We tested two models to identify the genetic and environmental processes underlying longitudinal changes in depression among adolescents. The first assumes that observed changes in covariance structure result from the unfolding of inherent, random individual differences in the overall levels and rates of change in depression over time (random growth curves). The second assumes that observed changes are due to time-specific random effects (innovations) accumulating over time (autoregressive effects). We found little evidence of age-specific genetic effects or persistent genetic innovations. Instead, genetic effects are consistent with a gradual unfolding in the liability to depression and rates of change with increasing age. Likewise, the environment also creates significant individual differences in overall levels of depression and rates of change. However, there are also time-specific environmental experiences that persist with fidelity. The implications of these differing genetic and environmental mechanisms in the etiology of depression are considered. PMID:25894924

Testing Models for the Contributions of Genes and Environment to Developmental Change in Adolescent Depression.

PubMed

Gillespie, Nathan A; Eaves, Lindon J; Maes, Hermine; Silberg, Judy L

2015-07-01

We tested two models to identify the genetic and environmental processes underlying longitudinal changes in depression among adolescents. The first assumes that observed changes in covariance structure result from the unfolding of inherent, random individual differences in the overall levels and rates of change in depression over time (random growth curves). The second assumes that observed changes are due to time-specific random effects (innovations) accumulating over time (autoregressive effects). We found little evidence of age-specific genetic effects or persistent genetic innovations. Instead, genetic effects are consistent with a gradual unfolding in the liability to depression and rates of change with increasing age. Likewise, the environment also creates significant individual differences in overall levels of depression and rates of change. However, there are also time-specific environmental experiences that persist with fidelity. The implications of these differing genetic and environmental mechanisms in the etiology of depression are considered.

Incidence, size and spatial structure of clones in second-growth stands of coast redwood, Sequoia sempervirens (Cupressaceae).

PubMed

Douhovnikoff, Vladimir; Cheng, Adelaide M; Dodd, Richard S

2004-07-01

The ecology and evolutionary potential of coast redwood (Sequoia sempervirens) is significantly influenced by the important role clonal spread plays in its reproduction and site persistence. In nine second-growth stands, amplified fragment length polymorphisms (AFLPs) were used to identify redwood clonal architecture. Clones (multistem genets) dominated sites by representing an average of 70% of stems measured, ranging in size from two to 20 stems. As a result, a relatively small number of genets can monopolize a disproportionate amount of site resources, are more likely to persist over time, and have greater on-site genetic representation. Clones were not limited to fairy-ring structures, but consisted of a wide range of shapes including concentric rings, ring chains, disjunct, and linear structures. Between-ramet distances of up to 40 m were measured, indicating that clonal reproduction is not limited to basal stump resprouting. Clonal structure in second-growth stands was similar to earlier reports from old growth, emphasizing the importance of site persistence and long-term, gradual site development. Smaller ramet numbers per genet in old growth is probably due to local within-genet self thinning. Management and conservation of redwoods will benefit from a better understanding of the dynamics and structure of clonal spread in these forests.

Digestive enzyme expression and epithelial structure of small intestine in neonatal rats after 16 days spaceflight

NASA Astrophysics Data System (ADS)

Miyake, M.; Yamasaki, M.; Hazama, A.; Ijiri, K.; Shimizu, T.

It is important to assure whether digestive system can develop normally in neonates during spaceflight. Because the small intestine changes its function and structure drastically around weaning known as redifferentiation. Lactase expression declines and sucrase increases in small intestine for digestion of solid food before weaning. In this paper, we compared this enzyme transition and structural development of small intestine in neonatal rats after spaceflight. To find digestive genes differentially expressed in fight rats, DNA membrane macroarray was also used. Eight-day old rats were loaded to Space Shuttle Columbia, and housed in the animal facility for 16 days in space (STS-90, Neurolab mission). Two control groups (AGC; asynchronous ground control and VIV; vivarium) against flight group (FLT) were prepared. There was no difference in structure (crypt depth) and cell differentiation of epithelium between FLT and AGC by immunohistochemical analysis. We found that the amount of sucrase mRNA compared to lactase was decreased in FLT by RT-PCR. It reflected the enzyme transition was inhibited. Increase of 5 genes (APO A-I, APO A-IV, ACE, aFABP and aminopeptidase M) and decrease of carboxypeptidase-D were detected in FLT using macroarray. We think nutrition differences (less nourishment and late weaning) during spaceflight may cause inhibition of enzyme transition at least partly. The weightlessness might contribute to the inhibition through behavioral change.

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...

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...

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

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

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

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.

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

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

A fine-scale assessment of using barriers to conserve native stream salmonids: a case study in Akokala Creek, Glacier National Park, USA

USGS Publications Warehouse

Muhlfeld, Clint C.; D'Angelo, Vincent S.; S. T. Kalinowski,; Landguth, Erin L.; C. C. Downs,; J. Tohtz,; Kershner, Jeffrey L.

2012-01-01

Biologists are often faced with the difficult decision in managing native salmonids of where and when to install barriers as a conservation action to prevent upstream invasion of nonnative fishes. However, fine-scale approaches to assess long-term persistence of populations within streams and watersheds chosen for isolation management are often lacking. We employed a spatially-explicit approach to evaluate stream habitat conditions, relative abundance, and genetic diversity of native westslope cutthroat trout (Oncorhynchus clarkii lewisi) within the Akokala Creek watershed in Glacier National Park- a population threatened by introgressive hybridization with nonnative rainbow trout (O. mykiss) from nearby sources. The systematic survey of 24 stream reaches showed broad overlap in fish population and suitable habitat characteristics among reaches and no natural barriers to fish migration were found. Analysis of population structure using 16 microsatellite loci showed modest amounts of genetic diversity among reaches, and that fish from Long Bow Creek were the only moderately distinct genetic group. We then used this information to assess the potential impacts of three barrier placement scenarios on long-term population persistence and genetic diversity. The two barrier placement scenarios in headwater areas generally failed to meet general persistence criteria for minimum population size (2,500 individuals, Ne = 500), maintenance of long-term genetic diversity (He), and no population subdivision. Conversely, placing a barrier near the stream mouth and selectively passing non-hybridized, migratory spawners entering Akokala Creek met all persistence criteria and may offer the best option to conserve native trout populations and life history diversity. Systematic, fine-scale stream habitat, fish distribution, and genetic assessments in streams chosen for barrier installation are needed in conjunction with broader scale assessments to understand the potential impacts of using barriers for conservation of native salmonid populations threatened by nonnative fish invasions.

Detecting and Characterizing Genomic Signatures of Positive Selection in Global Populations

PubMed Central

Liu, Xuanyao; Ong, Rick Twee-Hee; Pillai, Esakimuthu Nisha; Elzein, Abier M.; Small, Kerrin S.; Clark, Taane G.; Kwiatkowski, Dominic P.; Teo, Yik-Ying

2013-01-01

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event. PMID:23731540

The evolution of dual meat and milk cattle husbandry in Linearbandkeramik societies.

PubMed

Gillis, Rosalind E; Kovačiková, Lenka; Bréhard, Stéphanie; Guthmann, Emilie; Vostrovská, Ivana; Nohálová, Hana; Arbogast, Rose-Marie; Domboróczki, László; Pechtl, Joachim; Anders, Alexandra; Marciniak, Arkadiusz; Tresset, Anne; Vigne, Jean-Denis

2017-08-16

Cattle dominate archaeozoological assemblages from the north-central Europe between the sixth and fifth millennium BC and are frequently considered as exclusively used for their meat. Dairy products may have played a greater role than previously believed. Selective pressure on the lactase persistence mutation has been modelled to have begun between 6000 and 4000 years ago in central Europe. The discovery of milk lipids in late sixth millennium ceramic sieves in Poland may reflect an isolated regional peculiarity for cheese making or may signify more generalized milk exploitation in north-central Europe during the Early Neolithic. To investigate these issues, we analysed the mortality profiles based on age-at-death analysis of cattle tooth eruption, wear and replacement from 19 archaeological sites of the Linearbandkeramik (LBK) culture (sixth to fifth millennium BC). The results indicate that cattle husbandry was similar across time and space in the LBK culture with a degree of specialization for meat exploitation in some areas. Statistical comparison with reference age-at-death profiles indicate that mixed husbandry (milk and meat) was practised, with mature animals being kept. The analysis provides a unique insight into LBK cattle husbandry and how it evolved in later cultures in central and western Europe. It also opens a new perspective on how and why the Neolithic way of life developed through continental Europe and how dairy products became a part of the human diet. © 2017 The Authors.

Molecular epidemiology, cancer-related symptoms, and cytokines pathway

PubMed Central

Reyes-Gibby, Cielito C; Wu, Xifeng; Spitz, Margaret; Kurzrock, Razelle; Fisch, Michael; Bruera, Eduardo; Shete, Sanjay

2012-01-01

The Human Genome Project and HapMap have led to a better appreciation of the importance of common genetic variation in determining cancer risk, created potential for predicting response to therapy, and made possible the development of targeted prevention and therapeutic interventions. Advances in molecular epidemiology can be used to explore the role of genetic variation in modulating the risk for severe and persistent symptoms, such as pain, depression, and fatigue, in patients with cancer. The same genes that are implicated in cancer risk might also be involved in the modulation of therapeutic outcomes. For example, polymorphisms in several cytokine genes are potential markers for genetic susceptibility both for cancer risk and for cancer-related symptoms. These genetic polymorphisms are stable markers and easily and reliably assayed to explore the extent to which genetic variation might prove useful in identifying patients with cancer at high-risk of symptom development. Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalised and more effective therapies for persistent symptoms. PMID:18672213

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…

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…

Geneticization of deviant behavior and consequences for stigma: the case of mental illness.

PubMed

Phelan, Jo C

2005-12-01

One likely consequence of the genetics revolution is an increased tendency to understand human behavior in genetic terms. How might this "geneticization" affect stigma? Attribution theory predicts a reduction in stigma via reduced blame, anger, and punishment and increased sympathy and help. According to "genetic essentialist" thinking, genes are the basis of human identity and strongly deterministic of behavior. If such ideas are commonly accepted, geneticization should exacerbate stigma by increasing perceptions of differentness, persistence, seriousness, and transmissibility, which in turn should increase social distance and reproductive restrictiveness. I test these predictions using the case of mental illness and a vignette experiment embedded in a nationally representative survey. There was little support for attribution theory predictions. Consistent with genetic essentialism, genetic attributions increased the perceived seriousness and persistence of the mental illness and the belief that siblings and children would develop the same problem. Genetic attribution did not affect reproductive restrictiveness or social distance from the ill person but did increase social distance from the person's sibling, particularly regarding intimate forms of contact involving dating, marriage, and having children.

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

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.

Extinction and recolonization of maritime Antarctica in the limpet Nacella concinna (Strebel, 1908) during the last glacial cycle: toward a model of Quaternary biogeography in shallow Antarctic invertebrates.

PubMed

González-Wevar, C A; Saucède, T; Morley, S A; Chown, S L; Poulin, E

2013-10-01

Quaternary glaciations in Antarctica drastically modified geographical ranges and population sizes of marine benthic invertebrates and thus affected the amount and distribution of intraspecific genetic variation. Here, we present new genetic information in the Antarctic limpet Nacella concinna, a dominant Antarctic benthic species along shallow ice-free rocky ecosystems. We examined the patterns of genetic diversity and structure in this broadcast spawner along maritime Antarctica and from the peri-Antarctic island of South Georgia. Genetic analyses showed that N. concinna represents a single panmictic unit in maritime Antarctic. Low levels of genetic diversity characterized this population; its median-joining haplotype network revealed a typical star-like topology with a short genealogy and a dominant haplotype broadly distributed. As previously reported with nuclear markers, we detected significant genetic differentiation between South Georgia Island and maritime Antarctica populations. Higher levels of genetic diversity, a more expanded genealogy and the presence of more private haplotypes support the hypothesis of glacial persistence in this peri-Antarctic island. Bayesian Skyline plot and mismatch distribution analyses recognized an older demographic history in South Georgia. Approximate Bayesian computations did not support the persistence of N. concinna along maritime Antarctica during the last glacial period, but indicated the resilience of the species in peri-Antarctic refugia (South Georgia Island). We proposed a model of Quaternary Biogeography for Antarctic marine benthic invertebrates with shallow and narrow bathymetric ranges including (i) extinction of maritime Antarctic populations during glacial periods; (ii) persistence of populations in peri-Antarctic refugia; and (iii) recolonization of maritime Antarctica following the deglaciation process. © 2013 John Wiley & Sons Ltd.

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...

Facile Fabrication of Microparticles with pH-responsive Macropores for Small Intestine Targeted Drug Formulation.

PubMed

Homayun, Bahman; Sun, Chengmeng; Kumar, Ankit; Montemagno, Carlo; Choi, Hyo-Jick

2018-05-10

Oral drugs present the most convenient, economical, and painless route for self-administration. Despite commercialization of multiple technologies relying on micro- and nanocrystalline drugs, research on microparticles (MPs) based oral biopharmaceuticals delivery systems has still not culminated well enough in commercial products. This is largely due to the drugs being exposed to the destabilizing environment during MP synthesis process, and partly because of complicated process conditions. Hence, we developed a solvent swelling-evaporation method of producing pH-responsive MPs with micron-sized macropores using poly(methacrylic acid-co-ethyl acrylate) in 1:1 ratio (commercial name: Eudragit ® L100-55 polymer). We investigated the effects of temperature and evaporation time on pore formation, freeze-drying induced pore closure, and the release profile of model drugs (fluorescent beads, lactase, and pravastatin sodium) encapsulated MPs in simulated gastrointestinal tract conditions. Encapsulated lactase/pravastatin maintained > 60% of their activity due to the preservation of pore closure, which proved the potential of this proof-of-concept microencapsulation system. Importantly, the presence of macropores on MPs can be beneficial for easy drug loading, and solve the problem of bioactivity loss during the conventional MP fabrication-drug encapsulation steps. Therefore, pH-sensing MPs with macropores can contribute to the development of oral drug formulations for a wide variety of drugs and bio-macromolecules, having a various size ranging from genes to micron-sized ingredients with high therapeutic efficacy. Copyright © 2018. Published by Elsevier B.V.

Assessment of Lactose-Free Diet on the Phalangeal Bone Mineral Status in Italian Adolescents Affected by Adult-Type Hypolactasia

PubMed Central

Tagliati, Sylvie; Saccomandi, Daniela; Brusaferro, Andrea; Busoli, Laura; Scala, Andrea; Malaventura, Cristina; Borgna-Pignatti, Caterina

2018-01-01

Adult-type hypolactasia (ATH) is a clinical syndrome of primary lactase deficiency. A lactose-free diet is advisable to avoid the symptoms linked to the condition, but this potentially creates problems for optimal bone mineralization due to reduced calcium intake. To evaluate the effect of the lactose-free diet on the bone mineral status (BMS), we compared the phalangeal BMS of adolescents with ATH to that of peers on a normal diet. Also, we analyzed the correlations between BMS and dietary behavior, physical exercise, and calcium and vitamin D intake. A total of 102 cases and 102 healthy controls filled out a diet record and underwent phalangeal Quantitative Ultrasound (QUS). No difference in BMS was observed. The time spent on lactose-free diet (4.8 ± 3.1 years) was inversely correlated to the BMS. More than 98% of cases consumed lactose-free milk, but calcium and vitamin D intake were significantly lower. Calcium intake was correlated to physical exercise but not to BMS. Our results suggest that a lactose-free diet does not affect the phalangeal BMS of adolescents with primary lactase deficiency when their diet includes lactose-free cow’s milk. However, there is still a significantly lower calcium intake than in the population reference. The inverse correlation observed between the BMS and the time spent on a lactose-free diet suggests that a long-term follow-up is advisable. PMID:29723971

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.

Phenotypic switching in bacteria

NASA Astrophysics Data System (ADS)

Merrin, Jack

Living matter is a non-equilibrium system in which many components work in parallel to perpetuate themselves through a fluctuating environment. Physiological states or functionalities revealed by a particular environment are called phenotypes. Transitions between phenotypes may occur either spontaneously or via interaction with the environment. Even in the same environment, genetically identical bacteria can exhibit different phenotypes of a continuous or discrete nature. In this thesis, we pursued three lines of investigation into discrete phenotypic heterogeneity in bacterial populations: the quantitative characterization of the so-called bacterial persistence, a theoretical model of phenotypic switching based on those measurements, and the design of artificial genetic networks which implement this model. Persistence is the phenotype of a subpopulation of bacteria with a reduced sensitivity to antibiotics. We developed a microfluidic apparatus, which allowed us to monitor the growth rates of individual cells while applying repeated cycles of antibiotic treatments. We were able to identify distinct phenotypes (normal and persistent) and characterize the stochastic transitions between them. We also found that phenotypic heterogeneity was present prior to any environmental cue such as antibiotic exposure. Motivated by the experiments with persisters, we formulated a theoretical model describing the dynamic behavior of several discrete phenotypes in a periodically varying environment. This theoretical framework allowed us to quantitatively predict the fitness of dynamic populations and to compare survival strategies according to environmental time-symmetries. These calculations suggested that persistence is a strategy used by bacterial populations to adapt to fluctuating environments. Knowledge of the phenotypic transition rates for persistence may provide statistical information about the typical environments of bacteria. We also describe a design of artificial genetic networks that would implement a more general theoretical model of phenotypic switching. We will use a new cloning strategy in order to systematically assemble a large number of genetic features, such as site-specific recombination components from the R64 plasmid, which invert several coexisting DNA segments. The inversion of these segments would lead to discrete phenotypic transitions inside a living cell. These artificial phenotypic switches can be controlled precisely in experiments and may serve as a benchmark for their natural counterparts.

DECOMPOSTION OF GENETICALLY ENGINEERED TOBACCO UNDER FIELD CONDITIONS: PERSISTENCE OF THE PROTEINASE INHIBITOR I PRODUCT AND EFFECTS OF SOIL MICROBIAL RESPIRATION AND PROTOZOA, NEMATODE AND MICROARTHR

EPA Science Inventory

1. To evaluate the potential effects of genetically engineered (transgenic) plants on soil ecosystems, litterbags containing leaves of non-engineered (parental) and transgenic tobacco plants were buried in field plots. The transgenic tobacco plants were genetically engineered to ...

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...

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.

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...

Family of Origin, Race/Ethnicity, and Socioeconomic Attainment: Genotype and Intraindividual Processes

ERIC Educational Resources Information Center

Wickrama, K. A. S.; O'Neal, Catherine Walker

2013-01-01

Previous research has mainly focused on the persistent direct influence of early life contexts on young adult socioeconomic attainment, and less is known about intraindividual processes that are responsible for this persistent influence. The present study, using genetically informed longitudinal, prospective data from a nationally representative…

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

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...

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.

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.

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

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 substantially higher risk of extinction if the genetic restoration initiative had not been implemented. 6. Our results, along with those reporting increases in population size and improvements in biomedical correlates of inbreeding depression, provide strong evidence that genetic restoration substantially contributed to the observed increases in the Florida panther population. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

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...

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.

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

Genetic diversity and frequency of bovine viral diarrhea virus (BVDV) detected in cattle in Turkey

USDA-ARS?s Scientific Manuscript database

Rapid detection and culling of persistently infected animals and efficacious vaccination are key factors to control bovine viral diarrhea virus (BVDV) infections in cattle. The aim of this study was to investigate frequency of detection of persistently infected cattle and examine the diversity of bo...

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...

Preparation of lactose-free pasteurized milk with a recombinant thermostable β-glucosidase from Pyrococcus furiosus

PubMed Central

2013-01-01

Background Lactose intolerance is a common health concern causing gastrointestinal symptoms and avoidance of dairy products by afflicted individuals. Since milk is a primary source of calcium and vitamin D, lactose intolerant individuals often obtain insufficient amounts of these nutrients which may lead to adverse health outcomes. Production of lactose-free milk can provide a solution to this problem, although it requires use of lactase from microbial sources and increases potential for contamination. Use of thermostable lactase enzymes can overcome this issue by functioning under pasteurization conditions. Results A thermostable β-glucosidase gene from Pyrococcus furiosus was cloned in frame with the Saccharomyces cerecisiae a-factor secretory signal and expressed in Pichia pastoris strain X-33. The recombinant enzyme was purified by a one-step method of weak anion exchange chromatography. The optimum temperature and pH for this β-glucosidase activity was 100°C and pH 6.0, respectively. The enzyme activity was not significantly inhibited by Ca2+. We tested the additive amount, hydrolysis time, and the influence of glucose on the enzyme during pasteurization and found that the enzyme possessed a high level of lactose hydrolysis in milk that was not obviously influenced by glucose. Conclusions The thermostablity of this recombinant β-glucosidase, combined with its neutral pH activity and favorable temperature activity optima, suggest that this enzyme is an ideal candidate for the hydrolysis of lactose in milk, and it would be suitable for application in low-lactose milk production during pasteurization. PMID:24053641

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.

First dairying in green Saharan Africa in the fifth millennium BC.

PubMed

Dunne, Julie; Evershed, Richard P; Salque, Mélanie; Cramp, Lucy; Bruni, Silvia; Ryan, Kathleen; Biagetti, Stefano; di Lernia, Savino

2012-06-20

In the prehistoric green Sahara of Holocene North Africa-in contrast to the Neolithic of Europe and Eurasia-a reliance on cattle, sheep and goats emerged as a stable and widespread way of life, long before the first evidence for domesticated plants or settled village farming communities. The remarkable rock art found widely across the region depicts cattle herding among early Saharan pastoral groups, and includes rare scenes of milking; however, these images can rarely be reliably dated. Although the faunal evidence provides further confirmation of the importance of cattle and other domesticates, the scarcity of cattle bones makes it impossible to ascertain herd structures via kill-off patterns, thereby precluding interpretations of whether dairying was practiced. Because pottery production begins early in northern Africa the potential exists to investigate diet and subsistence practices using molecular and isotopic analyses of absorbed food residues. This approach has been successful in determining the chronology of dairying beginning in the 'Fertile Crescent' of the Near East and its spread across Europe. Here we report the first unequivocal chemical evidence, based on the δ(13)C and Δ(13)C values of the major alkanoic acids of milk fat, for the adoption of dairying practices by prehistoric Saharan African people in the fifth millennium bc. Interpretations are supported by a new database of modern ruminant animal fats collected from Africa. These findings confirm the importance of 'lifetime products', such as milk, in early Saharan pastoralism, and provide an evolutionary context for the emergence of lactase persistence in Africa.

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

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...

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...

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...

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...

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

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.

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.

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.

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 understanding and monitoring of municipal WWTPs as sources of fecal pollution in water resources. PMID:26002900

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.

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.

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

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.

Class III HD-Zip activity coordinates leaf development in Physcomitrella patens.

