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1

High microsatellite and mitochondrial diversity in Anatolian native horse breeds shows Anatolia as a genetic conduit between Europe and Asia.  

PubMed

The horse has been a food source, but more importantly, it has been a means for transport. Its domestication was one of the crucial steps in the history of human civilization. Despite the archaeological and molecular studies carried out on the history of horse domestication, which would contribute to conservation of the breeds, the details of the domestication of horses still remain to be resolved. We employed 21 microsatellite loci and mitochondrial control region partial sequences to analyse genetic variability within and among four Anatolian native horse breeds, Ayvac?k Pony, Malakan Horse, H?n?s Horse and Canik Horse, as well as samples from indigenous horses of unknown breed ancestry. The aims of the study were twofold: first, to produce data from the prehistorically and historically important land bridge, Anatolia, in order to assess its role in horse domestication and second, to analyse the data from a conservation perspective to help the ministry improve conservation and management strategies regarding native horse breeds. Even though the microsatellite data revealed a high allelic diversity, 98% of the genetic variation partitioned within groups. Genetic structure did not correlate with a breed or geographic origin. High diversity was also detected in mtDNA control region sequence analysis. Frequencies of two haplogroups (HC and HF) revealed a cline between Asia and Europe, suggesting Anatolia as a probable connection route between the two continents. This first detailed genetic study on Anatolian horse breeds revealed high diversity among horse mtDNA haplogroups in Anatolia and suggested Anatolia's role as a conduit between the two continents. The study also provides an important basis for conservation practices in Turkey. PMID:22497212

Koban, E; Denizci, M; Aslan, O; Aktoprakligil, D; Aksu, S; Bower, M; Balcioglu, B K; Ozdemir Bahadir, A; Bilgin, R; Erdag, B; Bagis, H; Arat, S

2012-08-01

2

Batrachochytrium dendrobatidis shows high genetic diversity and ecological niche specificity among haplotypes in the Maya Mountains of Belize.  

PubMed

The amphibian pathogen Batrachochytrium dendrobatidis (Bd) has been implicated in amphibian declines around the globe. Although it has been found in most countries in Central America, its presence has never been assessed in Belize. We set out to determine the range, prevalence, and diversity of Bd using quantitative PCR (qPCR) and sequencing of a portion of the 5.8 s and ITS1-2 regions. Swabs were collected from 524 amphibians of at least 26 species in the protected areas of the Maya Mountains of Belize. We sequenced a subset of 72 samples that had tested positive for Bd by qPCR at least once; 30 samples were verified as Bd. Eight unique Bd haplotypes were identified in the Maya Mountains, five of which were previously undescribed. We identified unique ecological niches for the two most broadly distributed haplotypes. Combined with data showing differing virulence shown in different strains in other studies, the 5.8 s - ITS1-2 region diversity found in this study suggests that there may be substantial differences among populations or haplotypes. Future work should focus on whether specific haplotypes for other genomic regions and possibly pathogenicity can be associated with haplotypes at this locus, as well as the integration of molecular tools with other ecological tools to elucidate the ecology and pathogenicity of Bd. PMID:22389681

Kaiser, Kristine; Pollinger, John

2012-01-01

3

Plasmodium vivax isolates from Cambodia and Thailand show high genetic complexity and distinct patterns of P. vivax multidrug resistance gene 1 (pvmdr1) polymorphisms.  

PubMed

Plasmodium vivax accounts for an increasing fraction of malaria infections in Thailand and Cambodia. We compared P. vivax genetic complexity and antimalarial resistance patterns in the two countries. Use of a heteroduplex tracking assay targeting the merozoite surface protein 1 gene revealed that vivax infections in both countries are frequently polyclonal (84%), with parasites that are highly diverse (HE = 0.86) but closely related (GST = 0.18). Following a history of different drug policies in Thailand and Cambodia, distinct patterns of antimalarial resistance have emerged: most Cambodian isolates harbor the P. vivax multidrug resistance gene 1 (pvmdr1) 976F mutation associated with chloroquine resistance (89% versus 8%, P < 0.001), whereas Thai isolates more often display increased pvmdr1 copy number (39% versus 4%, P < 0.001). Finally, genotyping of paired isolates from individuals suspected of suffering relapse supports a complex scheme of relapse whereby recurrence of multiple identical variants is sometimes accompanied by the appearance of novel variants. PMID:23509126

Lin, Jessica T; Patel, Jaymin C; Kharabora, Oksana; Sattabongkot, Jetsumon; Muth, Sinuon; Ubalee, Ratawan; Schuster, Anthony L; Rogers, William O; Wongsrichanalai, Chansuda; Juliano, Jonathan J

2013-06-01

4

Plasmodium vivax Isolates from Cambodia and Thailand Show High Genetic Complexity and Distinct Patterns of P. vivax Multidrug Resistance Gene 1 (pvmdr1) Polymorphisms  

PubMed Central

Plasmodium vivax accounts for an increasing fraction of malaria infections in Thailand and Cambodia. We compared P. vivax genetic complexity and antimalarial resistance patterns in the two countries. Use of a heteroduplex tracking assay targeting the merozoite surface protein 1 gene revealed that vivax infections in both countries are frequently polyclonal (84%), with parasites that are highly diverse (HE = 0.86) but closely related (GST = 0.18). Following a history of different drug policies in Thailand and Cambodia, distinct patterns of antimalarial resistance have emerged: most Cambodian isolates harbor the P. vivax multidrug resistance gene 1 (pvmdr1) 976F mutation associated with chloroquine resistance (89% versus 8%, P < 0.001), whereas Thai isolates more often display increased pvmdr1 copy number (39% versus 4%, P < 0.001). Finally, genotyping of paired isolates from individuals suspected of suffering relapse supports a complex scheme of relapse whereby recurrence of multiple identical variants is sometimes accompanied by the appearance of novel variants.

Lin, Jessica T.; Patel, Jaymin C.; Kharabora, Oksana; Sattabongkot, Jetsumon; Muth, Sinuon; Ubalee, Ratawan; Schuster, Anthony L.; Rogers, William O.; Wongsrichanalai, Chansuda; Juliano, Jonathan J.

2013-01-01

5

Three genetic grapevine leafroll-associated virus 3 variants identified from South African vineyards show high variability in their 5?UTR  

Microsoft Academic Search

Three genetic variants of grapevine leafroll-associated virus 3 (GLRaV-3) were identified in vineyards of the Western Cape,\\u000a South Africa. The GLRaV-3 variants were identified by single-strand conformation polymorphism (SSCP) profiles generated from\\u000a a region amplified in ORF5. ORF5 sequence data confirmed the three genetic variant groups, and a specific SSCP profile was\\u000a assigned to each variant group. The results of

A. E. C. Jooste; H. J. Maree; D. U. Bellstedt; D. E. Goszczynski; G. Pietersen; J. T. Burger

2010-01-01

6

High Points of Human Genetics  

ERIC Educational Resources Information Center

Discusses such high points of human genetics as the study of chromosomes, somatic cell hybrids, the population formula: the Hardy-Weinberg Law, biochemical genetics, the single-active X Theory, behavioral genetics and finally how genetics can serve humanity. (BR)

Stern, Curt

1975-01-01

7

Injuries on The Increase in High School Lacrosse, Study Shows  

MedlinePLUS

... please enable JavaScript. Injuries on the Increase in High School Lacrosse, Study Shows More than 22 percent ... Sports Injuries TUESDAY, July 22, 2014 (HealthDay News) -- High school lacrosse players are facing an increasing number ...

8

Underside of span over Pickering Creek, showing highly skewed piers, ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Underside of span over Pickering Creek, showing highly skewed piers, looking south. - Pennsylvania Railroad, Pickering Creek Trestle, Spanning Pickering Creek, south of Buckwalter Road, Pickering, Chester County, PA

9

Genetics Show Current Decline and Pleistocene Expansion in Northern Spotted Owls  

USGS Publications Warehouse

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.

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

2008-01-01

10

Human genetic affinities for Y-chromosome P49a,f/TaqI haplotypes show strong correspondence with linguistics.  

PubMed Central

Numerous population samples from around the world have been tested for Y chromosome-specific p49a,f/TaqI restriction polymorphisms. Here we review the literature as well as unpublished data on Y-chromosome p49a,f/TaqI haplotypes and provide a new nomenclature unifying the notations used by different laboratories. We use this large data set to study worldwide genetic variability of human populations for this paternally transmitted chromosome segment. We observe, for the Y chromosome, an important level of population genetics structure among human populations (FST = .230, P < .001), mainly due to genetic differences among distinct linguistic groups of populations (FCT = .246, P < .001). A multivariate analysis based on genetic distances between populations shows that human population structure inferred from the Y chromosome corresponds broadly to language families (r = .567, P < .001), in agreement with autosomal and mitochondrial data. Times of divergence of linguistic families, estimated from their internal level of genetic differentiation, are fairly concordant with current archaeological and linguistic hypotheses. Variability of the p49a,f/TaqI polymorphic marker is also significantly correlated with the geographic location of the populations (r = .613, P < .001), reflecting the fact that distinct linguistic groups generally also occupy distinct geographic areas. Comparison of Y-chromosome and mtDNA RFLPs in a restricted set of populations shows a globally high level of congruence, but it also allows identification of unequal maternal and paternal contributions to the gene pool of several populations.

Poloni, E S; Semino, O; Passarino, G; Santachiara-Benerecetti, A S; Dupanloup, I; Langaney, A; Excoffier, L

1997-01-01

11

Genetic correlations between horse show jumping competition traits in five European countries  

Microsoft Academic Search

Genetic correlations were computed for show jumping competition traits from national estimated breeding values (EBV) of stallions of five countries: Belgium, Denmark, France, Ireland and Sweden. Data involved 24,390 horses, i.e. 8993 stallions with EBV and their ancestors. There were 617 stallions with several EBVs in more than one country. Method involved MACE (Multi-Trait Across Country Evaluation) methodology based on

C. Ruhlmann; S. Janssens; J. Philipsson; E. Thorén-Hellsten; H. Crolly; K. Quinn; E. Manfredi; A. Ricard

2009-01-01

12

A UV-induced genetic network links the RSC complex to nucleotide excision repair and shows dose-dependent rewiring.  

PubMed

Efficient repair of UV-induced DNA damage requires the precise coordination of nucleotide excision repair (NER) with numerous other biological processes. To map this crosstalk, we generated a differential genetic interaction map centered on quantitative growth measurements of >45,000 double mutants before and after different doses of UV radiation. Integration of genetic data with physical interaction networks identified a global map of 89 UV-induced functional interactions among 62 protein complexes, including a number of links between the RSC complex and several NER factors. We show that RSC is recruited to both silenced and transcribed loci following UV damage where it facilitates efficient repair by promoting nucleosome remodeling. Finally, a comparison of the response to high versus low levels of UV shows that the degree of genetic rewiring correlates with dose of UV and reveals a network of dose-specific interactions. This study makes available a large resource of UV-induced interactions, and it illustrates a methodology for identifying dose-dependent interactions based on quantitative shifts in genetic networks. PMID:24360959

Srivas, Rohith; Costelloe, Thomas; Carvunis, Anne-Ruxandra; Sarkar, Sovan; Malta, Erik; Sun, Su Ming; Pool, Marijke; Licon, Katherine; van Welsem, Tibor; van Leeuwen, Fred; McHugh, Peter J; van Attikum, Haico; Ideker, Trey

2013-12-26

13

Clinical and genetic evaluation of a family showing both autism and epilepsy.  

PubMed

Autism is a strong genetic disorder, with an estimated heritability greater than 90%. Nonetheless, its specific genetic aetiology remains largely unknown. Autism is associated with epilepsy in early childhood and epilepsy occurs in 10-30% of individuals with autism. Here we report the case of a woman affected by a severe epileptic disorder with an onset at 14 years old. She is affected by a cryptogenetic focal epilepsy with complex partial (psychomotor) and secondarily generalized tonic-clonic seizures, which are drug resistant. The woman is married to a healthy man and has six children: two girls are healthy, a girl and two boys are affected by autism while one boy shows partial seizures. The three children with autism show moderate mental retardation and an EEG with no epileptiform alterations. The child with epileptic seizures shows an asymmetric EEG that is not necessarily pathological. In this family, no chromosomal rearrangements were detected by means of classical cytogenetic analyses. The presence of FRAXA alterations and of microdeletions of the 15q11-q13 chromosome region were also excluded. A genome-wide linkage analysis using microsatellite markers revealed several chromosome regions as possible susceptibility loci. PMID:20152887

Combi, R; Redaelli, S; Beghi, M; Clerici, M; Cornaggia, C M; Dalprà, L

2010-04-29

14

A neotropical polymorphic damselfly shows poor congruence between genetic and traditional morphological characters in Odonata.  

PubMed

The Neotropical damselfly genus Polythore consists of nineteen described morphospecies. We used the COI barcode locus (799 bp), male genitalia, wing venation, and geometrical pattern variation to clarify specific status in four Polythore procera populations in the Andean foothills of Colombia. Morphological data corroborates that all populations are P. procera, but molecular data suggests two well-supported reciprocal monophyletic clades. A high genetic divergence (? 3%) was observed between them, and different degrees of gene flow were estimated by MDIV among populations. Our results support a recent (1.4 mya) possible speciation with morphological stasis where unknown reproductive mechanisms may be involved. PMID:20736073

Herrera, Melissa Sánchez; Realpe, Emilio; Salazar, Camilo

2010-11-01

15

Mixtures of thermostable enzymes show high performance in biomass saccharification.  

PubMed

Optimal enzyme mixtures of six Trichoderma reesei enzymes and five thermostable enzyme components were developed for the hydrolysis of hydrothermally pretreated wheat straw, alkaline oxidised sugar cane bagasse and steam-exploded bagasse by statistically designed experiments. Preliminary studies to narrow down the optimization parameters showed that a cellobiohydrolase/endoglucanase (CBH/EG) ratio of 4:1 or higher of thermostable enzymes gave the maximal CBH-EG synergy in the hydrolysis of hydrothermally pretreated wheat straw. The composition of optimal enzyme mixtures depended clearly on the substrate and on the enzyme system studied. The optimal enzyme mixture of thermostable enzymes was dominated by Cel7A and required a relatively high amount of xylanase, whereas with T. reesei enzymes, the high proportion of Cel7B appeared to provide the required xylanase activity. The main effect of the pretreatment method was that the required proportion of xylanase was higher and the proportion of Cel7A lower in the optimized mixture for hydrolysis of alkaline oxidised bagasse than steam-exploded bagasse. In prolonged hydrolyses, less Cel7A was generally required in the optimal mixture. Five-component mixtures of thermostable enzymes showed comparable hydrolysis yields to those of commercial enzyme mixtures. PMID:24752938

Kallioinen, Anne; Puranen, Terhi; Siika-Aho, Matti

2014-07-01

16

Genetically obese mice do not show increased gut permeability or faecal bile acid hydrophobicity.  

PubMed

Gut barrier dysfunction may lead to metabolic endotoxaemia and low-grade inflammation. Recent publications have demonstrated gut barrier dysfunction in obesity induced by a diet high in fat, and a pathogenetic role for luminal bile acids has been proposed. We aimed to investigate whether genetically obese mice develop increased gut permeability and alterations in luminal bile acids on a diet with a regular fat content. We used seven obese male ob/ob mice of C57BL/6J background and ten male wild-type (WT) mice of the same strain. Faeces were collected for bile acid analysis. Intestinal permeability was measured in an Ussing chamber upon euthanasia, using 4 kDa fluorescein isothiocyanate dextran, as per mille (‰, 1/1000) of translocated dextran. We analysed the liver expression of lipopolysaccharide-binding protein (LBP), as well as serum LBP (ELISA). Intestinal permeability was not affected by genetic obesity (jejunum: 0·234 (sem 0·04) ‰ for obese v. 0·225 (sem 0·03) ‰ for WT, P= 0·93; colon: 0·222 (sem 0·06) ‰ for obese v. 0·184 (sem 0·03) ‰ for WT, P= 0·86), nor was liver LBP expression (relative expression: 0·55 (sem 0·08) for obese v. 0·55 (sem 0·13) for WT, P= 0·70). Serum LBP was 2·5-fold higher in obese than in WT mice (P= 0·001). Obese mice had increased daily excretion of total bile acids, but their faecal bile acid hydrophobicity was unchanged. In conclusion, genetic obesity did not impair gut barrier function in mice on a regular chow diet, nor was faecal bile acid hydrophobicity affected. PMID:23442231

Stenman, Lotta K; Holma, Reetta; Gylling, Helena; Korpela, Riitta

2013-09-28

17

UNC study shows genetic, non-invasive test could improve colon cancer screening  

Cancer.gov

A non-invasive test that includes detection of the genetic abnormalities related to cancer could significantly improve the effectiveness of colon cancer screening, according to research from the UNC School of Medicine and UNC Lineberger Comprehensive Cancer Center.

18

High-Resolution Observations of a Filament showing Activated Barb  

NASA Astrophysics Data System (ADS)

Analysis of a filament showing an activated barb using observations from the Dutch Open Telescope (DOT) on 2010 August 20 are presented. The DOT takes Doppler images in H?, among other wavelengths, in a region about 110 × 110 arcsec^{2} in area, at a cadence of 30~seconds. The offline image restoration technique of speckle reconstruction is applied to obtain diffraction limited images. The filament developed a new barb in 10~minutes, which disappeared within the next 35~minutes. Such a rapid formation and disappearance of a filament barb is unusual, and has not been reported earlier. Line-of-sight velocity maps were constructed from the Doppler images of the target filament. We observe flows in the filament spine towards the barb location prior to its formation, and flows in the barb towards the spine during its disappearance. Photospheric magnetograms from Heliospheric Magnetic Imager on board the Solar Dynamics Observatory, at a cadence of 45~seconds, were used to determine the changes in magnetic flux in the region surrounding the barb location. The variation of magnetic flux in this duration supports the view that barbs are rooted in minor magnetic polarity. Our analysis shows that barbs can be short-lived and formation and disappearance of the barb was associated with cancellation of magnetic flux.

Joshi, Anand; Martin, Sara F.; Mathew, Shibu; Srivastava, Nandita

2012-07-01

19

Natural Selection and Evolution: Using Multimedia Slide Shows to Emphasize the Role of Genetic Variation  

ERIC Educational Resources Information Center

Most middle school students comprehend that organisms have adaptations that enable their survival and that successful adaptations prevail in a population over time. Yet they often miss that those bird beaks, moth-wing colors, or whatever traits are the result of random, normal genetic variations that just happen to confer a negative, neutral, or…

Malone, Molly

2012-01-01

20

Molecular Epidemiological Analysis of Mycoplasma bovis Isolates from the United Kingdom Shows Two Genetically Distinct Clusters  

Microsoft Academic Search

Mycoplasma bovis is an important veterinary pathogen causing pneumonia, arthritis, and mastitis in infected cattle. We investigated the genetic diversity of 53 isolates collected in the United Kingdom between 1996 and 2002 with pulsed-field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP), and random amplified polymorphic DNA (RAPD) analysis. In addition, the influence of variable surface protein (Vsp) profiles on

Laura McAuliffe; Branko Kokotovic; Roger D. Ayling; Robin A. J. Nicholas

2004-01-01

21

Genetic analysis of an isolated red deer ( Cervus elaphus ) population showing signs of inbreeding depression  

Microsoft Academic Search

In the present study, we analysed 18 red deer specimens from a small (N?=?50) and isolated population in Schleswig-Holstein, northern Germany, with respect to variability at nine polymorphic microsatellite\\u000a loci and 439 bp of the mitochondrial DNA control region. Several cases of brachygnathy (shortened lower jaw), commonly associated\\u000a with inbreeding depression, have been recorded in the population. Genetic variability was very

F. E. Zachos; C. Althoff; Y. v. Steynitz; I. Eckert; G. B. Hartl

2007-01-01

22

A Japanese family showing high-frequency hearing loss with KCNQ4 and TECTA mutations.  

PubMed

Abstract Conclusions: We describe a Japanese family with high-frequency sensorineural hearing loss (SNHL) harboring a c.211delC mutation in the KCNQ4 gene. Families showing progressive high-frequency SNHL should be investigated for mutations in the KCNQ4 gene. Objective: To determine the responsible deafness gene in a Japanese family with dominantly inherited high-frequency SNHL of unknown etiology. Methods: We performed hearing tests for five members of the family, and the three affected with hearing loss underwent further audiological and vestibular examinations. Genetic analysis was performed to identify any possible causative mutations, as well as analysis of detailed clinical findings to determine the phenotype. Results: The three affected subjects showed high-frequency SNHL. Extensive audiologic evaluation suggested cochlear involvement and progressive hearing loss. As for bilateral caloric testing, two of the three affected subjects showed hyporeflexia with recurrent vestibular symptoms. We identified the c.211delC mutation in the KCNQ4 gene and the c.2967C>A (p.H989Q) mutation in the TECTA gene. Based on the genotype-phenotype correlation, the c.211delC mutation in the KCNQ4 gene was associated with high-frequency SNHL in this family. PMID:24655070

Ishikawa, Kotaro; Naito, Takehiko; Nishio, Shin-Ya; Iwasa, Yoh-Ichiro; Nakamura, Ken-Ichi; Usami, Shin-Ichi; Ichimura, Keiichi

2014-06-01

23

Multilocus microsatellite typing shows three different genetic clusters of Leishmania major in Iran.  

PubMed

Ten polymorphic microsatellite markers were used to analyse 25 strains of Leishmania major collected from cutaneous leishmaniasis cases in different endemic areas in Iran. Nine of the markers were polymorphic, revealing 21 different genotypes. The data displayed significant microsatellite polymorphism with rare allelic heterozygosity. Bayesian statistic and distance based analyses identified three genetic clusters among the 25 strains analysed. Cluster I represented mainly strains isolated in the west and south-west of Iran, with the exception of four strains originating from central Iran. Cluster II comprised strains from the central part of Iran, and cluster III included only strains from north Iran. The geographical distribution of L. major in Iran was supported by comparing the microsatellite profiles of the 25 Iranian strains to those of 105 strains collected in 19 Asian and African countries. The Iranian clusters I and II were separated from three previously described populations comprising strains from Africa, the Middle East and Central Asia whereas cluster III grouped together with the Central Asian population. The considerable genetic variability of L. major might be related to the existence of different populations of Phlebotomus papatasi and/or to differences in reservoir host abundance in different parts of Iran. PMID:21664984

Mahnaz, Tashakori; Al-Jawabreh, Amer; Kuhls, Katrin; Schönian, Gabriele

2011-10-01

24

Genetic variants showing apparent hot-spots in the human serum albumin gene.  

PubMed

The molecular defects of three different slow-migrating genetic variants of human serum albumin, albumins Kamloops (formerly RIH), Stirling and Amsterdam, previously characterized only by electrophoretic and dye-binding studies, are now reported. Two of them are proalbumin variants: sequential analysis of the purified whole proteins has established the mutation responsible for albumin Kamloops as -1Arg-->Gln, and for albumin Stirling as -2Arg-->His. A Glu-->Lys substitution in position 570 of the mature albumin molecule was determined in albumin Amsterdam by sequential analysis of two abnormal tryptic fragments. The three alloalbumins are caused by single-base changes all of which seem to represent hot-spots in the albumin gene. The possible functional consequences of the presence of a circulating alloalbumin are discussed. PMID:10556652

Galliano, M; Kragh-Hansen, U; Tárnoky, A L; Chapman, J C; Campagnoli, M; Minchiotti, L

1999-11-01

25

Bulinus globosus (Planorbidae; Gastropoda) populations in the Lake Victoria basin and coastal Kenya show extreme nuclear genetic differentiation.  