PubMed

Yip, Hoichong Karen; Floyd, Sandra K; Sakakibara, Keiko; Bowman, John L

2016-11-01

Land plant bodies develop from meristems, groups of pluripotent stem cells, which may persist throughout the life of a plant or, alternatively, have a transitory existence. Early diverging land plants exhibit indeterminate (persistent) growth in their haploid gametophytic generation, whereas later diverging lineages exhibit indeterminate growth in their diploid sporophytic generation, raising the question of whether genetic machinery directing meristematic functions was co-opted between generations. Class III HD-Zip (C3HDZ) genes are required for the establishment and maintenance of shoot apical meristems in flowering plants. We demonstrate that in the moss Physcomitrella patens, C3HDZ genes are expressed in transitory meristems in both the gametophytic and sporophytic generations, but not in the persistent shoot meristem of the gametyphyte. Loss-of-function of P. patens C3HDZ was engineered using ectopic expression of miR166, an endogenous regulator of C3HDZ gene activity. Loss of C3HDZ gene function impaired the function of gametophytic transitory meristematic activity but did not compromise the functioning of the persistent shoot apical meristem during the gametophyte generation. These results argue against a wholesale co-option of meristematic gene regulatory networks from the gametophyte to the sporophyte during land plant evolution, instead suggesting that persistent meristems with a single apical cell in P. patens and persistent complex meristems in flowering plants are regulated by different genetic programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Polygenic risk and the development and course of asthma: Evidence from a 4-decade longitudinal study

PubMed Central

Belsky, DW; Sears, MR; Hancox, RJ; Harrington, HL; Houts, R; Moffitt, TE; Sugden, K; Williams, B; Poulton, R; Caspi, A

2013-01-01

BACKGROUND Genome-wide association studies (GWAS) have discovered loci that predispose to asthma. To integrate these new discoveries with emerging models of asthma pathobiology, research is needed to test how genetic discoveries relate to developmental and biological characteristics of asthma. METHODS We derived a multi-locus profile of genetic risk from published GWAS of asthma case status. We then tested associations between this “genetic risk score” and developmental and biological characteristics of asthma in a population-based long-running birth cohort, the Dunedin Longitudinal Study (n=1,037). We evaluated asthma onset, persistence, atopy, airway hyperresponsiveness, incompletely reversible airflow obstruction, and asthma-related school and work absenteeism and hospitalization during 9 prospective assessments spanning ages 9–38 years, when 95% of surviving cohort members were seen. INTERPRETATION Cohort members at higher genetic risk experienced asthma onset earlier in life (HR=1.12 [1.01–1.26]). Childhood-onset asthma cases at higher genetic risk were more likely to become life-course-persistent asthma cases (RR=1.36 [1.14–1.63]). Asthma cases at higher genetic risk more often manifested atopy (RR=1.07 [1.01–1.14]), airway hyperresponsiveness (RR=1.16 [1.03–1.32]), and incompletely reversible airflow obstruction (RR=1.28 [1.04–1.57]). They were also more likely to miss school or work due to asthma (IRR=1.38 [1.02–1.86]) and to be hospitalized with breathing problems (HR=1.38 [1.07–1.79]). Genotypic information about asthma risk was independent of and additive to information derived from cohort members’ family histories of asthma. CONCLUSIONS Findings from this population study confirm that GWAS-discoveries for asthma associate with a childhood-onset phenotype and advance asthma genetics beyond the original GWAS-discoveries in three ways: (1) We show that genetic risks predict which childhood-onset asthma cases remit and which become life-course-persistent cases, although these predictions are not sufficiently sensitive or specific to support immediate clinical translation; (2) We elucidate a biological profile of the asthma that arises from these genetic risks: asthma characterized by atopy and airway hyperresponsiveness and leading to incompletely reversible airflow obstruction; and (3) We describe the real-life impact of GWAS-discoveries by quantifying genetic associations with missed school and work and hospitalization. PMID:24429243

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.

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

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.

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

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

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.

[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.

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.

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.

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.

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.

Supplementing formula-fed piglets with a low molecular weight fraction of bovine colostrum whey results in an improved intestinal barrier.

PubMed

De Vos, M; Huygelen, V; Van Raemdonck, G; Willemen, S; Fransen, E; Van Ostade, X; Casteleyn, C; Van Cruchten, S; Van Ginneken, C

2014-08-01

To test the hypothesis that a low molecular weight fraction of colostral whey could affect the morphology and barrier function of the small intestine, 30 3-d-old piglets (normal or low birth weight) were suckled (n = 5), artificially fed with milk formula (n = 5), or artificially fed with milk formula with a low molecular weight fraction of colostral whey (n = 5) until 10 d of age. The small intestine was sampled for histology (haematoxylin and eosin stain; anti-KI67 immunohistochemistry) and enzyme activities (aminopeptidase A, aminopeptidase N, dipeptidylpeptidase IV, lactase, maltase, and sucrase). In addition, intestinal permeability was evaluated via a dual sugar absorption test and via the measurement of occludin abundance. Artificially feeding of piglets reduced final BW (P < 0.001), villus height (P < 0.001), lactase (P < 0.001), and dipeptidylpeptidase IV activities (P < 0.07), whereas crypt depth (P < 0.001) was increased. No difference was observed with regard to the permeability measurements when comparing artificially fed with naturally suckling piglets. Supplementing piglets with the colostral whey fraction did not affect BW, enzyme activities, or the outcome of the dual sugar absorption test. On the contrary, the small intestines of supplemented piglets had even shorter villi (P = 0.001) than unsupplemented piglets and contained more occludin (P = 0.002). In conclusion, at 10 d of age, no differences regarding intestinal morphology and permeability measurements were observed between the 2 BW categories. In both weight categories, the colostral whey fraction affected the morphology of the small intestine but did not improve the growth performances or the in vivo permeability. These findings should be acknowledged when developing formulated milk for neonatal animals with the aim of improving the performance of low birth weight piglets.

Lactose intolerance and intestinal villi morphology in Thai people.

PubMed

Thong-Ngam, D; Suwangool, P; Prempracha, J; Tangkijvanich, P; Vivatvekin, B; Sriratanabun, A

2001-08-01

To study the relationship of lactose intolerance and intestinal villi morphology in Thai people. Subjects for this study were patients with functional dyspepsia who had no history of milk allergy and underwent gastroduodenoscopy. Two mucosal biopsy specimens were taken from beyond the distal end of the second part of the duodenum. The specimens were carefully orientated and were graded according to the following scheme: group I: finger shaped villi; group II: mixed finger and leaf shaped villi; group III: clubbing or blunting shaped villi. All subjects were tested for lactose malabsorption by breath hydrogen analysis after consuming 50 gram lactose. Breath hydrogen concentration was analyzed in samples collected intermittently by end-expiratory technique. A rise in breath hydrogen concentration of 20 PPM over baseline was considered evidence of lactose malabsorption. The twenty-five subjects were twenty females (80.0%) and five males (20.0%) who ranged in age from 18 to 53 years (mean 31 +/- 8.29). Sixteen subjects belonged to the finger shaped villi group (64.0%), five to the mixed finger and leaf shaped villi, group (20.0%) and four to the clubbing or blunting shaped villi group (16.0%). Results of breath hydrogen excretion test identified the prevalence of lactose intolerance in 68 per cent of the subjects: 15/16 (93.75%) of group I; 1/5 (20.0%) of group II and 1/4 (25%) of group III respectively (P<0.001). The symptom of diarrhea after lactose loading was correlated well in patients who had positive breath hydrogen analysis. As shown in this study, the lactose intolerance is not related to intestinal villi morphology. It is implied that primary lactase deficiency is more common in Thai people than secondary lactase deficiency.

Infantile colic: a systematic review of medical and conventional therapies.

PubMed

Hall, Belinda; Chesters, Janice; Robinson, Anske

2012-02-01

Infantile colic is a prevalent and distressing condition for which there is no proven standard therapy. The aim of this paper is to review medical and conventional treatments for infantile colic. A systematic literature review was undertaken of studies on medical and conventional interventions for infantile colic from 1980 to March 2009. The results and methodological rigour of included studies were analysed using the CONSORT (Consolidated Standards Of Reporting Trials) 2001 statement checklist and Centre for Evidence Based Medicine critical appraisal tools. Nineteen studies and two literature reviews were included for review. Pharmacological studies on Simethicone gave conflicting results and with Dicyclomine hydrochloride and Cimetropium bromide results were favourable but side effects were noted along with issues in study methodology. Some nutritional studies reported favourable results for the use of hydrolysed formulas in bottle-fed infants or low-allergen maternal diets in breastfed infants but not for the use of additional fibre or lactase. There were several issues in regards to methodological rigour. Behavioural studies on the use of increased stimulation gave unfavourable results, whereas results from the use of decreased stimulation and contingent music were favourable. These studies demonstrated poor methodological rigour. There is some scientific evidence to support the use of a casein hydrolysate formula in formula-fed infants or a low-allergen maternal diet in breastfed infants with infantile colic. However, there is little scientific evidence to support the use of Simethicone, Dicyclomine hydrochloride, Cimetropium bromide, lactase, additional fibre or behavioural interventions. Further research of good methodological quality on low-allergenic formulas and maternal diets is indicated. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Evaluation of differential disaccharide excretion in urine for non-invasive investigation of altered intestinal disaccharidase activity caused by alpha-glucosidase inhibition, primary hypolactasia, and coeliac disease.

PubMed Central

Bjarnason, I; Batt, R; Catt, S; Macpherson, A; Maxton, D; Menzies, I S

1996-01-01

BACKGROUND/AIM: The reliability of a quantitative method for the non-invasive assessment of intestinal disaccharide hydrolysis was assessed. METHODS: Differential excretion of intact disaccharide, expressed as ratios of lactulose to appropriate hydrolysable disaccharides in urine collected following combined ingestion, has been investigated in healthy volunteers with drug induced alpha-glucosidase inhibition, in subjects with primary hypolactasia, and patients with coeliac disease. RESULTS: Oral administration of the alpha-glucosidase inhibitor 'Acarbose' (BAY g 5421, 200 mg) together with sucrose and lactulose increased the urinary sucrose/lactulose excretion ratios (% dose/10 h) fivefold. The effect was quantitatively reproducible, a higher dose of 'Acarbose' (500 mg) increasing the excretion ratio to about 1.0 indicating complete inhibition of intestinal sucrase activity. The suitability of the method for measuring differences in dose/response and duration of action was assessed by comparing three different alpha-glucosidase inhibitors (BAY g 5421, BAY m 1099, and BAY o 1248) and found to be satisfactory. Subjects with primary adult hypolactasia had urine lactose/lactulose excretion ratios raised to values indicating reduced rather than complete absence of lactase activity whereas sucrose/lactulose ratios were not significantly affected. 'Whole' intestinal disaccharidase activity assessed by this method demonstrated impairment of lactase, sucrase, and isomaltase in eight, one, and seven, respectively, of 20 patients with coeliac disease. By contrast in vitro assay of jejunal biopsy tissue indicated pan-disaccharidase deficiency in all but five of these patients. This shows the importance of distinguishing between 'local' and 'whole' intestinal performance. CONCLUSIONS: Differential urinary excretion of ingested disaccharides provides a reliable, quantitative, and non-invasive technique for assessing profiles of intestinal disaccharidase activity. PMID:8949640

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.

Effect of freshwater sediment characteristics on the persistence of fecal indicator bacteria and genetic markers within a Southern California Watershed.

EPA Science Inventory

In this study, the relative aging of FIB and genetic markers for Enterococcus spp. (ENT1A), general Bacteroides (GenBac3), and human-associated Bacteroides (HF183) in varying freshwater sediments was evaluated. Freshwater sediment was collected from four different sites within th...

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...

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.

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.

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.

Acclimatization and Adaptive Capacity of Marine Species in a Changing Ocean.

PubMed

Foo, S A; Byrne, M

To persist in an ocean changing in temperature, pH and other stressors related to climate change, many marine species will likely need to acclimatize or adapt to avoid extinction. If marine populations possess adequate genetic variation in tolerance to climate change stressors, species might be able to adapt to environmental change. Marine climate change research is moving away from single life stage studies where individuals are directly placed into projected scenarios ('future shock' approach), to focus on the adaptive potential of populations in an ocean that will gradually change over coming decades. This review summarizes studies that consider the adaptive potential of marine invertebrates to climate change stressors and the methods that have been applied to this research, including quantitative genetics, laboratory selection studies and trans- and multigenerational experiments. Phenotypic plasticity is likely to contribute to population persistence providing time for genetic adaptation to occur. Transgenerational and epigenetic effects indicate that the environmental and physiological history of the parents can affect offspring performance. There is a need for long-term, multigenerational experiments to determine the influence of phenotypic plasticity, genetic variation and transgenerational effects on species' capacity to persist in a changing ocean. However, multigenerational studies are only practicable for short generation species. Consideration of multiple morphological and physiological traits, including changes in molecular processes (eg, DNA methylation) and long-term studies that facilitate acclimatization will be essential in making informed predictions of how the seascape and marine communities will be altered by climate change. © 2016 Elsevier Ltd. All rights reserved.

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.

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 management of cosmopolitan pests in Northern and Southern Europe. PMID:25266268

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.

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

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

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 and prioritize the conservation of species and areas most likely to be impacted by rapid climate change, human disturbance and invasive species. PMID:28069633

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.

Ditch network sustains functional connectivity and influences patterns of gene flow in an intensive agricultural landscape

PubMed Central

Favre-Bac, L; Mony, C; Ernoult, A; Burel, F; Arnaud, J-F

2016-01-01

In intensive agricultural landscapes, plant species previously relying on semi-natural habitats may persist as metapopulations within landscape linear elements. Maintenance of populations' connectivity through pollen and seed dispersal is a key factor in species persistence in the face of substantial habitat loss. The goals of this study were to investigate the potential corridor role of ditches and to identify the landscape components that significantly impact patterns of gene flow among remnant populations. Using microsatellite loci, we explored the spatial genetic structure of two hydrochorous wetland plants exhibiting contrasting local abundance and different habitat requirements: the rare and regionally protected Oenanthe aquatica and the more commonly distributed Lycopus europaeus, in an 83 km2 agricultural lowland located in northern France. Both species exhibited a significant spatial genetic structure, along with substantial levels of genetic differentiation, especially for L. europaeus, which also expressed high levels of inbreeding. Isolation-by-distance analysis revealed enhanced gene flow along ditches, indicating their key role in effective seed and pollen dispersal. Our data also suggested that the configuration of the ditch network and the landscape elements significantly affected population genetic structure, with (i) species-specific scale effects on the genetic neighborhood and (ii) detrimental impact of human ditch management on genetic diversity, especially for O. aquatica. Altogether, these findings highlighted the key role of ditches in the maintenance of plant biodiversity in intensive agricultural landscapes with few remnant wetland habitats. PMID:26486611

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.

Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors.

PubMed

Whitmer, Shannon L M; Ladner, Jason T; Wiley, Michael R; Patel, Ketan; Dudas, Gytis; Rambaut, Andrew; Sahr, Foday; Prieto, Karla; Shepard, Samuel S; Carmody, Ellie; Knust, Barbara; Naidoo, Dhamari; Deen, Gibrilla; Formenty, Pierre; Nichol, Stuart T; Palacios, Gustavo; Ströher, Ute

2018-01-30

Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection. Published by Elsevier Inc.

Demographic, lifestyle, and genetic determinants of circulating concentrations of 25-hydroxyvitamin D and vitamin D-binding protein in African American and European American women.

PubMed

Yao, Song; Hong, Chi-Chen; Bandera, Elisa V; Zhu, Qianqian; Liu, Song; Cheng, Ting-Yuan David; Zirpoli, Gary; Haddad, Stephen A; Lunetta, Kathryn L; Ruiz-Narvaez, Edward A; McCann, Susan E; Troester, Melissa A; Rosenberg, Lynn; Palmer, Julie R; Olshan, Andrew F; Ambrosone, Christine B

2017-06-01

Background: Vitamin D may have anticancer activities. The high prevalence of vitamin D deficiency in African Americans (AAs) may be a contributing factor to the cancer health disparities between AAs and European Americans (EAs). Objectives: We compared concentrations of 25(OH)D and vitamin D-binding protein (VDBP) in AA and EA women and investigated determinants of the vitamin D-biomarker concentrations in both populations. Design: We used data and biospecimens from 909 AA and 847 EA healthy control subjects from the Carolina Breast Cancer Study (CBCS) and the Women's Circle of Health Study (WCHS) in the African American Breast Cancer Epidemiology and Risk Consortium. We measured plasma 25(OH)D and VDBP concentrations in all participants and genotyped 67 vitamin D-related genes in AA women only. Results: AA women had lower 25(OH)D concentrations than did EA women (mean ± SD: 14.2 ± 8.1 compared with 21.1 ± 11.5 ng/mL, respectively; P < 0.0001) but similar concentrations of VDBP (mean ± SD: 344 ± 133 compared with 336 ± 124 μg/mL, respectively; P = 0.25). With VDBP and other factors controlled for, the observed racial difference in 25(OH)D concentrations did not diminish. Relations of demographic and lifestyle factors with 25(OH)D were similar between AA and EA women. Although none of the genetic variants that have been identified in previous genome-wide association studies of 25(OH)D concentrations in EAs were significant ( P > 0.05) in AAs, AA women who carried the allele of a functional single nucleotide polymorphism rs4988235, which has been previously associated with lactase expression and lactose tolerance, had higher dietary vitamin D intake and higher measured 25(OH)D concentrations. Conclusions: AA women have lower concentrations of total 25(OH)D than EA women do, but both groups have similar VDBP concentrations, suggesting that there are lower concentrations of free 25(OH)D in AAs. Although demographic and lifestyle determinants of 25(OH)D concentrations are similar between the 2 groups, genetic determinants may be ethnicity specific. Larger studies in AAs will be needed to fully elucidate the underlying determinants of low vitamin D concentrations in AA populations. © 2017 American Society for Nutrition.

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.

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

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

Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.

PubMed

Verstraeten, Natalie; Knapen, Wouter Joris; Kint, Cyrielle Ines; Liebens, Veerle; Van den Bergh, Bram; Dewachter, Liselot; Michiels, Joran Elie; Fu, Qiang; David, Charlotte Claudia; Fierro, Ana Carolina; Marchal, Kathleen; Beirlant, Jan; Versées, Wim; Hofkens, Johan; Jansen, Maarten; Fauvart, Maarten; Michiels, Jan

2015-07-02

Within bacterial populations, a small fraction of persister cells is transiently capable of surviving exposure to lethal doses of antibiotics. As a bet-hedging strategy, persistence levels are determined both by stochastic induction and by environmental stimuli called responsive diversification. Little is known about the mechanisms that link the low frequency of persisters to environmental signals. Our results support a central role for the conserved GTPase Obg in determining persistence in Escherichia coli in response to nutrient starvation. Obg-mediated persistence requires the stringent response alarmone (p)ppGpp and proceeds through transcriptional control of the hokB-sokB type I toxin-antitoxin module. In individual cells, increased Obg levels induce HokB expression, which in turn results in a collapse of the membrane potential, leading to dormancy. Obg also controls persistence in Pseudomonas aeruginosa and thus constitutes a conserved regulator of antibiotic tolerance. Combined, our findings signify an important step toward unraveling shared genetic mechanisms underlying persistence. Copyright © 2015 Elsevier Inc. All rights reserved.

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. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Crucial steps to life: From chemical reactions to code using agents.

PubMed

Witzany, Guenther

2016-02-01

The concepts of the origin of the genetic code and the definitions of life changed dramatically after the RNA world hypothesis. Main narratives in molecular biology and genetics such as the "central dogma," "one gene one protein" and "non-coding DNA is junk" were falsified meanwhile. RNA moved from the transition intermediate molecule into centre stage. Additionally the abundance of empirical data concerning non-random genetic change operators such as the variety of mobile genetic elements, persistent viruses and defectives do not fit with the dominant narrative of error replication events (mutations) as being the main driving forces creating genetic novelty and diversity. The reductionistic and mechanistic views on physico-chemical properties of the genetic code are no longer convincing as appropriate descriptions of the abundance of non-random genetic content operators which are active in natural genetic engineering and natural genome editing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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

Adoptive Cell Therapy for Patients with Melanoma, Using Tumor-Infiltrating Lymphocytes Genetically Engineered to Secrete Interleukin-2

PubMed Central

HEEMSKERK, BIANCA; LIU, KE; DUDLEY, MARK. E.; JOHNSON, LAURA A.; KAISER, ANDREW; DOWNEY, STEPHANIE; ZHENG, ZHILI; SHELTON, THOMAS E.; MATSUDA, KANT; ROBBINS, PAUL F.; MORGAN, RICHARD A.; ROSENBERG, STEVEN A.

2008-01-01

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) after lymphodepletion mediates regression in 50% of patients with metastatic melanoma. In vivo persistence and telomere length of the transferred cells correlate with antitumor response. In an attempt to prolong the in vivo survival of the transferred cells, TILs were genetically engineered to produce interleukin (IL)-2. In vitro, these transduced TILs secreted IL-2 while retaining tumor specificity and exhibited prolonged survival after IL-2 withdrawal. In a phase I/II clinical trial, seven evaluable patients received transduced TILs and one patient experienced a partial response associated with in vivo persistence of IL-2-transduced TILs in circulating lymphocytes. An additional five patients received transduced TILs in conjunction with IL-2 administration. Persistence of IL-2-transduced TILs was observed in three patients, including one partial responder. The transgene DNA as well as vector-derived IL-2 mRNA could be detected for 4 months in responding patients. The low response rate in this trial was possibly due to a reduction in telomere length in cells as a result of prolonged in vitro culture. In this study, insertion of the IL-2 gene into antitumor TILs increased their ability to survive after IL-2 withdrawal in vitro but did not increase their in vivo persistence or clinical effectiveness. PMID:18444786

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

An American termite in Paris: temporal colony dynamics.

PubMed

Baudouin, Guillaume; Dedeine, Franck; Bech, Nicolas; Bankhead-Dronnet, Stéphanie; Dupont, Simon; Bagnères, Anne-Geneviève

2017-12-01

Termites of the genus Reticulitermes are widespread invaders, particularly in urban habitats. Their cryptic and subterranean lifestyle makes them difficult to detect, and we know little about their colony dynamics over time. In this study we examined the persistence of Reticulitermes flavipes (Kollar) colonies in the city of Paris over a period of 15 years. The aim was (1) to define the boundaries of colonies sampled within the same four areas over two sampling periods, (2) to determine whether the colonies identified during the first sampling period persisted to the second sampling period, and (3) to compare the results obtained when colonies were delineated using a standard population genetic approach versus a Bayesian clustering method that combined both spatial and genetic information. Herein, colony delineations were inferred from genetic differences at nine microsatellite loci and one mitochondrial locus. Four of the 18 identified colonies did not show significant differences in their genotype distributions between the two sampling periods. While allelic richness was low, making it hard to reliably distinguish colony family type, most colonies appeared to retain the same breeding structure over time. These large and expansive colonies showed an important ability to fuse (39% were mixed-family colonies), contained hundreds of reproductives and displayed evidence of isolation-by-distance, suggesting budding dispersal. These traits, which favor colony persistence over time, present a challenge for pest control efforts, which apply treatment locally. The other colonies showed significant differences, but we cannot exclude the possibility that their genotype distributions simply changed over time.

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. hyperborea. Because no genetic baseline is currently available for this species, our results may represent a first step in informing conservation and mitigation strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ancient DNA reveals genetic stability despite demographic decline: 3,000 years of population history in the endemic Hawaiian petrel.

PubMed

Welch, Andreanna J; Wiley, Anne E; James, Helen F; Ostrom, Peggy H; Stafford, Thomas W; Fleischer, Robert C

2012-12-01

In the Hawaiian Islands, human colonization, which began approximately 1,200 to 800 years ago, marks the beginning of a period in which nearly 75% of the endemic avifauna became extinct and the population size and range of many additional species declined. It remains unclear why some species persisted whereas others did not. The endemic Hawaiian petrel (Pterodroma sandwichensis) has escaped extinction, but colonies on two islands have been extirpated and populations on remaining islands have contracted. We obtained mitochondrial DNA sequences from 100 subfossil bones, 28 museum specimens, and 289 modern samples to investigate patterns of gene flow and temporal changes in the genetic diversity of this endangered species over the last 3,000 years, as Polynesians and then Europeans colonized the Hawaiian Islands. Genetic differentiation was found to be high between both modern and ancient petrel populations. However, gene flow was substantial between the extirpated colonies on Oahu and Molokai and modern birds from the island of Lanai. No significant reductions in genetic diversity occurred over this period, despite fears in the mid-1900s that this species may have been extinct. Simulations show that even a decline to a stable effective population size of 100 individuals would result in the loss of only 5% of the expected heterozygosity. Simulations also show that high levels of genetic diversity may be retained due to the long generation time of this species. Such decoupling between population size and genetic diversity in long-lived species can have important conservation implications. It appears that a pattern of dispersal from declining colonies, in addition to long generation time, may have allowed the Hawaiian petrel to escape a severe genetic bottleneck, and the associated extinction vortex, and persist despite a large population decline after human colonization.