PubMed

Bulinus globosus, a key intermediate host for Schistosoma haematobium that causes urinary schistosomiasis, is a hermaphroditic freshwater Planorbid snail species that inhabits patchy and transient water bodies prone to large seasonal variations in water availability. Although capable of self-fertilizing, this species has been reported to be preferentially out crossing. In this study, we characterized the population genetic structure of 19 B. globosus populations sampled across the Lake Victoria basin and coastal Kenya using four polymorphic microsatellite loci. Population genetic structure was characterized and quantified using FST statistics and Bayesian clustering algorithms. The four loci used in this study contained sufficient statistical power to detect low levels of population genetic differentiation and were highly polymorphic with the number of alleles per locus across populations ranging from 16 to 22. Average observed and expected heterozygosities across loci in each population ranged from 0.13 to 0.69 and from 0.39 to 0.79, respectively. Twenty-five of the seventy-six possible population-locus comparisons significantly deviated from Hardy-Weinberg equilibrium proportions after Bonferroni corrections, mostly due to the deficiency of heterozygotes. Significant genetic differentiation was observed between populations and Bayesian inferences identified 15 genetic clusters. The excess homozygosity, significant inbreeding and population genetic differentiation observed in B. globosus populations are likely to be due to the habitat patchiness, mating system and the proneness to cyclic extinction and recolonization in transient habitats. PMID:23266524

Nyakaana, Silvester; Stothard, J Russell; Nalugwa, Allen; Webster, Bonnie L; Lange, Charles N; Jørgensen, Aslak; Rollinson, David; Kristensen, Thomas K

2013-11-01

26

Molecular Typing of Australian Scedosporium Isolates Showing Genetic Variability and Numerous S. aurantiacum  

PubMed Central

One hundred clinical isolates from a prospective nationwide study of scedosporiosis in Australia (2003–2005) and 46 additional isolates were genotyped by internal transcribed spacer–restriction fragment length polymorphism (ITS-RFLP) analysis, ITS sequencing, and M13 PCR fingerprinting. ITS-RFLP and PCR fingerprinting identified 3 distinct genetic groups. The first group corresponded to Scedosporium prolificans (n = 83), and the other 2 comprised isolates previously identified as S. apiospermum: one of these corresponded to S. apiospermum (n = 33) and the other to the newly described species S. aurantiacum (n = 30). Intraspecies variation was highest for S. apiospermum (58%), followed by S. prolificans (45%) and S. aurantiacum (28%) as determined by PCR fingerprinting. ITS sequence variation of 2.2% was observed among S. apiospermum isolates. No correlation was found between genotype of strains and their geographic origin, body site from which they were cultured, or colonization versus invasive disease. Twelve S. prolificans isolates from 2 suspected case clusters were examined by amplified fragment length polymorphism analysis. No specific clusters were confirmed.

Delhaes, Laurence; Harun, Azian; Chen, Sharon C.A.; Nguyen, Quoc; Slavin, Monica; Heath, Christopher H.; Maszewska, Krystyna; Halliday, Catriona; Robert, Vincent; Sorrell, Tania C.

2008-01-01

27

Eubacteria show their true colors: genetics of carotenoid pigment biosynthesis from microbes to plants.  

PubMed Central

The opportunities to understand eubacterial carotenoid biosynthesis and apply the lessons learned in this field to eukaryotes have improved dramatically in the last several years. On the other hand, many questions remain. Although the pigments illustrated in Fig. 2 represent only a small fraction of the carotenoids found in nature, the characterization of eubacterial genes required for their biosynthesis has not yet been completed. Identifying those eukaryotic carotenoid biosynthetic mutants, genes, and enzymes that have no eubacterial counterparts will also prove essential for a full description of the biochemical pathways (81). Eubacterial crt gene regulation has not been studied in detail, with the notable exceptions of M. xanthus and R. capsulatus (5, 33, 39, 45, 46, 84). Determination of the rate-limiting reaction(s) in carotenoid biosynthesis has thus far yielded species-specific results (12, 27, 47, 69), and the mechanisms of many of the biochemical conversions remain obscure. Predicted characteristics of some carotenoid biosynthesis gene products await confirmation by studying the purified proteins. Despite these challenges, (over)expression of eubacterial or eukaryotic carotenoid genes in heterologous hosts has already created exciting possibilities for the directed manipulation of carotenoid levels and content. Such efforts could, for example, enhance the nutritional value of crop plants or yield microbial production of novel and desirable pigments. In the future, the functional compatibility of enzymes from different organisms will form a central theme in the genetic engineering of carotenoid pigment biosynthetic pathways.

Armstrong, G A

1994-01-01

28

Molecular epidemiological analysis of Mycoplasma bovis isolates from the Pennsylvania Animal Diagnostic Laboratory showing genetic diversity.  

PubMed

We have examined the genetic variability of Mycoplasma bovis strains submitted to the Pennsylvania Animal Diagnostics Laboratory, University Park (PA-ADL), between December 2007 and December 2008. Of 4,868 total samples submitted for Mycoplasma testing, 302 were determined to be culture positive. Mycoplasma bovis (63.6%), Mycoplasma californicum (7.3%), Mycoplasma bovirhinis (2.7%), Mycoplasma bovigenitalium (0.7%), Mycoplasma alkalescens (4.9%), Mycoplasma putrefaciens (0.3%), and Mycoplasma dispar (1.3%) and unidentified Mycoplasma sp. (19.2%) were identified using PCR. Mycoplasma bovis represented the largest portion of the positive samples submitted. Each of the 192 M. bovis isolates was examined for variations in the BglII and MfeI restriction sites of the DNA using amplified fragment length polymorphism fingerprinting and subsequently compared with the M. bovis type strain PG45 (ATCC 25523). Similarity between strains was calculated using the Dice similarity coefficient, which ranged from approximately 0.7 to 1.0. When clustering the isolates at greater than 95% similarity, it was determined that 11 distinct clusters were present. The results are consistent with the existence of at least 2 clonally distinct groups. No clear geographical, month of isolation, or source origination relationship was identified, indicating that a currently unclassified characteristic is responsible for the strain heterogeneity. These data indicate strong heterogeneity of M. bovis isolates submitted to PA-ADL. Additionally, multiple sites throughout Pennsylvania had isolates of separate clonal lineages present concomitantly, indicating the ability of multiple overlapping outbreaks to occur at a single location. Mycoplasma bovis represents the largest portion of Mycoplasma species isolated from PA-ADL samples. We propose that amplified fragment length polymorphism may serve as a valuable tool for molecular characterization of M. bovis strains from the United States. PMID:21426978

Soehnlen, M K; Kariyawasam, S; Lumadue, J A; Pierre, T A; Wolfgang, D R; Jayarao, B M

2011-04-01

29

Genetic Structure and Demographic History Should Inform Conservation: Chinese Cobras Currently Treated as Homogenous Show Population Divergence  

PubMed Central

An understanding of population structure and genetic diversity is crucial for wildlife conservation and for determining the integrity of wildlife populations. The vulnerable Chinese cobra (Naja atra) has a distribution from the mouth of the Yangtze River down to northern Vietnam and Laos, within which several large mountain ranges and water bodies may influence population structure. We combined 12 microsatellite loci and 1117 bp of the mitochondrial cytochrome b gene to explore genetic structure and demographic history in this species, using 269 individuals from various localities in Mainland China and Vietnam. High levels of genetic variation were identified for both mtDNA and microsatellites. mtDNA data revealed two main (Vietnam + southern China + southwestern China; eastern + southeastern China) and one minor (comprising only two individuals from the westernmost site) clades. Microsatellite data divided the eastern + southeastern China clade further into two genetic clusters, which include individuals from the eastern and southeastern regions, respectively. The Luoxiao and Nanling Mountains may be important barriers affecting the diversification of lineages. In the haplotype network of cytchrome b, many haplotypes were represented within a “star” cluster and this and other tests suggest recent expansion. However, microsatellite analyses did not yield strong evidence for a recent bottleneck for any population or genetic cluster. The three main clusters identified here should be considered as independent management units for conservation purposes. The release of Chinese cobras into the wild should cease unless their origin can be determined, and this will avoid problems arising from unnatural homogenization.

Lin, Long-Hui; Qu, Yan-Fu; Li, Hong; Zhou, Kai-Ya; Ji, Xiang

2012-01-01

30

Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template  

Microsoft Academic Search

Natural and synthetic biological networks must function reliably in the face of fluctuating stoichiometry of their molecular components. These fluctuations are caused in part by changes in relative expression efficiency and the DNA template amount of the network-coding genes. Gene product levels could potentially be decoupled from these changes via built-in adaptation mechanisms, thereby boosting network reliability. Here, we show

Leonidas Bleris; Zhen Xie; David Glass; Asa Adadey; Eduardo Sontag; Yaakov Benenson

2011-01-01

31

Human genetic adaptation to high altitude.  

PubMed

Some 140 million persons live permanently at high altitudes (>2500 m) in North, Central and South America, East Africa, and Asia. Reviewed here are recent studies which address the question as to whether genetic adaptation to high altitude has occurred. Common to these studies are the use of the oxygen transport system and the passage of time as organizing principles, and the recognition of the multifaceted ways in which genetic factors can influence physiological processes. They differ in terms of study approach and sources of evidence for judging duration of high altitude residence. Migrant, family set, and admixture study designs have been used for comparisons within populations. These collectively demonstrate the existence of genetic influences on physiological characteristics of oxygen transport. Differences in oxygen transport-related traits between Tibetan, Andean and European populations have been interpreted as having demonstrated the existence of genetic influences on high altitude adaptation but there is not consensus as to which groups are the best-adapted. Part of the controversy lies in the kinds of evidence used to assess duration of high altitude habitation. More other information is needed for a fuller appreciation of duration of residence and also features of population history (genetic drift, gene flow) but existing data are consistent with Tibetans having lived at high altitude longer than the other groups studied. Another issue surrounds usage of the term "adaptation." The definition should be based on evolutionary biology and physiological traits linked to indices of differential fertility and/or mortality. Two examples are developed to illustrate such linkages; intrauterine growth restriction (IUGR) at high altitude and the prevalence of Chronic Mountain Sickness (CMS). Interpopulational as well as intrapopulational variation exists in these conditions which appear linked to characteristics of oxygen transport. Both adversely influence survival and appear to be less severe (IUGR) or less common (CMS) among Tibetans than other groups. Thus available evidence suggest that Tibetans are better adapted. Needed, however, are studies which are better controlled for population ancestry, especially in South America, to determine the extent to which Tibetans differ from Andean highlanders. More precise information is also needed regarding the genetic factors underlying characteristics of oxygen transport. Such studies in Tibetan, Andean and Europeans as well as other high altitude populations offers a promising avenue for clarifying the adaptive value of physiological components of oxygen transport and the extent to which such factors differ among high altitude populations. PMID:11443005

Moore, L G

2001-01-01

32

RFLP markers show genetic recombination in Botryotinia fuckeliana (Botrytis cinerea) and transposable elements reveal two sympatric species.  

PubMed

Molecular markers revealed that Botryotinia fuckeliana (the teleomorph of Botrytis cinerea), a haploid, filamentous, heterothallic ascomycete, contained a large amount of intrapopulation genetic variation. The markers were used to determine the mode of reproduction and the population structure of this fungus. We did not detect any differentiation between isolates from different organs, collection dates, varieties of grape, or locations in the Champagne region of France, but two unexpected sympatric populations were identified. One group of isolates (transposa) contained the transposable elements Boty and Flipper; the other (vacuma) did not. These groups differed from one another for all the other markers. RFLP markers showed that there was genetic recombination in both groups of isolates. We conclude that there are two sympatric populations of B. fuckeliana in Champagne. One species (transposa) seems to be local and well adapted, while the other one (vacuma) is presumably a heterogeneous migrant population. PMID:9364775

Giraud, T; Fortini, D; Levis, C; Leroux, P; Brygoo, Y

1997-11-01

33

High genetic diversity is not essential for successful introduction  

PubMed Central

Some introduced populations thrive and evolve despite the presumed loss of diversity at introduction. We aimed to quantify the amount of genetic diversity retained at introduction in species that have shown evidence of adaptation to their introduced environments. Samples were taken from native and introduced ranges of Arctotheca populifolia and Petrorhagia nanteuilii. Using microsatellite data, we identified the source for each introduction, estimated genetic diversity in native and introduced populations, and calculated the amount of diversity retained in introduced populations. These values were compared to those from a literature review of diversity in native, confamilial populations and to estimates of genetic diversity retained at introduction. Gene diversity in the native range of both species was significantly lower than for confamilials. We found that, on average, introduced populations showing evidence of adaptation to their new environments retained 81% of the genetic diversity from the native range. Introduced populations of P. nanteuilii had higher genetic diversity than found in the native source populations, whereas introduced populations of A. populifolia retained only 14% of its native diversity in one introduction and 1% in another. Our literature review has shown that most introductions demonstrating adaptive ability have lost diversity upon introduction. The two species studied here had exceptionally low native range genetic diversity. Further, the two introductions of A. populifolia represent the largest percentage loss of genetic diversity in a species showing evidence of substantial morphological change in the introduced range. While high genetic diversity may increase the likelihood of invasion success, the species examined here adapted to their new environments with very little neutral genetic diversity. This finding suggests that even introductions founded by small numbers of individuals have the potential to become invasive.

Rollins, Lee A; Moles, Angela T; Lam, Serena; Buitenwerf, Robert; Buswell, Joanna M; Brandenburger, Claire R; Flores-Moreno, Habacuc; Nielsen, Knud B; Couchman, Ellen; Brown, Gordon S; Thomson, Fiona J; Hemmings, Frank; Frankham, Richard; Sherwin, William B

2013-01-01

34

Modes of Gene Duplication Contribute Differently to Genetic Novelty and Redundancy, but Show Parallels across Divergent Angiosperms  

PubMed Central

Background Both single gene and whole genome duplications (WGD) have recurred in angiosperm evolution. However, the evolutionary effects of different modes of gene duplication, especially regarding their contributions to genetic novelty or redundancy, have been inadequately explored. Results In Arabidopsis thaliana and Oryza sativa (rice), species that deeply sample botanical diversity and for which expression data are available from a wide range of tissues and physiological conditions, we have compared expression divergence between genes duplicated by six different mechanisms (WGD, tandem, proximal, DNA based transposed, retrotransposed and dispersed), and between positional orthologs. Both neo-functionalization and genetic redundancy appear to contribute to retention of duplicate genes. Genes resulting from WGD and tandem duplications diverge slowest in both coding sequences and gene expression, and contribute most to genetic redundancy, while other duplication modes contribute more to evolutionary novelty. WGD duplicates may more frequently be retained due to dosage amplification, while inferred transposon mediated gene duplications tend to reduce gene expression levels. The extent of expression divergence between duplicates is discernibly related to duplication modes, different WGD events, amino acid divergence, and putatively neutral divergence (time), but the contribution of each factor is heterogeneous among duplication modes. Gene loss may retard inter-species expression divergence. Members of different gene families may have non-random patterns of origin that are similar in Arabidopsis and rice, suggesting the action of pan-taxon principles of molecular evolution. Conclusion Gene duplication modes differ in contribution to genetic novelty and redundancy, but show some parallels in taxa separated by hundreds of millions of years of evolution.

Wang, Yupeng; Wang, Xiyin; Tang, Haibao; Tan, Xu; Ficklin, Stephen P.; Feltus, F. Alex; Paterson, Andrew H.

2011-01-01

35

Review of genetic parameters estimated at stallion and young horse performance tests and their correlations with later results in dressage and show-jumping competition  

Microsoft Academic Search

Results from performance tests and competitions of young horses are used by major European warmblood horse breeding associations for genetic evaluations. The aim of this review was to compare genetic parameters for various tests of young horses to assess their efficiency in selection for dressage and show-jumping. Improved understanding of genetic information across countries is also necessary, as foreign trade

E. Thorén Hellsten; Å. Viklund; E. P. C. Koenen; A. Ricard; E. Bruns; J. Philipsson

2006-01-01

36

Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are Associated with Obesity-Related Traits  

PubMed Central

The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 ×10?7), hip circumference (p = 3.4 × 10?8), and weight (p = 9.1 × 10?7). In Sardinia, homozygotes for the rare “G” allele of this SNP (minor allele frequency = 0.46) were 1.3 BMI units heavier than homozygotes for the common “A” allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 × 10?6). Homozygotes for the rare “A” allele of this SNP (minor allele frequency = 0.12) were 1.8 BMI units heavier than homozygotes for the common “G” allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare “A” allele were, on average, 1.0–3.0 BMI units heavier than homozygotes for the more common “G” allele. In summary, we have completed a whole genome–association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population.

Chen, Wei-Min; Uda, Manuela; Albai, Giuseppe; Strait, James; Najjar, Samer; Nagaraja, Ramaiah; Orru, Marco; Usala, Gianluca; Dei, Mariano; Lai, Sandra; Maschio, Andrea; Busonero, Fabio; Mulas, Antonella; Ehret, Georg B; Fink, Ashley A; Weder, Alan B; Cooper, Richard S; Galan, Pilar; Chakravarti, Aravinda; Schlessinger, David; Cao, Antonio; Lakatta, Edward; Abecasis, Goncalo R

2007-01-01

37

Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.  

PubMed

The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x10(-7)), hip circumference (p = 3.4 x 10(-8)), and weight (p = 9.1 x 10(-7)). In Sardinia, homozygotes for the rare "G" allele of this SNP (minor allele frequency = 0.46) were 1.3 BMI units heavier than homozygotes for the common "A" allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6)). Homozygotes for the rare "A" allele of this SNP (minor allele frequency = 0.12) were 1.8 BMI units heavier than homozygotes for the common "G" allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p = 0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G" allele. In summary, we have completed a whole genome-association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population. PMID:17658951

Scuteri, Angelo; Sanna, Serena; Chen, Wei-Min; Uda, Manuela; Albai, Giuseppe; Strait, James; Najjar, Samer; Nagaraja, Ramaiah; Orrú, Marco; Usala, Gianluca; Dei, Mariano; Lai, Sandra; Maschio, Andrea; Busonero, Fabio; Mulas, Antonella; Ehret, Georg B; Fink, Ashley A; Weder, Alan B; Cooper, Richard S; Galan, Pilar; Chakravarti, Aravinda; Schlessinger, David; Cao, Antonio; Lakatta, Edward; Abecasis, Gonçalo R

2007-07-01

38

[Genetic susceptibility for acute high altitude disease].  

PubMed

Acute high altitude disease(AHAD), which can be divided into acute mountain disease (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE), is one of the special illnesses occurred at high altitude, commonly encountered by travelers to high altitudes (>2 500 m), which affects people's work capacity and health and could be even a life-threatening disease. Despite extensive investigations over the last century, the pathophysiology of AHAD remains elusive. Nevertheless, numerous researches have confirmed the existence of AHAD susceptibility differences. The aim of this paper was to review the epidemiological evidence for a genetic component to the various forms of AHAD so far, as well as to supply helpful reference to its epidemiological studies. PMID:23448926

Zhou, Wen-Ting; Hu, Yang

2013-02-01

39

Ettlia sp. YC001 showing high growth rate and lipid content under high CO2.  

PubMed

Over 100 green-colored colonies were isolated from environmental samples when cultivating on a BG11 agar medium, and 4 strains showing different morphologies were selected based on light microscopic observation. Among these strains, the microalgal species with the highest growth rate under 10% CO(2) was identified as Ettlia sp. YC001 using an 18S rDNA-based phylogenetic analysis and morphological comparison. The highest cell density of 3.10 g/L (based on dry cell weight) and biomass productivity of 0.19 g/L/d were obtained under 5% CO(2) after 16 days. The lipid content and productivity were also up to 42% of the dry cell weight and 80.0mg/L/d, respectively. The color of the Ettlia sp. YC001 culture changed from green to red after a month due to the accumulation of certain carotenoids. Therefore, it would seem that Ettlia sp. YC001 is appropriate for mitigating CO(2) due to its high biomass productivity, and a suitable candidate for producing biodiesel and high-value products. PMID:23147124

Yoo, Chan; Choi, Gang-Guk; Kim, Sun-Chang; Oh, Hee-Mock

2013-01-01

40

Populations of weedy crop-wild hybrid beets show contrasting variation in mating system and population genetic structure  

PubMed Central

Reproductive traits are key parameters for the evolution of invasiveness in weedy crop–wild hybrids. In Beta vulgaris, cultivated beets hybridize with their wild relatives in the seed production areas, giving rise to crop–wild hybrid weed beets. We investigated the genetic structure, the variation in first-year flowering and the variation in mating system among weed beet populations occurring within sugar beet production fields. No spatial genetic structure was found for first-year populations composed of F1 crop–wild hybrid beets. In contrast, populations composed of backcrossed weed beets emerging from the seed bank showed a strong isolation-by-distance pattern. Whereas gametophytic self-incompatibility prevents selfing in wild beet populations, all studied weed beet populations had a mixed-mating system, plausibly because of the introgression of the crop-derived Sf gene that disrupts self-incompatibility. No significant relationship between outcrossing rate and local weed beet density was found, suggesting no trends for a shift in the mating system because of environmental effects. We further reveal that increased invasiveness of weed beets may stem from positive selection on first-year flowering induction depending on the B gene inherited from the wild. Finally, we discuss the practical and applied consequences of our findings for crop-weed management.

Arnaud, Jean-Francois; Fenart, Stephane; Cordellier, Mathilde; Cuguen, Joel

2010-01-01

41

The age related markers lipofuscin and apoptosis show different genetic architecture by QTL mapping in short-lived Nothobranchius fish  

PubMed Central

Annual fish of the genus Nothobranchius show large variations in lifespan and expression of age-related phenotypes between closely related populations. We studied N. kadleci and its sister species N. furzeri GRZ strain, and found that N.kadleci is longer-lived than the N. furzeri. Lipofuscin and apoptosis measured in the liver increased with age in N. kadleci with different profiles: lipofuscin increased linearly, while apoptosis declined in the oldest animals. More lipofuscin (P < 0.001) and apoptosis (P < 0.001) was observed in N. furzeri than in N. kadleci at 16w age. Lipofuscin and apoptotic cells were then quantified in hybrids from the mating of N. furzeri to N. kadleci. F1 individuals showed heterosis for lipofuscin but additive effects for apoptosis. These two age-related phenotypes were not correlated in F2 hybrids. Quantitative trait loci analysis of 287 F2 fish using 237 markers identified two QTL accounting for 10% of lipofuscin variance (P < 0.001) with overdominance effect. Apoptotic cells revealed three significant- and two suggestive QTL explaining 19% of variance (P < 0.001), showing additive and dominance effects, and two interacting loci. Our results show that lipofuscin and apoptosis are markers of different age-dependent biological processes controlled by different genetic mechanisms.

Ng'oma, Enoch; Reichwald, Kathrin; Dorn, Alexander; Wittig, Michael; Balschun, Tobias; Franke, Andre; Platzer, Matthias; Cellerino, Allesandro

2014-01-01

42

HIV-1 dual/mixed tropic isolates show different genetic and phenotypic characteristics and response to maraviroc in vitro.  

PubMed

Dual/mixed-tropic HIV-1 strains are predominant in a significative proportion of patients, though few information is available regarding the genetic characteristics, quasispecies composition, and susceptibility against CCR5-antagonists of the primary-isolates. For this reason, we investigated in deep details, both phenotypically and genotypically, the characteristics of 54 HIV-1 primary-isolates obtained from HIV-infected patients. Tropism was assessed by multiple-cycles phenotypic-assay on U87MG-CD4(+)-CCR5(+)-/CXCR4(+)-expressing cells. In vitro selection in PBMCs of X4-tropic viral strains following maraviroc-treatment was also performed. Phenotypic-assay reported pure R5-tropic viruses in 31 (57.4%) isolates, dual/mixed-tropic viruses in 22 (40.7%), and pure X4-tropic virus in only 1 (1.8%). Among dual/mixed-tropic isolates, 12 showed a remarkably higher replication-efficacy in CCR5-expressing cells (R5(+)/X4), and 2 in CXCR4-expressing cells (R5/X4(+)). Genotypic-tropism testing showed a correlation between PSSM-scores, geno2pheno false-positive-rate, and V3-net-charge with both CCR5-usage and syncytium-inducing ability. Moreover, specific gp120- and gp41-mutations were significantly associated with tropism and/or syncytium-inducing ability. Ultra-deep V3-pyrosequencing showed the presence of a swarm of genetically distinct species with a preference for CCR5-coreceptor not only in all pure R5-isolates, but also in 6/7 R5(+)/X4-tropic isolates. In both pure-X4 and R5/X4(+)-isolates, we observed extensive prevalence of X4-using species. In vitro selection-experiments with CCR5-inhibitor maraviroc (up to 2 months) showed no-emergence of X4-tropic variants for all R5- and R5(+)/X4-isolates tested (while X4-virus remained fully-resistant). In conclusion, our study shows that dual/mixed-tropic viruses are constituted by different species, whereby those with characteristics R5(+)/X4 are genotypically and phenotypically similar to the pure-R5 isolates; thus the use of CCR5-antagonists in patients with R5(+)/X4-tropic viruses may be a therapeutic-option that deserves further investigations. PMID:21349294

Svicher, Valentina; Balestra, Emanuela; Cento, Valeria; Sarmati, Loredana; Dori, Luca; Vandenbroucke, Ina; D'Arrigo, Roberta; Buonomini, Anna Rita; Van Marck, Herwig; Surdo, Matteo; Saccomandi, Patrizia; Mostmans, Wendy; Aerssens, Jeroen; Aquaro, Stefano; Stuyver, Lieven J; Andreoni, Massimo; Ceccherini-Silberstein, Francesca; Perno, Carlo Federico

2011-04-01

43

Mouse BMD Quantitative Trait Loci Show Improved Concordance With Human Genome-wide Association Loci When Recalculated on a New, Common Mouse Genetic Map  

PubMed Central

Bone mineral density (BMD) is a heritable trait, and in mice, over 100 quantitative trait loci (QTLs) have been reported, but candidate genes have been identified for only a small percentage. Persistent errors in the mouse genetic map have negatively affected QTL localization, spurring the development of a new, corrected map. In this study, QTLs for BMD were remapped in 11 archival mouse data sets using this new genetic map. Since these QTLs all were mapped in a comparable way, direct comparisons of QTLs for concordance would be valid. We then compared human genome-wide association study (GWAS) BMD loci with the mouse QTLs. We found that 26 of the 28 human GWAS loci examined were located within the confidence interval of a mouse QTL. Furthermore, 14 of the GWAS loci mapped to within 3 cM of a mouse QTL peak. Lastly, we demonstrated that these newly remapped mouse QTLs can substantiate a candidate gene for a human GWAS locus, for which the peak single-nucleotide polymorphism (SNP) fell in an intergenic region. Specifically, we suggest that MEF2C (human chromosome 5, mouse chromosome 13) should be considered a candidate gene for the genetic regulation of BMD. In conclusion, use of the new mouse genetic map has improved the localization of mouse BMD QTLs, and these remapped QTLs show high concordance with human GWAS loci. We believe that this is an opportune time for a renewed effort by the genetics community to identify the causal variants regulating BMD using a synergistic mouse-human approach. © 2010 American Society for Bone and Mineral Research.

Ackert-Bicknell, Cheryl L; Karasik, David; Li, Qian; Smith, Randy V; Hsu, Yi-Hsiang; Churchill, Gary A; Paigen, Beverly J; Tsaih, Shirng-Wern

2010-01-01

44

Mouse BMD quantitative trait loci show improved concordance with human genome-wide association loci when recalculated on a new, common mouse genetic map.  

PubMed

Bone mineral density (BMD) is a heritable trait, and in mice, over 100 quantitative trait loci (QTLs) have been reported, but candidate genes have been identified for only a small percentage. Persistent errors in the mouse genetic map have negatively affected QTL localization, spurring the development of a new, corrected map. In this study, QTLs for BMD were remapped in 11 archival mouse data sets using this new genetic map. Since these QTLs all were mapped in a comparable way, direct comparisons of QTLs for concordance would be valid. We then compared human genome-wide association study (GWAS) BMD loci with the mouse QTLs. We found that 26 of the 28 human GWAS loci examined were located within the confidence interval of a mouse QTL. Furthermore, 14 of the GWAS loci mapped to within 3 cM of a mouse QTL peak. Lastly, we demonstrated that these newly remapped mouse QTLs can substantiate a candidate gene for a human GWAS locus, for which the peak single-nucleotide polymorphism (SNP) fell in an intergenic region. Specifically, we suggest that MEF2C (human chromosome 5, mouse chromosome 13) should be considered a candidate gene for the genetic regulation of BMD. In conclusion, use of the new mouse genetic map has improved the localization of mouse BMD QTLs, and these remapped QTLs show high concordance with human GWAS loci. We believe that this is an opportune time for a renewed effort by the genetics community to identify the causal variants regulating BMD using a synergistic mouse-human approach. PMID:20200990

Ackert-Bicknell, Cheryl L; Karasik, David; Li, Qian; Smith, Randy V; Hsu, Yi-Hsiang; Churchill, Gary A; Paigen, Beverly J; Tsaih, Shirng-Wern

2010-08-01

45

Development of new genomic microsatellite markers from robusta coffee (Coffea canephora Pierre ex A. Froehner) showing broad cross-species transferability and utility in genetic studies  

PubMed Central

Background Species-specific microsatellite markers are desirable for genetic studies and to harness the potential of MAS-based breeding for genetic improvement. Limited availability of such markers for coffee, one of the most important beverage tree crops, warrants newer efforts to develop additional microsatellite markers that can be effectively deployed in genetic analysis and coffee improvement programs. The present study aimed to develop new coffee-specific SSR markers and validate their utility in analysis of genetic diversity, individualization, linkage mapping, and transferability for use in other related taxa. Results A small-insert partial genomic library of Coffea canephora, was probed for various SSR motifs following conventional approach of Southern hybridisation. Characterization of repeat positive clones revealed a very high abundance of DNRs (1/15 Kb) over TNRs (1/406 kb). The relative frequencies of different DNRs were found as AT >> AG > AC, whereas among TNRs, AGC was the most abundant repeat. The SSR positive sequences were used to design 58 primer pairs of which 44 pairs could be validated as single locus markers using a panel of arabica and robusta genotypes. The analysis revealed an average of 3.3 and 3.78 alleles and 0.49 and 0.62 PIC per marker for the tested arabicas and robustas, respectively. It also revealed a high cumulative PI over all the markers using both sib-based (10-6 and 10-12 for arabicas and robustas respectively) and unbiased corrected estimates (10-20 and 10-43 for arabicas and robustas respectively). The markers were tested for Hardy-Weinberg equilibrium, linkage dis-equilibrium, and were successfully used to ascertain generic diversity/affinities in the tested germplasm (cultivated as well as species). Nine markers could be mapped on robusta linkage map. Importantly, the markers showed ~92% transferability across related species/genera of coffee. Conclusion The conventional approach of genomic library was successfully employed although with low efficiency to develop a set of 44 new genomic microsatellite markers of coffee. The characterization/validation of new markers demonstrated them to be highly informative, and useful for genetic studies namely, genetic diversity in coffee germplasm, individualization/bar-coding for germplasm protection, linkage mapping, taxonomic studies, and use as conserved orthologous sets across secondary genepool of coffee. Further, the relative frequency and distribution of different SSR motifs in coffee genome indicated coffee genome to be relatively poor in microsatellites compared to other plant species.

Hendre, Prasad Suresh; Phanindranath, Regur; Annapurna, V; Lalremruata, Albert; Aggarwal, Ramesh K

2008-01-01

46

High-throughput olfactory conditioning and memory retention test show variation in Nasonia parasitic wasps  

PubMed Central

Most of our knowledge on learning and memory formation results from extensive studies on a small number of animal species. Although features and cellular pathways of learning and memory are highly similar in this diverse group of species, there are also subtle differences. Closely related species of parasitic wasps display substantial variation in memory dynamics and can be instrumental to understanding both the adaptive benefit of and mechanisms underlying this variation. Parasitic wasps of the genus Nasonia offer excellent opportunities for multidisciplinary research on this topic. Genetic and genomic resources available for Nasonia are unrivaled among parasitic wasps, providing tools for genetic dissection of mechanisms that cause differences in learning. This study presents a robust, high-throughput method for olfactory conditioning of Nasonia using a host encounter as reward. A T-maze olfactometer facilitates high-throughput memory retention testing and employs standardized odors of equal detectability, as quantified by electroantennogram recordings. Using this setup, differences in memory retention between Nasonia species were shown. In both Nasonia vitripennis and Nasonia longicornis, memory was observed up to at least 5 days after a single conditioning trial, whereas Nasonia giraulti lost its memory after 2 days. This difference in learning may be an adaptation to species-specific differences in ecological factors, for example, host preference. The high-throughput methods for conditioning and memory retention testing are essential tools to study both ultimate and proximate factors that cause variation in learning and memory formation in Nasonia and other parasitic wasp species.

Hoedjes, K M; Steidle, J L M; Werren, J H; Vet, L E M; Smid, H M

2012-01-01

47

Landscape genetics of high mountain frog metapopulations  

USGS Publications Warehouse

Explaining functional connectivity among occupied habitats is crucial for understanding metapopulation dynamics and species ecology. Landscape genetics has primarily focused on elucidating how ecological features between observations influence gene flow. Functional connectivity, however, may be the result of both these between-site (landscape resistance) landscape characteristics and at-site (patch quality) landscape processes that can be captured using network based models. We test hypotheses of functional connectivity that include both between-site and at-site landscape processes in metapopulations of Columbia spotted frogs (Rana luteiventris) by employing a novel justification of gravity models for landscape genetics (eight microsatellite loci, 37 sites, n = 441). Primarily used in transportation and economic geography, gravity models are a unique approach as flow (e.g. gene flow) is explained as a function of three basic components: distance between sites, production/attraction (e.g. at-site landscape process) and resistance (e.g. between-site landscape process). The study system contains a network of nutrient poor high mountain lakes where we hypothesized a short growing season and complex topography between sites limit R. luteiventris gene flow. In addition, we hypothesized production of offspring is limited by breeding site characteristics such as the introduction of predatory fish and inherent site productivity. We found that R. luteiventris connectivity was negatively correlated with distance between sites, presence of predatory fish (at-site) and topographic complexity (between-site). Conversely, site productivity (as measured by heat load index, at-site) and growing season (as measured by frost-free period between-sites) were positively correlated with gene flow. The negative effect of predation and positive effect of site productivity, in concert with bottleneck tests, support the presence of source-sink dynamics. In conclusion, gravity models provide a powerful new modelling approach for examining a wide range of both basic and applied questions in landscape genetics.

Murphy, M. A.; Dezzani, R.; Pilliod, D. S.; Storfer, A.

2010-01-01

48

Landscape genetics of high mountain frog metapopulations.  

PubMed

Explaining functional connectivity among occupied habitats is crucial for understanding metapopulation dynamics and species ecology. Landscape genetics has primarily focused on elucidating how ecological features between observations influence gene flow. Functional connectivity, however, may be the result of both these between-site (landscape resistance) landscape characteristics and at-site (patch quality) landscape processes that can be captured using network based models. We test hypotheses of functional connectivity that include both between-site and at-site landscape processes in metapopulations of Columbia spotted frogs (Rana luteiventris) by employing a novel justification of gravity models for landscape genetics (eight microsatellite loci, 37 sites, n = 441). Primarily used in transportation and economic geography, gravity models are a unique approach as flow (e.g. gene flow) is explained as a function of three basic components: distance between sites, production/attraction (e.g. at-site landscape process) and resistance (e.g. between-site landscape process). The study system contains a network of nutrient poor high mountain lakes where we hypothesized a short growing season and complex topography between sites limit R. luteiventris gene flow. In addition, we hypothesized production of offspring is limited by breeding site characteristics such as the introduction of predatory fish and inherent site productivity. We found that R. luteiventris connectivity was negatively correlated with distance between sites, presence of predatory fish (at-site) and topographic complexity (between-site). Conversely, site productivity (as measured by heat load index, at-site) and growing season (as measured by frost-free period between-sites) were positively correlated with gene flow. The negative effect of predation and positive effect of site productivity, in concert with bottleneck tests, support the presence of source-sink dynamics. In conclusion, gravity models provide a powerful new modelling approach for examining a wide range of both basic and applied questions in landscape genetics. PMID:20723055

Murphy, Melanie A; Dezzani, R; Pilliod, D S; Storfer, A

2010-09-01

49

Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations  

PubMed Central

Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage?/CD34+/CD38?/CD90+) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% ± 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations.

Will, Britta; Zhou, Li; Vogler, Thomas O.; Ben-Neriah, Susanna; Schinke, Carolina; Tamari, Roni; Yu, Yiting; Bhagat, Tushar D.; Bhattacharyya, Sanchari; Barreyro, Laura; Heuck, Christoph; Mo, Yonkai; Parekh, Samir; McMahon, Christine; Pellagatti, Andrea; Boultwood, Jacqueline; Montagna, Cristina; Silverman, Lewis; Maciejewski, Jaroslaw; Greally, John M.; Ye, B. Hilda; List, Alan F.; Steidl, Christian

2012-01-01

50

Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations.  

PubMed

Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage(-)/CD34(+)/CD38(-)/CD90(+)) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% ± 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations. PMID:22753872

Will, Britta; Zhou, Li; Vogler, Thomas O; Ben-Neriah, Susanna; Schinke, Carolina; Tamari, Roni; Yu, Yiting; Bhagat, Tushar D; Bhattacharyya, Sanchari; Barreyro, Laura; Heuck, Christoph; Mo, Yonkai; Parekh, Samir; McMahon, Christine; Pellagatti, Andrea; Boultwood, Jacqueline; Montagna, Cristina; Silverman, Lewis; Maciejewski, Jaroslaw; Greally, John M; Ye, B Hilda; List, Alan F; Steidl, Christian; Steidl, Ulrich; Verma, Amit

2012-09-01

51

Pituitary adenoma showing intermittent secretion of high molecular weight adrenocorticotropin without evidence of Cushing's disease.  

PubMed

A 29-year-old woman was admitted in March 1998 due to high plasma ACTH levels, amenorrhea and uncontrolled diabetes mellitus (DM) which had persisted since 1991. Plasma ACTH levels showed a wide range of changes: they were usually high (59-240 pg/ml), intermittently very high (336-942 pg/ml), and sometimes normal or low. Plasma cortisol levels were usually normal but were sometimes high when the ACTH levels were very high. However, even when the plasma ACTH levels were very high, she did not show any cushingoid features. DM was diagnosed as non-insulin-dependent DM. Plasma ACTH showed an excessive response to CRH, while cortisol showed a delayed response. Plasma cortisol showed a poor response to ACTH-(1-24). ACTH receptor gene analysis revealed no mutations in the ACTH receptor-coding region. MRI showed a nonenhancing mass on the left side of the pituitary. Cavernous sinus sampling showed a very high plasma ACTH level in the left cavernous sinus compared with the levels in the right cavernous sinus and peripheral blood. Sephadex G-75 gel filtration of plasma ACTH immunoreactivity in plasma obtained by cavernous sinus sampling showed mainly high molecular forms of ACTH, probably proopiomelanocortin and ACTH-beta-lipotropin. This case is a very rare form of pituitary adenoma showing intermittent secretion of high molecular ACTH unaccompanied by cushingoid features. PMID:10640899

Hashimoto, K; Kaneda, T; Nagano, I; Asaba, K; Takeda, K; Takao, T

1999-01-01

52

Nondisease genetic testing: reporting of muscle SNPs shows effects on self-concept and health orientation scales  

Microsoft Academic Search

The purpose of this study was to assess the impact of genetic self-knowledge (nondisease genotype information) on individual self-concept and Health Orientation Scale (HOS). Adult volunteers (n=257) were recruited from an ongoing genetic association study identifying muscle quantitative trait loci (QTLs). Participants completed psychosocial assessments before and after 12 weeks of resistance training of the nondominant arm. At study exit,

Erynn S Gordon; Heather A Gordish-Dressman; Joseph Devaney; Priscilla Clarkson; Paul Thompson; Paul Gordon; Linda S Pescatello; Monica J Hubal; Emidio E Pistilli; Gary Gianetti; Bethany Kelsey; Eric P Hoffman

2005-01-01

53

Glycomic analysis of high density lipoprotein shows a highly sialylated particle.  

PubMed

Many of the functional proteins and lipids in high density lipoprotein (HDL) particles are potentially glycosylated, yet very little is known about the glycoconjugates of HDL. In this study, HDL was isolated from plasma by sequential micro-ultracentrifugation, followed by glycoprotein and glycolipid analysis. N-Glycans, glycopeptides, and gangliosides were extracted and purified followed by analysis with nano-HPLC Chip quadrupole time of flight mass spectrometry and MS/MS. HDL particles were found to be highly sialylated. Most of the N-glycans (?90%) from HDL glycoproteins were sialylated with one or two neuraminic acids (Neu5Ac). The most abundant N-glycan was a biantennary complex type glycan with two sialic acids (Hexose5HexNAc4Neu5Ac2) and was found in multiple glycoproteins using site-specific glycosylation analysis. The observed O-glycans were all sialylated, and most contained a core 1 structure with two Neu5Acs, including those that were associated with apolipoprotein CIII (ApoC-III) and fetuin A. GM3 (monosialoganglioside, NeuAc2-3Gal1-4Glc-Cer) and GD3 (disialoganglioside, NeuAc2-8NeuAc2-3Gal1-4Glc-Cer) were the major gangliosides in HDL. A 60% GM3 and 40% GD3 distribution was observed. Both GM3 and GD3 were composed of heterogeneous ceramide lipid tails, including d18:1/16:0 and d18:1/23:0. This report describes for the first time a glycomic approach for analyzing HDL, highlighting that HDL are highly sialylated particles. PMID:24417605

Huang, Jincui; Lee, Hyeyoung; Zivkovic, Angela M; Smilowitz, Jennifer T; Rivera, Nancy; German, J Bruce; Lebrilla, Carlito B

2014-02-01

54

Outlier SNPs show more genetic structure between two Bay of Fundy metapopulations of Atlantic salmon than do neutral SNPs.  

PubMed

Atlantic salmon of Eastern Canada were once of considerable importance to aboriginal, recreational, and commercial fisheries, yet many populations are now in decline, particularly those of the inner Bay of Fundy (iBoF), which were recently listed as endangered. We investigated whether nonneutral SNPs could be used to assign individual Atlantic salmon accurately to either the iBoF or the outer Bay of Fundy (oBoF) metapopulations because this has been difficult with existing neutral markers. We first searched for markers under diversifying selection by genotyping eight captively bred Bay of Fundy (BoF) populations for 320 SNP loci with the Sequenom MassARRAY™ system and then analysed the data set with four different F(ST) outlier detection programs. Three outlier loci were identified by both BayesFST and BayeScan whereas seven outlier loci, including the three previously mentioned, were identified by both Fdist and Arlequin. A subset of 14 nonneutral SNPs was more accurate (85% accuracy) than a subset of 67 neutral SNPs (75% accuracy) at assigning individual salmon back to their metapopulation. We then chose a subset of nine outlier SNP markers and used them to inexpensively genotype archived DNA samples from seven wild BoF populations using Invader™ chemistry. Hierarchical AMOVA of these independent wild samples corroborated our previous findings of significant genetic differentiation between iBoF and oBoF salmon metapopulations. Our research shows that identifying and using outlier loci is an important step towards achieving the goal of consistently and accurately distinguishing iBoF from oBoF Atlantic salmon, which will aid in their conservation. PMID:21429179

Freamo, Heather; O'Reilly, Patrick; Berg, Paul R; Lien, Sigbjørn; Boulding, Elizabeth G

2011-03-01

55

Student Problem Solving in High School Genetics.  

ERIC Educational Resources Information Center

Describes set of specific steps (procedural knowledge) used when solving monohybrid/dihybrid cross problems and extent to which students could justify execution of each step in terms of their conceptual knowledge of genetics and meiosis. Implications for genetics instruction are discussed. (JN)

Stewart, James

1983-01-01

56

Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are Associated with Obesity-Related Traits  

Microsoft Academic Search

The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify

Angelo Scuteri; Serena Sanna; Wei-Min Chen; Manuela Uda; Giuseppe Albai; James Strait; Samer Najjar; Ramaiah Nagaraja; Marco Orrú; Gianluca Usala; Mariano Dei; Sandra Lai; Andrea Maschio; Fabio Busonero; Antonella Mulas; Georg B Ehret; Ashley A Fink; Alan B Weder; Richard S Cooper; Pilar Galan; Aravinda Chakravarti; David Schlessinger; Antonio Cao; Edward Lakatta; Gonçalo R Abecasis

2007-01-01

57

RFLP Markers Show Genetic Recombination in Botryotinia fuckeliana (Botrytis cinerea) and Transposable Elements Reveal Two Sympatric Species  

Microsoft Academic Search

Molecular markers revealed that Botryotinia jiickeliana (the teleomorph of Botrytis cinerea), a haploid, filamentous, heterothallic ascomycete, contained a large amount of intrapopulation genetic variation. The markers were used to determine the mode of reproduction and the population structure of this fungus. We did not detect any differentiation between isolates from different organs, collection dates, varieties of grape, or locations in

Tatiana Giraud; Dominique Fortini; Caroline Levis; Pierre Leroux; Yves Brygoo

58

Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans  

Microsoft Academic Search

BACKGROUND: Candidate gene studies on the basis of biological hypotheses have been a practical approach to identify relevant genetic variation in complex traits. Based on previous reports and the roles in pain pathways, we have examined the effects of variations of loci in the genes of monoamine neurotransmitter systems including metabolizing enzymes, receptors and transporters on acute clinical pain responses

Hyungsuk Kim; Hyewon Lee; Janet Rowan; Jaime Brahim; Raymond A Dionne

2006-01-01

59

Georgian and kurd mtDNA sequence analysis shows a lack of correlation between languages and female genetic lineages.  

PubMed

Mitochondrial DNA sequences from Georgians and Kurds were analyzed in order to test the possible correlation between female lineages and languages in these two neighboring West Eurasian groups. Mitochondrial sequence pools in both populations are very similar despite their different linguistic and prehistoric backgrounds. Both populations present mtDNA lineages that clearly belong to the European gene pool, as shown by 1) similar nucleotide and sequence diversities; 2) a large number of sequences shared with the rest of European samples; 3) nonsignificant genetic distances; and 4) classification of the present lineages into the major European mtDNA haplogroups already described. The outlier position of the populations from the Caucasus according to classical genetic markers is not recognized in the present Georgian mtDNA sequence pool. This result suggests that the differentiation of mtDNA sequences in West Eurasia and the outlier features of Caucasian populations should be attributed to different processes. Moreover, the putative linguistic relationship between Caucasian groups and the Basques, another outlier population within Europe for classical genetic markers, is not detected by the analysis of mtDNA sequences. PMID:10766939

Comas, D; Calafell, F; Bendukidze, N; Fañanás, L; Bertranpetit, J

2000-05-01

60

A Twin Study of ADHD Symptoms in Early Adolescence: Hyperactivity-Impulsivity and Inattentiveness Show Substantial Genetic Overlap but Also Genetic Specificity  

ERIC Educational Resources Information Center

A previous paper in this journal revealed substantial genetic overlap between the ADHD dimensions of hyperactivity-impulsivity and inattentiveness in a sample of 8-year old twins drawn from a UK-representative population sample. Four years later, when the twins were 12 years old, more than 5,500 pairs drawn from the same sample were rated again on…

Greven, Corina U.; Rijsdijk, Fruhling V.; Plomin, Robert

2011-01-01

61

Lung cancer with loss of BRG1/BRM, shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features.  

PubMed

BRG1 and BRM, two core catalytic subunits in SWI/SNF chromatin remodeling complexes, have been suggested as tumor suppressors, yet their roles in carcinogenesis are unclear. Here, we present evidence that loss of BRG1 and BRM is involved in the progression of lung adenocarcinomas. Analysis of 15 lung cancer cell lines indicated that BRG1 mutations correlated with loss of BRG1 expression and that loss of BRG1 and BRM expression was frequent in E-cadherin-low and vimentin-high cell lines. Immunohistochemical analysis of 93 primary lung adenocarcinomas showed loss of BRG1 and BRM in 11 (12%) and 16 (17%) cases, respectively. Loss of expression of BRG1 and BRM was frequent in solid predominant adenocarcinomas and tumors with low thyroid transcription factor-1 (TTF-1, master regulator of lung) and low cytokeratin7 and E-cadherin (two markers for bronchial epithelial differentiation). Loss of BRG1 was correlated with the absence of lepidic growth patterns and was mutually exclusive of epidermal growth factor receptor (EGFR) mutations. In contrast, loss of BRM was found concomitant with lepidic growth patterns and EGFR mutations. Finally, we analyzed the publicly available dataset of 442 cases and found that loss of BRG1 and BRM was frequent in E-cadherin-low, TTF-1-low, and vimentin-high cases and correlated with poor prognosis. We conclude that loss of either or both BRG1 and BRM is involved in the progression of lung adenocarcinoma into solid predominant tumors with features of epithelial mesenchymal transition and loss of the bronchial epithelial phenotype. BRG1 loss was specifically involved in the progression of EGFR wild-type, but not EGFR-mutant tumors. PMID:23163725

Matsubara, Daisuke; Kishaba, Yuka; Ishikawa, Shumpei; Sakatani, Takashi; Oguni, Sachiko; Tamura, Tomoko; Hoshino, Hiroko; Sugiyama, Yukihiko; Endo, Shunsuke; Murakami, Yoshinori; Aburatani, Hiroyuki; Fukayama, Masashi; Niki, Toshiro

2013-02-01

62

Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake1234  

PubMed Central

Background: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake. Design: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 × 10?6 were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data. Results: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (? ± SE: 0.25 ± 0.04%; P = 1.68 × 10?8) and lower fat (? ± SE: ?0.21 ± 0.04%; P = 1.57 × 10?9) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)–increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (? ± SE: 0.10 ± 0.02%; P = 9.96 × 10?10), independent of BMI (after adjustment for BMI, ? ± SE: 0.08 ± 0.02%; P = 3.15 × 10?7). Conclusion: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

Tanaka, Toshiko; Ngwa, Julius S; van Rooij, Frank JA; Zillikens, M Carola; Wojczynski, Mary K; Frazier-Wood, Alexis C; Houston, Denise K; Kanoni, Stavroula; Lemaitre, Rozenn N; Luan, Jian'an; Mikkila, Vera; Renstrom, Frida; Sonestedt, Emily; Zhao, Jing Hua; Chu, Audrey Y; Qi, Lu; Chasman, Daniel I; de Oliveira Otto, Marcia C; Dhurandhar, Emily J; Feitosa, Mary F; Johansson, Ingegerd; Khaw, Kay-Tee; Lohman, Kurt K; Manichaikul, Ani; McKeown, Nicola M; Mozaffarian, Dariush; Singleton, Andrew; Stirrups, Kathleen; Viikari, Jorma; Ye, Zheng; Bandinelli, Stefania; Barroso, Ines; Deloukas, Panos; Forouhi, Nita G; Hofman, Albert; Liu, Yongmei; Lyytikainen, Leo-Pekka; North, Kari E; Dimitriou, Maria; Hallmans, Goran; Kahonen, Mika; Langenberg, Claudia; Ordovas, Jose M; Uitterlinden, Andre G; Hu, Frank B; Kalafati, Ioanna-Panagiota; Raitakari, Olli; Franco, Oscar H; Johnson, Andrew; Emilsson, Valur; Schrack, Jennifer A; Semba, Richard D; Siscovick, David S; Arnett, Donna K; Borecki, Ingrid B; Franks, Paul W; Kritchevsky, Stephen B; Lehtimaki, Terho; Loos, Ruth JF; Orho-Melander, Marju; Rotter, Jerome I; Wareham, Nicholas J; Witteman, Jacqueline CM; Ferrucci, Luigi; Dedoussis, George; Cupples, L Adrienne; Nettleton, Jennifer A

2013-01-01

63

Synchronization of cultured retinoblastoma cells for high-resolution chromosomes showing up to 1000 bands.  