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

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.

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.

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.

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.

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

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.

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.

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.

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.

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).

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

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

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.

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.

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

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.

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

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

Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

PubMed Central

Thymann, Thomas; Møller, Hanne K.; Stoll, Barbara; Støy, Ann Cathrine F.; Buddington, Randal K.; Bering, Stine B.; Jensen, Bent B.; Olutoye, Oluyinka O.; Siggers, Richard H.; Mølbak, Lars; Sangild, Per T.

2009-01-01

Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. a formula containing lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition for 48 h followed by total enteral nutrition with a lactose-based (n = 11) or maltodextrin-based (n = 11) formula for 36 h. A higher incidence (91% vs. 27%) and severity (score of 3.3 vs. 1.8) of NEC were observed in the maltodextrin than in the lactose group. This higher incidence of NEC in the maltodextrin group was associated with significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the middle region of the small intestine. Bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short-chain fatty acids were observed in the maltodextrin group. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during acute jejunal infusion of a maltodextrin- or a lactose-based formula (n = 8) into preterm pigs. We found lower net portal aldohexose absorption (4% vs. 42%) and greater intestinal recovery of undigested carbohydrate (68% vs. 27%) in pigs acutely perfused with the maltodextrin-based formula than those perfused with the lactose-based formula. The higher digestibility of the lactose than the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase than maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs. PMID:19808655

Influence of dietary forage and feed intake on carbohydrase activities and small intestinal morphology of calves.

PubMed

Kreikemeier, K K; Harmon, D L; Peters, J P; Gross, K L; Armendariz, C K; Krehbiel, C R

1990-09-01

Twenty (12 Holstein, 8 Longhorn cross) calves (198 kg and 7 mo old) were used in a randomized complete block design to evaluate the effects of dietary forage concentration and feed intake on carbohydrase activities and small intestinal (SI) morphology. Calves were individually fed 90% forage (alfalfa) or a 90% concentrate (50% sorghum: 50% wheat) diet at either one or two times NEm for 140 d and slaughtered; tissues and small intestinal digesta were collected. Increased feed intake increased (P less than .05) pancreatic weight, alpha-amylase and glucoamylase activities in the pancreas, SI length and SI digesta weight. Forage-fed calves gained faster (P less than .01) and had greater (P less than .05) pancreatic protein concentrations, alpha-amylase and glucoamylase activities in the pancreas and greater SI digesta alpha-amylase activities than grain-fed calves did. Increased feed intake increased (P less than .01) mucosal weight/cm small intestine only in forage-fed calves and increased (P less than .05) SI surface/volume only in grain-fed calves. Mucosal weight was greatest (P less than .05) at the terminal ileum, surface/volume was greatest (P less than .05) in the duodenum, and mucosal protein concentration was highest (P less than .05) in the SI mid-section. Mucosal lactase was higher (P less than .05) in proximal segments, whereas mucosal isomaltase was higher in middle and distal segments of the small intestine. For mucosal maltase activity, there was a feed intake x SI sampling site interaction (P less than .05) and for trehalase, a diet x feed intake x SI sampling site interaction (P less than .05). The SI distribution patterns of maltase and isomaltase were similar, as were those of trehalase and lactase. The alpha-amylase activity in the pancreas and SI morphology were influenced greatly by diet composition and feed intake by calves.

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; Galvin JE; Suzuki Y; Gottschalk L; Shaw PJ. Persistent short-term memory defects following sleep deprivation in a drosophila model of parkinson disease. SLEEP 2009;32(8):984-992. PMID:19725249

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 association was with the common variation across these behaviors rather than with the variation unique to any given behavior. The manuscript demonstrates a potentially advantageous technique for relating sets of hypothesized genes to complex traits or behaviors. PMID:27505405

Continent-wide panmixia of an African fruit bat facilitates transmission of potentially zoonotic viruses.

PubMed

Peel, Alison J; Sargan, David R; Baker, Kate S; Hayman, David T S; Barr, Jennifer A; Crameri, Gary; Suu-Ire, Richard; Broder, Christopher C; Lembo, Tiziana; Wang, Lin-Fa; Fooks, Anthony R; Rossiter, Stephen J; Wood, James L N; Cunningham, Andrew A

2013-01-01

The straw-coloured fruit bat, Eidolon helvum, is Africa's most widely distributed and commonly hunted fruit bat, often living in close proximity to human populations. This species has been identified as a reservoir of potentially zoonotic viruses, but uncertainties remain regarding viral transmission dynamics and mechanisms of persistence. Here we combine genetic and serological analyses of populations across Africa, to determine the extent of epidemiological connectivity among E. helvum populations. Multiple markers reveal panmixia across the continental range, at a greater geographical scale than previously recorded for any other mammal, whereas populations on remote islands were genetically distinct. Multiple serological assays reveal antibodies to henipaviruses and Lagos bat virus in all locations, including small isolated island populations, indicating that factors other than population size and connectivity may be responsible for viral persistence. Our findings have potentially important public health implications, and highlight a need to avoid disturbances that may precipitate viral spillover.

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 patients with persistent infection. However, answers to the questions as to whether TK-negative (TK - ) HSV-1 can establish persistent infection in brains of immunocompromised hosts and whether neurons in vivo are permissive for TK - HSV-1 remain elusive. Using three genetically engineered HSV-1 TK - mutants and two strains of nude mice deficient in T cells, we found that all three HSV-1 TK - mutants can efficiently establish persistent infection in the brain stem and trigeminal ganglion and detected glycoprotein C, a true late viral antigen, in brainstem neurons. Our study provides evidence that TK - HSV-1 can persist in neural tissues and replicate in brain neurons of immunocompromised hosts. Copyright © 2017 American Society for Microbiology.

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 immunocompromised patients with persistent infection. However, answers to the questions as to whether TK-negative (TK−) HSV-1 can establish persistent infection in brains of immunocompromised hosts and whether neurons in vivo are permissive for TK− HSV-1 remain elusive. Using three genetically engineered HSV-1 TK− mutants and two strains of nude mice deficient in T cells, we found that all three HSV-1 TK− mutants can efficiently establish persistent infection in the brain stem and trigeminal ganglion and detected glycoprotein C, a true late viral antigen, in brainstem neurons. Our study provides evidence that TK− HSV-1 can persist in neural tissues and replicate in brain neurons of immunocompromised hosts. PMID:27974554

Climate as a driver of tropical insular diversity: comparative phylogeography of two ecologically distinctive frogs in Puerto Rico

PubMed Central

Barker, Brittany S.; Rodríguez-Robles, Javier A.; Cook, Joseph A.

2014-01-01

The effects of late Quaternary climate on distributions and evolutionary dynamics of insular species are poorly understood in most tropical archipelagoes. We used ecological niche models under past and current climate to derive hypotheses regarding how stable climatic conditions shaped genetic diversity in two ecologically distinctive frogs in Puerto Rico. Whereas the Mountain Coquí, Eleutherodactylus portoricensis, is restricted to montane forest in the Cayey and Luquillo Mountains, the Red-eyed Coquí, E. antillensis, is a habitat generalist distributed across the entire Puerto Rican Bank (Puerto Rico and the Virgin Islands, excluding St. Croix). To test our hypotheses, we conducted phylogeographic and population genetic analyses based on mitochondrial and nuclear loci of each species across their range in Puerto Rico. Patterns of population differentiation in E. portoricensis, but not in E. antillensis, supported our hypotheses. For E. portoricensis, these patterns include: individuals isolated by long-term unsuitable climate in the Río Grande de Loíza Basin in eastern Puerto Rico belong to different genetic clusters; past and current climate strongly predicted genetic differentiation; and Cayey and Luquillo Mountains populations split prior to the last interglacial. For E. antillensis, these patterns include: genetic clusters did not fully correspond to predicted long-term unsuitable climate; and past and current climate weakly predicted patterns of genetic differentiation. Genetic signatures in E. antillensis are consistent with a recent range expansion into western Puerto Rico, possibly resulting from climate change and anthropogenic influences. As predicted, regions with a large area of long-term suitable climate were associated with higher genetic diversity in both species, suggesting larger and more stable populations. Finally, we discussed the implications of our findings for developing evidence-based management decisions for E. portoricensis, a taxon of special concern. Our findings illustrate the role of persistent suitable climatic conditions in promoting the persistence and diversification of tropical island organisms. PMID:26508809

Climate as a driver of tropical insular diversity: comparative phylogeography of two ecologically distinctive frogs in Puerto Rico.

PubMed

Barker, Brittany S; Rodríguez-Robles, Javier A; Cook, Joseph A

2015-08-01

The effects of late Quaternary climate on distributions and evolutionary dynamics of insular species are poorly understood in most tropical archipelagoes. We used ecological niche models under past and current climate to derive hypotheses regarding how stable climatic conditions shaped genetic diversity in two ecologically distinctive frogs in Puerto Rico. Whereas the Mountain Coquí, Eleutherodactylus portoricensis , is restricted to montane forest in the Cayey and Luquillo Mountains, the Red-eyed Coquí, E. antillensis , is a habitat generalist distributed across the entire Puerto Rican Bank (Puerto Rico and the Virgin Islands, excluding St. Croix). To test our hypotheses, we conducted phylogeographic and population genetic analyses based on mitochondrial and nuclear loci of each species across their range in Puerto Rico. Patterns of population differentiation in E. portoricensis , but not in E. antillensis , supported our hypotheses. For E. portoricensis , these patterns include: individuals isolated by long-term unsuitable climate in the Río Grande de Loíza Basin in eastern Puerto Rico belong to different genetic clusters; past and current climate strongly predicted genetic differentiation; and Cayey and Luquillo Mountains populations split prior to the last interglacial. For E. antillensis , these patterns include: genetic clusters did not fully correspond to predicted long-term unsuitable climate; and past and current climate weakly predicted patterns of genetic differentiation. Genetic signatures in E. antillensis are consistent with a recent range expansion into western Puerto Rico, possibly resulting from climate change and anthropogenic influences. As predicted, regions with a large area of long-term suitable climate were associated with higher genetic diversity in both species, suggesting larger and more stable populations. Finally, we discussed the implications of our findings for developing evidence-based management decisions for E. portoricensis , a taxon of special concern. Our findings illustrate the role of persistent suitable climatic conditions in promoting the persistence and diversification of tropical island organisms.

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

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. All rights reserved.

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.

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

Impact of Pathogen Population Heterogeneity and Stress-Resistant Variants on Food Safety.

PubMed

Abee, T; Koomen, J; Metselaar, K I; Zwietering, M H; den Besten, H M W

2016-01-01

This review elucidates the state-of-the-art knowledge about pathogen population heterogeneity and describes the genotypic and phenotypic analyses of persister subpopulations and stress-resistant variants. The molecular mechanisms underlying the generation of persister phenotypes and genetic variants are identified. Zooming in on Listeria monocytogenes, a comparative whole-genome sequence analysis of wild types and variants that enabled the identification of mutations in variants obtained after a single exposure to lethal food-relevant stresses is described. Genotypic and phenotypic features are compared to those for persistent strains isolated from food processing environments. Inactivation kinetics, models used for fitting, and the concept of kinetic modeling-based schemes for detection of variants are presented. Furthermore, robustness and fitness parameters of L. monocytogenes wild type and variants are used to model their performance in food chains. Finally, the impact of stress-resistant variants and persistence in food processing environments on food safety is discussed.

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.

Phenological mismatch and the effectiveness of assisted gene flow.

PubMed

Wadgymar, Susana M; Weis, Arthur E

2017-06-01

The persistence of narrowly adapted species under climate change will depend on their ability to migrate apace with their historical climatic envelope or to adapt in place to maintain fitness. This second path to persistence can only occur if there is sufficient genetic variance for response to new selection regimes. Inadequate levels of genetic variation can be remedied through assisted gene flow (AGF), that is the intentional introduction of individuals genetically adapted to localities with historic climates similar to the current or future climate experienced by the resident population. However, the timing of reproduction is frequently adapted to local conditions. Phenological mismatch between residents and migrants can reduce resident × migrant mating frequencies, slowing the introgression of migrant alleles into the resident genetic background and impeding evolutionary rescue efforts. Focusing on plants, we devised a method to estimate the frequency of resident × migrant matings based on flowering schedules and applied it in an experiment that mimicked the first generation of an AGF program with Chamaecrista fasciculata, a prairie annual, under current and expected future temperature regimes. Phenological mismatch reduced the potential for resident × migrant matings by 40-90%, regardless of thermal treatment. The most successful migrant sires were the most resident like in their flowering time, further biasing the genetic admixture between resident and migrant populations. Other loci contributing to local adaptation-heat-tolerance genes, for instance-may be in linkage disequilibrium with phenology when residents and migrants are combined into a single mating pool. Thus, introgression of potentially adaptive migrant alleles into the resident genetic background is slowed when selection acts against migrant phenology. Successful AGF programs may require sustained high immigration rates or preliminary breeding programs when phenologically matched migrant source populations are unavailable. © 2016 Society for Conservation Biology.

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.

TRANSGENIC PLANTS: ENVIRONMENTAL PERSISTENCE AND EFFECTS ON SOIL AND PLANT ECOSYSTEMS

EPA Science Inventory

The genetic engineering of plants has facilitated the production of valuable agricultural and forestry crops. Transgenic plants have been created that have increased resistance to pests, herbicides, pathogens, and environmental stress, enhanced qualitative and quantitative trait...

HIV Integration at Certain Sites in Host DNA Is Linked to the Expansion and Persistence of Infected Cells | Poster

Cancer.gov

Editor’s note: This article was originally published on the Center for Cancer Research website. When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites

Contrasting patterns of variation in weedy traits and unique crop features in divergent populations of US weedy rice (Oryza sativa sp.) in Arkansas and California.

PubMed

Kanapeckas, Kimberly L; Tseng, Te-Ming; Vigueira, Cynthia C; Ortiz, Aida; Bridges, William C; Burgos, Nilda R; Fischer, Albert J; Lawton-Rauh, Amy

2018-06-01

Weed evolution from crops involves changes in key traits, but it is unclear how genetic and phenotypic variation contribute to weed diversification and productivity. Weedy rice is a conspecific weed of rice (Oryza sativa) worldwide. We used principal component analysis and hierarchical clustering to understand how morphologically and evolutionarily distinct US weedy rice populations persist in rice fields in different locations under contrasting management regimes. Further, we used a representative subset of 15 sequence-tagged site fragments of expressed genes from global Oryza to assess genome-wide sequence variation among populations. Crop hull color and crop-overlapping maturity dates plus awns, seed (panicle) shattering (> 50%), pigmented pericarp and stature variation (30.2% of total phenotypic variance) characterize genetically less diverse California weedy rice. By contrast, wild-like hull color, seed shattering (> 50%) and stature differences (55.8% of total phenotypic variance) typify genetically diverse weedy rice ecotypes in Arkansas. Recent de-domestication of weedy species - such as in California weedy rice - can involve trait combinations indistinguishable from the crop. This underscores the need for strict seed certification with genetic monitoring and proactive field inspection to prevent proliferation of weedy plant types. In established populations, tillage practice may affect weed diversity and persistence over time. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Strain-specific outcomes of repeated social defeat and chronic fluoxetine treatment in the mouse.

PubMed

Razzoli, Maria; Carboni, Lucia; Andreoli, Michela; Michielin, Francesca; Ballottari, Alice; Arban, Roberto

2011-01-01

Social stress is a risk factor for affective disorders in vulnerable individuals. Although the biological nature of stress susceptibility/resilience remains to be elucidated, genetic variation is considered amongst the principal contributors to brain disorders. Furthermore, genetic predisposition may be determinant for the therapeutic outcome, as proposed for antidepressant treatments. In the present studies we compared the inherently diverse genetic backgrounds of 2 mouse strains by assessing the efficacy of a chronic antidepressant treatment in a repeated social stress procedure. C57BL/6J and BalbC mice underwent 10-day social defeats followed by 28-day fluoxetine treatment (10 mg/kg/mL, p.o.). In C57BL/6J, most of the social defeat-induced changes were of metabolic nature including persistently altered feed efficiency and decreased abdominal fat stores that were ameliorated by fluoxetine. BalbC mouse behavior was persistently affected by social defeat both in the social avoidance and the forced swim tests, and in either procedure it was restored by chronic fluoxetine, whereas their endocrine parameters were mostly unaffected. The highlighted strain-specific responsivity to the metabolic and behavioral consequences of social defeat and to the chronic antidepressant treatment offers a promising research tool to further explore the underlying neural mechanisms and genetic basis of stress susceptibility and treatment response. Copyright © 2010 Elsevier Inc. All rights reserved.

Decay of Bacteroidales genetic markers in relation to traditional fecal indicators for water quality modeling of drinking water sources.

PubMed

Sokolova, Ekaterina; Aström, Johan; Pettersson, Thomas J R; Bergstedt, Olof; Hermansson, Malte

2012-01-17

The implementation of microbial fecal source tracking (MST) methods in drinking water management is limited by the lack of knowledge on the transport and decay of host-specific genetic markers in water sources. To address these limitations, the decay and transport of human (BacH) and ruminant (BacR) fecal Bacteroidales 16S rRNA genetic markers in a drinking water source (Lake Rådasjön in Sweden) were simulated using a microbiological model coupled to a three-dimensional hydrodynamic model. The microbiological model was calibrated using data from outdoor microcosm trials performed in March, August, and November 2010 to determine the decay of BacH and BacR markers in relation to traditional fecal indicators. The microcosm trials indicated that the persistence of BacH and BacR in the microcosms was not significantly different from the persistence of traditional fecal indicators. The modeling of BacH and BacR transport within the lake illustrated that the highest levels of genetic markers at the raw water intakes were associated with human fecal sources (on-site sewers and emergency sewer overflow). This novel modeling approach improves the interpretation of MST data, especially when fecal pollution from the same host group is released into the water source from different sites in the catchment.

Widespread movement of invasive cattle fever ticks (Rhipicephalus microplus) in southern Texas leads to shared local infestations on cattle and deer.

PubMed

Busch, Joseph D; Stone, Nathan E; Nottingham, Roxanne; Araya-Anchetta, Ana; Lewis, Jillian; Hochhalter, Christian; Giles, John R; Gruendike, Jeffrey; Freeman, Jeanne; Buckmeier, Greta; Bodine, Deanna; Duhaime, Roberta; Miller, Robert J; Davey, Ronald B; Olafson, Pia U; Scoles, Glen A; Wagner, David M

2014-04-17

Rhipicephalus (Boophilus) microplus is a highly-invasive tick that transmits the cattle parasites (Babesia bovis and B. bigemina) that cause cattle fever. R. microplus and Babesia are endemic in Mexico and ticks persist in the United States inside a narrow tick eradication quarantine area (TEQA) along the Rio Grande. This containment area is threatened by unregulated movements of illegal cattle and wildlife like white-tailed deer (WTD; Odocoileus virginianus). Using 11 microsatellite loci we genotyped 1,247 R. microplus from 63 Texas collections, including outbreak infestations from outside the TEQA. We used population genetic analyses to test hypotheses about ecological persistence, tick movement, and impacts of the eradication program in southern Texas. We tested acaricide resistance with larval packet tests (LPTs) on 47 collections. LPTs revealed acaricide resistance in 15/47 collections (32%); 11 were outside the TEQA and three were resistant to multiple acaricides. Some collections highly resistant to permethrin were found on cattle and WTD. Analysis of genetic differentiation over time at seven properties revealed local gene pools with very low levels of differentiation (FST 0.00-0.05), indicating persistence over timespans of up to 29 months. However, in one neighborhood differentiation varied greatly over a 12-month period (FST 0.03-0.13), suggesting recurring immigration from distinct sources as another persistence mechanism. Ticks collected from cattle and WTD at the same location are not differentiated (FST = 0), implicating ticks from WTD as a source of ticks on cattle (and vice versa) and emphasizing the importance of WTD to tick control strategies. We identified four major genetic groups (K = 4) using Bayesian population assignment, suggesting multiple introductions to Texas. Two dispersal mechanisms give rise to new tick infestations: 1) frequent short-distance dispersal from the TEQA; and 2) rare long-distance, human-mediated dispersal from populations outside our study area, probably Mexico. The threat of cattle fever tick transport into Texas is increased by acaricide resistance and the ability of R. microplus to utilize WTD as an alternate host. Population genetic analyses may provide a powerful tool for tracking invasions in other parts of the world where these ticks are established.

Genetic variation reveals influence of landscape connectivity on population dynamics and resiliency of western trout in disturbance-prone habitats

USGS Publications Warehouse

Helen M. Neville,; Gresswell, Robert E.; Dunham, Jason B.

2012-01-01

Salmonid fishes have evolved and persisted in dynamic ecosystems where disturbance events vary in frequency, magnitude, timing, and duration, as well as the specific nature of associated effects (e.g., changes in thermal or flow regimes, geomorphology, or water chemistry). In the western United States, one of the major drivers of disturbance in stream ecosystems is fire. Although there is a growing consensus that fish populations can ultimately benefit from the productive and heterogeneous habitats created by fire, to persist they obviously have to withstand the immediate and shorter-term effects of fire, which can reduce or even extirpate local populations. Movement among interconnected stream habitats is thought to be an important strategy enabling persistence during and following fire, and there is mounting concern that the extensive isolation of salmonid populations in fragmented habitats is reducing their resiliency to fire. In spite of this concern, there are few direct observations of salmonid responses to fire. In fact, guidance is based largely on a broader understanding of the influences of landscape structure and disturbance in general on salmonid fishes, and there is considerable uncertainty about how best to manage for salmonid resilience to wildfire. Studies are limited by the difficult logistics of following fish responses in the face of unpredictable events such as wildfires. Therefore, BACI (Before-After-Control-Impact) study designs are nearly impossible, and replication is similarly challenging because fires are often low-frequency events. Furthermore, conventional ecological study approaches (e.g., studies of fish distribution, abundance, life histories, and movement) are logistically difficult to implement. Overall, a major challenge to understanding resilience of salmonid populations in fire-prone environments is related to moving beyond localized case studies to those with broader applicability in wildfire management . Genetic data can be useful for overcoming many of the limitations inherent in ecological studies. Here we review several case studies of western trout where population genetic data have provided insight about fish responses to fragmentation and disturbance more generally, and specifically in relation to fire. Results of these studies confirm the importance of movement and landscape connectivity for ensuring fish persistence in fire-prone landscapes, and highlight the usefulness of genetic approaches for broad-scale evaluation and monitoring of population responses to fire and related management actions.