PubMed

A method that allows high-resolution cytogenetic analysis of retinoblastoma cells in primary culture and subpassages is described. This method is based on the addition of high concentrations of bromodeoxyuridine or thymidine to obtain chromosomes subsequently banded to show 600-1000 bands. The results are compared with the standard harvest after 24 hours or long-term culture, and with low-temperature synchronization after long-term culture. After blocking with bromodeoxyuridine or thymidine, the chromosomes are significantly longer than after cold synchronization or after the unsynchronized techniques. When they are GTG, RHG, or GBG banded, more than 40% of the mitoses are in the earlier phases with chromosomes showing more than 600 bands per haploid set. This method significantly improves the general quality of retinoblastoma tumor cell chromosomes and increases diagnostic and prognostic accuracy. PMID:2758401

Lemieux, N; Richer, C L

1989-07-01

64

Genetic Variants of Coagulation Factor XI Show Association with Ischemic Stroke Up to 70 Years of Age  

PubMed Central

Background and Purpose Coagulation factor XI (FXI) has an important role in the propagation and stabilization of a thrombus upon vessel injury. High FXI levels have been implicated in thrombotic diseases including ischemic stroke. The aim of our study was to investigate whether FXI gene (F11) variants are associated with ischemic stroke. Methods The discovery sample, the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668 controls, all aged 18-70 years. Replication was performed in the Lund Stroke Register (LSR) and Malmö Diet and Cancer study (MDC), together including 1213 patients and 788 controls up to 70 years of age, and in total 3145 patients and 1793 controls (18-102 years). Seven F11 single-nucleotide polymorphisms (SNPs) were selected using a tagging approach. Results The SNPs rs3733403, rs925451, and rs1593 showed independent associations with overall ischemic stroke in SAHLSIS, ORs of 0.74 (95% CI 0.59-0.94), 1.24 (95% CI 1.06-1.46), and 0.70 (95% CI 0.55-0.90), respectively. The association for rs925451 was replicated in the LSR and MDC sample in a pre-specified analysis of subjects aged 70 years or younger, OR of 1.16 (95% CI 1.00-1.34), whereas no SNP was replicated when all ages were included. In line with this, one F11 haplotype was associated with overall ischemic stroke in the discovery sample and in the replication sample ?70 years. Conclusions We found significant associations between F11 variation and overall ischemic stroke up to 70 years of age. These findings motivate further studies on the role of F11 in ischemic stroke, especially in younger individuals.

Hanson, Ellen; Nilsson, Staffan; Jood, Katarina; Norrving, Bo; Engstrom, Gunnar; Blomstrand, Christian; Lindgren, Arne; Melander, Olle; Jern, Christina

2013-01-01

65

High volume molecular genetic identification of single nucleotide polymorphisms using Genetic Bit Analysis Application to human genetic diagnosis  

SciTech Connect

The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.

Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T. [Molecular Tool, Inc., Baltimore, MD (United States)] [and others

1994-09-01

66

Northern Slavs from Serbia do not show a founder effect at autosomal and Y-chromosomal STRs and retain their paternal genetic heritage.  

PubMed

Studies on Y-chromosomal markers revealed significant genetic differentiation between Southern and Northern (Western and Eastern) Slavic populations. The northern Serbian region of Vojvodina is inhabited by Southern Slavic Serbian majority and, inter alia, Western Slavic (Slovak) and Eastern Slavic (Ruthenian) minorities. In the study, 15 autosomal STR markers were analysed in unrelated Slovaks, Ruthenians and Serbs from northern Serbia and western Slovakia. Additionally, Slovak males from Serbia were genotyped for 17 Y-chromosomal STR loci. The results were compared to data available for other Slavic populations. Genetic distances for autosomal markers revealed homogeneity between Serbs from northern Serbia and Slovaks from western Slovakia and distinctiveness of Serbian Slovaks and Ruthenians. Y-STR variation showed a clear genetic departure of the Slovaks and Ruthenians inhabiting Vojvodina from their Serbian neighbours and genetic similarity to the Northern Slavic populations of Slovakia and Ukraine. Admixture estimates revealed negligible Serbian paternal ancestry in both Northern Slavic minorities of Vojvodina, providing evidence for their genetic isolation from the Serbian majority population. No reduction of genetic diversity at autosomal and Y-chromosomal markers was found, excluding genetic drift as a reason for differences observed at autosomal STRs. Analysis of molecular variance detected significant population stratification of autosomal and Y-chromosomal microsatellites in the three Slavic populations of northern Serbia, indicating necessity for separate databases used for estimations of frequencies of autosomal and Y-chromosomal STR profiles in forensic casework. Our results demonstrate that regarding Y-STR haplotypes, Serbian Slovaks and Ruthenians fit in the Eastern European metapopulation defined in the Y chromosome haplotype reference database. PMID:24315599

R?ba?a, Krzysztof; Veselinovi?, Igor; Siváková, Daniela; Patskun, Erika; Kravchenko, Sergey; Szczerkowska, Zofia

2014-01-01

67

Pinus pinaster seedlings and their fungal symbionts show high plasticity in phosphorus acquisition in acidic soils.  

PubMed

Young seedlings of maritime pine (Pinus pinaster Soland in Aït.) were grown in rhizoboxes using intact spodosol soil samples from the southwest of France, in Landes of Gascogne, presenting a large variation of phosphorus (P) availability. Soils were collected from a 93-year-old unfertilized stand and a 13-year-old P. pinaster stand with regular annual fertilization of either only P or P and nitrogen (N). After 6 months of culture in controlled conditions, different morphotypes of ectomycorrhiza (ECM) were used for the measurements of acid phosphatase activity and molecular identification of fungal species using amplification of the ITS region. Total biomass, N and P contents were measured in roots and shoots of plants. Bicarbonate- and NaOH-available inorganic P (Pi), organic P (Po) and ergosterol concentrations were measured in bulk and rhizosphere soil. The results showed that bulk soil from the 93-year-old forest stand presented the highest Po levels, but relatively higher bicarbonate-extractable Pi levels compared to 13-year-old unfertilized stand. Fertilizers significantly increased the concentrations of inorganic P fractions in bulk soil. Ergosterol contents in rhizosphere soil were increased by fertilizer application. The dominant fungal species was Rhizopogon luteolus forming 66.6% of analysed ECM tips. Acid phosphatase activity was highly variable and varied inversely with bicarbonate-extractable Pi levels in the rhizosphere soil. Total P or total N in plants was linearly correlated with total plant biomass, but the slope was steep only between total P and biomass in fertilized soil samples. In spite of high phosphatase activity in ECM tips, P availability remained a limiting nutrient in soil samples from unfertilized stands. Nevertheless young P. pinaster seedlings showed a high plasticity for biomass production at low P availability in soils. PMID:19840995

Ali, M A; Louche, J; Legname, E; Duchemin, M; Plassard, C

2009-12-01

68

A new two-phase dimeticone pediculicide shows high efficacy in a comparative bioassay  

PubMed Central

Background Dimeticones kill head lice by physical means. Here we assessed in a comparative bioassay the ex vivo efficacy of "NYDA® sensitiv", a new two-phase dimeticone-based pediculicide similar to a product established on the market, but without fragrances. Methods We compared efficacy of the new product to a positive dimeticone control group, a sample of four other insecticidal and natural head lice products marketed in Germany, and an untreated control. In a bioassay, lice were exposed ex vivo to products and examined for activity for up to 24 hours, following a standard protocol. Results After 6 and 24 hours, 13.7 and 88.5% of untreated control lice did not show major vital signs. In contrast, no lice showed major vital signs 5 minutes after treatment with the new product or the control dimeticone group (NYDA®). This effect persisted at all observation points (100% efficacy). Efficacy of 0.5% permethrin (Infectopedicul®) ranged between 76 and 96% in evaluations between 5 min and 6 hours. All lice treated with a coconut-based compound (mosquito® Läuseshampoo) did not show major vital signs after 5 min, but mortality was only 58% after one hour. Pyrethrum extract (Goldgeist® forte) showed an efficacy of 22 - 52% between 5 min and 3 hours after treatment; after 6 hours, 76% of lice were judged dead. An oxyphthirine®-based compound (Liberalice DUO LP-PRO®) killed 22 - 54% of lice in the first 6 hours. Conclusions The two-phase dimeticone compound NYDA® sensitiv is highly efficacious. The removal of fragrances as compared to an established dimeticone product did not affect in vitro efficacy.

2009-01-01

69

A new high molecular mass protein showing unique localization in desmosomal plaque.  

PubMed

A high molecular mass protein of 680 kD was identified and purified from the isolated desmosomes in bovine muzzle epidermal cells. This protein, called "desmoyokin" (from the English, yoke) here, showed no binding ability with keratin filaments in vitro, and its molecule had a characteristic dumbell shape approximately 170 nm in length. We have succeeded in obtaining one monoclonal antibody specific to desmoyokin. By the use of this monoclonal antibody and antidesmoplakin monoclonal antibody, desmoyokin was shown to be colocalized with desmoplakin at the immunofluorescence microscopic level; desmoyokin occurred only in the stratified epithelium, not in the simple epithelium nor in the other tissues. At the electron microscopic level, these two proteins were clearly seen to be sorted out in the plaque of desmosomes with desmoyokin at the periphery and desmoplakin at the center of the disk-shaped desmosomal plaque, suggesting that these two plaque proteins play distinct roles in forming and maintaining the desmosomes in stratified epithelium. PMID:2677021

Hieda, Y; Tsukita, S; Tsukita, S

1989-10-01

70

Acinic cell carcinoma of minor salivary gland showing features of high-grade transformation  

PubMed Central

Introduction: Acinic cell carcinoma (AciCC) of salivary gland is a relatively infrequent tumor. Though known for its low-grade behavior, its unpredictable element of recurrence and malignancy should never be ignored. Case Report: A male patient with complaints of pain and swelling in the left jaw region since a year was operated based on the computed tomography (CT) and incisional biopsy report. Histopathology (routine staining, special staining, immunostaining and electron microscopy) of the excised specimen revealed it to be a variant of AciCC from minor salivary gland. Discussion: To the best of our knowledge, this is the first case of AciCC showing propensity for high-grade transformation (HGT), arising from minor salivary gland, being reported. The rarity of such variants and the importance of various investigative techniques in the diagnosis of such cases are discussed.

Ilayaraja, Vadivel; Prasad, H; Anuthama, Krishnamurthy; Sruthi, Ranganath

2014-01-01

71

Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo  

Microsoft Academic Search

Dendritic cells (DCs) are key regulators of immune responses that activate naive antigen-specific T lymphocytes. In draining lymph nodes, antigen-bearing DCs are reported to be rare and short-lived. How such small numbers of short-lived DCs can activate rare antigen-specific T cells is unclear. Here we show that after immunization of mouse skins by gene gun, the number of antigen-bearing DCs

Sanjay Garg; Alp Oran; Janine Wajchman; Shin Sasaki; Charles H Maris; Judith A Kapp; Joshy Jacob

2003-01-01

72

High nuclearity nickel compounds with three, four or five metal atoms showing antibacterial activity.  

PubMed

The effect on DNA and the antibacterial activity of a series of high nuclearity nickel compounds with three, four and five metal atoms were examined. The compounds have a mixed ligand composition with salicylhydroxamic acid and di-2-pyridyl-ketonoxime as chelate agents. In the trinuclear compound Ni(3)(shi)(2)(Hpko)(2)(py)(2)(1), two metal ions show a square planar geometry while the third one is in an octahedral environment. The compounds with four and five nickel atoms construct metallacrown cores with two distinct connectivities. The tetranuclear vacant metallacrown [12-MC(Ni(II)N(Hshi)2(pko)2)-4](2+) shows the connectivity pattern [-O-Ni-O-N-Ni-N-](2), while the pentanuclear ([Ni(II)][12-MC(Ni(II)N(shi)2(pko)2)-4])(2+) follows the pattern [-Ni-O-N-](4). Two distinct arrangements of the chelates around the ring metal ions were observed; a 6-5-6-5-6-5-6-5 arrangement for the [12-MC(Ni(II)N(Hshi)2(pko)2)-4] core and a 6-6-5-5-6-6-5-5 arrangement for the [12-MC(Ni(II)N(shi)2(pko)2)-4] core. Magnetic variable temperature susceptibility study of the trinuclear compound revealed the presence of one paramagnetic nickel(II) ion with strong crystal field dependence, with D=5.0(4) cm(-1), g(xy)=2.7(3) and g(z)=2.3(3). The effect of the synthesized Ni(II) complexes on the integrity and electrophoretic mobility of nucleic acids was examined. Only compounds 2, 3 and 4 altered the mobility of pDNA, forming high molecular weight concatamers at low concentrations or precipitates at higher concentrations. Antibacterial activity screening of the above compounds suggests that nickel compounds 2, 3 and 4 were the most active and can act as potent antibacterial agents. PMID:12576289

Alexiou, Maria; Tsivikas, Ioannis; Dendrinou-Samara, Catherine; Pantazaki, Anastasia A; Trikalitis, Pantelis; Lalioti, Nikolia; Kyriakidis, Dimitris A; Kessissoglou, Dimitris P

2003-01-15

73

Factor VIIIa A2 Subunit Shows a High Affinity Interaction with Factor IXa  

PubMed Central

Factor (F) VIIIa forms a number of contacts with FIXa in assembling the FXase enzyme complex. Surface plasmon resonance was used to examine the interaction between immobilized biotinylated active site-modified FIXa, and FVIII and FVIIIa subunits. The FVIIIa A2 subunit bound FIXa with high affinity (Kd = 3.9 ± 1.6 nm) that was similar to the A3C1C2 subunit (Kd = 3.6 ± 0.6 nm). This approach was used to evaluate a series of baculovirus-expressed, isolated A2 domain (bA2) variants where alanine substitutions were made for individual residues within the sequence 707-714, the C-terminal region of A2 thought to be FIXa interactive. Three of six bA2 variants examined displayed 2- to 4-fold decreased affinity for FIXa as compared with WT bA2. The variant bA2 proteins were also tested in two reconstitution systems to determine activity and affinity parameters in forming FXase and FVIIIa. Vmax values for all variants were similar to the WT values, indicating that these residues do not affect cofactor function. All variants showed substantially greater increases in apparent Kd relative to WT in reconstituting the FXase complex (8- to 26-fold) compared with reconstituting FVIIIa (1.3- to 6-fold) suggesting that the mutations altered interaction with FIXa. bA2 domain variants with Ala replacing Lys707, Asp712, and Lys713 demonstrated the greatest increases in apparent Kd (17- to 26-fold). These results indicate a high affinity interaction between the FVIIIa A2 subunit and FIXa and show a contribution of several residues within the 707-714 sequence to this binding.

Griffiths, Amy E.; Rydkin, Ivan; Fay, Philip J.

2013-01-01

74

Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1).  

PubMed

Programmed death-1 (PD-1) is a coinhibitory inducible receptor present on T-cells and macrophages. Tumor cells with increased programmed death ligand-1 (PD-L1) are believed to escape immunity through activation of PD-1/PD-L1 pathway and suppression of effector-immune responses. Recent strategies targeting the PD-1/PD-L1 axis have shown promising results in patients with several tumors types, including lung carcinomas. Preliminary data suggest that PD-L1 protein expression might have predictive response to such therapies. Sarcomatoid carcinomas (SCs) of the lung include rare subtypes of poorly differentiated non-small-cell lung carcinomas of high grade and aggressive behavior. The biology of these neoplasms is poorly understood and they frequently show increased local inflammatory and lymphocytic infiltration. Here, we report the expression of PD-L1 in 13 SCs from two large retrospective lung cancer cohorts. Using automated quantitative immunofluoresence and a mouse monoclonal antibody directed against the extracellular domain of PD-L1, we show that 9 of 13 patients (69.2%) with SCs are positive for PD-L1 and their levels are higher than in conventional non-small-cell lung carcinoma. These results provide rationale for the potential use of targeted immunotherapy in lung SCs. PMID:23676558

Velcheti, Vamsidhar; Rimm, David L; Schalper, Kurt A

2013-06-01

75

Children with High Functioning Autism show increased prefrontal and temporal cortex activity during error monitoring  

PubMed Central

Evidence exists for deficits in error monitoring in autism. These deficits may be particularly important because they may contribute to excessive perseveration and repetitive behavior in autism. We examined the neural correlates of error monitoring using fMRI in 8–12-year-old children with high-functioning autism (HFA, n=11) and typically developing children (TD, n=15) during performance of a Go/No-Go task by comparing the neural correlates of commission errors versus correct response inhibition trials. Compared to TD children, children with HFA showed increased BOLD fMRI signal in the anterior medial prefrontal cortex (amPFC) and the left superior temporal gyrus (STempG) during commission error (versus correct inhibition) trials. A follow-up region-of-interest analysis also showed increased BOLD signal in the right insula in HFA compared to TD controls. Our findings of increased amPFC and STempG activity in HFA, together with the increased activity in the insula, suggest a greater attention towards the internally-driven emotional state associated with making an error in children with HFA. Since error monitoring occurs across different cognitive tasks throughout daily life, an increased emotional reaction to errors may have important consequences for early learning processes.

Goldberg, Melissa C.; Spinelli, Simona; Joel, Suresh; Pekar, James J.; Denckla, Martha B.; Mostofsky, Stewart H.

2010-01-01

76

Protein-polymer functionalized aqueous ferrofluids showing high T2 relaxivity.  

PubMed

Controlled size, shape and dispersibility of superparamagnetic iron oxide nanoparticles (SPIONs), has been achieved in a protein-polymer colloidal dispersion. Stable ferrofluid (FF) is synthesized in an aqueous medium of collagen, bovine serum albumin and poly(vinyl) alcohol that equilibrates with time, at ambient conditions, into an organized matrix with iron oxide particles sterically caged at defined sites. It mimics a biomineralization system; hence the process is termed biomimetics. Though the exact mechanism is not understood at this stage, we have established, with serial dilution of the protein-polymer solution that the SPIONs are formed inside the self-contained clusters of the two proteins and the polymer, which show a tendency to self assemble. More than the interparticle dipolar attractions of magnetic particles, electrostatic interactions play a role in cluster formation and collagen is responsible for the overall stability, supported by systematic dynamic light scattering data. The basic aim of this study was to increase magnetization of a previously synthesized ferrofluid without hampering stability, by reducing the total macromolecular concentration. Thrice the magnetization was achieved and in addition, the synthesized FFs exhibited very high transverse relaxivity and showed good contrast in mice liver, in the in vivo studies. PMID:24734534

Bhattacharya, S; Sheikh, L; Tiwari, V; Ghosh, M; Patel, J N; Patel, A B; Nayar, S

2014-05-01

77

A novel lectin from Agrocybe aegerita shows high binding selectivity for terminal N-acetylglucosamine  

PubMed Central

A novel lectin was isolated from the mushroom Agrocybe aegerita (designated AAL-2) by affinity chromatography with GlcNAc (N-acetylglucosamine)-coupled Sepharose 6B after ammonium sulfate precipitation. The AAL-2 coding sequence (1224 bp) was identified by performing a homologous search of the five tryptic peptides identified by MS against the translated transcriptome of A. aegerita. The molecular mass of AAL-2 was calculated to be 43.175 kDa from MS, which was consistent with the data calculated from the amino acid sequence. To analyse the carbohydrate-binding properties of AAL-2, a glycan array composed of 465 glycan candidates was employed, and the result showed that AAL-2 bound with high selectivity to terminal non-reducing GlcNAc residues, and further analysis revealed that AAL-2 bound to terminal non-reducing GlcNAc residues with higher affinity than previously well-known GlcNAc-binding lectins such as WGA (wheatgerm agglutinin) and GSL-II (Griffonia simplicifolia lectin-II). ITC (isothermal titration calorimetry) showed further that GlcNAc bound to AAL-2 in a sequential manner with moderate affinity. In the present study, we also evaluated the anti-tumour activity of AAL-2. The results showed that AAL-2 could bind to the surface of hepatoma cells, leading to induced cell apoptosis in vitro. Furthermore, AAL-2 exerted an anti-hepatoma effect via inhibition of tumour growth and prolongation of survival time of tumour-bearing mice in vivo.

Jiang, Shuai; Chen, Yijie; Wang, Man; Yin, Yalin; Pan, Yongfu; Gu, Bianli; Yu, Guojun; Li, Yamu; Wong, Barry Hon Cheung; Liang, Yi; Sun, Hui

2012-01-01

78

Molecular Characterization of Chinese Hamster Cells Mutants Affected in Adenosine Kinase and Showing Novel Genetic and Biochemical Characteristics  

Microsoft Academic Search

Background  Two isoforms of the enzyme adenosine kinase (AdK), which differ at their N-terminal ends, are found in mammalian cells. However,\\u000a there is no information available regarding the unique functional aspects or regulation of these isoforms.\\u000a \\u000a \\u000a \\u000a \\u000a Results  We show that the two AdK isoforms differ only in their first exons and the promoter regions; hence they arise via differential\\u000a splicing of their

Xianying A Cui; Tanvi Agarwal; Bhag Singh; Radhey S Gupta

2011-01-01

79

Optimizing High Speed Flip-Flop Using Genetic Algorithm  

Microsoft Academic Search

In this paper, the optimization of power-delay-product (PDP) of a high-speed flip-flop via transistor sizing is presented. The optimization is performed using the genetic algorithm (GA). The flip-flop which is used in this optimization is called modified hybrid latch flip-flop (MHLFF). The genetic algorithm is implemented in MATLAB with the fitness function expressed in terms of the power and the

Fatemeh Aezinia; Ali Afzali-kusha; Caro Lucas

2006-01-01

80

Interdisciplinarity, Debate And Movie Clips As Highly Motivating Factors In Live Shows - Five Years Of Success  

NASA Astrophysics Data System (ADS)

A live show on any subject that includes experiments and continuous interaction with the audience is a well known approach for EPO activities that many are carrying out all over. We present such an initiative with some added ingredients such as interdisciplinarity, the use of movie clips, and especially the debate between the two presenters, a debate that is all the more attractive to the public if it not fully staged but closely represents their actual points of view. José Montesinos, from the "Orotava" Canarian Foundation for the History of Science, is and plays the role of the more mature math professor who has grown weary of the overrated value given in science to mathematics and its consequences. This poses a constant challenge to his colleague, Erik Stengler, from the Science Museum of Tenerife, the young down-to-earth hands-on scientist, who defends the usual view that science and technology are to be judged by their achievements, which have brought about the advancement of modern society. With this approach and as a collaboration between our institutions, we have produced and toured highly successful activities on: Einstein and Relativity (from 2005 to 2008, "Einstein Goes To School," including a theatre play); circularity, the number ?, forces of inertia and the Newtonian revolution (in 2008/2009, "The Tension Between Circularity and The Straight Line"); and the foundations of modern astronomy (in 2009/2010 "Kepler and Galileo, Messengers of the Stars"). Audiences were very varied - students, adult students, general public, prison inmates, teachers - and all appreciated the presentations as fun, thought-provoking and highly motivating, and valued especially the interdisciplinary character of the activity. Movie clips have shown to be especially useful to recover the attention of the young when they lose the thread due to the short attention spans they presently have.