Widespread movement of invasive cattle fever ticks (Rhipicephalus microplus) in southern Texas leads to shared local infestations on cattle and deer

PubMed Central

2014-01-01

Background Rhipicephalus (Boophilus) microplus is a highly-invasive tick that transmits the cattle parasites (Babesia bovis and B. bigemina) that cause cattle fever. R. microplus and Babesia are endemic in Mexico and ticks persist in the United States inside a narrow tick eradication quarantine area (TEQA) along the Rio Grande. This containment area is threatened by unregulated movements of illegal cattle and wildlife like white-tailed deer (WTD; Odocoileus virginianus). Methods Using 11 microsatellite loci we genotyped 1,247 R. microplus from 63 Texas collections, including outbreak infestations from outside the TEQA. We used population genetic analyses to test hypotheses about ecological persistence, tick movement, and impacts of the eradication program in southern Texas. We tested acaricide resistance with larval packet tests (LPTs) on 47 collections. Results LPTs revealed acaricide resistance in 15/47 collections (32%); 11 were outside the TEQA and three were resistant to multiple acaricides. Some collections highly resistant to permethrin were found on cattle and WTD. Analysis of genetic differentiation over time at seven properties revealed local gene pools with very low levels of differentiation (FST 0.00-0.05), indicating persistence over timespans of up to 29 months. However, in one neighborhood differentiation varied greatly over a 12-month period (FST 0.03-0.13), suggesting recurring immigration from distinct sources as another persistence mechanism. Ticks collected from cattle and WTD at the same location are not differentiated (FST = 0), implicating ticks from WTD as a source of ticks on cattle (and vice versa) and emphasizing the importance of WTD to tick control strategies. We identified four major genetic groups (K = 4) using Bayesian population assignment, suggesting multiple introductions to Texas. Conclusions Two dispersal mechanisms give rise to new tick infestations: 1) frequent short-distance dispersal from the TEQA; and 2) rare long-distance, human-mediated dispersal from populations outside our study area, probably Mexico. The threat of cattle fever tick transport into Texas is increased by acaricide resistance and the ability of R. microplus to utilize WTD as an alternate host. Population genetic analyses may provide a powerful tool for tracking invasions in other parts of the world where these ticks are established. PMID:24742041

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.

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 palaeoclimate) to interpret phylogeographic patterns. PMID:24284819

Predicting evolutionary rescue via evolving plasticity in stochastic environments

PubMed Central

Baskett, Marissa L.

2016-01-01

Phenotypic plasticity and its evolution may help evolutionary rescue in a novel and stressful environment, especially if environmental novelty reveals cryptic genetic variation that enables the evolution of increased plasticity. However, the environmental stochasticity ubiquitous in natural systems may alter these predictions, because high plasticity may amplify phenotype–environment mismatches. Although previous studies have highlighted this potential detrimental effect of plasticity in stochastic environments, they have not investigated how it affects extinction risk in the context of evolutionary rescue and with evolving plasticity. We investigate this question here by integrating stochastic demography with quantitative genetic theory in a model with simultaneous change in the mean and predictability (temporal autocorrelation) of the environment. We develop an approximate prediction of long-term persistence under the new pattern of environmental fluctuations, and compare it with numerical simulations for short- and long-term extinction risk. We find that reduced predictability increases extinction risk and reduces persistence because it increases stochastic load during rescue. This understanding of how stochastic demography, phenotypic plasticity, and evolution interact when evolution acts on cryptic genetic variation revealed in a novel environment can inform expectations for invasions, extinctions, or the emergence of chemical resistance in pests. PMID:27655762

Diluting the founder effect: cryptic invasions expand a marine invader's range

PubMed Central

Roman, Joe

2006-01-01

Most invasion histories include an estimated arrival time, followed by range expansion. Yet, such linear progression may not tell the entire story. The European green crab (Carcinus maenas) was first recorded in the US in 1817, followed by an episodic expansion of range to the north. Its population has recently exploded in the Canadian Maritimes. Although it has been suggested that this northern expansion is the result of warming sea temperatures or cold-water adaptation, Canadian populations have higher genetic diversity than southern populations, indicating that multiple introductions have occurred in the Maritimes since the 1980s. These new genetic lineages, probably from the northern end of the green crab's native range in Europe, persist in areas that were once thought to be too cold for the original southern invasion front. It is well established that ballast water can contain a wide array of nonindigenous species. Ballast discharge can also deliver genetic variation on a level comparable to that of native populations. Such gene flow not only increases the likelihood of persistence of invasive species, but it can also rapidly expand the range of long-established nonindigenous species. PMID:16959635

When the time seems ripe: eugenics, the annals, and the subtle persistence of typological thinking.

PubMed

Weiss, Kenneth M; Lambert, Brian W

2011-05-01

This journal began in 1925 as the Annals of Eugenics. Much has changed since then. The original Editors' primary eugenic objective was not achieved, and eugenics justifiably became notorious for racism and gross abuse of human rights. But one founding aim was to publish advances in statistical genetics, and that objective prospered in the journal's pages from its beginning to the present day. The online availability of the original issues will be useful to those interested in the history of both eugenics and human genetics and will provide a reminder of how the careless use of genetical concepts can go astray. © 2010 The Authors Annals of Human Genetics © 2010 Blackwell Publishing Ltd/University College London.

Prolonged thrombocytopenia in a child with severe neonatal alloimmune reaction and Noonan syndrome.

PubMed

Salva, Inês; Batalha, Sara; Maia, Raquel; Kjollerstrom, Paula

2016-06-01

Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.

Past, present, and future of a freshwater fish metapopulation in a threatened landscape.

PubMed

Vera-Escalona, Iván; Senthivasan, Shreeram; Habit, Evelyn; Ruzzante, Daniel E

2018-02-12

It is well documented that hydropower plants can affect the dynamics of fish populations through landscape alterations and the creation of new barriers. Less emphasis has been placed on the examination of the genetic consequences for fish populations of the construction of dams. The relatively few studies that focus on genetics often do not consider colonization history and even fewer tend to use this information for conservation purposes. As a case study, we used a 3-pronged approach to study the influence of historical processes, contemporary landscape features, and potential future anthropogenic changes in landscape on the genetic diversity of a fish metapopulation. Our goal was to identify the metapopulation's main attributes, detect priority areas for conservation, and assess the consequences of the construction of hydropower plants for the persistence of the metapopulation. We used microsatellite markers and coalescent approaches to examine historical colonization processes, traditional population genetics, and simulations of future populations under alternate scenarios of population size reduction and gene flow. Historical gene flow appeared to have declined relatively recently and contemporary populations appeared highly susceptible to changes in landscape. Gene flow is critical for population persistence. We found that hydropower plants could lead to a rapid reduction in number of alleles and to population extirpation 50-80 years after their construction. More generally, our 3-pronged approach for the analyses of empirical genetic data can provide policy makers with information on the potential impacts of landscape changes and thus lead to more robust conservation efforts. © 2018 Society for Conservation Biology.

Chronic West Nile virus infection in kea (Nestor notabilis).

PubMed

Bakonyi, Tamás; Gajdon, Gyula K; Schwing, Raoul; Vogl, Wolfgang; Häbich, Annett-Carolin; Thaller, Denise; Weissenböck, Herbert; Rudolf, Ivo; Hubálek, Zdenek; Nowotny, Norbert

2016-02-01

Six kea (Nestor notabilis) in human care, naturally infected with West Nile virus (WNV) lineage 2 in Vienna, Austria, in 2008, developed mild to fatal neurological signs. WNV RNA persisted and the virus evolved in the birds' brains, as demonstrated by (phylo)genetic analyses of the complete viral genomes detected in kea euthanized between 2009 and 2014. WNV antibodies persisted in the birds, too. Chronic WNV infection in the brain might contribute to the circulation of the virus through oral transmission to predatory birds. Copyright © 2015 Elsevier B.V. All rights reserved.

Guidelines for pubertal suspension and gender reassignment for transgender adolescents.

PubMed

Hembree, Wylie C

2011-10-01

Pubertal suppression at Tanner stage 2 should be considered in adolescents with persistent gender identity disorder (GID). Issues related to achievement of adult height, timing of initiating sex steroid treatment, future fertility options, preventing uterine bleeding, and required modifications of genital surgery remain concerns. Concerns have been raised about altering neuropsychological development during cessation of puberty and reinitiation of puberty by the sex steroid opposite those determined by genetic sex. Collaborative assessment and treatment of dysphoric adolescents with persistent GID resolves these concerns and deepens our understanding of gender development.

GENETIC ADAPTATION TO CHRONIC CONTAMINANT EXPOSURE BY A SMALL ESTUARINE FISH

EPA Science Inventory

Investigations of the non-migratory fish species Fundulus heteroclitus indigenous to a highly chemically contaminated site is providing novel insights into stressor costs and adaptive strategies. Specifically, we are studying an abundant and persistent population of F. heterocli...

FROM MOLECULES TO POPULATIONS: USING POPULATION GENETICS TO ANSWER THE SO WHAT QUESTION

EPA Science Inventory

Important endpoints for ecological risk assessments are usually those that affect population or species persistence rather than individual-level responses. Nonetheless, ecological risk assessments are generally based on measures of individual-level responses. Extrapolation of i...

Fragile X Syndrome: Genetic Predisposition to Psychopathology.

ERIC Educational Resources Information Center

Bregman, Joel D.; And Others

1988-01-01

Psychiatric evaluation of 14 males (ages 3-27 years) with the fragile X syndrome found pervasive hyperactivity, impulsivity, and attentional deficits, and a significant degree of anxiety. However, diagnostic criteria for persistent pervasive developmental disorder and autism were not met. (Author/DB)

CARs: Driving T-cell specificity to enhance anti-tumor immunity

PubMed Central

Kebriaei, Partow; Kelly, Susan S.; Manuri, Pallavi; Jena, Bipulendu; Jackson, Rineka; Shpall, Elizabeth; Champlin, Richard; Cooper, Laurence J. N.

2013-01-01

Adoptive transfer of antigen-specific T cells is a compelling tool to treat cancer. To overcome issues of immune tolerance which limits the endogenous adaptive immune response to tumor-associated antigens, robust systems for the genetic modification and characterization of T cells expressing chimeric antigen receptors (CARs) to redirect specificity have been produced. Refinements with regards to persistence and trafficking of the genetically modified T cells are underway to help improve the potency of genetically modified T cells. Clinical trials utilizing this technology demonstrate feasibility, and increasingly, antitumor activity, paving the way for multi-center trials to establish the efficacy of this novel T-cell therapy. PMID:22202074

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 modeling together with analyses of population genetic structure. One of the major questions that will be addressed is whether populations have persisted over long periods of time and if the contemporary population structure has derived from events earlier than the Pleistocene. Population genetic structure will then be used to propose strategies that will optimize conservation of genetic resources.

HIV Integration at Certain Sites in Host DNA is Linked to the Expansion and Persistence of Infected Cells | Center for Cancer Research

Cancer.gov

When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites in the host cell DNA, the site of integration marks each infected cell. Patients infected with

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

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.

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.

Interactions of transgenic Bacillus thuringiensis insecticidal crops with spiders (Araneae)

USDA-ARS?s Scientific Manuscript database

Genetically modified crops expressing insecticidal proteins from Bacillus thuringiensis (Bt) have dramatically increased in acreage since their introduction in the mid-1990’s. Although the insecticidal mechanisms of Bt target specific pests, concerns persist regarding direct and indirect effects on...

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.

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.

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

PubMed Central

Josefsson, Lina; von Stockenstrom, Susanne; Faria, Nuno R.; Sinclair, Elizabeth; Bacchetti, Peter; Killian, Maudi; Epling, Lorrie; Tan, Alice; Ho, Terence; Lemey, Philippe; Shao, Wei; Hunt, Peter W.; Somsouk, Ma; Wylie, Will; Douek, Daniel C.; Loeb, Lisa; Custer, Jeff; Hoh, Rebecca; Poole, Lauren; Deeks, Steven G.; Hecht, Frederick; Palmer, Sarah

2013-01-01

The source and dynamics of persistent HIV-1 during long-term combinational antiretroviral therapy (cART) are critical to understanding the barriers to curing HIV-1 infection. To address this issue, we isolated and genetically characterized HIV-1 DNA from naïve and memory T cells from peripheral blood and gut-associated lymphoid tissue (GALT) from eight patients after 4–12 y of suppressive cART. Our detailed analysis of these eight patients indicates that persistent HIV-1 in peripheral blood and GALT is found primarily in memory CD4+ T cells [CD45RO+/CD27(+/−)]. The HIV-1 infection frequency of CD4+ T cells from peripheral blood and GALT was higher in patients who initiated treatment during chronic compared with acute/early infection, indicating that early initiation of therapy results in lower HIV-1 reservoir size in blood and gut. Phylogenetic analysis revealed an HIV-1 genetic change between RNA sequences isolated before initiation of cART and intracellular HIV-1 sequences from the T-cell subsets after 4–12 y of suppressive cART in four of the eight patients. However, evolutionary rate analyses estimated no greater than three nucleotide substitutions per gene region analyzed during all of the 4–12 y of suppressive therapy. We also identified a clearly replication-incompetent viral sequence in multiple memory T cells in one patient, strongly supporting asynchronous cell replication of a cell containing integrated HIV-1 DNA as the source. This study indicates that persistence of a remarkably stable population of infected memory cells will be the primary barrier to a cure, and, with little evidence of viral replication, this population could be maintained by homeostatic cell proliferation or other processes. PMID:24277811

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.

Approximate Bayesian estimation of extinction rate in the Finnish Daphnia magna metapopulation.

PubMed

Robinson, John D; Hall, David W; Wares, John P

2013-05-01

Approximate Bayesian computation (ABC) is useful for parameterizing complex models in population genetics. In this study, ABC was applied to simultaneously estimate parameter values for a model of metapopulation coalescence and test two alternatives to a strict metapopulation model in the well-studied network of Daphnia magna populations in Finland. The models shared four free parameters: the subpopulation genetic diversity (θS), the rate of gene flow among patches (4Nm), the founding population size (N0) and the metapopulation extinction rate (e) but differed in the distribution of extinction rates across habitat patches in the system. The three models had either a constant extinction rate in all populations (strict metapopulation), one population that was protected from local extinction (i.e. a persistent source), or habitat-specific extinction rates drawn from a distribution with specified mean and variance. Our model selection analysis favoured the model including a persistent source population over the two alternative models. Of the closest 750,000 data sets in Euclidean space, 78% were simulated under the persistent source model (estimated posterior probability = 0.769). This fraction increased to more than 85% when only the closest 150,000 data sets were considered (estimated posterior probability = 0.774). Approximate Bayesian computation was then used to estimate parameter values that might produce the observed set of summary statistics. Our analysis provided posterior distributions for e that included the point estimate obtained from previous data from the Finnish D. magna metapopulation. Our results support the use of ABC and population genetic data for testing the strict metapopulation model and parameterizing complex models of demography. © 2013 Blackwell Publishing Ltd.

Genome-Wide Association Studies of Drug-Resistance Determinants.

PubMed

Volkman, Sarah K; Herman, Jonathan; Lukens, Amanda K; Hartl, Daniel L

2017-03-01

Population genetic strategies that leverage association, selection, and linkage have identified drug-resistant loci. However, challenges and limitations persist in identifying drug-resistance loci in malaria. In this review we discuss the genetic basis of drug resistance and the use of genome-wide association studies, complemented by selection and linkage studies, to identify and understand mechanisms of drug resistance and response. We also discuss the implications of nongenetic mechanisms of drug resistance recently reported in the literature, and present models of the interplay between nongenetic and genetic processes that contribute to the emergence of drug resistance. Throughout, we examine artemisinin resistance as an example to emphasize challenges in identifying phenotypes suitable for population genetic studies as well as complications due to multiple-factor drug resistance. Copyright © 2016. Published by Elsevier Ltd.

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.

From Treating Childhood Malnutrition to Public Health Nutrition.

PubMed

James, W Philip T

2018-01-01

This analysis sets out an overview of an IUNS presentation of a European clinician's assessment of the challenges of coping with immediate critical clinical problems and how to use metabolic and a mechanistic understanding of disease when developing nutritional policies. Critically ill malnourished children prove very sensitive to both mineral and general nutritional overload, but after careful metabolic control they can cope with a high-quality, energy-rich diet provided their initial lactase deficiency and intestinal atrophy are taken into account. Detailed intestinal perfusion studies also showed that gastroenteritis can be combatted by multiple frequent glucose/saline feeds, which has saved millions of lives. However, persisting pancreatic islet cell damage may explain our findings of pandemic rates of adult diabetes in Asia, the Middle East and Mexico and perhaps elsewhere including Africa and Latin America. These handicaps together with the magnitude of epigenetic changes emphasized the importance of a whole life course approach to nutritional policy making. Whole body calorimetric analyses of energy requirements allowed a complete revision of estimates for world food needs and detailed clinical experience showed the value of redefining stunting and wasting in childhood and the value of BMI for classifying appropriate adult weights, underweight and obesity. Lithium tracer studies of dietary salt sources should also dictate priorities in population salt-reduction strategies. Metabolic and clinical studies combined with meticulous measures of population dietary intakes now suggest the need for far more radical steps to lower the dietary goals for both free sugars and total dietary fat unencumbered by flawed cohort studies that neglect not only dietary errors but also the intrinsic inter-individual differences in metabolic responses to most nutrients. Key Messages: Detailed clinical and metabolic analyses of physiological responses combined with rigorous dietary and preferably biomarker of mechanistic pathways should underpin a new approach not only to clinical care but also to the development of more radical nutritional policies. © 2018 S. Karger AG, Basel.

Enhancing the Teaching of Evolution in Public Health.

PubMed

Omenn, Gilbert S

2011-12-01

Public health courses are emerging as popular undergraduate offerings, especially at universities with schools of public health. It is important to note that evolution has shaped the burden of disease in the modern world in which we practice and educate for public health. Human cultures and technologies have modified life on Planet Earth and have co-evolved with myriad other species, including microorganisms, plant and animal sources of food, invertebrate vectors of disease, and intermediate bird, mammal, and primate hosts. Molecular mechanisms of evolution have produced differential resistance or susceptibility to infectious agents, including malaria, plague, smallpox, TB, measles, and diarrheal and respiratory diseases. The domestication of sheep and cattle led to natural selection in favor of human populations able to digest milk throughout life through persistence into adulthood of lactase enzyme expression in the intestine, a major story of anthropology. The emergence of a "Western diet" of dairy, refined cereal grains, refined sugars, vegetable oils, alcoholic beverages, salt, and omega-6-rich meats has dramatically altered glycemic load, fatty acid composition, macro-nutrients, acid-base balance, sodium/potassium ratio, and fiber content. This is a major story of nutrition and disease. The results include epidemics of atherosclerotic cardiovascular disease, obesity, diabetes, high blood pressure, osteoporosis, certain cancers, and bowel, inflammatory, and autoimmune disorders. Another interesting phenomenon is the selection of excessive hemostatic activity from platelets and the plasma clotting proteins; what was protective against death from bleeding after injuries among hunter-gatherers or from pregnancy-related hemorrhage now contributes to thrombosis underlying heart attacks and strokes. Conversely, there is little pressure against hemostasis and thrombosis since deaths from these causes occur mostly after the reproductive years of life. Learning about evolution over millennia for humans and over hours or days for microbes enlivens the experience of understanding evolutionary biology in public health context.

Glacial refugia, recolonization patterns and diversification forces in Alpine-endemic Megabunus harvestmen.

PubMed

Wachter, Gregor A; Papadopoulou, Anna; Muster, Christoph; Arthofer, Wolfgang; Knowles, L Lacey; Steiner, Florian M; Schlick-Steiner, Birgit C

2016-06-01

The Pleistocene climatic fluctuations had a huge impact on all life forms, and various hypotheses regarding the survival of organisms during glacial periods have been postulated. In the European Alps, evidence has been found in support of refugia outside the ice shield (massifs de refuge) acting as sources for postglacial recolonization of inner-Alpine areas. In contrast, evidence for survival on nunataks, ice-free areas above the glacier, remains scarce. Here, we combine multivariate genetic analyses with ecological niche models (ENMs) through multiple timescales to elucidate the history of Alpine Megabunus harvestmen throughout the ice ages, a genus that comprises eight high-altitude endemics. ENMs suggest two types of refugia throughout the last glacial maximum, inner-Alpine survival on nunataks for four species and peripheral refugia for further four species. In some geographic regions, the patterns of genetic variation are consistent with long-distance dispersal out of massifs de refuge, repeatedly coupled with geographic parthenogenesis. In other regions, long-term persistence in nunataks may dominate the patterns of genetic divergence. Overall, our results suggest that glacial cycles contributed to allopatric diversification in Alpine Megabunus, both within and at the margins of the ice shield. These findings exemplify the power of ENM projections coupled with genetic analyses to identify hypotheses about the position and the number of glacial refugia and thus to evaluate the role of Pleistocene glaciations in driving species-specific responses of recolonization or persistence that may have contributed to observed patterns of biodiversity. © 2016 John Wiley & Sons Ltd.

Bt crop effects on functional guilds of non-target arthropods: A meta-analysis (journal)

EPA Science Inventory

Background: Uncertainty persists over the environmental effects of genetically-engineered crops that produce the insecticidal Cry proteins of Bacillus thuringiensis (Bt). We performed meta-analyses on a modified public database to synthesize current knowledge about the effects of...

Marijuana: A Review of Medical Research with Implications for Adolescents.

ERIC Educational Resources Information Center

Margolis, Robert; Popkin, Nancy

1980-01-01

Recent evidence indicates that marijuana is more harmful than had previously been suspected. A review of research in the following areas is presented: tolerance and persistence, reproductive system, respiratory system, immune system, central nervous system, genetic and chromosomal effects, and behavioral effects. (Author)

CHANGES IN GENETIC DIVERSITY OF A WHITE SUCKER POPULATION FOLLOWING EXPERIMENTAL WHOLE-LAKE ACIDIFICATION

EPA Science Inventory

Despite great strides to reduce sulfur dioxide emissions over the last decade, acid precipitation remains a persistent threat to North American fish communities. A demographic analysis of white suckers in an experimentally acidified oligotrophic lake in northwest Ontario demonst...

The Design and Implementation of Eco-Evolutionary PVA Models: An Integrative Approach Using HexSim

EPA Science Inventory

To persist into the future, species of conservation concern must remain both demographically and genetically viable. Developing mitigation and recovery strategies to ensure species’ viability necessitates the use of forecasting models that can incorporate ecological and/or...

Tolerance and potential for adaptation of a Baltic Sea rockweed under predicted climate change conditions.

PubMed

Rugiu, Luca; Manninen, Iita; Rothäusler, Eva; Jormalainen, Veijo

2018-03-01

Climate change is threating species' persistence worldwide. To predict species responses to climate change we need information not just on their environmental tolerance but also on its adaptive potential. We tested how the foundation species of rocky littoral habitats, Fucus vesiculosus, responds to combined hyposalinity and warming projected to the Baltic Sea by 2070-2099. We quantified responses of replicated populations originating from the entrance, central, and marginal Baltic regions. Using replicated individuals, we tested for the presence of within-population tolerance variation. Future conditions hampered growth and survival of the central and marginal populations whereas the entrance populations fared well. Further, both the among- and within-population variation in responses to climate change indicated existence of genetic variation in tolerance. Such standing genetic variation provides the raw material necessary for adaptation to a changing environment, which may eventually ensure the persistence of the species in the inner Baltic Sea. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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.

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.

When The Time Seems Ripe: Eugenics, the Annals, and the subtle persistence of typological thinking

PubMed Central

WEISS, KENNETH M; LAMBERT, BRIAN W

2010-01-01

SUMMARY This journal began in 1926 as the Annals of Eugenics. Much has changed since then. The original Editors’ primary eugenic objective was not achieved, and eugenics justifiably became notorious for racism and gross abuse of human rights. But one founding aim was to publish advances in statistical genetics, and that objective prospered in the journal’s pages from its beginning to the present day. The online availability of the original issues will be useful to those interested in the history of both eugenics and human genetics, and will provide a reminder of how the careless use of genetical concepts can go astray. PMID:21488850

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

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.

Placental genetic variations in circadian clock-related genes increase the risk of placental abruption.

PubMed

Qiu, Chunfang; Gelaye, Bizu; Denis, Marie; Tadesse, Mahlet G; Enquobahrie, Daniel A; Ananth, Cande V; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E; Williams, Michelle A

2016-01-01

The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrend<0.001). The ORs were 1.00, 2.16, 3.24 and 4.48 across quartiles. Associations persisted after the maternal-wGRS was included in the model. There was evidence of an additive contribution of placental and maternal genetic contributions to PA risk. Participants with placental- and maternal-wGRS in the highest quartile, compared with those in the lowest quartile, had a 15.57-fold (95% CI 3.34-72.60) increased odds of PA. Placental variants in circadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome.

Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase.

PubMed

Fischer, Kimberlee M; Cottage, Christopher T; Wu, Weitao; Din, Shabana; Gude, Natalie A; Avitabile, Daniele; Quijada, Pearl; Collins, Brett L; Fransioli, Jenna; Sussman, Mark A

2009-11-24

Despite numerous studies demonstrating the efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain for donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing the regenerative potential of adoptively transferred cardiac progenitor cells (CPCs) via genetic engineering to overexpress Pim-1, a cardioprotective kinase that enhances cell survival and proliferation. Intramyocardial injections of CPCs overexpressing Pim-1 were given to infarcted female mice. Animals were monitored over 4, 12, and 32 weeks to assess cardiac function and engraftment of Pim-1 CPCs with echocardiography, in vivo hemodynamics, and confocal imagery. CPCs overexpressing Pim-1 showed increased proliferation and expression of markers consistent with cardiogenic lineage commitment after dexamethasone exposure in vitro. Animals that received CPCs overexpressing Pim-1 also produced greater levels of cellular engraftment, persistence, and functional improvement relative to control CPCs up to 32 weeks after delivery. Salutary effects include reduction of infarct size, greater number of c-kit(+) cells, and increased vasculature in the damaged region. Myocardial repair is significantly enhanced by genetic engineering of CPCs with Pim-1 kinase. Ex vivo gene delivery to enhance cellular survival, proliferation, and regeneration may overcome current limitations of stem cell-based therapeutic approaches.

The Diagnosis and Management of Hyperinsulinaemic Hypoglycaemia.

PubMed

Roženková, Klára; Güemes, Maria; Shah, Pratik; Hussain, Khalid

2015-06-01

Insulin secretion from pancreatic β-cells is tightly regulated to keep fasting blood glucose concentrations within the normal range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is a heterozygous condition in which insulin secretion becomes unregulated and its production persists despite low blood glucose levels. It is the most common cause of severe and persistent hypoglycaemia in neonates and children. The most severe and permanent forms are due to congenital hyperinsulinism (CHI). Recent advances in genetics have linked CHI to mutations in 9 genes that play a key role in regulating insulin secretion (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A and HNF1A). Histologically, CHI can be divided into 3 types; diffuse, focal and atypical. Given the biochemical nature of HH (non-ketotic), a delay in the diagnosis and management can result in irreversible brain damage. Therefore, it is essential to diagnose and treat HH promptly. Advances in molecular genetics, imaging methods (18F-DOPA PET-CT), medical therapy and surgical approach (laparoscopic surgery) have completely changed the management and improved the outcome of these children. This review provides an overview of the genetic and molecular mechanisms leading to development of HH in children. The article summarizes the current diagnostic methods and management strategies for the different types of CHI.

Spatiotemporal dynamics of Puumala hantavirus associated with its rodent host, Myodes glareolus

PubMed Central

Weber de Melo, Vanessa; Sheikh Ali, Hanan; Freise, Jona; Kühnert, Denise; Essbauer, Sandra; Mertens, Marc; Wanka, Konrad M; Drewes, Stephan; Ulrich, Rainer G; Heckel, Gerald

2015-01-01

Many viruses significantly impact human and animal health. Understanding the population dynamics of these viruses and their hosts can provide important insights for epidemiology and virus evolution. Puumala virus (PUUV) is a European hantavirus that may cause regional outbreaks of hemorrhagic fever with renal syndrome in humans. Here, we analyzed the spatiotemporal dynamics of PUUV circulating in local populations of its rodent reservoir host, the bank vole (Myodes glareolus) during eight years. Phylogenetic and population genetic analyses of all three genome segments of PUUV showed strong geographical structuring at a very local scale. There was a high temporal turnover of virus strains in the local bank vole populations, but several virus strains persisted through multiple years. Phylodynamic analyses showed no significant changes in the local effective population sizes of PUUV, although vole numbers and virus prevalence fluctuated widely. Microsatellite data demonstrated also a temporally persisting subdivision between local vole populations, but these groups did not correspond to the subdivision in the virus strains. We conclude that restricted transmission between vole populations and genetic drift play important roles in shaping the genetic structure and temporal dynamics of PUUV in its natural host which has several implications for zoonotic risks of the human population. PMID:26136821

Identification of rare and novel deletions that cause (δβ)0-thalassaemia and hereditary persistence of foetal haemoglobin in Indian population.

PubMed

Mayuranathan, Thiyagaraj; Rayabaram, Janakiram; Das, Reena; Arora, Neeraj; Edison, Eunice S; Chandy, Mammen; Srivastava, Alok; Velayudhan, Shaji R

2014-06-01

Hereditary persistence of foetal haemoglobin (HPFH) and (δβ)(0) -thalassaemia are conditions caused by large deletions that involve δ- and β-globin genes in the β-globin cluster, and they are characterized by increased haemoglobin (HbF) levels in adults. Significant phenotypic diversity is observed between the different mutations that cause these conditions. Molecular characterization of these deletions is important for accurate molecular diagnosis, and they will also provide the information on the cis-acting genetic regulatory elements present in the β-globin cluster. We performed gap-PCR, multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescent multiplex PCR (QF-MPCR) and DNA sequencing to detect and characterize the deletions in the β-globin cluster. We characterized six different deletions resulting in (δβ)(0) -thalassaemia or HPFH in 51 unrelated families. With the help of multiple genetic tools, we performed comprehensive genetic analysis of HPFH and (δβ)(0) -thalassaemia in Indian population and could define the molecular basis of these conditions in this population. We also identified two novel HPFH mutations, 49.98 kb (HPFH-9) and 86.7 kb (HPFH-10) deletions, in this population. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ice-age survival of Atlantic cod: agreement between palaeoecology models and genetics

PubMed Central

Bigg, Grant R; Cunningham, Clifford W; Ottersen, Geir; Pogson, Grant H; Wadley, Martin R; Williamson, Phillip

2007-01-01

Scant scientific attention has been given to the abundance and distribution of marine biota in the face of the lower sea level, and steeper latitudinal gradient in climate, during the ice-age conditions that have dominated the past million years. Here we examine the glacial persistence of Atlantic cod (Gadus morhua) populations using two ecological-niche-models (ENM) and the first broad synthesis of multi-locus gene sequence data for this species. One ENM uses a maximum entropy approach (Maxent); the other is a new ENM for Atlantic cod, using ecophysiological parameters based on observed reproductive events rather than adult distribution. Both the ENMs were tested for present-day conditions, then used to hindcast ranges at the last glacial maximum (LGM) ca 21 kyr ago, employing climate model data. Although the LGM range of Atlantic cod was much smaller, and fragmented, both the ENMs agreed that populations should have been able to persist in suitable habitat on both sides of the Atlantic. The genetic results showed a degree of trans-Atlantic divergence consistent with genealogically continuous populations on both sides of the North Atlantic since long before the LGM, confirming the ENM results. In contrast, both the ENMs and the genetic data suggest that the Greenland G. morhua population post-dates the LGM. PMID:17999951

The effects of probiotics in lactose intolerance: A systematic review.

PubMed

Oak, Sophia J; Jha, Rajesh

2018-02-09

Over 60 percent of the human population has a reduced ability to digest lactose due to low levels of lactase enzyme activity. Probiotics are live bacteria or yeast that supplements the gastrointestinal flora. Studies have shown that probiotics exhibit various health beneficial properties such as improvement of intestinal health, enhancement of the immune responses, and reduction of serum cholesterol. Accumulating evidence has shown that probiotic bacteria in fermented and unfermented milk products can be used to alleviate the clinical symptoms of lactose intolerance (LI). In this systematic review, the effectiveness of probiotics in the treatment of LI was evaluated using 15 randomized double-blind studies. Eight probiotic strains with the greatest number of proven benefits were studied. Results showed varying degrees of efficacy but an overall positive relationship between probiotics and lactose intolerance.

Lactation persistency as a component trait of the selection index and increase in reliability by using single nucleotide polymorphism in net merit defined as the first five lactation milk yields and herd life.

PubMed

Togashi, K; Hagiya, K; Osawa, T; Nakanishi, T; Yamazaki, T; Nagamine, Y; Lin, C Y; Matsumoto, S; Aihara, M; Hayasaka, K

2012-08-01

We first sought to clarify the effects of discounted rate, survival rate, and lactation persistency as a component trait of the selection index on net merit, defined as the first five lactation milks and herd life (HL) weighted by 1 and 0.389 (currently used in Japan), respectively, in units of genetic standard deviation. Survival rate increased the relative economic importance of later lactation traits and the first five lactation milk yields during the first 120 months from the start of the breeding scheme. In contrast, reliabilities of the estimated breeding value (EBV) in later lactation traits are lower than those of earlier lactation traits. We then sought to clarify the effects of applying single nucleotide polymorphism (SNP) on net merit to improve the reliability of EBV of later lactation traits to maximize their increased economic importance due to increase in survival rate. Net merit, selection accuracy, and HL increased by adding lactation persistency to the selection index whose component traits were only milk yields. Lactation persistency of the second and (especially) third parities contributed to increasing HL while maintaining the first five lactation milk yields compared with the selection index whose only component traits were milk yields. A selection index comprising the first three lactation milk yields and persistency accounted for 99.4% of net merit derived from a selection index whose components were identical to those for net merit. We consider that the selection index comprising the first three lactation milk yields and persistency is a practical method for increasing lifetime milk yield in the absence of data regarding HL. Applying SNP to the second- and third-lactation traits and HL increased net merit and HL by maximizing the increased economic importance of later lactation traits, reducing the effect of first-lactation milk yield on HL (genetic correlation (rG) = -0.006), and by augmenting the effects of the second- and third-lactation milk yields on HL (rG = 0.118 and 0.257, respectively).

Early Identification and Treatment of Antisocial Behavior.

PubMed

Frick, Paul J

2016-10-01

Severe and persistent antisocial behavior is a prevalent, serious, and costly mental health problem. Individuals who are most likely to show persistent antisocial behavior through adolescence and into adulthood often show patterns of severe and varied conduct problems early in childhood. Treatments that intervene early in the development of these problems are most effective and least costly. Furthermore, there appear to be several common causal pathways that differ in their genetic, emotional, cognitive, and contextual characteristics. These pathways are differentiated by the level of callous-unemotional traits displayed by the individual. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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 these variants with contemporaneous variants circulating in other countries. We found that periodic seasonal RSV transmission at the local level appears to require regular new introductions of variants. However, importantly, the evidence suggests that the source of new variants is mostly geographically restricted, and we hypothesize that year-to-year RSV persistence is at the country level rather than the global level. This has implications for control. PMID:26355091

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.

Antimicrobial resistance of Staphylococcus aureus isolates from dairy cows and genetic diversity of resistant isolates

USDA-ARS?s Scientific Manuscript database

Staphylococcus aureus is a frequent and major contagious mastitis bacterial pathogen. The antibiotic treatment cure rates vary considerably from 4% to 92%. Staphylococcus aureus readily becomes resistant to antibiotics, resulting in persistent noncurable intramammary infection that usually results i...

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.

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

The interplay between genetic and bioelectrical signaling permits a spatial regionalisation of membrane potentials in model multicellular ensembles

PubMed Central

Cervera, Javier; Meseguer, Salvador; Mafe, Salvador

2016-01-01

The single cell-centred approach emphasises ion channels as specific proteins that determine individual properties, disregarding their contribution to multicellular outcomes. We simulate the interplay between genetic and bioelectrical signals in non-excitable cells from the local single-cell level to the long range multicellular ensemble. The single-cell genetic regulation is based on mean-field kinetic equations involving the mRNA and protein concentrations. The transcription rate factor is assumed to depend on the absolute value of the cell potential, which is dictated by the voltage-gated cell ion channels and the intercellular gap junctions. The interplay between genetic and electrical signals may allow translating single-cell states into multicellular states which provide spatio-temporal information. The model results have clear implications for biological processes: (i) bioelectric signals can override slightly different genetic pre-patterns; (ii) ensembles of cells initially at the same potential can undergo an electrical regionalisation because of persistent genetic differences between adjacent spatial regions; and (iii) shifts in the normal cell electrical balance could trigger significant changes in the genetic regulation. PMID:27731412

The interplay between genetic and bioelectrical signaling permits a spatial regionalisation of membrane potentials in model multicellular ensembles.

PubMed

Cervera, Javier; Meseguer, Salvador; Mafe, Salvador

2016-10-12

The single cell-centred approach emphasises ion channels as specific proteins that determine individual properties, disregarding their contribution to multicellular outcomes. We simulate the interplay between genetic and bioelectrical signals in non-excitable cells from the local single-cell level to the long range multicellular ensemble. The single-cell genetic regulation is based on mean-field kinetic equations involving the mRNA and protein concentrations. The transcription rate factor is assumed to depend on the absolute value of the cell potential, which is dictated by the voltage-gated cell ion channels and the intercellular gap junctions. The interplay between genetic and electrical signals may allow translating single-cell states into multicellular states which provide spatio-temporal information. The model results have clear implications for biological processes: (i) bioelectric signals can override slightly different genetic pre-patterns; (ii) ensembles of cells initially at the same potential can undergo an electrical regionalisation because of persistent genetic differences between adjacent spatial regions; and (iii) shifts in the normal cell electrical balance could trigger significant changes in the genetic regulation.

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).

Etiological heterogeneity in the development of antisocial behavior: the Virginia Twin Study of Adolescent Behavioral Development and the Young Adult Follow-Up.

PubMed

Silberg, Judy L; Rutter, Michael; Tracy, Kelly; Maes, Hermine H; Eaves, Lindon

2007-08-01

Longitudinal, genetically informed, prospective data collected on a large population of male twins (n=1037) were used to examine developmental differences in the etiology of antisocial behavior. Analyses were carried out on both mother- and child-reported symptoms of conduct disorder (CD) in 10- to 17-year-old twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and self-reported antisocial behavior by the twins as young adults from the Young Adult Follow-Up (YAFU) study. The following trends were identified: (1) a single genetic factor influencing antisocial behavior beginning at age 10 through young adulthood ('life-course persistent'); (2) a shared-environmental effect beginning in adolescence ('adolescent-onset'); (3) a transient genetic effect at puberty; and (4) a genetic influence specific to adult antisocial behavior. Overall, these etiological findings are consistent with predictions from Moffitt's developmental theory of antisocial behavior. The genetic effect at puberty at ages 12-15 is also consistent with a genetically mediated influence on the timing of puberty affecting the expression of genetic differences in antisocial outcomes.

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.

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.

Strong genetic contribution to peer relationship difficulties at school entry: findings from a longitudinal twin study.

PubMed

Boivin, Michel; Brendgen, Mara; Vitaro, Frank; Dionne, Ginette; Girard, Alain; Pérusse, Daniel; Tremblay, Richard E

2013-01-01

This study assessed the genetic and environmental contributions to peer difficulties in the early school years. Twins' peer difficulties were assessed longitudinally in kindergarten (796 twins, Mage = 6.1 years), Grade 1 (948 twins, Mage = 7.1 years), and Grade 4 (868 twins, Mage = 10 years) through multiple informants. The multivariate results revealed that genetic factors accounted for a strong part of both yearly and stable peer difficulties. At the univariate level, the genetic contributions emerged progressively, as did a growing consensus among informants with respect to those who experienced peer difficulties. These results underline the need to intervene early and persistently, and to target the child and the peer context to prevent peer difficulties and their consequences. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

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, and other bred for high binge-like drinking. We have a much more clear idea now about some important experiments remaining to be performed. PMID:25306777

Predicting the effects of climate change on population connectivity and genetic diversity of an imperiled freshwater mussel, Cumberlandia monodonta (Bivalvia: Margaritiferidae), in riverine systems.

PubMed

Inoue, Kentaro; Berg, David J

2017-01-01

In the face of global climate change, organisms may respond to temperature increases by shifting their ranges poleward or to higher altitudes. However, the direction of range shifts in riverine systems is less clear. Because rivers are dendritic networks, there is only one dispersal route from any given location to another. Thus, range shifts are only possible if branches are connected by suitable habitat, and stream-dwelling organisms can disperse through these branches. We used Cumberlandia monodonta (Bivalvia: Unionoida: Margaritiferidae) as a model species to investigate the effects of climate change on population connectivity because a majority of contemporary populations are panmictic. We combined ecological niche models (ENMs) with population genetic simulations to investigate the effects of climate change on population connectivity and genetic diversity of C. monodonta. The ENMs were constructed using bioclimatic and landscape data to project shifts in suitable habitat under future climate scenarios. We then used forward-time simulations to project potential changes in genetic diversity and population connectivity based on these range shifts. ENM results under current conditions indicated long stretches of highly suitable habitat in rivers where C. monodonta persists; populations in the upper Mississippi River remain connected by suitable habitat that does not impede gene flow. Future climate scenarios projected northward and headwater-ward range contraction and drastic declines in habitat suitability for most extant populations throughout the Mississippi River Basin. Simulations indicated that climate change would greatly reduce genetic diversity and connectivity across populations. Results suggest that a single, large population of C. monodonta will become further fragmented into smaller populations, each of which will be isolated and begin to differentiate genetically. Because C. monodonta is a widely distributed species and purely aquatic, our results suggest that persistence and connectivity of stream-dwelling organisms will be significantly altered in response to future climate change. © 2016 John Wiley & Sons Ltd.

Reduced evolutionary rate in reemerged Ebola virus transmission chains.

PubMed

Blackley, David J; Wiley, Michael R; Ladner, Jason T; Fallah, Mosoka; Lo, Terrence; Gilbert, Merle L; Gregory, Christopher; D'ambrozio, Jonathan; Coulter, Stewart; Mate, Suzanne; Balogun, Zephaniah; Kugelman, Jeffrey; Nwachukwu, William; Prieto, Karla; Yeiah, Adolphus; Amegashie, Fred; Kearney, Brian; Wisniewski, Meagan; Saindon, John; Schroth, Gary; Fakoli, Lawrence; Diclaro, Joseph W; Kuhn, Jens H; Hensley, Lisa E; Jahrling, Peter B; Ströher, Ute; Nichol, Stuart T; Massaquoi, Moses; Kateh, Francis; Clement, Peter; Gasasira, Alex; Bolay, Fatorma; Monroe, Stephan S; Rambaut, Andrew; Sanchez-Lockhart, Mariano; Scott Laney, A; Nyenswah, Tolbert; Christie, Athalia; Palacios, Gustavo

2016-04-01

On 29 June 2015, Liberia's respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak ("flare-up") of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over.

Reduced evolutionary rate in reemerged Ebola virus transmission chains

PubMed Central

Blackley, David J.; Wiley, Michael R.; Ladner, Jason T.; Fallah, Mosoka; Lo, Terrence; Gilbert, Merle L.; Gregory, Christopher; D’ambrozio, Jonathan; Coulter, Stewart; Mate, Suzanne; Balogun, Zephaniah; Kugelman, Jeffrey; Nwachukwu, William; Prieto, Karla; Yeiah, Adolphus; Amegashie, Fred; Kearney, Brian; Wisniewski, Meagan; Saindon, John; Schroth, Gary; Fakoli, Lawrence; Diclaro, Joseph W.; Kuhn, Jens H.; Hensley, Lisa E.; Jahrling, Peter B.; Ströher, Ute; Nichol, Stuart T.; Massaquoi, Moses; Kateh, Francis; Clement, Peter; Gasasira, Alex; Bolay, Fatorma; Monroe, Stephan S.; Rambaut, Andrew; Sanchez-Lockhart, Mariano; Scott Laney, A.; Nyenswah, Tolbert; Christie, Athalia; Palacios, Gustavo

2016-01-01

On 29 June 2015, Liberia’s respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak (“flare-up”) of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over. PMID:27386513

Mate-sampling costs and sexy sons.

PubMed

Kokko, H; Booksmythe, I; Jennions, M D

2015-01-01

Costly female mating preferences for purely Fisherian male traits (i.e. sexual ornaments that are genetically uncorrelated with inherent viability) are not expected to persist at equilibrium. The indirect benefit of producing 'sexy sons' (Fisher process) disappears: in some models, the male trait becomes fixed; in others, a range of male trait values persist, but a larger trait confers no net fitness advantage because it lowers survival. Insufficient indirect selection to counter the direct cost of producing fewer offspring means that preferences are lost. The only well-cited exception assumes biased mutation on male traits. The above findings generally assume constant direct selection against female preferences (i.e. fixed costs). We show that if mate-sampling costs are instead derived based on an explicit account of how females acquire mates, an initially costly mating preference can coevolve with a male trait so that both persist in the presence or absence of biased mutation. Our models predict that empirically detecting selection at equilibrium will be difficult, even if selection was responsible for the location of the current equilibrium. In general, it appears useful to integrate mate sampling theory with models of genetic consequences of mating preferences: being explicit about the process by which individuals select mates can alter equilibria. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

First genealogy for a wild marine fish population reveals multigenerational philopatry.

PubMed

Salles, Océane C; Pujol, Benoit; Maynard, Jeffrey A; Almany, Glenn R; Berumen, Michael L; Jones, Geoffrey P; Saenz-Agudelo, Pablo; Srinivasan, Maya; Thorrold, Simon R; Planes, Serge

2016-11-15

Natal philopatry, the return of individuals to their natal area for reproduction, has advantages and disadvantages for animal populations. Natal philopatry may generate local genetic adaptation, but it may also increase the probability of inbreeding that can compromise persistence. Although natal philopatry is well documented in anadromous fishes, marine fish may also return to their birth site to spawn. How philopatry shapes wild fish populations is, however, unclear because it requires constructing multigenerational pedigrees that are currently lacking for marine fishes. Here we present the first multigenerational pedigree for a marine fish population by repeatedly genotyping all individuals in a population of the orange clownfish (Amphiprion percula) at Kimbe Island (Papua New Guinea) during a 10-y period. Based on 2927 individuals, our pedigree analysis revealed that longitudinal philopatry was recurrent over five generations. Progeny tended to settle close to their parents, with related individuals often sharing the same colony. However, successful inbreeding was rare, and genetic diversity remained high, suggesting occasional inbreeding does not impair local population persistence. Local reproductive success was dependent on the habitat larvae settled into, rather than the habitat they came from. Our study suggests that longitudinal philopatry can influence both population replenishment and local adaptation of marine fishes. Resolving multigenerational pedigrees during a relatively short period, as we present here, provides a framework for assessing the ability of marine populations to persist and adapt to accelerating climate change.

First genealogy for a wild marine fish population reveals multigenerational philopatry

PubMed Central

Salles, Océane C.; Pujol, Benoit; Maynard, Jeffrey A.; Almany, Glenn R.; Berumen, Michael L.; Jones, Geoffrey P.; Saenz-Agudelo, Pablo; Srinivasan, Maya; Thorrold, Simon R.; Planes, Serge

2016-01-01

Natal philopatry, the return of individuals to their natal area for reproduction, has advantages and disadvantages for animal populations. Natal philopatry may generate local genetic adaptation, but it may also increase the probability of inbreeding that can compromise persistence. Although natal philopatry is well documented in anadromous fishes, marine fish may also return to their birth site to spawn. How philopatry shapes wild fish populations is, however, unclear because it requires constructing multigenerational pedigrees that are currently lacking for marine fishes. Here we present the first multigenerational pedigree for a marine fish population by repeatedly genotyping all individuals in a population of the orange clownfish (Amphiprion percula) at Kimbe Island (Papua New Guinea) during a 10-y period. Based on 2927 individuals, our pedigree analysis revealed that longitudinal philopatry was recurrent over five generations. Progeny tended to settle close to their parents, with related individuals often sharing the same colony. However, successful inbreeding was rare, and genetic diversity remained high, suggesting occasional inbreeding does not impair local population persistence. Local reproductive success was dependent on the habitat larvae settled into, rather than the habitat they came from. Our study suggests that longitudinal philopatry can influence both population replenishment and local adaptation of marine fishes. Resolving multigenerational pedigrees during a relatively short period, as we present here, provides a framework for assessing the ability of marine populations to persist and adapt to accelerating climate change. PMID:27799530

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

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.