Stengler, E.; Sirera, J. M.

2011-09-01

81

X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity  

SciTech Connect

The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

Game, John C.; Williamson, Marsha S.; Baccari, Clelia

2004-01-07

82

High levels of genetic diversity in Penaeus monodon populations from the east coast of India.  

PubMed

Quality production of the shrimp Penaeus monodon in hatchery operations depends heavily on the evaluation of genetic diversity and population structure of brood stocks. Mitochondrial DNA (mtDNA) sequences have been widely used to study genetic variability and relationships in many crustacean groups, and these same markers may be incorporated into evaluation studies of shrimp broods and populations. For this purpose we looked at variation in mitochondrial D-loop sequences as an indicator of genetic diversity in shrimp populations from a region of India that represents the main sources of new material for brood stocks. In our study of these populations the overall mean genetic diversity was 0.191. The highest level of genetic diversity (0.357) was observed in the Kakinada population, whereas the lowest diversity (0.0171) was observed in the Nellore population. The results also indicate that overall, the populations along the Andhra Pradesh coast are genetically diverse despite the fact that there is considerable gene flow between them. From the results, it is evident that east cost of India shows high genetic diversity among P. monodon broods and no evidence of loss of diversity due to excessive inbreeding. The fact that the genetic variability of these populations has been maintained, despite ten years of dependence on these broods, shows that at the present time there is no indication of over exploitation. PMID:24363984

Khedkar, Gulab Dattarao; Reddy, A Chandrashekar; Ron, Tetszuan Benny; Haymer, David

2013-01-01

83

High levels of genetic variation in Indian field and house mice  

Microsoft Academic Search

Genetic variation in the Indian pygmy field miceMus booduga and theMus terricolor complex and in the house mouseMus musculus tytleri was analysed electro phoretically at 20 enzymatic and nonenzymatic protein loci. The results show an unusually high genetic\\u000a variation in the field mice in terms of per cent polymorphism (P = 75 to 90 at 0-95 level), observed heterozygosity (Ho

S. Singh; T. Sharma

1997-01-01

84

[Comparative chromosome painting shows the red panda (Ailurus fulgens) has a highly conserved karyotype].  

PubMed

We have established a comparative chromosome map between red panda (Ailurus fulgens, 2n = 36) and dog by chromosome painting with biotin-labelled chromosome-specific probes of the dog. Dog probes specific for the 38 automates delineated 71 homologous segments in the metaphase chromosomes of red panda. Of the 38 autosomal paints, 18 probes each delineated one homologous segment in red panda genome, while the other 20 ones each detected two to five homologous segments. The dog X chromosome-specific paint delineated the whole X chromosome of the red panda. The results indicate that at least 28 fissions (breaks), 49 fusions and 4 inversions were needed to "convert" the dog karyotype to that of the red panda, suggesting that extensive chromosome rearrangements differentiate the karyotypes of red panda and dog. Based on the established comparative chromosome homologies of dog and domestic cat, we could infer that there were 26 segments of conserved synteny between red panda and domestic cat. Comparative analysis of the distribution patterns of conserved segments defined by dog paints in red panda and domestic cat genomes revealed at least 2 cryptic inversions in two large chromosomal regions of conserved synteny between red panda and domestic cat. The karyotype of red panda shows high degree of homology with that of domestic cat. PMID:11901994

Tian, Ying; Nie, Wen-Hui; Wang, Jin-Huan; Yang, Yun-Fei; Yang, Feng-Tang

2002-02-01

85

High genetic diversity in a potentially vulnerable tropical tree species despite extreme habitat loss.  

PubMed

Over the last 150 years, Singapore's primary forest has been reduced to less than 0.2% of its previous area, resulting in extinctions of native flora and fauna. Remaining species may be threatened by genetic erosion and inbreeding. We surveyed >95% of the remaining primary forest in Singapore and used eight highly polymorphic microsatellite loci to assess genetic diversity indices of 179 adults (>30 cm stem diameter), 193 saplings (>1 yr), and 1,822 seedlings (<1 yr) of the canopy tree Koompassia malaccensis (Fabaceae). We tested hypotheses relevant to the genetic consequences of habitat loss: (1) that the K. malaccensis population in Singapore experienced a genetic bottleneck and a reduction in effective population size, and (2) K. malaccensis recruits would exhibit genetic erosion and inbreeding compared to adults. Contrary to expectations, we detected neither a population bottleneck nor a reduction in effective population size, and high genetic diversity in all age classes. Genetic diversity indices among age classes were not significantly different: we detected overall high expected heterozygosity (He = 0.843-0.854), high allelic richness (R = 16.7-19.5), low inbreeding co-efficients (FIS = 0.013-0.076), and a large proportion (30.1%) of rare alleles (i.e. frequency <1%). However, spatial genetic structure (SGS) analyses showed significant differences between the adults and the recruits. We detected significantly greater SGS intensity, as well as higher relatedness in the 0-10 m distance class, for seedlings and saplings compared to the adults. Demographic factors for this population (i.e. <200 adult trees) are a cause for concern, as rare alleles could be lost due to stochastic factors. The high outcrossing rate (tm = 0.961), calculated from seedlings, may be instrumental in maintaining genetic diversity and suggests that pollination by highly mobile bee species in the genus Apis may provide resilience to acute habitat loss. PMID:24367531

Noreen, Annika M E; Webb, Edward L

2013-01-01

86

Genetic alterations in pediatric high-grade astrocytomas  

Microsoft Academic Search

High-grade astrocytomas are tumors that are uncommon in children. Relatively few studies have been performed on their molecular properties and so it is not certain whether they follow different genetic pathways from those described in adult diffuse astrocytomas. In this study, we evaluated 24 pediatric high-grade astrocytomas (11 anaplastic astrocytomas and 13 glioblastomas) all of which were sporadic and primary.

Yue Cheng; Ho-Keung Ng; Shang-Fu Zhang; Min Ding; Jesse Chung-Sean Pang; Jian Zheng; Wai-Sang Poon

1999-01-01

87

Epithelioid GBMs show a high percentage of BRAF V600E mutation.  

PubMed

BRAF V600E mutation has been identified in up to 2/3 of pleomorphic xanthoastrocytomas (PXAs), World Health Organization grade II, as well as in varying percentages of PXAs with anaplastic features (PXA-A), gangliogliomas, extracerebellar pilocytic astrocytomas, and, rarely, giant cell glioblastoma multiforme (GC-GBMs). GC-GBMs and epithelioid GBMs (E-GBMs) can be histologically challenging to distinguish from PXA-A. We undertook this study specifically to address whether these 2 tumor types also showed the mutation. We tested our originally reported cohort of 8 E-GBMs and 2 rhabdoid GBMs (R-GBM) as well as 5 new E-GBMs (1 pediatric, 4 adult) and 9 GC-GBMs (2 pediatric, 7 adult) (n=24) for BRAF V600E mutational status. Twenty-one of 24 had sufficient material for IDH-1 immunostaining, which is usually absent in PXAs, PXA-As, and primary GBMs but present in secondary GBMs. Patients ranged in age from 4 to 67 years. BRAF V600E mutation was identified in 7/13 of E-GBMs, including 3 of our original cases; patients with mutation were aged 10 to 50 years. None of the 9 GC-GBMs or 2 R-GBMs manifested this mutation, including pediatric patients. The sole secondary E-GBM was the single case manifesting positive IDH-1 immunoreactivity. A high percentage of E-GBMs manifest BRAF V600E mutation, paralleling PXAs. All R-GBMs and GC-GBMs were negative, although larger multi-institutional cohorts will have to be tested to extend this result. BRAF V600E mutational analyses should be performed on E-GBMs, particularly in all pediatric and young-aged adults, given the potential for BRAF inhibitor therapy in this subset of GBM patients. PMID:23552385

Kleinschmidt-DeMasters, Bette Kay; Aisner, Dara L; Birks, Diane K; Foreman, Nicholas K

2013-05-01

88

Iridoschisis: high frequency ultrasound imaging. Evidence for a genetic defect?  

PubMed Central

AIMS: To elucidate changes in the anatomy of the anterior chamber associated with iridoschisis, a rare form of iris atrophy, and their potential contribution to angle closure glaucoma. METHODS: Both eyes of a 71-year-old woman with bilateral iridoschisis and fibrous dysplasia and her asymptomatic 50-year-old daughter were scanned with a very high frequency (50 MHz) ultrasound system. RESULTS: The symptomatic patient exhibited diffuse changes in the iris stoma with an intact posterior iris pigmented layer in both eyes. These changes were clinically compatible with the lack of iris transillumination defects. Additionally, iris bowing with a resultant narrowing of the angle occurred. The asymptomatic daughter showed discrete, but less severe iris stromal changes. CONCLUSION: This is the first detailed study of high frequency ultrasonic imaging of the iris in iridoschisis. The observed structural changes suggest angle narrowing by forward bowing of the anterior iris stroma may be a mechanism of IOP elevation in this condition. The ultrasonic detection of iris changes in the asymptomatic daughter of the symptomatic patient and the association of iridoschisis with fibrous dysplasia suggest a possible genetic component in the pathogenesis of this condition. Images

Danias, J; Aslanides, I M; Eichenbaum, J W; Silverman, R H; Reinstein, D Z; Coleman, D J

1996-01-01

89

Study Shows Aspirin Reduces Colorectal Cancer in Those at High Risk  

Cancer.gov

Findings from the first large clinical trial of its kind indicate that taking high doses of aspirin daily for at least 2 years substantially reduces the risk of colorectal cancer among people at increased risk of the disease.

90

Genetic Predisposition to High Blood Pressure Associates With Cardiovascular Complications Among Patients With Type 2 Diabetes  

PubMed Central

Hypertension and type 2 diabetes (T2D) commonly coexist, and both conditions are major risk factors for cardiovascular disease (CVD). We aimed to examine the association between genetic predisposition to high blood pressure and risk of CVD in individuals with T2D. The current study included 1,005 men and 1,299 women with T2D from the Health Professionals Follow-up Study and Nurses’ Health Study, of whom 732 developed CVD. A genetic predisposition score was calculated on the basis of 29 established blood pressure–associated variants. The genetic predisposition score showed consistent associations with risk of CVD in men and women. In the combined results, each additional blood pressure–increasing allele was associated with a 6% increased risk of CVD (odds ratio [OR] 1.06 [95% CI 1.03–1.10]). The OR was 1.62 (1.22–2.14) for risk of CVD comparing the extreme quartiles of the genetic predisposition score. The genetic association for CVD risk was significantly stronger in patients with T2D than that estimated in the general populations by a meta-analysis (OR per SD of genetic score 1.22 [95% CI 1.10–1.35] vs. 1.10 [1.08–1.12]; I2 = 71%). Our data indicate that genetic predisposition to high blood pressure is associated with an increased risk of CVD in individuals with T2D.

Qi, Qibin; Forman, John P.; Jensen, Majken K.; Flint, Alan; Curhan, Gary C.; Rimm, Eric B.; Hu, Frank B.; Qi, Lu

2012-01-01

91

Source-Sink Estimates of Genetic Introgression Show Influence of Hatchery Strays on Wild Chum Salmon Populations in Prince William Sound, Alaska  

PubMed Central

The extent to which stray, hatchery-reared salmon affect wild populations is much debated. Although experiments show that artificial breeding and culture influence the genetics of hatchery salmon, little is known about the interaction between hatchery and wild salmon in a natural setting. Here, we estimated historical and contemporary genetic population structures of chum salmon (Oncorhynchus keta) in Prince William Sound (PWS), Alaska, with 135 single nucleotide polymorphism (SNP) markers. Historical population structure was inferred from the analysis of DNA from fish scales, which had been archived since the late 1960’s for several populations in PWS. Parallel analyses with microsatellites and a test based on Hardy-Weinberg proportions showed that about 50% of the fish-scale DNA was cross-contaminated with DNA from other fish. These samples were removed from the analysis. We used a novel application of the classical source-sink model to compare SNP allele frequencies in these archived fish-scales (1964–1982) with frequencies in contemporary samples (2008–2010) and found a temporal shift toward hatchery allele frequencies in some wild populations. Other populations showed markedly less introgression, despite moderate amounts of hatchery straying. The extent of introgression may reflect similarities in spawning time and life-history traits between hatchery and wild fish, or the degree that hybrids return to a natal spawning area. The source-sink model is a powerful means of detecting low levels of introgression over several generations.

Jasper, James R.; Habicht, Christopher; Moffitt, Steve; Brenner, Rich; Marsh, Jennifer; Lewis, Bert; Creelman Fox, Elisabeth; Grauvogel, Zac; Rogers Olive, Serena D.; Grant, W. Stewart

2013-01-01

92

High Blood Pressure Medicines Show Promise for Treating Heart Disease. Research Activities, No. 352, December 2009.  

National Technical Information Service (NTIS)

Two medications typically used to treat high blood pressure appear to be effective in treating a common type of heart disease known as stable ischemic heart disease, according to a new comparative effectiveness review funded by the Agency for Healthcare R...

2009-01-01

93

Studies Show High Schools' Shortcomings: Young Adults Surveyed about Their Experiences  

ERIC Educational Resources Information Center

Two national studies paint a portrait of the bumpy road that many students face after high school and suggest that better academic preparation and guidance could have smoothed the way. The studies, each based primarily on separate surveys of 1,300 or more 18- to 25-year-olds, come from Public Agenda, a nonprofit opinion-research group in New York…

Viadero, Debra

2005-01-01

94

Proteins with Highly Similar Native Folds Can Show Vastly Dissimilar Folding Behavior When Desolvated**  

PubMed Central

Proteins can be exposed to vastly different environments such as the cytosol or membranes, but the delicate balance between external factors and intrinsic determinants of protein structure, stability, and folding is only poorly understood. Here we used electron capture dissociation to study horse and tuna heart Cytochromes c in the complete absence of solvent. The significantly different stability of their highly similar native folds after transfer into the gas phase, and their strikingly different folding behavior in the gas phase, can be rationalized on the basis of electrostatic interactions such as salt bridges. In the absence of hydrophobic bonding, protein folding is far slower and more complex than in solution.

Schennach, Moritz; Breuker, Kathrin

2014-01-01

95

Blue myoglobin reconstituted with an iron porphycene shows extremely high oxygen affinity.  

PubMed

Myoglobin will be a good scaffold for engineering a function into proteins. To modulate the physiological function of myoglobin, almost all approaches have been demonstrated by site-directed mutagenesis, however, there are few studies which show a significant improvement in the function. In contrast, we focused on the replacement of heme in the protein with an artificial prosthetic group. Recently, we prepared a novel myoglobin reconstituted with an iron porphycene as a structural isomer of mesoheme. The bluish colored reconstituted myoglobin is relatively stable and the deoxymyoglobin reversibly binds ligands. Interestingly, the O2 affinity of the reconstituted myoglobin, 1.1 x 109 M-1, is a significant 1,400-fold higher than that of the native myoglobin. Furthermore, the unfavorable autoxidation kinetics show 7-fold decrease in rate for the reconstituted myoglobin relative to the native myoglobin, indicating the stable oxy-form against autoxidation. The net results come from the slow dissociation of the O2 ligand in the reconstituted myoglobin, koff = 0.11 s-1, because of the formation of strong hydrogen bond between His64 and negatively charged dioxygen. The present study indicates that the replacement of native heme with an artificially created prosthetic group will give us a unique function into a hemoprotein. PMID:12236710

Hayashi, Takashi; Dejima, Hirohisa; Matsuo, Takashi; Sato, Hideaki; Murata, Dai; Hisaeda, Yoshio

2002-09-25

96

International web survey shows high prevalence of symptomatic testosterone deficiency in men  

PubMed Central

Introduction Though the clinical significance of testosterone deficiency is becoming increasingly apparent, its prevalence in the general population remains unrecognised. A large web-based survey was undertaken over 3 years to study the scale of this missed diagnosis. Methods An online questionnaire giving the symptoms characterising testosterone deficiency syndrome (Aging Male Symptoms – AMS – scale) was set up on three web sites, together with questions about possible contributory factors. Results. Of over 10,000 men, mainly from the UK and USA, who responded, 80% had moderate or severe scores likely to benefit from testosterone replacement therapy (TRT). The average age was 52, but with many in their 40s when the diagnosis of ‘late onset hypogonadism’ is not generally considered. Other possible contributory factors to the high testosterone deficiency scores reported were obesity (29%), alcohol (17.3%), testicular problems such as mumps orchitis (11.4%), prostate problems (5.6%), urinary infection (5.2%) and diabetes 5.7%. Conclusions In this self-selected large international sample of men, there was a very high prevalence of scores which if clinically relevant would warrant a therapeutic trial of testosterone treatment. This study suggests that there are large numbers of men in the community whose testosterone deficiency is neither being diagnosed nor treated.

TRINICK, TOM R; FENELEY, MARK R; WELFORD, HUGH; CARRUTHERS, MALCOLM

2011-01-01

97

Synthesis and conformational analysis of a series of galactosyl enkephalin analogues showing high analgesic activity.  

PubMed Central

Two galactosyl derivatives of [DMet2,Pro5] enkephalin-amide (compound 1), namely [DMet2,Pro5] enkephalin [N1.5-beta-D-galactopyranosyl] amide (compound 2) and O1.5-(beta-D-galactopyranosyl) [DMet2,Hyp5] enkephalin-amide (compound 3) have been synthesized. Such glycosylpeptides have been shown to be extremely potent analgesic agonists. The conformational analysis of these three compounds in DMSO-d6 solution has been carried out using two-dimensional NMR methods. Both the parent compound (1) and the beta N-galactosyl derivative (2) show similar NMR parameters which are consistent with fairly rigid beta-strands at both the N-terminus and C-terminus, connected by a glycine residue that displays a mixture between multiple conformational states. Thus, although the beta N-galactosyl derivative (2) has been shown to be significantly more potent than the parent compound (1) in the tail immersion and paw pressure tests of analgesia, no correlation can be established between the conformation of (1) and (2) in DMSO and the difference in analgesic activity. In contrast, important conformational differences with respect to (1) and (2) have been detected in the beta O-galactosyl derivative (3). In this case, only one of the likely conformations for (1) and (2) are consistent with the experimental data. These data show that the position of the galactose residue in compound (3) causes Gly3 to loose flexibility leading to a more rigid folded conformation. Such a change in conformation could be related to the difference in analgesic activity between (2) and (3). Images

Torres, J L; Pepermans, H; Valencia, G; Reig, F; Garcia-Anton, J M; Van Binst, G

1989-01-01

98

Updated clinical results show experimental agent ibrutinib as highly active in CLL patients  

Cancer.gov

Updated results from a Phase Ib/II clinical trial led by the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute indicates that a novel therapeutic agent for chronic lymphocytic leukemia (CLL) is highly active and well tolerated in patients who have relapsed and are resistant to other therapy. The agent, ibrutinib (PCI-32765), is the first drug designed to target Bruton's tyrosine kinase (BTK), a protein essential for CLL-cell survival and proliferation. CLL is the most common form of leukemia, with about 15,000 new cases annually in the U.S. About 4,400 Americans die of the disease each year.

99

Are recurrence rates for "traditional" transvaginal prolapse repairs really that high? What does the evidence show?  

PubMed

Pelvic organ prolapse (POP) is a common and bothersome condition. Multiple methods for surgical repair exist, and much attention has been given to improving the efficacy of repair by implementing mesh interposition. Standard (native tissue-based) repairs in the anterior compartment have long been thought to be associated with high anatomical recurrence rates and the currently available randomized controlled trials (RCTs) support this thinking. However, subjective improvement in pelvic pressure and bulging and quality of life indices are similarly improved in both standard and mesh-augmented repairs. No RCTs are available to compare standard and mesh-augmented repairs in the posterior compartment. Despite the presence of RCTs, the data is often inconsistent and questions remain regarding the optimal criteria to describe POP recurrence. While there is a role for both types of repair, the optimal patient scenario is not known. PMID:23400836

Gomelsky, Alex; Vince, Randy

2013-06-01

100

Decarbonizing urban transport in European cities: four cases show possibly high co-benefits  

NASA Astrophysics Data System (ADS)

Cities worldwide are increasingly becoming agents of climate change mitigation, while simultaneously aiming for other goals, such as improved accessibility and clean air. Based on stakeholder interviews and data analysis, we assess the current state of urban mobility in the four European cities of Barcelona, Malmö, Sofia and Freiburg. We then provide scenarios of increasingly ambitious policy packages, reducing greenhouse gas emissions from urban transport by up to 80% from 2010 to 2040. We find significant concurrent co-benefits in cleaner air, reduced noise ambience, fewer traffic-related injuries and deaths, more physical activity, less congestion and monetary fuel savings. Our scenarios suggest that non-motorized transport, especially bicycles, can occupy high modal shares, particularly in cities with less than 0.5 million inhabitants. We think that this kind of multi-criteria assessment of social costs and benefits is a useful complement to cost-benefit analysis of climate change mitigation measures.

Creutzig, Felix; Mühlhoff, Rainer; Römer, Julia

2012-12-01

101

Genetic causes of high and low serum HDL-cholesterol  

PubMed Central

Plasma levels of HDL cholesterol (HDL-C) have a strong inherited basis with heritability estimates of 40-60%. The well-established inverse relationship between plasma HDL-C levels and the risk of coronary artery disease (CAD) has led to an extensive search for genetic factors influencing HDL-C concentrations. Over the past 30 years, candidate gene, genome-wide linkage, and most recently genome-wide association (GWA) studies have identified several genetic variations for plasma HDL-C levels. However, the functional role of several of these variants remains unknown, and they do not always correlate with CAD. In this review, we will first summarize what is known about HDL metabolism, monogenic disorders associated with both low and high HDL-C levels, and candidate gene studies. Then we will focus this review on recent genetic findings from the GWA studies and future strategies to elucidate the remaining substantial proportion of HDL-C heritability. Comprehensive investigation of the genetic factors conferring to low and high HDL-C levels using integrative approaches is important to unravel novel pathways and their relations to CAD, so that more effective means of diagnosis, treatment, and prevention will be identified.

Weissglas-Volkov, Daphna; Pajukanta, Paivi

2010-01-01

102

Soils of the Chinese Hubei province show a very high diversity of Sinorhizobium fredii strains.  

PubMed

Biodiversity studies of native soybean-nodulating rhizobia in soils from the Chinese Hubei province (Honghu county; pH 8, alluvial soil) have been carried out. Inoculation of an American (Williams) and an Asiatic (Peking) soybean cultivar with eleven soil samples led to the isolation of 167 rhizobia strains. The ratio (%) of slow-/fast-growing isolates was different depending on the trap plant used. All isolates were able to nodulate both cultivars, although the N2-fixation efficiency (measured as plant-top dry weight) was different among them. A total of thirty-three isolates were selected for further characterisation on the basis of physiological parameters, PCR-RFLP of symbiotic genes and Low Molecular Weight RNA, lipopolysaccharide, protein and plasmid profiles. Low Molecular Weight RNA profiling indicates that all the isolates belong to species Sinorhizobium fredii. The dendrogram obtained with the physiological parameters has been useful to classify the isolates at strain level, although plasmid profiling was the most discriminating technique to detect differences among the analysed soybean-rhizobia isolates, showing there is not two isolates identical each other. Plasmid profile analyses also revealed that some of the investigated strains contain low molecular weight plasmids (7-8-kb). They are, to our knowledge, the smallest ever found in rhizobia and they could be the starting point for the construction of the first group of vectors based on a native rhizobia replicon. PMID:12583720

Camacho, M; Santamaría, C; Temprano, F; Rodríguez-Navarro, D N; Daza, A; Espuny, R; Bellogín, R; Ollero, F J; Lyra de, M C C P; Buendía-Clavería, A; Zhou, J; Li, F D; Mateos, C; Velázquez, E; Vinardell, J M; Ruiz-Sainz, J E

2002-12-01

103

Tetranuclear silver(i) clusters showing high ionic conductivity in a bicontinuous cubic mesophase.  