Genetic improvement and diversity in Snake River wheatgrass (Elymus wawawaiensis) (Poaceae: Triticeae)

USDA-ARS?s Scientific Manuscript database

With the increased emphasis to use native plant materials in range revegetation programs in the western US, it is critical to develop native grasses that are competitive with invasive weeds, easy to establish, persistent, and produce high seed yield. One such native grass species with appreciable d...

Molecular Epidemiology of Glanders, Pakistan

PubMed Central

Hornstra, Heidie; Pearson, Talima; Georgia, Shalamar; Liguori, Andrew; Dale, Julia; Price, Erin; O’Neill, Matthew; DeShazer, David; Muhammad, Ghulam; Saqib, Muhammad; Naureen, Abeera

2009-01-01

We collected epidemiologic and molecular data from Burkholderia mallei isolates from equines in Punjab, Pakistan from 1999 through 2007. We show that recent outbreaks are genetically distinct from available whole genome sequences and that these genotypes are persistent and ubiquitous in Punjab, probably due to human-mediated movement of equines. PMID:19961695

Hybrid vigor for the invasive exotic Brazilian peppertree (Schinus terebinthifolius Raddi., Anacardiaceae) in Florida

USDA-ARS?s Scientific Manuscript database

How can successful invaders overcome reduced genetic variation via small founder population sizes to persist, thrive, and successfully adapt to a new set of environmental conditions? An expanding body of literature posits hybridization, both inter- and intraspecific, as a driver of the evolution of...

Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population Level Effects: Report of Pellston Workgroup 3

EPA Science Inventory

The continuing persistence and genetic diversity of populations is a key concern for environmental regulations. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-speci...

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

The Khare lab in the Laboratory of Molecular Biology, NCI Center for Cancer Research, NIH, is looking to recruit highly motivated researchers interested in a postdoctoral fellowship to study the molecular and genetic basis of complex microbial behaviors. Our lab is focused on multiple research avenues including interspecies interactions, antibiotic persistence, and adaptation

Reduction in fecundity and shifts in cellular processes by a native virus on an invasive insect

USDA-ARS?s Scientific Manuscript database

Pathogens and their vectors have co-evolutionary histories that are intricately intertwined with their ecologies, environments and genetic interactions. The majority of non-persistently transmitted plant viruses are transmitted by aphid species. One important aphid vector in soybean-growing regions ...

Molecular evolution of flowering time loci in U.S. weedy rice

USDA-ARS?s Scientific Manuscript database

Weedy rice is a persistent weed of cultivated rice (Oryza sativa) fields worldwide, which competes with the crop and drastically reduces rice yields. Within the US, two main populations of genetically differentiated weedy rice exist, the straw-hulled (SH) group and the black-hulled awned (BHA) grou...

Biotic interactions and sunlight affect persistence of fecal indicator bacteria and microbial source tracking genetic markers in the Upper Mississippi River

EPA Science Inventory

Sanitary quality of recreational waters is assessed by enumerating fecal indicator bacteria (FIB) (Escherichia coli and enterococci); organisms present in the gastrointestinal tract of humans and many other animals, hence providing no information about the pollution source. Micro...

Teaching Evolution through Inquiry-Based Lessons of Uncontroversial Science

ERIC Educational Resources Information Center

DeSantis, Larisa R. G.

2009-01-01

Antibiotic resistance, genetically modified produce, avian flu, and invasive species persistence are just a few scientific issues pulled from the headlines that affect society on a daily basis. Understanding these issues requires knowledge of evolutionary processes. Educating students about evolution may never have been as necessary as it is…

Analysis of genome sequences from plant pathogenic Rhodococcus reveals genetic novelties in virulence loci

USDA-ARS?s Scientific Manuscript database

Members of Gram-positive Actinobacteria cause economically important diseases to plants. Within the Rhodococcus genus, some members can cause growth deformities and persist as pathogens on a wide range of host plants. The current model predicts that phytopathogenic isolates require a cluster of thre...

Population genomics reveals structure at the individual, host-tree scale and persistence of genotypic variants of the undomesticated yeast Saccharomyces paradoxus in a natural woodland.

PubMed

Xia, Wenjing; Nielly-Thibault, Lou; Charron, Guillaume; Landry, Christian R; Kasimer, Dahlia; Anderson, James B; Kohn, Linda M

2017-02-01

Genetic diversity in experimental, domesticated and wild populations of the related yeasts, Saccharomyces cerevisiae and Saccharomyces paradoxus, has been well described at the global scale. We investigated the population genomics of a local population on a small spatial scale to address two main questions. First, is there genomic variation in a S. paradoxus population at a spatial scale spanning centimetres (microsites) to tens of metres? Second, does the distribution of genomic variants persist over time? Our sample consisted of 42 S. paradoxus strains from 2014 and 43 strains from 2015 collected from the same 72 microsites around four host trees (Quercus rubra and Quercus alba) within 1 km 2 in a mixed hardwood forest in southern Ontario. Six additional S. paradoxus strains recovered from adjacent maple and beech trees in 2015 are also included in the sample. Whole-genome sequencing and genomic SNP analysis revealed five differentiated groups (clades) within the sampled area. The signal of persistence of genotypes in their microsites from 2014 to 2015 was highly significant. Isolates from the same tree tended to be more related than strains from different trees, with limited evidence of dispersal between trees. In growth assays, one genotype had a significantly longer lag phase than the other strains. Our results indicate that different clades coexist at fine spatial scale and that population structure persists over at least a one-year interval in these wild yeasts, suggesting the efficacy of yearly sampling to follow longer term genetic dynamics in future studies. © 2016 John Wiley & Sons Ltd.

Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and Nutrient Transporters Gene Expression in Newborn and Weaning Pigs

PubMed Central

Liu, Hong; Wang, Jun; Mou, Daolin; Che, Lianqiang; Fang, Zhengfeng; Feng, Bin; Lin, Yan; Xu, Shengyu; Li, Jian; Wu, De

2017-01-01

This study was conducted to explore whether exposure to bisphenol A (BPA) during pregnancy could change intestinal digestion and absorption function in offspring using pigs as a model, and whether methyl donor (MET) could counteract the BPA-induced impacts. Fifty Landrace × Yorkshire sows were divided into four dietary groups throughout gestation: control diet (CON); control diet supplemented with BPA (50 mg/kg); control diet supplemented with MET (3 g/kg betaine, 400 mg/kg choline, 150 μg/kg vitamin B12, and 15 mg/kg folic acid); and control diet with BPA and MET supplementation (BPA + MET). Intestine samples were collected from pigs’ offspring at birth and weaning. Maternal BPA exposure during pregnancy significantly reduced the ratio of jejunum villus height to crypt depth, decreased the jejunum sucrase activity, down-regulated the mRNA expression of jejunum peptide transporter 1 (Pept1) and DNA methyl transferase 3a (DNMT3a), and decreased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). Maternal MET supplementation significantly raised the ratio of villus height to crypt depth in jejunum and ileum, improved the jejunum lactase activity, up-regulated the mRNA expression of jejunum Pept1, lactase (LCT), DNMT1, DNMT3a, and methylenetetrahydrofolate reductase (MTHFR), and increased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05). However, the ratio of jejunum villus height to crypt depth was higher in BPA + MET treatment compared with CON and BPA treatment (p < 0.05). Meanwhile, there was no difference in the jejunum sucrase activity, the mRNA expression of jejunum Pept1 and DNMT3a, and the DNA methylation level of jejunum Pept1 between CON and BPA + MET treatment. These results indicated that maternal exposure to BPA during gestation might suppress offspring’s intestinal digestion and absorption function, whereas supplementation of MET could counteract these damages, which might be associated with DNA methylation. PMID:28445388

Comprehensive Enzymatic Analysis of the Cellulolytic System in Digestive Fluid of the Sea Hare Aplysia kurodai. Efficient Glucose Release from Sea Lettuce by Synergistic Action of 45 kDa Endoglucanase and 210 kDa ß-Glucosidase

PubMed Central

Tsuji, Akihiko; Tominaga, Keiko; Nishiyama, Nami; Yuasa, Keizo

2013-01-01

Although many endo-ß-1,4-glucanases have been isolated in invertebrates, their cellulolytic systems are not fully understood. In particular, gastropod feeding on seaweed is considered an excellent model system for production of bioethanol and renewable bioenergy from third-generation feedstocks (microalgae and seaweeds). In this study, enzymes involved in the conversion of cellulose and other polysaccharides to glucose in digestive fluids of the sea hare (Aplysia kurodai) were screened and characterized to determine how the sea hare obtains glucose from sea lettuce (Ulva pertusa). Four endo-ß-1,4-glucanases (21K, 45K, 65K, and 95K cellulase) and 2 ß-glucosidases (110K and 210K) were purified to a homogeneous state, and the synergistic action of these enzymes during cellulose digestion was analyzed. All cellulases exhibited cellulase and lichenase activities and showed distinct cleavage specificities against cellooligosaccharides and filter paper. Filter paper was digested to cellobiose, cellotriose, and cellotetraose by 21K cellulase, whereas 45K and 65K enzymes hydrolyzed the filter paper to cellobiose and glucose. 210K ß-glucosidase showed unique substrate specificity against synthetic and natural substrates, and 4-methylumbelliferyl (4MU)-ß-glucoside, 4MU–ß-galactoside, cello-oligosaccharides, laminarin, and lichenan were suitable substrates. Furthermore, 210K ß-glucosidase possesses lactase activity. Although ß-glucosidase and cellulase are necessary for efficient hydrolysis of carboxymethylcellulose to glucose, laminarin is hydrolyzed to glucose only by 210K ß-glucosidase. Kinetic analysis of the inhibition of 210K ß-glucosidase by D-glucono-1,5-lactone suggested the presence of 2 active sites similar to those of mammalian lactase-phlorizin hydrolase. Saccharification of sea lettuce was considerably stimulated by the synergistic action of 45K cellulase and 210K ß-glucosidase. Our results indicate that 45K cellulase and 210K ß-glucosidase are the core components of the sea hare digestive system for efficient production of glucose from sea lettuce. These findings contribute important new insights into the development of biofuel processing biotechnologies from seaweed. PMID:23762366

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.

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

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.

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

The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals.

PubMed

Shaw, Liam; Ribeiro, Andre L R; Levine, Adam P; Pontikos, Nikolas; Balloux, Francois; Segal, Anthony W; Roberts, Adam P; Smith, Andrew M

2017-09-12

The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed the salivary microbiomes of an extended family of Ashkenazi Jewish individuals living in several cities and investigated associations with both shared household and host genetic similarities. We found that environmental effects dominated over genetic effects. While there was weak evidence of geographical structuring at the level of cities, we observed a large and significant effect of shared household on microbiome composition, supporting the role of the immediate shared environment in dictating the presence or absence of taxa. This effect was also seen when including adults who had grown up in the same household but moved out prior to the time of sampling, suggesting that the establishment of the salivary microbiome earlier in life may affect its long-term composition. We found weak associations between host genetic relatedness and microbiome dissimilarity when using family pedigrees as proxies for genetic similarity. However, this association disappeared when using more-accurate measures of kinship based on genome-wide genetic markers, indicating that the environment rather than host genetics is the dominant factor affecting the composition of the salivary microbiome in closely related individuals. Our results support the concept that there is a consistent core microbiome conserved across global scales but that small-scale effects due to a shared living environment significantly affect microbial community composition. IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years. Copyright © 2017 Shaw et al.

Loss of dendritic connectivity in southern California's urban riverscape facilitates decline of an endemic freshwater fish

USGS Publications Warehouse

Richmond, Jonathan Q.; Backlin, Adam R.; Galst-Cavalcante, Carey; O'Brien, John W.; Fisher, Robert N.

2018-01-01

Life history adaptations and spatial configuration of metapopulation networks allow certain species to persist in extreme fluctuating environments, yet long-term stability within these systems relies on the maintenance of linkage habitat. Degradation of such linkages in urban riverscapes can disrupt this dynamic in aquatic species, leading to increased extinction debt in local populations experiencing environment-related demographic flux. We used microsatellites and mtDNA to examine the effects of collapsed network structure in the endemic Santa Ana sucker Catostomus santaanae of southern California, a threatened species affected by natural flood-drought cycles, ‘boom-and-bust’ demography, hybridization, and presumed artificial transplantation. Our results show a predominance of drift-mediated processes in shaping population structure, and that reverse mechanisms for counterbalancing the genetic effects of these phenomena have dissipated with the collapse of dendritic connectivity. We use approximate Bayesian models to support two cases of artificial transplantation, and provide evidence that one of the invaded systems better represents the historic processes that maintained genetic variation within watersheds than any remaining drainages where C. santaanae is considered native. We further show that a stable dry gap in the northern range is preventing genetic dilution of pure C. santaanae persisting upstream of a hybrid assemblage involving a non-native sucker, and that local accumulation of genetic variation in the same drainage is influenced by position within the network. This work has important implications for declining species that have historically relied on dendritic metapopulation networks to maintain source-sink dynamics in phasic environments, but no longer possess this capacity in urban-converted landscapes.

Toward an Understanding of the Evolution of Staphylococcus aureus Strain USA300 during Colonization in Community Households

PubMed Central

Uhlemann, Anne-Catrin; Kennedy, Adam D.; Martens, Craig; Porcella, Stephen F.; DeLeo, Frank R.; Lowy, Franklin D.

2012-01-01

Staphylococcus aureus is a frequent cause of serious infections and also a human commensal. The emergence of community-associated methicillin-resistant S. aureus led to a dramatic increase in skin and soft tissue infections worldwide. This epidemic has been driven by a limited number of clones, such as USA300 in the United States. To better understand the extent of USA300 evolution and diversification within communities, we performed comparative whole-genome sequencing of three clinical and five colonizing USA300 isolates collected longitudinally from three unrelated households over a 15-month period. Phylogenetic analysis that incorporated additional geographically diverse USA300 isolates indicated that all but one likely arose from a common recent ancestor. Although limited genetic adaptation occurred over the study period, the greatest genetic heterogeneity occurred between isolates from different households and within one heavily colonized household. This diversity allowed for a more accurate tracking of interpersonal USA300 transmission. Sequencing of persisting USA300 isolates revealed mutations in genes involved in major aspects of S. aureus function: adhesion, cell wall biosynthesis, virulence, and carbohydrate metabolism. Genetic variations also included accumulation of multiple polymorphisms within select genes of two multigene operons, suggestive of small genome rearrangements rather than de novo single point mutations. Such rearrangements have been underappreciated in S. aureus and may represent novel means of strain variation. Subtle genetic changes may contribute to USA300 fitness and persistence. Elucidation of small genome rearrangements reveals a potentially new and intriguing mechanism of directed S. aureus genome diversification in environmental niches and during pathogen–host interactions. PMID:23104992

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

Genetic regulation of pre-pubertal development of body mass index: a longitudinal study of Japanese twin boys and girls.

PubMed

Silventoinen, Karri; Kaprio, Jaakko; Yokoyama, Yoshie

2011-03-01

We analyzed the genetic architecture of prepubertal development of relative weight to height in 216 monozygotic and 159 dizygotic complete Japanese twin pairs (52% girls). Ponderal index at birth (kg/m(3)) and body mass index (BMI, kg/m(2)) from 1 to 11 years of age were used. Additive genetic factors explained the major proportion (52-74%) of the variation of BMI from 1 to 11 years of age. Environmental factors common to both co-twins also showed some effect (7-28%), but at most ages this was not statistically significant. Strong genetic tracking was found for BMI from 1 to 11 years of age, but there was also evidence for a persistent effect of common environmental factors. Our results suggest that the genetic architecture of BMI development in the Japanese population is generally similar to that found in previous twin studies in Caucasian populations.

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.

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.

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

The effects of inbreeding, genetic dissimilarity and phenotype on male reproductive success in a dioecious plant

PubMed Central

Austerlitz, Frédéric; Gleiser, Gabriela; Teixeira, Sara; Bernasconi, Giorgina

2012-01-01

Pollen fate can strongly affect the genetic structure of populations with restricted gene flow and significant inbreeding risk. We established an experimental population of inbred and outbred Silene latifolia plants to evaluate the effects of (i) inbreeding depression, (ii) phenotypic variation and (iii) relatedness between mates on male fitness under natural pollination. Paternity analysis revealed that outbred males sired significantly more offspring than inbred males. Independently of the effects of inbreeding, male fitness depended on several male traits, including a sexually dimorphic (flower number) and a gametophytic trait (in vitro pollen germination rate). In addition, full-sib matings were less frequent than randomly expected. Thus, inbreeding, phenotype and genetic dissimilarity simultaneously affect male fitness in this animal-pollinated plant. While inbreeding depression might threaten population persistence, the deficiency of effective matings between sibs and the higher fitness of outbred males will reduce its occurrence and counter genetic erosion. PMID:21561968

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.

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.

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

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.

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.

Update on cellular encapsulation.

PubMed

Smith, Kate E; Johnson, Robert C; Papas, Klearchos K

2018-05-06

There is currently a significant disparity between the number of patients who need lifesaving transplants and the number of donated human organs. Xenotransplantation is a way to address this disparity and attempts to enable the use of xenogeneic tissues have persisted for centuries. While immunologic incompatibilities have presented a persistent impediment to their use, encapsulation may represent a way forward for the use of cell-based xenogeneic therapeutics without the need for immunosuppression. In conjunction with modern innovations such as the use of bioprinting, incorporation of immune modulating molecules into capsule membranes, and genetic engineering, the application of xenogeneic cells to treat disorders ranging from pain to liver failure is becoming increasingly realistic. The present review discusses encapsulation in the context of xenotransplantation, focusing on the current status of clinical trials, persistent issues such as antigen shedding, oxygen availability, and donor selection, and recent developments that may address these limitations. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

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

The Diagnosis and Management of Hyperinsulinaemic Hypoglycaemia

PubMed Central

Roženková, Klára; Güemes, Maria; Shah, Pratik; Hussain, Khalid

2015-01-01

Insulin secretion from pancreatic β-cells is tightly regulated to keep fasting blood glucose concentrations within the normal range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is a heterozygous condition in which insulin secretion becomes unregulated and its production persists despite low blood glucose levels. It is the most common cause of severe and persistent hypoglycaemia in neonates and children. The most severe and permanent forms are due to congenital hyperinsulinism (CHI). Recent advances in genetics have linked CHI to mutations in 9 genes that play a key role in regulating insulin secretion (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A and HNF1A). Histologically, CHI can be divided into 3 types; diffuse, focal and atypical. Given the biochemical nature of HH (non-ketotic), a delay in the diagnosis and management can result in irreversible brain damage. Therefore, it is essential to diagnose and treat HH promptly. Advances in molecular genetics, imaging methods (18F-DOPA PET-CT), medical therapy and surgical approach (laparoscopic surgery) have completely changed the management and improved the outcome of these children. This review provides an overview of the genetic and molecular mechanisms leading to development of HH in children. The article summarizes the current diagnostic methods and management strategies for the different types of CHI. PMID:26316429

Antibiotic resistance genes show enhanced mobilization through suspended growth and biofilm-based wastewater treatment processes.

PubMed

Petrovich, Morgan; Chu, Binh; Wright, Dorothy; Griffin, Jim; Elfeki, Maryam; Murphy, Brian T; Poretsky, Rachel; Wells, George

2018-05-01

Wastewater treatment plants (WWTPs) are known to harbor antibiotic resistance genes (ARGs) that are disseminated into the environment via effluent. However, few studies have compared abundance, mobilization and selective pressures for ARGs in WWTPs as a function of variations in secondary treatment bioprocesses. We used shotgun metagenomics to provide a comprehensive analysis of ARG composition, relationship to mobile genetic elements and co-occurrences with antibiotic production genes (APGs) throughout two full-scale municipal WWTPs, one of which employs biofilm-based secondary treatment and another that uses a suspended growth system. Results showed that abundances of ARGs declined by over 90% per genome equivalent in both types of wastewater treatment processes. However, the fractions of ARGs associated with mobile genetic elements increased substantially between influent and effluent in each plant, indicating significant mobilization of ARGs throughout both treatment processes. Strong positive correlations between ARGs and APGs were found for the aminoglycoside antibiotic class in the suspended growth system and for the streptogramin antibiotic class in the biofilm system. The biofilm and suspended growth WWTPs exhibited similarities in ARG abundances, composition and mobilization trends. However, clear differences were observed for within-plant ARG persistence. These findings suggest that both biofilm and suspended growth-based WWTPs may promote genetic mobilization of persistent ARGs that are then disseminated in effluent to receiving water bodies.

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.

Stand maintenance and genetic diversity of bermudagrass pastures under different stocking intensities during a 38 year period

USDA-ARS?s Scientific Manuscript database

Stocking management strategies can affect production and persistence of bermudagrass [Cynodon dactylon (L) Pers] (BG) pastures. ‘Coastal’ (COS) and common (COM) bermudagrass (BG) pastures were stocked at different controlled intensities (STK) during a 38-yr period which was initiated in 1969. On ave...

The effect of resource history on the functioning of soil microbial communities is maintained across time

Treesearch

A. Keiser; M. Strickland; N. Fierer; M. Bradford

2011-01-01

Historical resource conditions appear to influence microbial community function. With time, historical influences might diminish as populations respond to the contemporary environment. Alternatively, they may persist given factors such as contrasting genetic potentials for adaptation to a new environment. Using experimental microcosms, we test competing hypotheses that...

Arrhythmogenic right ventricular cardiomyopathy in monozygotic twin sisters, and persistent left superior vena cava in one complicating implantation of ICD.

PubMed

Astarcıoğlu, Mehmet Ali; Yaymacı, Mehmet; Şen, Taner; Kilit, Celal; Amasyalı, Basri

2015-10-01

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized histologically by fibro-fatty replacement of heart muscle, and clinically by ventricular arrhythmias and right ventricular dysfunction. This report presents monozygotic twins with ARVC, suggesting a genetic abnormality as the most probable cause.

Registration of two wheat germplasm lines fixed for Pm58

USDA-ARS?s Scientific Manuscript database

Powdery mildew, caused by Blumeria graminis (D.C.) f. sp. tritici, is a persistent threat to global wheat (Triticum aestivum L.) production. To broaden the genetic base for resistance to powdery mildew in wheat, germplasm lines U6714-A-011 (Reg. No.___, PI___) and U6714-B-056 (Reg. No.___, PI___) we...

Spatiotemporal variation in resource selection: Insights from the American marten (Martes Americana)

Treesearch

Andrew J. Shirk; Martin G. Raphael; Samuel A. Cushman

2014-01-01

Behavioral and genetic adaptations to spatiotemporal variation in habitat conditions allow species to maximize their biogeographic range and persist over time in dynamic environments. An understanding of these local adaptations can be used to guide management and conservation of populations over broad extents encompassing diverse habitats. This understanding is often...

Allozyme variation in Picea mariana from Newfoundland: Discussion

Treesearch

William B. Critchfield

1987-01-01

In their recent paper describing the distribution of genetic variation in black spruce (Picea mariana (Mill.) B.S.P.) on the island of Newfoundland, Yeh et el. (1986) concluded that a center of variability in west-central Newfoundland derived from ancestral populations that persisted on the island during the last (Wisconsin) glaciation. They...