PubMed

The synthesis and characterization of tetranuclear silver triazole metallomesogens, [Ag4(L(4)-Cn)6][BF4]4 (L(4)-Cn = 4-alkyl-1,2,4-triazoles where Cn stands for CnH2n+1 with n = 12, 14, 16, and 18), are reported. Upon heating, a phase transition sequence of Cr ? SmC ? Cub ? SmA ? isotropic liquid is observed for all of these compounds. Depending on the alkyl chain length, two types of cubic phases are found in this series of compounds. Those with shorter alkyl chains (n = 12 and 14) exhibit a micellar cubic phase, whereas long alkyl chains (n =16 and 18) show a bicontinuous cubic phase. Superior ionic conductivity at the bicontinuous cubic mesophase for [Ag4(L4-C16)6][BF4]4 is observed because of the presence of a three-dimensional ion-transporting channel. Doping a small amount of AgBF4 enhances the ionic conduction dramatically, presumably via promotion of the migration of Ag(I) ions in the channels. PMID:24893070

Su, Padi Y S; Tseng, Jing C W; Lee, Kwang-Ming; Wang, Ju-Chun; Lin, Ivan J B

2014-06-16

104

High-precision radiocarbon dating shows recent and rapid initial human colonization of East Polynesia  

PubMed Central

The 15 archipelagos of East Polynesia, including New Zealand, Hawaii, and Rapa Nui, were the last habitable places on earth colonized by prehistoric humans. The timing and pattern of this colonization event has been poorly resolved, with chronologies varying by >1000 y, precluding understanding of cultural change and ecological impacts on these pristine ecosystems. In a meta-analysis of 1,434 radiocarbon dates from the region, reliable short-lived samples reveal that the colonization of East Polynesia occurred in two distinct phases: earliest in the Society Islands A.D. ?1025–1120, four centuries later than previously assumed; then after 70–265 y, dispersal continued in one major pulse to all remaining islands A.D. ?1190–1290. We show that previously supported longer chronologies have relied upon radiocarbon-dated materials with large sources of error, making them unsuitable for precise dating of recent events. Our empirically based and dramatically shortened chronology for the colonization of East Polynesia resolves longstanding paradoxes and offers a robust explanation for the remarkable uniformity of East Polynesian culture, human biology, and language. Models of human colonization, ecological change and historical linguistics for the region now require substantial revision.

Wilmshurst, Janet M.; Hunt, Terry L.; Lipo, Carl P.; Anderson, Atholl J.

2011-01-01

105

Development of simultaneous pitch encoding: infants show a high voice superiority effect.  

PubMed

Infants must learn to make sense of real-world auditory environments containing simultaneous and overlapping sounds. In adults, event-related potential studies have demonstrated the existence of separate preattentive memory traces for concurrent note sequences and revealed perceptual dominance for encoding of the voice with higher fundamental frequency of 2 simultaneous tones or melodies. Here, we presented 2 simultaneous streams of notes (15 semitones apart) to 7-month-old infants. On 50% of trials, either the higher or the lower note was modified by one semitone, up or down, leaving 50% standard trials. Infants showed mismatch negativity (MMN) to changes in both voices, indicating separate memory traces for each voice. Furthermore, MMN was earlier and larger for the higher voice as in adults. When in the context of a second voice, representation of the lower voice was decreased and that of the higher voice increased compared with when each voice was presented alone. Additionally, correlations between MMN amplitude and amount of weekly music listening suggest that experience affects the development of auditory memory. In sum, the ability to process simultaneous pitches and the dominance of the highest voice emerge early during infancy and are likely important for the perceptual organization of sound in realistic environments. PMID:22419678

Marie, Céline; Trainor, Laurel J

2013-03-01

106

Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities for PPARs.  

PubMed

PPARs regulate the expression of genes for energy metabolism in a ligand-dependent manner. PPARs can influence fatty acid oxidation, the level of circulating triglycerides, glucose uptake and insulin sensitivity. Here, we demonstrate that 5-hydroxyeicosapentaenoic acid (HEPE), 8-HEPE, 9-HEPE, 12-HEPE and 18-HEPE (hydroxylation products of EPA) obtained from methanol extracts of Pacific krill (Euphausia pacifica) can act as PPAR ligands. Two of these products, 8-HEPE and 9-HEPE, enhanced the transcription levels of GAL4-PPARs to a significantly greater extent than 5-HEPE, 12-HEPE, 18-HEPE, EPA, and EPA ethyl-ester. 8-HEPE also activated significantly higher transcription of GAL4-PPAR?, GAL4-PPAR?, and GAL4-PPAR? than EPA at concentrations greater than 4, 64, and 64 ?M, respectively. We also demonstrated that 8-HEPE increased the expression levels of genes regulated by PPARs in FaO, 3T3-F442A, and C2C12 cells. Furthermore, 8-HEPE enhanced adipogenesis and glucose uptake. By contrast, at the same concentrations, EPA showed weak or little effect, indicating that 8-HEPE was the more potent inducer of physiological effects. PMID:24668940

Yamada, Hidetoshi; Oshiro, Eriko; Kikuchi, Sayaka; Hakozaki, Mayuka; Takahashi, Hideyuki; Kimura, Ken-Ichi

2014-05-01

107

Innovations at Miami practice show promise for treating high-risk Medicare patients.  

PubMed

Patients with five or more chronic conditions drive most Medicare costs. Our organization, ChenMed, developed a scalable primary care-led delivery model that focuses on this population while getting reimbursed through full-risk capitation by Medicare Advantage plans. ChenMed is a primary care-led group practice based in Florida that serves low-to-moderate-income elderly patients, largely through the Medicare Advantage program. Our model includes a number of innovations: a one-stop-shop approach for delivering multispecialty services in the community, smaller physician panel sizes of 350-450 patients that allow for intensive health coaching and preventive care, on-site physician pharmacy dispensing, a collaborative physician culture with peer review, and customized information technology. These innovations have improved patient medication adherence, increased the time doctors and patients spend together, and led to high rates of patient satisfaction. Additionally, our Medicare patients have substantially lower rates of hospital use than their peers in the Miami Medicare market. Creating chronic disease centers focused on seniors with multiple chronic conditions is a promising delivery system innovation with major potential to improve the cost and quality of care. PMID:23733982

Tanio, Craig; Chen, Christopher

2013-06-01

108

Beta-adrenoceptor activation shows high-frequency fatigue in skeletal muscle fibers of the rat.  

PubMed

The effect of terbutaline (a beta 2-adrenergic agonist) on high-frequency fatigue (HFF) was studied in small bundles of rat soleus muscle fibers. HFF, the decline in force during continuous stimulation (50 Hz for 20 s), was reduced by 10-20% with 10 microM terbutaline. A similar reduction in HFF with 2 mM dibutyryl-adenosine 3',5'-cyclic monophosphate (DBcAMP) implicated adenosine 3',5'-cyclic monophosphate (cAMP) as the second messenger in the terbutaline effect. Sodium (Na-K)-pump inhibition with 1 mM ouabain depressed peak tetanic force but did not significantly alter either the subsequent fatigue or the effect of terbutaline on fatigue. This suggested that the pump was neither rate limiting in HFF nor involved in the terbutaline effect. Nevertheless, a significant hyperpolarization recorded with terbutaline implied that beta 2-adrenoceptor activation stimulated the Na-K pump at rest. Caffeine (1 mM) slowed HFF and prevented additional effects with terbutaline. Caffeine is known to potentiate Ca2+ release from the sarcoplasmic reticulum (SR), and we suggest that terbutaline, acting via cAMP, facilitates Ca2+ release from the SR to better maintain myoplasmic Ca2+ concentration during continuous tetanic stimulation. PMID:8203484

Cairns, S P; Dulhunty, A F

1994-05-01

109

Nitrogen-doped diamond electrode shows high performance for electrochemical reduction of nitrobenzene.  

PubMed

Effective electrode materials are critical to electrochemical reduction, which is a promising method to pre-treat anti-oxidative and bio-refractory wastewater. Herein, nitrogen-doped diamond (NDD) electrodes that possess superior electrocatalytic properties for reduction were fabricated by microwave-plasma-enhanced chemical vapor deposition technology. Nitrobenzene (NB) was chosen as the probe compound to investigate the material's electro-reduction activity. The effects of potential, electrolyte concentration and pH on NB reduction and aniline (AN) formation efficiencies were studied. NDD exhibited high electrocatalytic activity and selectivity for reduction of NB to AN. The NB removal efficiency and AN formation efficiency were 96.5% and 88.4% under optimal conditions, respectively; these values were 1.13 and 3.38 times higher than those of graphite electrodes. Coulombic efficiencies for NB removal and AN formation were 27.7% and 26.1%, respectively; these values were 4.70 and 16.6 times higher than those of graphite electrodes under identical conditions. LC-MS analysis revealed that the dominant reduction pathway on the NDD electrode was NB to phenylhydroxylamine (PHA) to AN. PMID:24361797

Zhang, Qing; Liu, Yanming; Chen, Shuo; Quan, Xie; Yu, Hongtao

2014-01-30

110

Ocean acidification shows negligible impacts on high-latitude bacterial community structure in coastal pelagic mesocosms  

NASA Astrophysics Data System (ADS)

The impact of ocean acidification and carbonation on microbial community structure was assessed during a large-scale in situ costal pelagic mesocosm study, included as part of the EPOCA 2010 Arctic campaign. The mesocosm experiment included ambient conditions (fjord) and nine mesocosms with pCO2 levels ranging from ~145 to ~1420 ?atm. Samples for the present study were collected at ten time points (t-1, t1, t5, t7, t12, t14, t18, t22, t26 to t28) in seven treatments (ambient fjord (~145), 2 × ~185, ~270, ~685, ~820, ~1050 ?atm) and were analysed for "small" and "large" size fraction microbial community composition using 16S RNA (ribosomal ribonucleic acid) amplicon sequencing. This high-throughput sequencing analysis produced ~20 000 000 16S rRNA V4 reads, which comprised 7000 OTUs. The main variables structuring these communities were sample origins (fjord or mesocosms) and the community size fraction (small or large size fraction). The community was significantly different between the unenclosed fjord water and enclosed mesocosms (both control and elevated CO2 treatments) after nutrients were added to the mesocosms, suggesting that the addition of nutrients is the primary driver of the change in mesocosm community structure. The relative importance of each structuring variable depended greatly on the time at which the community was sampled in relation to the phytoplankton bloom. The sampling strategy of separating the small and large size fraction was the second most important factor for community structure. When the small and large size fraction bacteria were analysed separately at different time points, the only taxon pCO2 was found to significantly affect were the Gammaproteobacteria after nutrient addition. Finally, pCO2 treatment was found to be significantly correlated (non-linear) with 15 rare taxa, most of which increased in abundance with higher CO2.

Roy, A.-S.; Gibbons, S. M.; Schunck, H.; Owens, S.; Caporaso, J. G.; Sperling, M.; Nissimov, J. I.; Romac, S.; Bittner, L.; Mühling, M.; Riebesell, U.; LaRoche, J.; Gilbert, J. A.

2013-01-01

111

Genetics  

MedlinePLUS

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

112

A Phalaenopsis variety with floral organs showing C class homeotic transformation and its revertant may enable Phalaenopsis as a potential molecular genetic material.  

PubMed

The Orchidaceae is one of the most famous garden plants, and improvement of the orchid is very important in horticulture field. However, molecular information is largely unknown. We found a Phalaenopsis variety harboring floral organs showing C class homeotic change. Column is composed of the anthers with the receptive stigmatic surface just underneath them in wild type. However the C class variety produced column with sepal or petal like structure at the abaxial side. This is the typical abnormality as C class mutants in plants. Further, wild type looking revertant was found from the meristem tissue cultured population. This result strongly indicates the existence of active transposable element in Phalaenopsis genome. This transposon may enable Phalaenopsis as a good material for molecular genetic analysis in Orchidaceae. PMID:21670548

Ejima, Chika; Kobayashi, Yuuki; Honda, Hiroaki; Shimizu, Noriko; Kiyohara, Shunsuke; Hamasaki, Ryota; Sawa, Shinichiro

2011-01-01

113

Dietary Differentiation and the Evolution of Population Genetic Structure in a Highly Mobile Carnivore  

PubMed Central

Recent studies on highly mobile carnivores revealed cryptic population genetic structures correlated to transitions in habitat types and prey species composition. This led to the hypothesis that natal-habitat-biased dispersal may be responsible for generating population genetic structure. However, direct evidence for the concordant ecological and genetic differentiation between populations of highly mobile mammals is rare. To address this we analyzed stable isotope profiles (?13C and ?15N values) for Eastern European wolves (Canis lupus) as a quantifiable proxy measure of diet for individuals that had been genotyped in an earlier study (showing cryptic genetic structure), to provide a quantitative assessment of the relationship between individual foraging behavior and genotype. We found a significant correlation between genetic distances and dietary differentiation (explaining 46% of the variation) in both the marginal test and crucially, when geographic distance was accounted for as a co-variable. These results, interpreted in the context of other possible mechanisms such as allopatry and isolation by distance, reinforce earlier studies suggesting that diet and associated habitat choice are influencing the structuring of populations in highly mobile carnivores.

Pilot, Malgorzata; Jedrzejewski, Wlodzimierz; Sidorovich, Vadim E.; Meier-Augenstein, Wolfram; Hoelzel, A. Rus

2012-01-01

114

High risks of losing genetic diversity in an endemic mauritian gecko: implications for conservation.  

PubMed

Genetic structure can be a consequence of recent population fragmentation and isolation, or a remnant of historical localised adaptation. This poses a challenge for conservationists since misinterpreting patterns of genetic structure may lead to inappropriate management. Of 17 species of reptile originally found in Mauritius, only five survive on the main island. One of these, Phelsuma guimbeaui (lowland forest day gecko), is now restricted to 30 small isolated subpopulations following severe forest fragmentation and isolation due to human colonisation. We used 20 microsatellites in ten subpopulations and two mitochondrial DNA (mtDNA) markers in 13 subpopulations to: (i) assess genetic diversity, population structure and genetic differentiation of subpopulations; (ii) estimate effective population sizes and migration rates of subpopulations; and (iii) examine the phylogenetic relationships of haplotypes found in different subpopulations. Microsatellite data revealed significant population structure with high levels of genetic diversity and isolation by distance, substantial genetic differentiation and no migration between most subpopulations. MtDNA, however, showed no evidence of population structure, indicating that there was once a genetically panmictic population. Effective population sizes of ten subpopulations, based on microsatellite markers, were small, ranging from 44 to 167. Simulations suggested that the chance of survival and allelic diversity of some subpopulations will decrease dramatically over the next 50 years if no migration occurs. Our DNA-based evidence reveals an urgent need for a management plan for the conservation of P. guimbeaui. We identified 18 threatened and 12 viable subpopulations and discuss a range of management options that include translocation of threatened subpopulations to retain maximum allelic diversity, and habitat restoration and assisted migration to decrease genetic erosion and inbreeding for the viable subpopulations. PMID:24963708

Buckland, Steeves; Cole, Nik C; Groombridge, Jim J; Küpper, Clemens; Burke, Terry; Dawson, Deborah A; Gallagher, Laura E; Harris, Stephen

2014-01-01

115

High Risks of Losing Genetic Diversity in an Endemic Mauritian Gecko: Implications for Conservation  

PubMed Central

Genetic structure can be a consequence of recent population fragmentation and isolation, or a remnant of historical localised adaptation. This poses a challenge for conservationists since misinterpreting patterns of genetic structure may lead to inappropriate management. Of 17 species of reptile originally found in Mauritius, only five survive on the main island. One of these, Phelsuma guimbeaui (lowland forest day gecko), is now restricted to 30 small isolated subpopulations following severe forest fragmentation and isolation due to human colonisation. We used 20 microsatellites in ten subpopulations and two mitochondrial DNA (mtDNA) markers in 13 subpopulations to: (i) assess genetic diversity, population structure and genetic differentiation of subpopulations; (ii) estimate effective population sizes and migration rates of subpopulations; and (iii) examine the phylogenetic relationships of haplotypes found in different subpopulations. Microsatellite data revealed significant population structure with high levels of genetic diversity and isolation by distance, substantial genetic differentiation and no migration between most subpopulations. MtDNA, however, showed no evidence of population structure, indicating that there was once a genetically panmictic population. Effective population sizes of ten subpopulations, based on microsatellite markers, were small, ranging from 44 to 167. Simulations suggested that the chance of survival and allelic diversity of some subpopulations will decrease dramatically over the next 50 years if no migration occurs. Our DNA-based evidence reveals an urgent need for a management plan for the conservation of P. guimbeaui. We identified 18 threatened and 12 viable subpopulations and discuss a range of management options that include translocation of threatened subpopulations to retain maximum allelic diversity, and habitat restoration and assisted migration to decrease genetic erosion and inbreeding for the viable subpopulations.

Buckland, Steeves; Cole, Nik C.; Groombridge, Jim J.; Kupper, Clemens; Burke, Terry; Dawson, Deborah A.; Gallagher, Laura E.; Harris, Stephen

2014-01-01

116

High and Distinct Range-Edge Genetic Diversity despite Local Bottlenecks  

PubMed Central

The genetic consequences of living on the edge of distributional ranges have been the subject of a largely unresolved debate. Populations occurring along persistent low latitude ranges (rear-edge) are expected to retain high and unique genetic diversity. In contrast, currently less favourable environmental conditions limiting population size at such range-edges may have caused genetic erosion that prevails over past historical effects, with potential consequences on reducing future adaptive capacity. The present study provides an empirical test of whether population declines towards a peripheral range might be reflected on decreasing diversity and increasing population isolation and differentiation. We compare population genetic differentiation and diversity with trends in abundance along a latitudinal gradient towards the peripheral distribution range of Saccorhizapolyschides, a large brown seaweed that is the main structural species of kelp forests in SW Europe. Signatures of recent bottleneck events were also evaluated to determine whether the recently recorded distributional shifts had a negative influence on effective population size. Our findings show decreasing population density and increasing spatial fragmentation and local extinctions towards the southern edge. Genetic data revealed two well supported groups with a central contact zone. As predicted, higher differentiation and signs of bottlenecks were found at the southern edge region. However, a decrease in genetic diversity associated with this pattern was not verified. Surprisingly, genetic diversity increased towards the edge despite bottlenecks and much lower densities, suggesting that extinctions and recolonizations have not strongly reduced diversity or that diversity might have been even higher there in the past, a process of shifting genetic baselines.

Assis, Jorge; Castilho Coelho, Nelson; Alberto, Filipe; Valero, Myriam; Raimondi, Pete; Reed, Dan; Alvares Serrao, Ester

2013-01-01

117

Sarcoidosis with high serum levels of vascular endothelial growth factor (VEGF), showing RS3PE-like symptoms in extremities  

Microsoft Academic Search

We report a patient with sarcoidosis who showed edema in the distal portion of all extremities, particularly the legs, as seen in remitting seronegative symmetrical synovitis with pitting edema (RS3PE). Magnetic resonance imaging demonstrated diffuse abnormal intensity in subcutaneous tissues of both legs, and skin biopsy led to a diagnosis of sarcoidosis. Vascular endothelial growth factor (VEGF) showed a high

Masayuki Matsuda; Kumi Sakurai; Tomohisa Fushimi; Kanji Yamamoto; Shiho Rokuhara; Naritoshi Hosaka; Shu-ichi Ikeda

2004-01-01

118

High-definition genome profiling for genetic marker discovery  

Microsoft Academic Search

Genetic mapping is a key step towards isolating genes and genetic markers associated with phenotypic traits by elucidating their genetic positions. The success of this approach depends on precision in pinpointing genetic positions and the effectiveness of the discovery process. Recent advances in microarray technology and the increasing availability of genomic information have provided an opportunity to use microarrays to

Tong Zhu; John Salmeron

2007-01-01

119

High-throughput neuroimaging-genetics computational infrastructure.  

PubMed

Many contemporary neuroscientific investigations face significant challenges in terms of data management, computational processing, data mining, and results interpretation. These four pillars define the core infrastructure necessary to plan, organize, orchestrate, validate, and disseminate novel scientific methods, computational resources, and translational healthcare findings. Data management includes protocols for data acquisition, archival, query, transfer, retrieval, and aggregation. Computational processing involves the necessary software, hardware, and networking infrastructure required to handle large amounts of heterogeneous neuroimaging, genetics, clinical, and phenotypic data and meta-data. Data mining refers to the process of automatically extracting data features, characteristics and associations, which are not readily visible by human exploration of the raw dataset. Result interpretation includes scientific visualization, community validation of findings and reproducible findings. In this manuscript we describe the novel high-throughput neuroimaging-genetics computational infrastructure available at the Institute for Neuroimaging and Informatics (INI) and the Laboratory of Neuro Imaging (LONI) at University of Southern California (USC). INI and LONI include ultra-high-field and standard-field MRI brain scanners along with an imaging-genetics database for storing the complete provenance of the raw and derived data and meta-data. In addition, the institute provides a large number of software tools for image and shape analysis, mathematical modeling, genomic sequence processing, and scientific visualization. A unique feature of this architecture is the Pipeline environment, which integrates the data management, processing, transfer, and visualization. Through its client-server architecture, the Pipeline environment provides a graphical user interface for designing, executing, monitoring validating, and disseminating of complex protocols that utilize diverse suites of software tools and web-services. These pipeline workflows are represented as portable XML objects which transfer the execution instructions and user specifications from the client user machine to remote pipeline servers for distributed computing. Using Alzheimer's and Parkinson's data, we provide several examples of translational applications using this infrastructure. PMID:24795619

Dinov, Ivo D; Petrosyan, Petros; Liu, Zhizhong; Eggert, Paul; Hobel, Sam; Vespa, Paul; Woo Moon, Seok; Van Horn, John D; Franco, Joseph; Toga, Arthur W

2014-01-01

120

High-throughput neuroimaging-genetics computational infrastructure  

PubMed Central

Many contemporary neuroscientific investigations face significant challenges in terms of data management, computational processing, data mining, and results interpretation. These four pillars define the core infrastructure necessary to plan, organize, orchestrate, validate, and disseminate novel scientific methods, computational resources, and translational healthcare findings. Data management includes protocols for data acquisition, archival, query, transfer, retrieval, and aggregation. Computational processing involves the necessary software, hardware, and networking infrastructure required to handle large amounts of heterogeneous neuroimaging, genetics, clinical, and phenotypic data and meta-data. Data mining refers to the process of automatically extracting data features, characteristics and associations, which are not readily visible by human exploration of the raw dataset. Result interpretation includes scientific visualization, community validation of findings and reproducible findings. In this manuscript we describe the novel high-throughput neuroimaging-genetics computational infrastructure available at the Institute for Neuroimaging and Informatics (INI) and the Laboratory of Neuro Imaging (LONI) at University of Southern California (USC). INI and LONI include ultra-high-field and standard-field MRI brain scanners along with an imaging-genetics database for storing the complete provenance of the raw and derived data and meta-data. In addition, the institute provides a large number of software tools for image and shape analysis, mathematical modeling, genomic sequence processing, and scientific visualization. A unique feature of this architecture is the Pipeline environment, which integrates the data management, processing, transfer, and visualization. Through its client-server architecture, the Pipeline environment provides a graphical user interface for designing, executing, monitoring validating, and disseminating of complex protocols that utilize diverse suites of software tools and web-services. These pipeline workflows are represented as portable XML objects which transfer the execution instructions and user specifications from the client user machine to remote pipeline servers for distributed computing. Using Alzheimer's and Parkinson's data, we provide several examples of translational applications using this infrastructure1.

Dinov, Ivo D.; Petrosyan, Petros; Liu, Zhizhong; Eggert, Paul; Hobel, Sam; Vespa, Paul; Woo Moon, Seok; Van Horn, John D.; Franco, Joseph; Toga, Arthur W.

2014-01-01

121

A class of highly polymorphic tetranucleotide repeats for canine genetic mapping  

Microsoft Academic Search

We have identified and characterized a new class of polymorphic markers for the canine genome from a simple tetranucleotide\\u000a repeat sequence, (GAAA)n. Genetic markers derived from this repeat are highly polymorphic compared with other canine microsatellites, yet are stable\\u000a enough to be useful for following Mendelian inheritance in multigeneration pedigrees. We show further that (GAAA)n repeats are distributed throughout the

L. V. Francisco; A. A. Langsten; C. S. Mellersh; C. L. Neal; E. A. Ostrander

1996-01-01

122

MHC ANTIGEN-BINDING LOCUS SHOWS STRONG SIGNAL OF SELECTION AND HIGH VARIABILITY IN FUNDULUS HETEROCLITUS POPULATIONS  

EPA Science Inventory

The major histocompatibility system provides a unique genetic locus in vertebrates to assess genetic diversity and to look for the effects of selecti.on on the immune system. Fish population studies using MHC are fairly new, and thus far they have focused on endangered population...