EXTENDED FERTILITY AND COMPATIBILITY OF PROGENY WITHINT HE AGROSTIS HYBRIDIZING COMPLEX: IMPLICATIONS FOR TRANSGENE ESCAPE AND PERSISTENCE WITHIN WILD POPULATION

EPA Science Inventory

Agrostis stolonifera L. (creeping bentgrass) is a turf grass that is of interest for introduction of herbicide and disease resistance, and stress tolerance traits by genetic engineering. A. stolonifera is a member of a hybridizing complex that includes at least eleven Agrostis sp...

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

USDA-ARS?s Scientific Manuscript database

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

Pharmacogenetics in obstetric anesthesia.

PubMed

Landau, Ruth; Kraft, John C

2010-06-01

Genomic research in pain, anesthesia and analgesia generated some hope that pharmacogenetics may guide anesthesiologists to provide effective medicine in a 'tailored' manner. Within the field of obstetric anesthesia, relatively few studies have evaluated the effect of polymorphisms on the perception of labor or postcesarean pain or the response to analgesics for childbirth. Because of the multifactorial nature of labor and delivery pain and particularly challenging clinical context, many consider that 'titration of drugs to the desired effect works just fine'. With recent evidence highlighting an association between severe postdelivery pain and persistent pain, early recognition of an increased susceptibility for acute pain has become particularly relevant. Neuraxial labor analgesia is influenced by a common polymorphism of the mu-opioid receptor gene. This polymorphism also affects the analgesic response to systemic opioids for postcesarean pain and other types of surgeries. Finally, the risk for persistent pain after cesarean deliveries may be associated with a certain genetic profile. Although still premature to anticipate clinical implications and a change in practice based on these recent discoveries, genetic variability clearly appears to affect pain perception, response to analgesics and predisposition for the development of chronic pain.

Effects of plants genetically modified for insect resistance on nontarget organisms.

PubMed

O'Callaghan, Maureen; Glare, Travis R; Burgess, Elisabeth P J; Malone, Louise A

2005-01-01

Insect resistance, based on Bacillus thuringiensis (Bt) endotoxins, is the second most widely used trait (after herbicide resistance) in commercial genetically modified (GM) crops. Other modifications for insect resistance, such as proteinase inhibitors and lectins, are also being used in many experimental crops. The extensive testing on nontarget plant-feeding insects and beneficial species that has accompanied the long-term and wide-scale use of Bt plants has not detected significant adverse effects. GM plants expressing other insect-resistant proteins that have a broader spectrum of activity have been tested on only a limited number of nontarget species. Little is known about the persistence of transgene-derived proteins in soil, with the exception of Bt endotoxins, which can persist in soil for several months. Bt plants appear to have little impact on soil biota such as earthworms, collembolans, and general soil microflora. Further research is required on the effects of GM plants on soil processes such as decomposition. Assessment of nontarget impacts is an essential part of the risk assessment process for insect-resistant GM plants.

Using biological data to test climate change refugia

NASA Astrophysics Data System (ADS)

Morelli, T. L.; Maher, S. P.

2015-12-01

The concept of refugia has been discussed from theoretical and paleontological perspectives to address how populations persisted during periods of unfavorable climate. Recently, several studies have applied the idea to contemporary landscapes to identify locations that are buffered from climate change effects so as to favor greater persistence of valued resources relative to other areas. Refugia are now being discussed among natural resource agencies as a potential adaptation option in the face of anthropogenic climate change. Using downscaled climate data, we identified hypothetical refugial meadows in the Sierra Nevada and then tested them using survey and genetic data from Belding's ground squirrel (Urocitellus beldingi) populations. We predicted that refugial meadows would show higher genetic diversity, higher rates of occupancy and lower rates of extirpation over time. At each step of the research, we worked with managers to ensure the largest impact. Although no panacea, identifying climate change refugia could be an important strategy for prioritizing habitats for management intervention in order to conserve populations. This research was supported by the California LCC, the Northeast Climate Science Center, and NSF.

The origin of a new focus of infection with Echinococcus granulosus in Tasmania.

PubMed

Constantine, C C; Lymbery, A J; Thompson, R C; Obendorf, D L

1991-12-01

Hydatid cysts were discovered in cattle on King Island, north of Tasmania, where Echinococcus granulosus was thought to have been eradicated. Using enzyme electrophoresis, isolates from King Island were compared genetically with isolates from Tasmania and the mainland of Australia. The genetic distinctness of the King Island isolates make it unlikely that they originated from a recent introduction from either Tasmania or mainland Australia. Alternative possibilities, that the infection resulted from a recent introduction from another source or from previously undetected persistence of E. granulosus on King Island, could not be distinguished from available data.

Spatiotemporal Dynamics of Genetic Variation in the Iberian Lynx along Its Path to Extinction Reconstructed with Ancient DNA

PubMed Central

Casas-Marce, Mireia; Marmesat, Elena; Soriano, Laura; Martínez-Cruz, Begoña; Lucena-Perez, Maria; Nocete, Francisco; Rodríguez-Hidalgo, Antonio; Canals, Antoni; Nadal, Jordi; Detry, Cleia; Bernáldez-Sánchez, Eloísa; Fernández-Rodríguez, Carlos; Pérez-Ripoll, Manuel; Stiller, Mathias; Hofreiter, Michael; Rodríguez, Alejandro; Revilla, Eloy; Delibes, Miguel; Godoy, José A.

2017-01-01

Abstract There is the tendency to assume that endangered species have been both genetically and demographically healthier in the past, so that any genetic erosion observed today was caused by their recent decline. The Iberian lynx (Lynx pardinus) suffered a dramatic and continuous decline during the 20th century, and now shows extremely low genome- and species-wide genetic diversity among other signs of genomic erosion. We analyze ancient (N = 10), historical (N = 245), and contemporary (N = 172) samples with microsatellite and mitogenome data to reconstruct the species' demography and investigate patterns of genetic variation across space and time. Iberian lynx populations transitioned from low but significantly higher genetic diversity than today and shallow geographical differentiation millennia ago, through a structured metapopulation with varying levels of diversity during the last centuries, to two extremely genetically depauperate and differentiated remnant populations by 2002. The historical subpopulations show varying extents of genetic drift in relation to their recent size and time in isolation, but these do not predict whether the populations persisted or went finally extinct. In conclusion, current genetic patterns were mainly shaped by genetic drift, supporting the current admixture of the two genetic pools and calling for a comprehensive genetic management of the ongoing conservation program. This study illustrates how a retrospective analysis of demographic and genetic patterns of endangered species can shed light onto their evolutionary history and this, in turn, can inform conservation actions. PMID:28962023

Recent invasion of the mountain birch Betula pubescens ssp. tortuosa above the treeline due to climate change: genetic and ecological study in northern Sweden.

PubMed

Truong, C; Palmé, A E; Felber, F

2007-01-01

Mountain birch, Betula pubescens ssp. tortuosa, forms the treeline in northern Sweden. A recent shift in the range of the species associated with an elevation of the treeline is commonly attributed to climate warming. Using microsatellite markers, we explored the genetic structure of populations along an altitudinal gradient close to the treeline. Low genetic differentiation was found between populations, whereas high genetic diversity was maintained within populations. High level of gene flow compensated for possible losses of genetic diversity at higher elevations and dissipated the founding effect of newly established populations above the treeline. Spatial autocorrelation analysis showed low spatial genetic structure within populations because of extensive gene flow. At the treeline, significant genetic structure within the juvenile age class at small distances did not persist in the adult age class, indicating recent expansion of young recruits due to the warming of the climate. Finally, seedling performance above the treeline was positively correlated with parameters related to temperature. These data confirm the high migration potential of the species in response to fluctuating environmental conditions and indicate that it is now invading higher altitudes due to the recent warming of the climate.

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. Although this study deals with selection for 3-parity milk production, the same principle applies to selection for lifetime milk production.

Genome Analysis of Listeria monocytogenes Sequence Type 8 Strains Persisting in Salmon and Poultry Processing Environments and Comparison with Related Strains

PubMed Central

Fagerlund, Annette; Langsrud, Solveig; Schirmer, Bjørn C. T.; Møretrø, Trond; Heir, Even

2016-01-01

Listeria monocytogenes is an important foodborne pathogen responsible for the disease listeriosis, and can be found throughout the environment, in many foods and in food processing facilities. The main cause of listeriosis is consumption of food contaminated from sources in food processing environments. Persistence in food processing facilities has previously been shown for the L. monocytogenes sequence type (ST) 8 subtype. In the current study, five ST8 strains were subjected to whole-genome sequencing and compared with five additionally available ST8 genomes, allowing comparison of strains from salmon, poultry and cheese industry, in addition to a human clinical isolate. Genome-wide analysis of single-nucleotide polymorphisms (SNPs) confirmed that almost identical strains were detected in a Danish salmon processing plant in 1996 and in a Norwegian salmon processing plant in 2001 and 2011. Furthermore, we show that L. monocytogenes ST8 was likely to have been transferred between two poultry processing plants as a result of relocation of processing equipment. The SNP data were used to infer the phylogeny of the ST8 strains, separating them into two main genetic groups. Within each group, the plasmid and prophage content was almost entirely conserved, but between groups, these sequences showed strong divergence. The accessory genome of the ST8 strains harbored genetic elements which could be involved in rendering the ST8 strains resilient to incoming mobile genetic elements. These included two restriction-modification loci, one of which was predicted to show phase variable recognition sequence specificity through site-specific domain shuffling. Analysis indicated that the ST8 strains harbor all important known L. monocytogenes virulence factors, and ST8 strains are commonly identified as the causative agents of invasive listeriosis. Therefore, the persistence of this L. monocytogenes subtype in food processing facilities poses a significant concern for food safety. PMID:26953695

Demographic and genetic viability of a medium-sized ground-dwelling mammal in a fire prone, rapidly urbanizing landscape.

PubMed

Ramalho, Cristina E; Ottewell, Kym M; Chambers, Brian K; Yates, Colin J; Wilson, Barbara A; Bencini, Roberta; Barrett, Geoff

2018-01-01

The rapid and large-scale urbanization of peri-urban areas poses major and complex challenges for wildlife conservation. We used population viability analysis (PVA) to evaluate the influence of urban encroachment, fire, and fauna crossing structures, with and without accounting for inbreeding effects, on the metapopulation viability of a medium-sized ground-dwelling mammal, the southern brown bandicoot (Isoodon obesulus), in the rapidly expanding city of Perth, Australia. We surveyed two metapopulations over one and a half years, and parameterized the PVA models using largely field-collected data. The models revealed that spatial isolation imposed by housing and road encroachment has major impacts on I. obesulus. Although the species is known to persist in small metapopulations at moderate levels of habitat fragmentation, the models indicate that these populations become highly vulnerable to demographic decline, genetic deterioration, and local extinction under increasing habitat connectivity loss. Isolated metapopulations were also predicted to be highly sensitive to fire, with large-scale fires having greater negative impacts on population abundance than small-scale ones. To reduce the risk of decline and local extirpation of I. obesulus and other small- to medium-sized ground-dwelling mammals in urbanizing, fire prone landscapes, we recommend that remnant vegetation and vegetated, structurally-complex corridors between habitat patches be retained. Well-designed road underpasses can be effective to connect habitat patches and reduce the probability of inbreeding and genetic differentiation; however, adjustment of fire management practices to limit the size of unplanned fires and ensure the retention of long unburnt vegetation will also be required to ensure persistence. Our study supports the evidence that in rapidly urbanizing landscapes, a pro-active conservation approach is required that manages species at the metapopulation level and that prioritizes metapopulations and habitat with greater long-term probability of persistence and conservation capacity, respectively. This strategy may help us prevent future declines and local extirpations, and currently relatively common species from becoming rare.

Parasitological Confirmation and Analysis of Leishmania Diversity in Asymptomatic and Subclinical Infection following Resolution of Cutaneous Leishmaniasis.

PubMed

Rosales-Chilama, Mariana; Gongora, Rafael E; Valderrama, Liliana; Jojoa, Jimena; Alexander, Neal; Rubiano, Luisa C; Cossio, Alexandra; Adams, Emily R; Saravia, Nancy G; Gomez, María Adelaida

2015-12-01

The contribution of individuals with subclinical infection to the transmission and endemicity of cutaneous leishmaniasis (CL) is unknown. Immunological evidence of exposure to Leishmania in residents of endemic areas has been the basis for defining the human population with asymptomatic infection. However, parasitological confirmation of subclinical infection is lacking. We investigated the presence and viability of Leishmania in blood and non-invasive mucosal tissue samples from individuals with immunological evidence of subclinical infection in endemic areas for CL caused by Leishmania (Viannia) in Colombia. Detection of Leishmania kDNA was conducted by PCR-Southern Blot, and parasite viability was confirmed by amplification of parasite 7SLRNA gene transcripts. A molecular tool for genetic diversity analysis of parasite populations causing persistent subclinical infection based on PCR amplification and sequence analysis of an 82bp region between kDNA conserved blocks 1 and 2 was developed. Persistent Leishmania infection was demonstrated in 40% (46 of 114) of leishmanin skin test (LST) positive individuals without active disease; parasite viability was established in 59% of these (27 of 46; 24% of total). Parasite burden quantified from circulating blood monocytes, nasal, conjunctival or tonsil mucosal swab samples was comparable, and ranged between 0.2 to 22 parasites per reaction. kDNA sequences were obtained from samples from 2 individuals with asymptomatic infection and from 26 with history of CL, allowing genetic distance analysis that revealed diversity among sequences and clustering within the L. (Viannia) subgenus. Our results provide parasitological confirmation of persistent infection among residents of endemic areas of L. (Viannia) transmission who have experienced asymptomatic infection or recovered from CL, revealing a reservoir of infection that potentially contributes to the endemicity and transmission of disease. kDNA genotyping establishes proof-of-principle of the feasibility of genetic diversity analysis in previously inaccessible and unexplored parasite populations in subclinically infected individuals.

Demographic and genetic viability of a medium-sized ground-dwelling mammal in a fire prone, rapidly urbanizing landscape

PubMed Central

Ottewell, Kym M.; Chambers, Brian K.; Yates, Colin J.; Wilson, Barbara A.; Bencini, Roberta; Barrett, Geoff

2018-01-01

The rapid and large-scale urbanization of peri-urban areas poses major and complex challenges for wildlife conservation. We used population viability analysis (PVA) to evaluate the influence of urban encroachment, fire, and fauna crossing structures, with and without accounting for inbreeding effects, on the metapopulation viability of a medium-sized ground-dwelling mammal, the southern brown bandicoot (Isoodon obesulus), in the rapidly expanding city of Perth, Australia. We surveyed two metapopulations over one and a half years, and parameterized the PVA models using largely field-collected data. The models revealed that spatial isolation imposed by housing and road encroachment has major impacts on I. obesulus. Although the species is known to persist in small metapopulations at moderate levels of habitat fragmentation, the models indicate that these populations become highly vulnerable to demographic decline, genetic deterioration, and local extinction under increasing habitat connectivity loss. Isolated metapopulations were also predicted to be highly sensitive to fire, with large-scale fires having greater negative impacts on population abundance than small-scale ones. To reduce the risk of decline and local extirpation of I. obesulus and other small- to medium-sized ground-dwelling mammals in urbanizing, fire prone landscapes, we recommend that remnant vegetation and vegetated, structurally-complex corridors between habitat patches be retained. Well-designed road underpasses can be effective to connect habitat patches and reduce the probability of inbreeding and genetic differentiation; however, adjustment of fire management practices to limit the size of unplanned fires and ensure the retention of long unburnt vegetation will also be required to ensure persistence. Our study supports the evidence that in rapidly urbanizing landscapes, a pro-active conservation approach is required that manages species at the metapopulation level and that prioritizes metapopulations and habitat with greater long-term probability of persistence and conservation capacity, respectively. This strategy may help us prevent future declines and local extirpations, and currently relatively common species from becoming rare. PMID:29444118

Extensive long-distance pollen dispersal and highly outcrossed mating in historically small and disjunct populations of Acacia woodmaniorum (Fabaceae), a rare banded iron formation endemic.

PubMed

Millar, Melissa A; Coates, David J; Byrne, Margaret

2014-10-01

Understanding patterns of pollen dispersal and variation in mating systems provides insights into the evolutionary potential of plant species and how historically rare species with small disjunct populations persist over long time frames. This study aims to quantify the role of pollen dispersal and the mating system in maintaining contemporary levels of connectivity and facilitating persistence of small populations of the historically rare Acacia woodmaniorum. Progeny arrays of A. woodmaniorum were genotyped with nine polymorphic microsatellite markers. A low number of fathers contributed to seed within single pods; therefore, sampling to remove bias of correlated paternity was implemented for further analysis. Pollen immigration and mating system parameters were then assessed in eight populations of varying size and degree of isolation. Pollen immigration into small disjunct populations was extensive (mean minimum estimate 40 % and mean maximum estimate 57 % of progeny) and dispersal occurred over large distances (≤1870m). Pollen immigration resulted in large effective population sizes and was sufficient to ensure adaptive and inbreeding connectivity in small disjunct populations. High outcrossing (mean tm = 0·975) and a lack of apparent inbreeding suggested that a self-incompatibility mechanism is operating. Population parameters, including size and degree of geographic disjunction, were not useful predictors of pollen dispersal or components of the mating system. Extensive long-distance pollen dispersal and a highly outcrossed mating system are likely to play a key role in maintaining genetic diversity and limiting negative genetic effects of inbreeding and drift in small disjunct populations of A. woodmaniorum. It is proposed that maintenance of genetic connectivity through habitat and pollinator conservation will be a key factor in the persistence of this and other historically rare species with similar extensive long-distance pollen dispersal and highly outcrossed mating systems. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company.

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 correlation might depend on common genetic effects. The WISC-IV indices showed a relatively large genetic influence, while earlier findings about the etiology of temperament and character traits using the whole CATSS sample were replicated in this sub-sample of twins. Conclusions. The results indicate that what individuals make of themselves intentionally (i.e., their character) was not associated to intelligence. Persistence, a temperament dimension that measures heritable individual differences in eagerness of effort, ambition, perfectionism, and resistance to discouragement despite frustration and fatigue, was weakly linked to intelligence. Suggesting that, at least during adolescence, interventions targeting character development are not limited by the individual's intelligence.

Complementary Network-Based Approaches for Exploring Genetic Structure and Functional Connectivity in Two Vulnerable, Endemic Ground Squirrels

PubMed Central

Zero, Victoria H.; Barocas, Adi; Jochimsen, Denim M.; Pelletier, Agnès; Giroux-Bougard, Xavier; Trumbo, Daryl R.; Castillo, Jessica A.; Evans Mack, Diane; Linnell, Mark A.; Pigg, Rachel M.; Hoisington-Lopez, Jessica; Spear, Stephen F.; Murphy, Melanie A.; Waits, Lisette P.

2017-01-01

The persistence of small populations is influenced by genetic structure and functional connectivity. We used two network-based approaches to understand the persistence of the northern Idaho ground squirrel (Urocitellus brunneus) and the southern Idaho ground squirrel (U. endemicus), two congeners of conservation concern. These graph theoretic approaches are conventionally applied to social or transportation networks, but here are used to study population persistence and connectivity. Population graph analyses revealed that local extinction rapidly reduced connectivity for the southern species, while connectivity for the northern species could be maintained following local extinction. Results from gravity models complemented those of population graph analyses, and indicated that potential vegetation productivity and topography drove connectivity in the northern species. For the southern species, development (roads) and small-scale topography reduced connectivity, while greater potential vegetation productivity increased connectivity. Taken together, the results of the two network-based methods (population graph analyses and gravity models) suggest the need for increased conservation action for the southern species, and that management efforts have been effective at maintaining habitat quality throughout the current range of the northern species. To prevent further declines, we encourage the continuation of management efforts for the northern species, whereas conservation of the southern species requires active management and additional measures to curtail habitat fragmentation. Our combination of population graph analyses and gravity models can inform conservation strategies of other species exhibiting patchy distributions. PMID:28659969

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

Complementary Network-Based Approaches for Exploring Genetic Structure and Functional Connectivity in Two Vulnerable, Endemic Ground Squirrels.

PubMed

Zero, Victoria H; Barocas, Adi; Jochimsen, Denim M; Pelletier, Agnès; Giroux-Bougard, Xavier; Trumbo, Daryl R; Castillo, Jessica A; Evans Mack, Diane; Linnell, Mark A; Pigg, Rachel M; Hoisington-Lopez, Jessica; Spear, Stephen F; Murphy, Melanie A; Waits, Lisette P

2017-01-01

The persistence of small populations is influenced by genetic structure and functional connectivity. We used two network-based approaches to understand the persistence of the northern Idaho ground squirrel ( Urocitellus brunneus) and the southern Idaho ground squirrel ( U. endemicus ), two congeners of conservation concern. These graph theoretic approaches are conventionally applied to social or transportation networks, but here are used to study population persistence and connectivity. Population graph analyses revealed that local extinction rapidly reduced connectivity for the southern species, while connectivity for the northern species could be maintained following local extinction. Results from gravity models complemented those of population graph analyses, and indicated that potential vegetation productivity and topography drove connectivity in the northern species. For the southern species, development (roads) and small-scale topography reduced connectivity, while greater potential vegetation productivity increased connectivity. Taken together, the results of the two network-based methods (population graph analyses and gravity models) suggest the need for increased conservation action for the southern species, and that management efforts have been effective at maintaining habitat quality throughout the current range of the northern species. To prevent further declines, we encourage the continuation of management efforts for the northern species, whereas conservation of the southern species requires active management and additional measures to curtail habitat fragmentation. Our combination of population graph analyses and gravity models can inform conservation strategies of other species exhibiting patchy distributions.

Tracking climate change in a dispersal-limited species: reduced spatial and genetic connectivity in a montane salamander.

PubMed

Velo-Antón, G; Parra, J L; Parra-Olea, G; Zamudio, K R

2013-06-01

Tropical montane taxa are often locally adapted to very specific climatic conditions, contributing to their lower dispersal potential across complex landscapes. Climate and landscape features in montane regions affect population genetic structure in predictable ways, yet few empirical studies quantify the effects of both factors in shaping genetic structure of montane-adapted taxa. Here, we considered temporal and spatial variability in climate to explain contemporary genetic differentiation between populations of the montane salamander, Pseudoeurycea leprosa. Specifically, we used ecological niche modelling (ENM) and measured spatial connectivity and gene flow (using both mtDNA and microsatellite markers) across extant populations of P. leprosa in the Trans-Mexican Volcanic Belt (TVB). Our results indicate significant spatial and genetic isolation among populations, but we cannot distinguish between isolation by distance over time or current landscape barriers as mechanisms shaping population genetic divergences. Combining ecological niche modelling, spatial connectivity analyses, and historical and contemporary genetic signatures from different classes of genetic markers allows for inference of historical evolutionary processes and predictions of the impacts future climate change will have on the genetic diversity of montane taxa with low dispersal rates. Pseudoeurycea leprosa is one montane species among many endemic to this region and thus is a case study for the continued persistence of spatially and genetically isolated populations in the highly biodiverse TVB of central Mexico. © 2013 John Wiley & Sons Ltd.

A Road Map for 21st Century Genetic Restoration: Gene Pool Enrichment of the Black-Footed Ferret.

PubMed

Wisely, Samantha M; Ryder, Oliver A; Santymire, Rachel M; Engelhardt, John F; Novak, Ben J

2015-01-01

Interspecies somatic cell nuclear transfer (iSCNT) could benefit recovery programs of critically endangered species but must be weighed with the risks of failure. To weigh the risks and benefits, a decision-making process that evaluates progress is needed. Experiments that evaluate the efficiency and efficacy of blastocyst, fetal, and post-parturition development are necessary to determine the success or failure or species-specific iSCNT programs. Here, we use the black-footed ferret (Mustela nigripes) as a case study for evaluating this emerging biomedical technology as a tool for genetic restoration. The black-footed ferret has depleted genetic variation yet genome resource banks contain genetic material of individuals not currently represented in the extant lineage. Thus, genetic restoration of the species is in theory possible and could help reduce the persistent erosion of genetic diversity from drift. Extensive genetic, genomic, and reproductive science tools have previously been developed in black-footed ferrets and would aid in the process of developing an iSCNT protocol for this species. Nonetheless, developing reproductive cloning will require years of experiments and a coordinated effort among recovery partners. The information gained from a well-planned research effort with the goal of genetic restoration via reproductive cloning could establish a 21st century model for evaluating and implementing conservation breeding that would be applicable to other genetically impoverished species. © The American Genetic Association. 2015.