123

MHC ANTIGEN BINDING LOCUS DRB1 SHOWS STRONG SIGNAL OF SELECTION AND HIGH VARIABILITY IN FUNDULUS HETERCLITUS POPULATIONS  

EPA Science Inventory

The major histocompatibility system provides a unique complex of genetic loci in vertebrates to assess genetic diversity and to look for the effects of selection on the adaptive immune system. Studies using mammals and birds have demonstrated relationships between MHC genotyp...

124

High Levels of Genetic Recombination during Nasopharyngeal Carriage and Biofilm Formation in Streptococcus pneumoniae  

PubMed Central

ABSTRACT Transformation of genetic material between bacteria was first observed in the 1920s using Streptococcus pneumoniae as a model organism. Since then, the mechanism of competence induction and transformation has been well characterized, mainly using planktonic bacteria or septic infection models. However, epidemiological evidence suggests that genetic exchange occurs primarily during pneumococcal nasopharyngeal carriage, which we have recently shown is associated with biofilm growth, and is associated with cocolonization with multiple strains. However, no studies to date have comprehensively investigated genetic exchange during cocolonization in vitro and in vivo or the role of the nasopharyngeal environment in these processes. In this study, we show that genetic exchange during dual-strain carriage in vivo is extremely efficient (10?2) and approximately 10,000,000-fold higher than that measured during septic infection (10?9). This high transformation efficiency was associated with environmental conditions exclusive to the nasopharynx, including the lower temperature of the nasopharynx (32 to 34°C), limited nutrient availability, and interactions with epithelial cells, which were modeled in a novel biofilm model in vitro that showed similarly high transformation efficiencies. The nasopharyngeal environmental factors, combined, were critical for biofilm formation and induced constitutive upregulation of competence genes and downregulation of capsule that promoted transformation. In addition, we show that dual-strain carriage in vivo and biofilms formed in vitro can be transformed during colonization to increase their pneumococcal fitness and also, importantly, that bacteria with lower colonization ability can be protected by strains with higher colonization efficiency, a process unrelated to genetic exchange.

Marks, Laura R.; Reddinger, Ryan M.; Hakansson, Anders P.

2012-01-01

125

High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12.  

PubMed Central

Epidemiological studies have shown that genetic factors contribute to the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Recent genome scans and replication studies have identified replicated linkage between CD and a locus on chromosome 16 (the IBD1 locus), replicated linkage between IBD (especially UC) and a locus on chromosome 12q (the IBD2 locus), and replicated linkage between IBD (especially CD) and a locus on chromosome 6p (the IBD3 locus). Since the estimated locus-specific lambdas values for the regions of replicated linkage do not account for the overall lambdas in CD, and since the published genome scans in IBD show at least nominal evidence for linkage to regions on all but two chromosomes, we performed an independent genome scan using 751 microsatellite loci in 127 CD-affected relative pairs from 62 families. Single-point nonparametric linkage analysis using the GENEHUNTER-PLUS program shows evidence for linkage to the adjacent D14S261 and D14S283 loci on chromosome 14q11-12 (LOD = 3.00 and 1.70, respectively), and the maximal multipoint LOD score is observed at D14S261 (LOD = 3.60). In the multipoint analysis, nominal evidence for linkage (P<.05) is observed near D2S117 (LOD = 1.25), near D3S3045 (LOD = 1.31), between D7S40 and D7S648 (LOD = 0.91), and near D18S61 (LOD = 1.15). Our finding of significant linkage to D14S261 and the finding of suggestive linkage to the same locus in an independent study (multipoint LOD = 2.8) satisfies criteria for confirmed linkage, so we propose that the region of interest on chromosome 14q11-12 should be designated the IBD4 locus.

Duerr, R H; Barmada, M M; Zhang, L; Pfutzer, R; Weeks, D E

2000-01-01

126

Toward a generalized and high-throughput enzyme screening system based on artificial genetic circuits.  

PubMed

Large-scale screening of enzyme libraries is essential for the development of cost-effective biological processes, which will be indispensable for the production of sustainable biobased chemicals. Here, we introduce a genetic circuit termed the Genetic Enzyme Screening System that is highly useful for high-throughput enzyme screening from diverse microbial metagenomes. The circuit consists of two AND logics. The first AND logic, the two inputs of which are the target enzyme and its substrate, is responsible for the accumulation of a phenol compound in cell. Then, the phenol compound and its inducible transcription factor, whose activation turns on the expression of a reporter gene, interact in the other logic gate. We confirmed that an individual cell harboring this genetic circuit can present approximately a 100-fold higher cellular fluorescence than the negative control and can be easily quantified by flow cytometry depending on the amounts of phenolic derivatives. The high sensitivity of the genetic circuit enables the rapid discovery of novel enzymes from metagenomic libraries, even for genes that show marginal activities in a host system. The crucial feature of this approach is that this single system can be used to screen a variety of enzymes that produce a phenol compound from respective synthetic phenyl-substrates, including cellulase, lipase, alkaline phosphatase, tyrosine phenol-lyase, and methyl parathion hydrolase. Consequently, the highly sensitive and quantitative nature of this genetic circuit along with flow cytometry techniques could provide a widely applicable toolkit for discovering and engineering novel enzymes at a single cell level. PMID:24295047

Choi, Su-Lim; Rha, Eugene; Lee, Sang Jun; Kim, Haseong; Kwon, Kilkoang; Jeong, Young-Su; Rhee, Young Ha; Song, Jae Jun; Kim, Hak-Sung; Lee, Seung-Goo

2014-03-21

127

Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice.  

PubMed

Obesity is a highly heritable disease driven by complex interactions between genetic and environmental factors. Human genome-wide association studies (GWAS) have identified a number of loci contributing to obesity; however, a major limitation of these studies is the inability to assess environmental interactions common to obesity. Using a systems genetics approach, we measured obesity traits, global gene expression, and gut microbiota composition in response to a high-fat/high-sucrose (HF/HS) diet of more than 100 inbred strains of mice. Here we show that HF/HS feeding promotes robust, strain-specific changes in obesity that are not accounted for by food intake and provide evidence for a genetically determined set point for obesity. GWAS analysis identified 11 genome-wide significant loci associated with obesity traits, several of which overlap with loci identified in human studies. We also show strong relationships between genotype and gut microbiota plasticity during HF/HS feeding and identify gut microbial phylotypes associated with obesity. PMID:23312289

Parks, Brian W; Nam, Elizabeth; Org, Elin; Kostem, Emrah; Norheim, Frode; Hui, Simon T; Pan, Calvin; Civelek, Mete; Rau, Christoph D; Bennett, Brian J; Mehrabian, Margarete; Ursell, Luke K; He, Aiqing; Castellani, Lawrence W; Zinker, Bradley; Kirby, Mark; Drake, Thomas A; Drevon, Christian A; Knight, Rob; Gargalovic, Peter; Kirchgessner, Todd; Eskin, Eleazar; Lusis, Aldons J

2013-01-01

128

Genetic Control of Obesity and Gut Microbiota Composition in Response to High-Fat, High-Sucrose Diet in Mice  

PubMed Central

SUMMARY Obesity is a highly heritable disease driven by complex interactions between genetic and environmental factors. Human genome-wide association studies (GWAS) have identified a number of loci contributing to obesity; however, a major limitation of these studies is the inability to assess environmental interactions common to obesity. Using a systems genetics approach, we measured obesity traits, global gene expression, and gut microbiota composition in response to a high-fat/high-sucrose (HF/HS) diet of more than 100 inbred strains of mice. Here we show that HF/HS feeding promotes robust, strain-specific changes in obesity that is not accounted for by food intake and provide evidence for a genetically determined set-point for obesity. GWAS analysis identified 11 genome-wide significant loci associated with obesity traits, several of which overlap with loci identified in human studies. We also show strong relationships between genotype and gut microbiota plasticity during HF/HS feeding and identify gut microbial phylotypes associated with obesity.

Parks, Brian W.; Nam, Elizabeth; Org, Elin; Kostem, Emrah; Norheim, Frode; Hui, Simon T.; Pan, Calvin; Civelek, Mete; Rau, Christoph D.; Bennett, Brian J.; Mehrabian, Margarete; Ursell, Luke K.; He, Aiqing; Castellani, Lawrence W.; Zinker, Bradley; Kirby, Mark; Drake, Thomas A.; Drevon, Christian A.; Knight, Rob; Gargalovic, Peter; Kirchgessner, Todd; Eskin, Eleazar; Lusis, Aldons J.

2013-01-01

129

"The Show"  

ERIC Educational Resources Information Center

For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the state's best…

Gehring, John

2004-01-01

130

Genetics  

NSDL National Science Digital Library

This Genetics activity helps students to understand the basic principles of genetics, including concepts of recessive and dominant alleles, relationships of phenotype to genotype, Punnett squares, and pedigree analysis. The introductory section on inheritance of albinism demonstrates how understanding meiosis and fertilization provides the basis for understanding inheritance and Punnett squares. The next two sections, Coin Toss Genetics and analysis of class data on the sex makeup of sibships, help students understand the probabilistic nature of Punnett square predictions. The final activities analyze the genetics of sickle cell anemia and pedigrees for families with albinism and achondroplasia.

Doherty, Jennifer; Waldron, Ingrid; Poethig, Scott

131

Pol III binding in six mammalian genomes shows high conservation among amino acid isotypes, despite divergence in tRNA gene usage  

PubMed Central

RNA polymerase III (pol III) transcription of transfer RNA (tRNA) genes is essential for generating the tRNA adapter molecules that link genetic sequence and protein translation. By mapping pol III occupancy genome-wide in the livers of mouse, rat, human, macaque, dog and opossum, we found that pol III binding to individual tRNA genes varies substantially in strength and location. However, taking into account tRNA redundancies by grouping pol III occupancy into 46 anticodon isoacceptor families or 21 amino acid-based isotype classes shows strong conservation. Similarly, pol III occupancy of amino-acid isotypes is almost invariant among transcriptionally and evolutionarily diverse tissues in mouse. Thus, synthesis of functional tRNA isotypes has been highly constrained, though the usage of individual tRNA genes has evolved rapidly.

Kutter, Claudia; Brown, Gordon D.; Goncalves, Angela; Wilson, Michael D.; Watt, Stephen; Brazma, Alvis; White, Robert J.; Odom, Duncan T.

2011-01-01

132

31-year-old female shows marked improvement in depression, agitation, and panic attacks after genetic testing was used to inform treatment.  

PubMed

This case describes a 31-year-old female Caucasian patient with complaints of ongoing depression, agitation, and severe panic attacks. The patient was untreated until a recent unsuccessful trial of citalopram followed by venlafaxine which produced a partial response. Genetic testing was performed to assist in treatment decisions and revealed the patient to be heterozygous for polymorphisms in 5HT2C, ANK3, and MTHFR and homozygous for a polymorphism in SLC6A4 and the low activity (Met/Met) COMT allele. In response to genetic results and clinical presentation, venlafaxine was maintained and lamotrigine was added leading to remission of agitation and depression. PMID:24744941

Lawrence, Scott

2014-01-01

133

High-quality DNA from fingernails for genetic analysis.  

PubMed

The availability of high-quality germline DNA is an important prerequisite for a variety of genetic analyses. We have shown previously that fingernail clippings provide an optimal source of autologous, constitutional DNA for PCR-based applications. However, most existing protocols for nucleic acid purification from nails do not provide sufficiently high yields of pure and intact DNA for more demanding downstream analyses such as next generation sequencing (NGS). We have extensively tested and systematically modified a number of different protocols for DNA purification from nail material to optimize the yield and quality. The integrity of DNA was determined by PCR amplification of short (<300 bp), mid-range (>400 bp), and long-range (>2 kb) sequences using different target genes. Among the methods tested, the Prepfiler Forensic DNA Extraction kit was identified as the most appropriate approach to isolation of high-quality DNA from nail clippings. A standardized input of 20 mg nail material (1 to 10 pieces of fingernail clippings) yielded a mean of 1 ?g DNA (range, 0.5 to 2.3 ?g). Subsequent PCR-analysis revealed efficient amplifiability of short and mid-range targets in 93% and 90%, and long-range fragments in 60% of the samples tested. The adequacy for next generation sequencing applications was demonstrated by successful high-resolution HLA-typing in ten transplant recipients. Hence, the protocol presented facilitates the exploitation of fingernail material even for demanding genomic analyses both in research and diagnostics. PMID:24795088

Preuner, Sandra; Danzer, Martin; Pröll, Johannes; Pötschger, Ulrike; Lawitschka, Anita; Gabriel, Christian; Lion, Thomas

2014-07-01

134

A Comprehensive Analysis of High School Genetics Standards: Are States Keeping Pace with Modern Genetics?  

PubMed Central

Science education in the United States will increasingly be driven by testing and accountability requirements, such as those mandated by the No Child Left Behind Act, which rely heavily on learning outcomes, or “standards,” that are currently developed on a state-by-state basis. Those standards, in turn, drive curriculum and instruction. Given the importance of standards to teaching and learning, we investigated the quality of life sciences/biology standards with respect to genetics for all 50 states and the District of Columbia, using core concepts developed by the American Society of Human Genetics as normative benchmarks. Our results indicate that the states’ genetics standards, in general, are poor, with more than 85% of the states receiving overall scores of Inadequate. In particular, the standards in virtually every state have failed to keep pace with changes in the discipline as it has become genomic in scope, omitting concepts related to genetic complexity, the importance of environment to phenotypic variation, differential gene expression, and the differences between inherited and somatic genetic disease. Clearer, more comprehensive genetics standards are likely to benefit genetics instruction and learning, help prepare future genetics researchers, and contribute to the genetic literacy of the U.S. citizenry.

Dougherty, M.J.; Pleasants, C.; Solow, L.; Wong, A.; Zhang, H.

2011-01-01

135

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits  

PubMed Central

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10?8), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

Jackson, Anne U.; Monda, Keri L.; Kilpelainen, Tuomas O.; Esko, Tonu; Magi, Reedik; Li, Shengxu; Workalemahu, Tsegaselassie; Feitosa, Mary F.; Croteau-Chonka, Damien C.; Day, Felix R.; Fall, Tove; Ferreira, Teresa; Gustafsson, Stefan; Locke, Adam E.; Mathieson, Iain; Scherag, Andre; Vedantam, Sailaja; Wood, Andrew R.; Liang, Liming; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Karpe, Fredrik; Min, Josine L.; Nicholson, George; Clegg, Deborah J.; Person, Thomas; Krohn, Jon P.; Bauer, Sabrina; Buechler, Christa; Eisinger, Kristina; Bonnefond, Amelie; Froguel, Philippe; Hottenga, Jouke-Jan; Prokopenko, Inga; Waite, Lindsay L.; Harris, Tamara B.; Smith, Albert Vernon; Shuldiner, Alan R.; McArdle, Wendy L.; Caulfield, Mark J.; Munroe, Patricia B.; Gronberg, Henrik; Chen, Yii-Der Ida; Li, Guo; Beckmann, Jacques S.; Johnson, Toby; Thorsteinsdottir, Unnur; Teder-Laving, Maris; Khaw, Kay-Tee; Wareham, Nicholas J.; Zhao, Jing Hua; Amin, Najaf; Oostra, Ben A.; Kraja, Aldi T.; Province, Michael A.; Cupples, L. Adrienne; Heard-Costa, Nancy L.; Kaprio, Jaakko; Ripatti, Samuli; Surakka, Ida; Collins, Francis S.; Saramies, Jouko; Tuomilehto, Jaakko; Jula, Antti; Salomaa, Veikko; Erdmann, Jeanette; Hengstenberg, Christian; Loley, Christina; Schunkert, Heribert; Lamina, Claudia; Wichmann, H. Erich; Albrecht, Eva; Gieger, Christian; Hicks, Andrew A.; Johansson, Asa; Pramstaller, Peter P.; Kathiresan, Sekar; Speliotes, Elizabeth K.; Penninx, Brenda; Hartikainen, Anna-Liisa; Jarvelin, Marjo-Riitta; Gyllensten, Ulf; Boomsma, Dorret I.; Campbell, Harry; Wilson, James F.; Chanock, Stephen J.; Farrall, Martin; Goel, Anuj; Medina-Gomez, Carolina; Rivadeneira, Fernando; Estrada, Karol; Uitterlinden, Andre G.; Hofman, Albert; Zillikens, M. Carola; den Heijer, Martin; Kiemeney, Lambertus A.; Maschio, Andrea; Hall, Per; Tyrer, Jonathan; Teumer, Alexander; Volzke, Henry; Kovacs, Peter; Tonjes, Anke; Mangino, Massimo; Spector, Tim D.; Hayward, Caroline; Rudan, Igor; Hall, Alistair S.; Samani, Nilesh J.; Attwood, Antony Paul; Sambrook, Jennifer G.; Hung, Joseph; Palmer, Lyle J.; Lokki, Marja-Liisa; Sinisalo, Juha; Boucher, Gabrielle; Huikuri, Heikki; Lorentzon, Mattias; Ohlsson, Claes; Eklund, Niina; Eriksson, Johan G.; Barlassina, Cristina; Rivolta, Carlo; Nolte, Ilja M.; Snieder, Harold; Van der Klauw, Melanie M.; Van Vliet-Ostaptchouk, Jana V.; Gejman, Pablo V.; Shi, Jianxin; Jacobs, Kevin B.; Wang, Zhaoming; Bakker, Stephan J. L.; Mateo Leach, Irene; Navis, Gerjan; van der Harst, Pim; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Yang, Jian; Chasman, Daniel I.; Ridker, Paul M.; Rose, Lynda M.; Lehtimaki, Terho; Raitakari, Olli; Absher, Devin; Iribarren, Carlos; Basart, Hanneke; Hovingh, Kees G.; Hypponen, Elina; Power, Chris; Anderson, Denise; Beilby, John P.; Hui, Jennie; Jolley, Jennifer; Sager, Hendrik; Bornstein, Stefan R.; Schwarz, Peter E. H.; Kristiansson, Kati; Perola, Markus; Lindstrom, Jaana; Swift, Amy J.; Uusitupa, Matti; Atalay, Mustafa; Lakka, Timo A.; Rauramaa, Rainer; Bolton, Jennifer L.; Fowkes, Gerry; Fraser, Ross M.; Price, Jackie F.; Fischer, Krista; KrjutA?kov, Kaarel; Metspalu, Andres; Mihailov, Evelin; Langenberg, Claudia; Luan, Jian'an; Ong, Ken K.; Chines, Peter S.; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Edkins, Sarah; Franks, Paul W.; Hallmans, Goran; Shungin, Dmitry; Morris, Andrew David; Palmer, Colin N. A.; Erbel, Raimund; Moebus, Susanne; Nothen, Markus M.; Pechlivanis, Sonali; Hveem, Kristian; Narisu, Narisu; Hamsten, Anders; Humphries, Steve E.; Strawbridge, Rona J.; Tremoli, Elena; Grallert, Harald; Thorand, Barbara; Illig, Thomas; Koenig, Wolfgang; Muller-Nurasyid, Martina; Peters, Annette; Boehm, Bernhard O.; Kleber, Marcus E.; Marz, Winfried; Winkelmann, Bernhard R.; Kuusisto, Johanna; Laakso, Markku; Arveiler, Dominique; Cesana, Giancarlo; Kuulasmaa, Kari; Virtamo, Jarmo; Yarnell, John W. G.; Kuh, Diana; Wong, Andrew; Lind, Lars; de Faire, Ulf; Gigante, Bruna; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Dedoussis, George; Dimitriou, Maria; Kolovou, Genovefa; Kanoni, Stavroula; Stirrups, Kathleen; Bonnycastle, Lori L.; Nj?lstad, Inger; Wilsgaard, Tom; Ganna, Andrea; Rehnberg, Emil; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena; Assimes, Themistocles L.; Barroso, Ines; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Frayling, Timothy; Groop, Leif C.; Haritunians, Talin; Hunter, David; Ingelsson, Erik; Kaplan, Robert; Mohlke, Karen L.; O'Connell, Jeffrey R.; Schlessinger, David

2013-01-01

136

Awareness of Societal Issues among High School Biology Teachers Teaching Genetics  

ERIC Educational Resources Information Center

The purpose of this study was to investigate how aware high school biology teachers are of societal issues (values, moral, ethic, and legal issues) while teaching genetics, genetics engineering, molecular genetics, human heredity, and evolution. The study includes a short historical review of World War II atrocities during the Holocaust when…

Lazarowitz, Reuven; Bloch, Ilit

2005-01-01

137

A tellurium-substituted Lindqvist-type polyoxoniobate showing high H(2) evolution catalyzed by tellurium nanowires via photodecomposition.  

PubMed

A new tellurium-substituted Lindqvist-type polyoxoniobate [H2TeNb5O19](5-) was synthesized as a tetramethylammonium salt. When irradiated with a Xe lamp, a water-methanol solution of this cluster showed exceptionally high H2-evolution activity suggesting cocatalysis by the hexaniobate cluster and metallic tellurium, both of which are formed as photodecomposition products. PMID:24292440

Son, Jung-Ho; Wang, Jiarui; Osterloh, Frank E; Yu, Ping; Casey, William H

2014-01-25

138

Copper tolerance and genetic diversity of Porcellionides sexfasciatus (ISOPODA) in a highly contaminated mine habitat.  

PubMed

Organisms inhabiting metal-contaminated areas may develop metal tolerance, with either phenotypic adjustments or genetic changes (adaptation) or with both. In the present study, three populations of the terrestrial isopod Porcellionides sexfasciatus, collected at an abandoned mine area, were compared to assess the effects of metal contamination on tolerance to lethal and sublethal levels of copper, through comparison of survival, avoidance, and feeding. The effects of metal contamination on genetic diversity were considered using random amplified polymorphic DNA (RAPD) markers. No evidence of increased metal tolerance of the population inhabiting the contaminated site was found. There was no correlation between metal exposure and within-population genetic variance, but the three populations were clearly separated from each other. In conclusion, the populations of P. sexfasciatus in the mine landscape live rather isolated from each other and show no differential tolerance to Cu or indications of genetic erosion. Their phenotypic plasticity provides a means to survive despite exposure to extremely high metal concentrations in the soil. PMID:23322508

Costa, Dalila; Bouchon, Didier; van Straalen, Nico M; Sousa, José Paulo; Ribeiro, Rui

2013-04-01

139

High-velocity Frictional Behavior of Dunite, Biotite Gneiss, Phyllite and Coal Show Evidence for Melting and Thermal Degasing  

NASA Astrophysics Data System (ADS)

We conducted high-velocity frictional experiments on dunite, biotite gneiss, phyllite gouge and coal gouge at Kyoto University using a rotary high-velocity frictional testing machine. The purpose was to examine the effect of frictional melting in various rock types and to explore the effect of thermal degassing using coal as an analogue for a volatile fault zone. Experiments were conducted dry at equivalent slip rates of 1 m/s (1200 rpm) at normal stresses of 0.6-16 MPa for distances up to 90 m. Solid cylinders (25 mm diameter) of dunite and biotite gneiss were sheared with aluminum-alloy jackets at high stress, whereas phyllite and coal gouges were sheared with Teflon sleeves at low stress. The metal jackets allow high stress experiments to be performed and are inferred to melt before rock melting occurs. Dunite sheared at 10-16 MPa shows a weakening-strengthening followed by second weakening on melting, similar to previous experiments on gabbro without a metal jacket. Dunite melting is confirmed by, as yet unidentified, dendritic microlites, and a rapid reduction of steady-state frictional strength to 0.15. Under similar conditions, biotite gneiss shows apparent melting, but undergoes continuous strengthening without reaching steady state. Bituminous coal gouge sheared at 0.6 MPa undergoes a highly reproducible rapid weakening from 0.75 to 0.2, with odorous white gas emissions, sometimes accompanied by liquid hydrocarbons. Shear stress decreases prior to gasification and rapidly oscillating sample shortening/elongation occurs during gas emission. A slowly sheared sample (15 rpm) did not show weakening or gas emission. This is the first experimental demonstration of weakening associated with devolatilization during rapid slip. Vitrinite reflectance measurements on sheared coal samples may provide constraints on the temperature during gasification. Phyllite gouge sheared under the same conditions shows a gradual weakening to a steady-state strength of about 0.2; the weakening mechanism is not yet understood. Video presentations with mechanical and petrological data will illustrate these different behaviors.

O'Hara, K. D.; Mizoguchi, K.; Shimamoto, T.

2004-12-01

140

In vivo methods for testing allergenicity show that high hydrostatic pressure hydrolysates of ?-lactoglobulin are immunologically inert.  