Stereotypic Movement Disorders.

PubMed

Katherine, Mackenzie

2018-04-01

This review summarizes motor stereotypies in terms of description, prevalence, pathophysiology, diagnosis and management. They are fixed and persistent movements. Stereotypies begin before 3 years of age and continue into adulthood. Primary motor stereotypies occur in children of normal intelligence, whereas secondary stereotypies ensue in the setting of an additional diagnosis such as autism spectrum disorder or other neurologic disorders. They are highly associated with comorbidities such as anxiety, obsessive-compulsive symptoms, inattention, and tics. The pathophysiology of stereotypies involves fronto-striatal overactive dopaminergic pathways, and underactive cholinergic and GABAergic inhibitory pathways. No genetic markers have been identified despite a clear genetic predisposition. Behavioral therapy is the principle treatment. Future studies will focus on identifying genetic markers, and on better understanding the functional and structural neurobiology of these movements. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Genetic homogeneity of the invasive lionfish across the Northwestern Atlantic and the Gulf of Mexico based on Single Nucleotide Polymorphisms.

PubMed

Pérez-Portela, R; Bumford, A; Coffman, B; Wedelich, S; Davenport, M; Fogg, A; Swenarton, M K; Coleman, F; Johnston, M A; Crawford, D L; Oleksiak, M F

2018-03-22

Despite the devastating impact of the lionfish (Pterois volitans) invasion on NW Atlantic ecosystems, little genetic information about the invasion process is available. We applied Genotyping by Sequencing techniques to identify 1,220 single nucleotide polymorphic sites (SNPs) from 162 lionfish samples collected between 2013 and 2015 from two areas chronologically identified as the first and last invaded areas in US waters: the east coast of Florida and the Gulf of Mexico. We used population genomic analyses, including phylogenetic reconstruction, Bayesian clustering, genetic distances, Discriminant Analyses of Principal Components, and coalescence simulations for detection of outlier SNPs, to understand genetic trends relevant to the lionfish's long-term persistence. We found no significant differences in genetic structure or diversity between the two areas (F ST p-values > 0.01, and t-test p-values > 0.05). In fact, our genomic analyses showed genetic homogeneity, with enough gene flow between the east coast of Florida and Gulf of Mexico to erase previous signals of genetic divergence detected between these areas, secondary spreading, and bottlenecks in the Gulf of Mexico. These findings suggest rapid genetic changes over space and time during the invasion, resulting in one panmictic population with no signs of divergence between areas due to local adaptation.

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 FOXP2 and CNTNAP2, suggests that the genetic neuropathological origins of stuttering differ from those of verbal dyspraxia and SLI. Published by Elsevier Inc.

Research review: the shared environment as a key source of variability in child and adolescent psychopathology.

PubMed

Burt, S Alexandra

2014-04-01

Behavioral genetic research has historically concluded that the more important environmental influences were nonshared or result in differences between siblings, whereas environmental influences that create similarities between siblings (referred to as shared environmental influences) were indistinguishable from zero. Recent theoretical and meta-analytic work {Burt. Psychological Bulletin [135 (2009) 608]} has challenged this conclusion as it relates to child and adolescent psychopathology, however, arguing that the shared environment is a moderate, persistent, and identifiable source of individual differences in such outcomes prior to adulthood. The current review seeks to bolster research on the shared environment by highlighting both the logistic advantages inherent in studies of the shared environment, as well as the use of nontraditional but still genetically informed research designs to study shared environmental influences. Although often moderate in magnitude prior to adulthood and free of unsystematic measurement error, shared environmental influences are nevertheless likely to have been underestimated in prior research. Moreover, the shared environment is likely to include proximal effects of the family, as well as the effects of more distal environmental contexts such as neighborhood and school. These risk and protective factors could influence the child either as main effects or as moderators of genetic influence (i.e. gene-environment interactions). Finally, because the absence of genetic relatedness in an otherwise nonindependent dataset also qualifies as 'genetically informed', studies of the shared environment are amenable to the use of novel and non-traditional designs (with appropriate controls for selection). The shared environment makes important contributions to most forms of child and adolescent psychopathology. Empirical examinations of the shared environment would thus be of real and critical value for understanding the development and persistence of common mental health issues prior to adulthood. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Projected climate changes threaten ancient refugia of kelp forests in the North Atlantic.

PubMed

Assis, Jorge; Araújo, Miguel B; Serrão, Ester A

2018-01-01

Intraspecific genetic variability is critical for species adaptation and evolution and yet it is generally overlooked in projections of the biological consequences of climate change. We ask whether ongoing climate changes can cause the loss of important gene pools from North Atlantic relict kelp forests that persisted over glacial-interglacial cycles. We use ecological niche modelling to predict genetic diversity hotspots for eight species of large brown algae with different thermal tolerances (Arctic to warm temperate), estimated as regions of persistence throughout the Last Glacial Maximum (20,000 YBP), the warmer Mid-Holocene (6,000 YBP), and the present. Changes in the genetic diversity within ancient refugia were projected for the future (year 2100) under two contrasting climate change scenarios (RCP2.6 and RCP8.5). Models predicted distributions that matched empirical distributions in cross-validation, and identified distinct refugia at the low latitude ranges, which largely coincide among species with similar ecological niches. Transferred models into the future projected polewards expansions and substantial range losses in lower latitudes, where richer gene pools are expected (in Nova Scotia and Iberia for cold affinity species and Gibraltar, Alboran, and Morocco for warm-temperate species). These effects were projected for both scenarios but were intensified under the extreme RCP8.5 scenario, with the complete borealization (circum-Arctic colonization) of kelp forests, the redistribution of the biogeographical transitional zones of the North Atlantic, and the erosion of global gene pools across all species. As the geographic distribution of genetic variability is unknown for most marine species, our results represent a baseline for identification of locations potentially rich in unique phylogeographic lineages that are also climatic relics in threat of disappearing. © 2017 John Wiley & Sons Ltd.

Endocrine and molecular investigations in a cohort of 25 adolescent males with prominent/persistent pubertal gynecomastia.

PubMed

Paris, F; Gaspari, L; Mbou, F; Philibert, P; Audran, F; Morel, Y; Biason-Lauber, A; Sultan, C

2016-03-01

Pubertal gynecomastia is a common condition observed in up to 65% of adolescent males. It is usually idiopathic and tends to regress within 1-2 years. In this descriptive cross-sectional study, we investigated 25 adolescent males with prominent (>B3) and/or persistent (>2 years) pubertal gynecomastia (P/PPG) to determine whether a hormonal/genetic defect might underline this condition. Endocrine investigation revealed the absence of hormonal disturbance for 18 boys (72%). Three patients presented Klinefelter syndrome and three a partial androgen insensitivity syndrome (PAIS) as a result of p.Ala646Asp and p.Ala45Gly mutations of the androgen receptor gene. The last patient showed a 17α-hydroxylase/17,20-lyase deficiency as a result of a compound heterozygous mutation of the CYP17A1 gene leading to p.Pro35Thr(P35T) and p.Arg239Stop(R239X) in the P450c17 protein. Enzymatic activity was analyzed: the mutant protein bearing the premature stop codon R239X showed a complete loss of 17α-hydroxylase and 17,20-lyase activity. The mutant P35T seemed to retain 15-20% of 17α-hydroxylase and about 8-10% of 17,20-lyase activity. This work demonstrates that P/PPG had an endocrine/genetic cause in 28% of our cases. PAIS may be expressed only by isolated gynecomastia as well as by 17α-hydroxylase/17,20-lyase deficiency. Isolated P/PPG is not always a 'physiological' condition and should thus be investigated through adequate endocrine and genetic investigations, even though larger studies are needed to better determine the real prevalence of genetic defects in such patients. © 2016 American Society of Andrology and European Academy of Andrology.

Loss of dendritic connectivity in southern California's urban riverscape facilitates decline of an endemic freshwater fish.

PubMed

Richmond, Jonathan Q; Backlin, Adam R; Galst-Cavalcante, Carey; O'Brien, John W; Fisher, Robert N

2018-01-01

Life history adaptations and spatial configuration of metapopulation networks allow certain species to persist in extreme fluctuating environments, yet long-term stability within these systems relies on the maintenance of linkage habitat. Degradation of such linkages in urban riverscapes can disrupt this dynamic in aquatic species, leading to increased extinction debt in local populations experiencing environment-related demographic flux. We used microsatellites and mtDNA to examine the effects of collapsed network structure in the endemic Santa Ana sucker Catostomus santaanae of southern California, a threatened species affected by natural flood-drought cycles, "boom-and-bust" demography, hybridization and presumed artificial transplantation. Our results show a predominance of drift-mediated processes in shaping population structure and that reverse mechanisms for counterbalancing the genetic effects of these phenomena have dissipated with the collapse of dendritic connectivity. We use approximate Bayesian models to support two cases of artificial transplantation and provide evidence that one of the invaded systems better represents the historic processes that maintained genetic variation within watersheds than any remaining drainages where C. santaanae is considered native. We further show that a stable dry gap in the northern range is preventing genetic dilution of pure C. santaanae persisting upstream of a hybrid assemblage involving a non-native sucker and that local accumulation of genetic variation in the same drainage is influenced by position within the network. This work has important implications for declining species that have historically relied on dendritic metapopulation networks to maintain source-sink dynamics in phasic environments, but no longer possess this capacity in urban-converted landscapes. © 2017 John Wiley & Sons Ltd.

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.

All roads lead to weediness: patterns of genomic divergence reveal extensive recurrent weedy rice origins from South Asian Oryza

USDA-ARS?s Scientific Manuscript database

Weedy rice (Oryza spp.), a weedy relative of cultivated rice (O. sativa), invades and persists in cultivated rice fields worldwide. Many weedy rice populations have evolved similar adaptive traits, considered part of the “agricultural weed syndrome,” making this an ideal model to study the genetic b...

Spread of Chikungunya Virus East/Central/South African Genotype in Northeast Brazil.

PubMed

Charlys da Costa, Antonio; Thézé, Julien; Komninakis, Shirley Cavalcante Vasconcelos; Sanz-Duro, Rodrigo Lopes; Felinto, Marta Rejane Lemos; Moura, Lúcia Cristina Corrêa; Barroso, Ivoneide Moreira de Oliveira; Santos, Lucineide Eliziario Correia; Nunes, Mardjane Alves de Lemos; Moura, Adriana Avila; Lourenço, José; Deng, Xutao; Delwart, Eric L; Guimarães, Maria Raquel Dos Anjos Silva; Pybus, Oliver G; Sabino, Ester C; Faria, Nuno R

2017-10-01

We investigated an outbreak of exanthematous illness in Maceió by using molecular surveillance; 76% of samples tested positive for chikungunya virus. Genetic analysis of 23 newly generated genomes identified the East/Central/South African genotype, suggesting that this lineage has persisted since mid-2014 in Brazil and may spread in the Americas and beyond.

Of Mice and Men: Will the Intersection of Social Science and Genetics Create New Approaches for Intimate Partner Violence?

ERIC Educational Resources Information Center

Janssen, Patricia A.; Nicholls, Tonia L.; Kumar, Ravinesh A.; Stefanakis, Harry; Spidel, Alicia L.; Simpson, Elizabeth M.

2005-01-01

The past two decades have yielded a recognition that intimate partner violence is ubiquitous. Although violence within relationships is bidirectional, there is acknowledgment that violence directed against women is more persistent and dangerous. Strategies for treatment of men have been largely unsuccessful, and studies of women-centered…

Cell wall chitosan is necessary for virulence in the opportunistic pathogen Cryptococcus neoformans.

PubMed

Baker, Lorina G; Specht, Charles A; Lodge, Jennifer K

2011-09-01

Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis. Its cell wall is composed of glucans, proteins, chitin, and chitosan. Multiple genetic approaches have defined a chitosan-deficient syndrome that includes slow growth and decreased cell integrity. Here we demonstrate chitosan is necessary for virulence and persistence in the mammalian host.

Noonan Syndrome Complicated by Primary Pulmonary Lymphangiectasia.

PubMed

Ford, Jaclyn Jo; Trotter, Carol W

2015-01-01

Noonan syndrome is a genetic disorder that has several features common to other conditions, making diagnosis a challenge. This column summarizes the case of a neonate with an atypical presentation of Noonan syndrome involving a fatal type of lymphangiectasia resulting in persistent pleural effusions. Radiographic features of this condition are presented along with the complexities of diagnosis and treatment.

Rapamycin restores BDNF-LTP and the persistence of long-term memory in a model of Down's syndrome.

PubMed

Andrade-Talavera, Yuniesky; Benito, Itziar; Casañas, Juan José; Rodríguez-Moreno, Antonio; Montesinos, María Luz

2015-10-01

Down's syndrome (DS) is the most prevalent genetic intellectual disability. Memory deficits significantly contribute to the cognitive dysfunction in DS. Previously, we discovered that mTOR-dependent local translation, a pivotal process for some forms of synaptic plasticity, is deregulated in a DS mouse model. Here, we report that these mice exhibit deficits in both synaptic plasticity (i.e., BDNF-long term potentiation) and the persistence of spatial long-term memory. Interestingly, these deficits were fully reversible using rapamycin, a Food and Drug Administration-approved specific mTOR inhibitor; therefore, rapamycin may be a novel pharmacotherapy to improve cognition in DS. Copyright © 2015 Elsevier Inc. All rights reserved.

A full genomic characterization of the development of a stable Small Colony Variant cell-type by a clinical Staphylococcus aureus strain.

PubMed

Bui, Long M G; Kidd, Stephen P

2015-12-01

A key to persistent and recurrent Staphylococcus aureus infections is its ability to adapt to diverse and toxic conditions. This ability includes a switch into a biofilm or to the quasi-dormant Small Colony Variant (SCV). The development and molecular attributes of SCVs have been difficult to study due to their rapid reversion to their parental cell-type. We recently described the unique induction of a matrix-embedded and stable SCV cell-type in a clinical S. aureus strain (WCH-SK2) by growing the cells with limiting conditions for a prolonged timeframe. Here we further study their characteristics. They possessed an increased viability in the presence of antibiotics compared to their non-SCV form. Their stability implied that there had been genetic changes; we therefore determined both the genome sequence of WCH-SK2 and its stable SCV form at a single base resolution, employing Single Molecular Real-Time (SMRT) sequencing that enabled the methylome to also be determined. The genetic features of WCH-SK2 have been identified; the SCCmec type, the pathogenicity and genetic islands and virulence factors. The genetic changes that had occurred in the stable SCV form were identified; most notably being in MgrA, a global regulator, and RsbU, a phosphoserine phosphatase within the regulatory pathway of the sigma factor SigB. There was a shift in the methylomes of the non-SCV and stable SCV forms. We have also shown a similar induction of this cell-type in other S. aureus strains and performed a genetic comparison to these and other S. aureus genomes. We additionally map RNAseq data to the WCH-SK2 genome in a transcriptomic analysis of the parental, SCV and stable SCV cells. The results from this study represent the unique identification of a suite of epigenetic, genetic and transcriptional factors that are implicated in the switch in S. aureus to its persistent SCV form. Copyright © 2015 Elsevier B.V. All rights reserved.

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 among populations depending on the fire regime, and supporting the role of fire in generating genetic divergence for adaptive traits. PMID:25008363

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.

A Road Map for 21st Century Genetic Restoration: Gene Pool Enrichment of the Black-Footed Ferret

PubMed Central

Ryder, Oliver A.; Santymire, Rachel M.; Engelhardt, John F.; Novak, Ben J.

2015-01-01

Interspecies somatic cell nuclear transfer (iSCNT) could benefit recovery programs of critically endangered species but must be weighed with the risks of failure. To weigh the risks and benefits, a decision-making process that evaluates progress is needed. Experiments that evaluate the efficiency and efficacy of blastocyst, fetal, and post-parturition development are necessary to determine the success or failure or species-specific iSCNT programs. Here, we use the black-footed ferret (Mustela nigripes) as a case study for evaluating this emerging biomedical technology as a tool for genetic restoration. The black-footed ferret has depleted genetic variation yet genome resource banks contain genetic material of individuals not currently represented in the extant lineage. Thus, genetic restoration of the species is in theory possible and could help reduce the persistent erosion of genetic diversity from drift. Extensive genetic, genomic, and reproductive science tools have previously been developed in black-footed ferrets and would aid in the process of developing an iSCNT protocol for this species. Nonetheless, developing reproductive cloning will require years of experiments and a coordinated effort among recovery partners. The information gained from a well-planned research effort with the goal of genetic restoration via reproductive cloning could establish a 21st century model for evaluating and implementing conservation breeding that would be applicable to other genetically impoverished species. PMID:26304983

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

Conservation genetics of extremely isolated urban populations of the northern dusky salamander (Desmognathus fuscus) in New York City

PubMed Central

Zak, Yana; Pehek, Ellen

2013-01-01

Urbanization is a major cause of amphibian decline. Stream-dwelling plethodontid salamanders are particularly susceptible to urbanization due to declining water quality and hydrological changes, but few studies have examined these taxa in cities. The northern dusky salamander (Desmognathus fuscus) was once common in the New York City metropolitan area, but has substantially declined throughout the region in recent decades. We used five tetranucleotide microsatellite loci to examine population differentiation, genetic variation, and bottlenecks among five remnant urban populations of dusky salamanders in NYC. These genetic measures provide information on isolation, prevalence of inbreeding, long-term prospects for population persistence, and potential for evolutionary responses to future environmental change. All populations were genetically differentiated from each other, and the most isolated populations in Manhattan have maintained very little genetic variation (i.e. <20% heterozygosity). A majority of the populations also exhibited evidence of genetic bottlenecks. These findings contrast with published estimates of high genetic variation within and lack of structure between populations of other desmognathine salamanders sampled over similar or larger spatial scales. Declines in genetic variation likely resulted from population extirpations and the degradation of stream and terrestrial paths for dispersal in NYC. Loss of genetic variability in populations isolated by human development may be an underappreciated cause and/or consequence of the decline of this species in urbanized areas of the northeast USA. PMID:23646283

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.

A multivariate analysis of genetic variation in the advertisement call of the gray treefrog, Hyla versicolor.

PubMed

Welch, Allison M; Smith, Michael J; Gerhardt, H Carl

2014-06-01

Genetic variation in sexual displays is crucial for an evolutionary response to sexual selection, but can be eroded by strong selection. Identifying the magnitude and sources of additive genetic variance underlying sexually selected traits is thus an important issue in evolutionary biology. We conducted a quantitative genetics experiment with gray treefrogs (Hyla versicolor) to investigate genetic variances and covariances among features of the male advertisement call. Two energetically expensive traits showed significant genetic variation: call duration, expressed as number of pulses per call, and call rate, represented by its inverse, call period. These two properties also showed significant genetic covariance, consistent with an energetic constraint to call production. Combining the genetic variance-covariance matrix with previous estimates of directional sexual selection imposed by female preferences predicts a limited increase in call duration but no change in call rate despite significant selection on both traits. In addition to constraints imposed by the genetic covariance structure, an evolutionary response to sexual selection may also be limited by high energetic costs of long-duration calls and by preferences that act most strongly against very short-duration calls. Meanwhile, the persistence of these preferences could be explained by costs of mating with males with especially unattractive calls. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Spatiotemporal Dynamics of Genetic Variation in the Iberian Lynx along Its Path to Extinction Reconstructed with Ancient DNA.

PubMed

Casas-Marce, Mireia; Marmesat, Elena; Soriano, Laura; Martínez-Cruz, Begoña; Lucena-Perez, Maria; Nocete, Francisco; Rodríguez-Hidalgo, Antonio; Canals, Antoni; Nadal, Jordi; Detry, Cleia; Bernáldez-Sánchez, Eloísa; Fernández-Rodríguez, Carlos; Pérez-Ripoll, Manuel; Stiller, Mathias; Hofreiter, Michael; Rodríguez, Alejandro; Revilla, Eloy; Delibes, Miguel; Godoy, José A

2017-11-01

There is the tendency to assume that endangered species have been both genetically and demographically healthier in the past, so that any genetic erosion observed today was caused by their recent decline. The Iberian lynx (Lynx pardinus) suffered a dramatic and continuous decline during the 20th century, and now shows extremely low genome- and species-wide genetic diversity among other signs of genomic erosion. We analyze ancient (N = 10), historical (N = 245), and contemporary (N = 172) samples with microsatellite and mitogenome data to reconstruct the species' demography and investigate patterns of genetic variation across space and time. Iberian lynx populations transitioned from low but significantly higher genetic diversity than today and shallow geographical differentiation millennia ago, through a structured metapopulation with varying levels of diversity during the last centuries, to two extremely genetically depauperate and differentiated remnant populations by 2002. The historical subpopulations show varying extents of genetic drift in relation to their recent size and time in isolation, but these do not predict whether the populations persisted or went finally extinct. In conclusion, current genetic patterns were mainly shaped by genetic drift, supporting the current admixture of the two genetic pools and calling for a comprehensive genetic management of the ongoing conservation program. This study illustrates how a retrospective analysis of demographic and genetic patterns of endangered species can shed light onto their evolutionary history and this, in turn, can inform conservation actions. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal

PubMed Central

Aguilar, Andres; Roemer, Gary; Debenham, Sally; Binns, Matthew; Garcelon, David; Wayne, Robert K.

2004-01-01

The San Nicolas Island fox (Urocyon littoralis dickeyi) is genetically the most monomorphic sexually reproducing animal population yet reported and has no variation in hypervariable genetic markers. Such low levels of variation imply lower resistance to pathogens, reduced fitness, and problems in distinguishing kin from non-kin. In vertebrates, the MHC contains genes that influence disease resistance and kin recognition and may be under intense balancing selection in some populations. Hence, genetic variation at the MHC might persist despite the extreme monomorphism shown by neutral markers. We examine variation of five loci within the MHC of San Nicolas Island foxes and find remarkably high levels of variation. Further, we show by simulation that genetic monomorphism at neutral loci and high MHC variation could arise only through an extreme population bottleneck of <10 individuals, ≈10–20 generations ago, accompanied by unprecedented selection coefficients of >0.5 on MHC loci. These results support the importance of balancing selection as a mechanism to maintain variation in natural populations and expose the difficulty of using neutral markers as surrogates for variation in fitness-related loci. PMID:14990802

Milk consumption and lactose intolerance in adults.

PubMed

Qiao, Rong; Huang, ChengYu; Du, HuiZhang; Zeng, Guo; Li, Ling; Ye, Sheng

2011-10-01

To investigate relations between milk consumption and lactose intolerance (LI) in adults and to explore the effect of milk consumption on lactase activity. Total of 182 subjects aged 20-70 years were recruited and interviewed by questionnaires, and their accumulative cow's milk intake (AMI) was calculated. LI was evaluated by hydrogen breath test (HBT). A negative correlation was found between AMI and severity of observed LI symptom (r=-0.2884; P<0.05). Binary logistic regression analysis showed a negative correlation between LI and duration and frequency of milk consumption (OR, 0.317 and 0.465, respectively; both P<0.05) and a positive correlation between LI and amount of milk consumed per sitting (OR, 6.337; P<0.05). LI is related to various milk consumption behaviors. Most Chinese adults with LI may tolerate moderate milk consumption <160 mL. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.