PubMed

The major milk allergen ?-lactoglobulin (?-LG) exhibits an enhanced susceptibility to proteolysis under high hydrostatic pressure and this may be an efficient method to produce hypoallergenic hydrolysates. The aim of this work was to evaluate the in vivo allergenicity of 3 ?-LG hydrolysates produced under atmospheric pressure or high-pressure conditions. Hydrolysates were chosen based on previous experiments that showed that they provide a complete removal of intact ?-LG but differed in vitro IgE-binding properties that could be traced to the peptide pattern. The ability to trigger systemic anaphylaxis was assessed using C3H/HeJ mice orally sensitized to ?-LG. Outcome measures included symptom score, body temperature, serum mouse mast cell protease 1 (mMCP-1), and quantification of circulating basophils. Mast cell degranulation in vivo was assessed by passive cutaneous anaphylaxis. The 3 tested hydrolysates showed an abrogated allergenicity as revealed by the absence of anaphylactic symptoms and a decrease in body temperature. We demonstrated that the peptides present in the hydrolysates had lost their ability to cross-link 2 human IgE antibodies to induce mast cell degranulation, thus indicating that most of the peptides formed retain just one relevant IgE-binding epitope. The orally sensitized mouse model is a useful tool to address the in vivo allergenicity of novel milk formulas and demonstrates the safety of hydrolysates produced under high-pressure conditions. PMID:22281318

López-Expósito, I; Chicón, R; Belloque, J; López-Fandiño, R; Berin, M C

2012-02-01

141

Advances in the genetics of schizophrenia: will high-risk copy number variants be useful in clinical genetics or diagnostics?  

PubMed Central

Schizophrenia is a highly heritable, common mental illness, affecting 1% of the population worldwide. It is currently diagnosed using exclusive clinical criteria, and at present there are no genetic tests to facilitate this process. There are also no reliable means to predict who will develop the disease in later life. Genetic counselling uses crude estimates of risk based on family history, as the strongest predictive factor is having an affected first-degree relative. It has recently become apparent that large de novo deletions in the genome (copy number variants, or CNVs) can increase risk of the disease by tenfold or more. The purpose of this report is to assess whether these ‘high risk’ pathogenic CNVs might be useful in a clinical genetic or diagnostic setting. Routine use of laboratory techniques such as comparative genome hybridisation will reveal these de novo CNVs in standard investigative procedures for referrals to clinical genetics. The lack of disease specificity of CNVs presents problems for their use in diagnosis at present. Currently, there is also insufficient evidence in relation to schizophrenia to suggest that clear clinical benefit would be gained from learning one's genetic status pre-symptomatically. However, this is likely to change rapidly in the near future as knowledge of the genetic and environmental basis of schizophrenia accrues and increasingly effective measures for early intervention and risk reduction are developed.

Vassos, Evangelos; Holden, Simon; Patch, Christine; McGuire, Philip; Lewis, Cathryn

2009-01-01

142

Sarcoidosis with high serum levels of vascular endothelial growth factor (VEGF), showing RS3PE-like symptoms in extremities.  

PubMed

We report a patient with sarcoidosis who showed edema in the distal portion of all extremities, particularly the legs, as seen in remitting seronegative symmetrical synovitis with pitting edema (RS3PE). Magnetic resonance imaging demonstrated diffuse abnormal intensity in subcutaneous tissues of both legs, and skin biopsy led to a diagnosis of sarcoidosis. Vascular endothelial growth factor (VEGF) showed a high serum level, which decreased soon after starting oral prednisolone, in parallel with an improvement in the limb edema. In this patient VEGF as well as infiltration by sarcoid granuloma in the skin might have played an important role in the pathogenesis of RS3PE-like symptoms in the extremities. When painful pitting edema is seen predominantly in the distal portion of all extremities, sarcoidosis as well as RS3PE should be considered as a possible diagnosis. PMID:15168155

Matsuda, Masayuki; Sakurai, Kumi; Fushimi, Tomohisa; Yamamoto, Kanji; Rokuhara, Shiho; Hosaka, Naritoshi; Ikeda, Shu-ichi

2004-06-01

143

Mixing does the magic: a rapid synthesis of high surface area noble metal nanosponges showing broadband nonlinear optical response.  

PubMed

Here we report an instantaneous formation of high surface area metal nanosponges through a one-step inexpensive method in a completely green solvent, water. Merely by optimizing the concentration of the precursors and the reducing agent, we were able to generate a three-dimensional porous structure made up of nanowire networks. This is a general process, involves a simple, room temperature reduction of metal salts with sodium borohydride, and is therefore scalable to any amount. Further, these nanoporous metals because of their network structures show optical limiting behavior of a true broadband nature that would find applications in optoelectronic nanodevices. PMID:20443580

Krishna, Katla Sai; Sandeep, C S Suchand; Philip, Reji; Eswaramoorthy, Muthusamy

2010-05-25

144

Perspectives of couples with high risk of transmitting genetic disorders  

Microsoft Academic Search

Objective: To investigate the preference for preimplantation genetic diagnosis (PGD) as an alternative to prenatal diagnosis (PND) in a large group of couples representing a wide array of genetic disorders. We also investigated the couple's familiarity with PGD and presented time trade-off scenarios for PGD versus PND, as PGD treatment is regularly accompanied by waiting lists. Design: Questionnaire study. Setting:

Anna M. Musters; Moniek Twisk; Nico J. Leschot; Cor Oosterwijk; Johanna C. Korevaar; Sjoerd Repping; Fulco van der Veen; Mariette Goddijn

2010-01-01

145

High School Students' Use of Meiosis When Solving Genetics Problems.  

ERIC Educational Resources Information Center

Paints a different picture of students' reasoning with meiosis as they solved complex, computer-generated genetics problems, some of which required them to revise their understanding of meiosis in response to anomalous data. Students were able to develop a rich understanding of meiosis and can utilize that knowledge to solve genetics problems.…

Wynne, Cynthia F.; Stewart, Jim; Passmore, Cindy

2001-01-01

146

A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment  

PubMed Central

Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments.

Gaburro, Stefano; Stiedl, Oliver; Giusti, Pietro; Sartori, Simone B.; Landgraf, Rainer; Singewald, Nicolas

2011-01-01

147

Accessing Genetic Information with High-Density DNA Arrays  

NASA Astrophysics Data System (ADS)

Rapid access to genetic information is central to the revolution taking place in molecular genetics. The simultaneous analysis of the entire human mitochondrial genome is described here. DNA arrays containing up to 135,000 probes complementary to the 16.6-kilobase human mitochondrial genome were generated by light-directed chemical synthesis. A two-color labeling scheme was developed that allows simultaneous comparison of a polymorphic target to a reference DNA or RNA. Complete hybridization patterns were revealed in a matter of minutes. Sequence polymorphisms were detected with single-base resolution and unprecedented efficiency. The methods described are generic and can be used to address a variety of questions in molecular genetics including gene expression, genetic linkage, and genetic variability.

Chee, Mark; Yang, Robert; Hubbell, Earl; Berno, Anthony; Huang, Xiaohua C.; Stern, David; Winkler, Jim; Lockhart, David J.; Morris, Macdonald S.; Fodor, Stephen P. A.

1996-10-01

148

High Quality Typhoon Cloud Image Restoration by Combining Genetic Algorithm with Contourlet Transform  

SciTech Connect

An efficient typhoon cloud image restoration algorithm is proposed. Having implemented contourlet transform to a typhoon cloud image, noise is reduced in the high sub-bands. Weight median value filter is used to reduce the noise in the contourlet domain. Inverse contourlet transform is done to obtain the de-noising image. In order to enhance the global contrast of the typhoon cloud image, in-complete Beta transform (IBT) is used to determine non-linear gray transform curve so as to enhance global contrast for the de-noising typhoon cloud image. Genetic algorithm is used to obtain the optimal gray transform curve. Information entropy is used as the fitness function of the genetic algorithm. Experimental results show that the new algorithm is able to well enhance the global for the typhoon cloud image while well reducing the noises in the typhoon cloud image.

Zhang Changjiang; Wang Xiaodong [College of Mathematics, Physics and Information Engineering, Zhejiang Normal University, Jinhua (China)

2008-11-06

149

The pronociceptive dorsal reticular nucleus contains mostly tonic neurons and shows a high prevalence of spontaneous activity in block preparation.  

PubMed

Despite the importance and significant clinical impact of understanding information processing in the nociceptive system, the functional properties of neurons in many parts of this system are still unknown. In this work we performed whole cell patch-clamp recording in rat brain stem blocks to characterize the electrophysiological properties of neurons in the dorsal reticular nucleus (DRt), a region known to be involved in pronociceptive modulation. We also compared properties of DRt neurons with those in the adjacent parvicellular reticular nucleus and in neighboring regions outside the reticular formation. We found that neurons in the DRt and parvicellular reticular nucleus had similar electrophysiological properties and exhibited mostly toniclike firing patterns, whereas neurons outside the reticular formation showed a larger diversity of firing patterns. Interestingly, more than one-half of the neurons also showed spontaneous activity. While the general view of the reticular formation, being a loosely associated mesh of groups of neurons with diverse function, and earlier reports suggests more electrophysiological heterogeneity, we showed that this is indeed not the case. Our results indicate that functional difference of neurons in the reticular formation may mostly be determined by their connectivity profiles and not by their intrinsic electrophysiological properties. The dominance of tonic neurons in the DRt supports previous conclusions that these neurons encode stimulus intensity through their firing frequency, while the high prevalence of spontaneous activity most likely shapes nociceptive modulation by this brain stem region. PMID:24431401

Sousa, Mafalda; Szucs, Peter; Lima, Deolinda; Aguiar, Paulo

2014-04-01

150

[A case of hepatoma patient who showed an abnormally high level of serum IRI with the beads method].  

PubMed

A fifty four years old hepatoma patient admitted to the hospital for a surgical operation. Preoperative laboratory examination demonstrated that his serum IRI level was very high (423 microU/ml) when measured with a beads method, however RIA or a microplate method demonstrated normal values. We studied the mechanism of the discrepancy of IRI values. 1) Both the beads and microplate methods demonstrated the same IRI values when the patient's serum insulin was roughly purified with Sep-Pak. The beads method showed high IRI values in serum which passed through Sep-Pak, therefore contained no insulin. 2) The similar results were observed when the patient's serum fractionated by a gel-chromatography (Biogel P-30). The beads method demonstrated high IRI values in both insulin fractions and the fractions containing serum proteins bigger than 40,000 molecular weight. The microplate method demonstrated only one large peak of insulin. 3) When non-specific IgG of guinea pig was used as a fixed antibody instead of human insulin antibody of guinea pig that was used in the beads method, the patient's serum showed the similar values as that obtained with the beads method. We thereby concluded that the abnormal level of IRI by the beads method was derived from the unknown substance reacting with IgG of guinea pig in the patient's serum. After the surgical resection of hepatoma, the levels of IRI measured by the beads method decreased significantly, suggesting that the substance is related to hepatoma cells. PMID:1326201

Kamada, T; Kisanuki, R; Nishimura, T; Masumitsu, M; Shiraishi, K; Tanabe, G; Shimazu, H; Otsuji, S

1992-02-01

151

Genetic analyses of several Drosophila ananassae-complex species show a low-frequency major gene for parthenogenesis that maps to chromosome 2.  

PubMed

Parthenogenetic strains of several species have been found in the genus Drosophila. The mode of diploidization in the eggs of females has been found to be post-meiotic nuclear fusion. The genetic basis for this parthenogenesis is not understood but is believed to be under the control of a complex polygenic system. We found parthenogenetic females in an isofemale strain (LAE345) of D. pallidosa-like collected in 1981 at Lae, Papua New Guinea, and established a parthenogenetically reproducing strain. Parthenogenetic strains of D. ananassae and D. pallidosa collected at Taputimu, American Samoa had also been established by Futch (1972). D. ananassae, D. pallidosa and D. pallidosa-like are very closely related species belonging to the ananassae complex of the ananassae species subgroup of the melanogaster species group. Using these three species, we found that more than 80% of females from parthenogenetic strains produced progeny parthenogenetically and that inter-specific hybrid females also produced impaternate progeny. In the present report, we demonstrate that the mode of parthenogenesis of D. ananassae appears to be the post-meiotic nuclear doubling of a single meiotic product, and that a major gene responsible for the parthenogenesis maps to the left arm of the second chromosome of D. ananassae. We also suggest that the genetic basis for parthenogenesis capacity may be identical among the three closely related species. We discuss the function of the gene required for parthenogenesis and its significance for the evolutionary process. PMID:15219153

Matsuda, Muneo; Tobari, Yoshiko N

2004-04-01

152

A genetically encoded, high-signal-to-noise maltose sensor  

PubMed Central

We describe the generation of a family of high-signal-to-noise single-wavelength genetically encoded indicators for maltose. This was achieved by insertion of circularly permuted fluorescent proteins into a bacterial periplasmic binding protein (PBP), Escherichia coli maltodextrin-binding protein, resulting in a four-color family of maltose indicators. The sensors were iteratively optimized to have sufficient brightness and maltose-dependent fluorescence increases for imaging, under both one- and two-photon illumination. We demonstrate that maltose affinity of the sensors can be tuned in a fashion largely independent of the fluorescent readout mechanism. Using literature mutations, the binding specificity could be altered to moderate sucrose preference, but with a significant loss of affinity. We use the soluble sensors in individual E. coli bacteria to observe rapid maltose transport across the plasma membrane, and membrane fusion versions of the sensors on mammalian cells to visualize the addition of maltose to extracellular media. The PBP superfamily includes scaffolds specific for a number of analytes whose visualization would be critical to the reverse engineering of complex systems such as neural networks, biosynthetic pathways, and signal transduction cascades. We expect the methodology outlined here to be useful in the development of indicators for many such analytes.

Marvin, Jonathan S; Schreiter, Eric R; Echevarria, Ileabett M; Looger, Loren L

2011-01-01

153

A Novel Halophilic Lipase, LipBL, Showing High Efficiency in the Production of Eicosapentaenoic Acid (EPA)  

PubMed Central

Background Among extremophiles, halophiles are defined as microorganisms adapted to live and thrive in diverse extreme saline environments. These extremophilic microorganisms constitute the source of a number of hydrolases with great biotechnological applications. The interest to use extremozymes from halophiles in industrial applications is their resistance to organic solvents and extreme temperatures. Marinobacter lipolyticus SM19 is a moderately halophilic bacterium, isolated previously from a saline habitat in South Spain, showing lipolytic activity. Methods and Findings A lipolytic enzyme from the halophilic bacterium Marinobacter lipolyticus SM19 was isolated. This enzyme, designated LipBL, was expressed in Escherichia coli. LipBL is a protein of 404 amino acids with a molecular mass of 45.3 kDa and high identity to class C ?-lactamases. LipBL was purified and biochemically characterized. The temperature for its maximal activity was 80°C and the pH optimum determined at 25°C was 7.0, showing optimal activity without sodium chloride, while maintaining 20% activity in a wide range of NaCl concentrations. This enzyme exhibited high activity against short-medium length acyl chain substrates, although it also hydrolyzes olive oil and fish oil. The fish oil hydrolysis using LipBL results in an enrichment of free eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), relative to its levels present in fish oil. For improving the stability and to be used in industrial processes LipBL was immobilized in different supports. The immobilized derivatives CNBr-activated Sepharose were highly selective towards the release of EPA versus DHA. The enzyme is also active towards different chiral and prochiral esters. Exposure of LipBL to buffer-solvent mixtures showed that the enzyme had remarkable activity and stability in all organic solvents tested. Conclusions In this study we isolated, purified, biochemically characterized and immobilized a lipolytic enzyme from a halophilic bacterium M. lipolyticus, which constitutes an enzyme with excellent properties to be used in the food industry, in the enrichment in omega-3 PUFAs.

Perez, Dolores; Martin, Sara; Fernandez-Lorente, Gloria; Filice, Marco; Guisan, Jose Manuel; Ventosa, Antonio; Garcia, Maria Teresa; Mellado, Encarnacion

2011-01-01

154

The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry  

PubMed Central

Background Using immunohistochemistry (IHC) to select cases for mismatch repair (MMR) genetic testing, we failed to identify a large kindred with the deleterious PMS2 mutation c.989-1G?>?T. The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions. Methods All carriers and obligate carriers of the mutation were identified. All cancer diagnoses were confirmed. IHC and MSI-analysis were performed on available tumours. Penetrances of cancers included in the Amsterdam and the Bethesda Criteria, for MSI-high tumours and MSI-high and low tumours were calculated by the Kaplan-Meier algorithm. Results Probability for co-segregation of the mutation and cancers by chance was 0.000004. Fifty-six carriers or obligate carriers were identified. There was normal staining for PMS2 in 15/18 (83.3%) of tumours included in the AMS1/AMS2/Bethesda criteria. MSI-analysis showed that 15/21 (71.4%) of tumours were MSI-high and 4/21 (19.0%) were MSI-low. Penetrance at 70 years was 30.6% for AMS1 cancers (colorectal cancers), 42.8% for AMS2 cancers, 47.2% for Bethesda cancers, 55.6% for MSI-high and MSI-low cancers and 52.2% for MSI-high cancers. Conclusions The mutation met class 5 criteria for pathogenicity. IHC was insensitive in detecting tumours caused by the mutation. Penetrance of cancers that displayed MSI was 56% at 70 years. Besides colorectal cancers, the most frequent expressions were carcinoma of the endometrium and breast in females and stomach and prostate in males.

2014-01-01

155

The short-lived annual fish Nothobranchius furzeri shows a typical teleost aging process reinforced by high incidence of age-dependent neoplasias.  

PubMed

The annual fish Nothobranchius furzeri is the shortest-lived vertebrate which can be cultured in captivity. Here, we performed a histopathological analysis of age-related lesions in this species. Post-mortem analysis revealed lesions in liver (~90%), kidney (~75%), heart (~70%) and gonads (~40%) which are similar to those previously described in the small teleost Poecilia reticulata. In addition, a high incidence of neoplasias was observed in liver (~35%) and kidney (~25%). Different laboratory strains of N. furzeri show large genetic differences in longevity. Cross-sectional analysis revealed a clear age-dependent increase in the incidence of liver neoplasias which was accelerated in a short-lived strain. Cross-sectional analysis of gonads revealed sex-specific differences in the occurrence of lesions, with males being more severely affected than females. In conclusion, our analysis demonstrates that short life span in N. furzeri is a consequence of a typical teleost aging process which determines systemic failure of homeostasis functions rather than of a single organ or apparatus. Unlike other teleosts, however, this scenario is reinforced by high incidence of age-dependent neoplasias, making this species a promising model to analyze the molecular pathways of age-dependent spontaneous tumorigenesis. PMID:21056099

Di Cicco, Emiliano; Tozzini, Eva Terzibasi; Rossi, Giacomo; Cellerino, Alessandro

2011-04-01

156

A long-term culture of human hepatocytes which show a high growth potential and express their differentiated phenotypes.  

PubMed

The present study succeeded for the first time in cultivating for more than 2 months human normal hepatocytes which showed a high growth potential and expressed their differentiated phenotypes. Constituents of culture medium were critical for this culture, and the medium optimized for their growth contained fresh human serum, fetal bovine serum, Swiss 3T3-cell conditioned medium, L-ascorbic acid 2-phosphate, epidermal growth factor, nicotinamide, and dimethyl sulfoxide. Hepatocytes steadily replicated and formed colonies which continued to increase in size up to around 35 days. The number of hepatocytes in the most replicative colonies increased 17-fold during 31 days. Cells in colonies expressed normal differentiated hepatocytic phenotypes for as long as 35 days. These hepatocytes retained normal liver functions at least for 70 days such as to secrete albumin, and to metabolize lidocaine and D-galactose. PMID:10066444

Hino, H; Tateno, C; Sato, H; Yamasaki, C; Katayama, S; Kohashi, T; Aratani, A; Asahara, T; Dohi, K; Yoshizato, K

1999-03-01

157

Accessing Genetic Information with High-Density DNA Arrays  

Microsoft Academic Search

Rapid access to genetic information is central to the revolution taking place in molecular genetics. The simultaneous analysis of the entire human mitochondrial genome is described here. DNA arrays containing up to 135,000 probes complementary to the 16.6-kilobase human mitochondrial genome were generated by light-directed chemical synthesis. A two-color labeling scheme was developed that allows simultaneous comparison of a polymorphic

Mark Chee; Robert Yang; Earl Hubbell; Anthony Berno; Xiaohua C. Huang; David Stern; Jim Winkler; David J. Lockhart; Macdonald S. Morris; Stephen P. A. Fodor

1996-01-01

158

Genetic variation and recombination of RdRp and HSP 70h genes of Citrus tristeza virus isolates from orange trees showing symptoms of citrus sudden death disease  

PubMed Central

Background Citrus sudden death (CSD), a disease that rapidly kills orange trees, is an emerging threat to the Brazilian citrus industry. Although the causal agent of CSD has not been definitively determined, based on the disease's distribution and symptomatology it is suspected that the agent may be a new strain of Citrus tristeza virus (CTV). CTV genetic variation was therefore assessed in two Brazilian orange trees displaying CSD symptoms and a third with more conventional CTV symptoms. Results A total of 286 RNA-dependent-RNA polymerase (RdRp) and 284 heat shock protein 70 homolog (HSP70h) gene fragments were determined for CTV variants infecting the three trees. It was discovered that, despite differences in symptomatology, the trees were all apparently coinfected with similar populations of divergent CTV variants. While mixed CTV infections are common, the genetic distance between the most divergent population members observed (24.1% for RdRp and 11.0% for HSP70h) was far greater than that in previously described mixed infections. Recombinants of five distinct RdRp lineages and three distinct HSP70h lineages were easily detectable but respectively accounted for only 5.9 and 11.9% of the RdRp and HSP70h gene fragments analysed and there was no evidence of an association between particular recombinant mosaics and CSD. Also, comparisons of CTV population structures indicated that the two most similar CTV populations were those of one of the trees with CSD and the tree without CSD. Conclusion We suggest that if CTV is the causal agent of CSD, it is most likely a subtle feature of population structures within mixed infections and not merely the presence (or absence) of a single CTV variant within these populations that triggers the disease.

Gomes, Clarissa PC; Nagata, Tatsuya; de Jesus, Waldir C; Neto, Carlos R Borges; Pappas, Georgios J; Martin, Darren P

2008-01-01

159

Mammosphere cells from high-passage MCF7 cell line show variable loss of tumorigenicity and radioresistance.  

PubMed

Mammosphere culture of cancer cell lines is an important approach used for enrichment of stem-like cancer cells (SLCs), but over-subcultured cell lines have been experimentally shown to change properties over time. It remains unclear if mammosphere cells (MSs) derived from high-passage cancer cell lines retain the tumorigenicity and radioresistance seen in MSs from primary or low-passage cell lines. In this study, we report that mammospheres derived from MCF-7 sublines after different passage numbers were consistently enriched for CD44+/CD24(-/low) cells but were not consistently enriched for tumorigenic and radioresistant cells. The tumorigenicity and radioresistance of MSs were associated with their sphere-forming ability, proliferation ability in vitro, and intracellular reactive oxygen species (ROS) levels. The radioresistant MSs showed significant cell cycle arrest in G2/M phase after X-ray irradiation and expressed higher ataxia telangiectasia mutated (ATM) mRNA levels. These results suggest that MSs from high-passage cancer cell lines were not consistently enriched for stem-like cancer cells with higher tumorigenicity and enhanced radioresistance. PMID:22108532

Xie, Guozhu; Zhan, Junfang; Tian, Yunhong; Liu, Ying; Chen, Zhixian; Ren, Chen; Sun, Quanquan; Lian, Jianping; Chen, Longhua; Ruan, Jian; Ye, Changsheng; Sun, Aimin; Yuan, Yawei

2012-03-01

160

A Novel 5-Enolpyruvylshikimate-3-Phosphate Synthase Shows High Glyphosate Tolerance in Escherichia coli and Tobacco Plants  

PubMed Central

A key enzyme in the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the primary target of the broad-spectrum herbicide glyphosate. Identification of new aroA genes coding for EPSPS with a high level of glyphosate tolerance is essential for the development of glyphosate-tolerant crops. In the present study, the glyphosate tolerance of five bacterial aroA genes was evaluated in the E. coli aroA-defective strain ER2799 and in transgenic tobacco plants. All five aroA genes could complement the aroA-defective strain ER2799, and AM79 aroA showed the highest glyphosate tolerance. Although glyphosate treatment inhibited the growth of both WT and transgenic tobacco plants, transgenic plants expressing AM79 aroA tolerated higher concentration of glyphosate and had a higher fresh weight and survival rate than plants expressing other aroA genes. When treated with high concentration of glyphosate, lower shikimate content was detected in the leaves of transgenic plants expressing AM79 aroA than transgenic plants expressing other aroA genes. These results suggest that AM79 aroA could be a good candidate for the development of transgenic glyphosate-tolerant crops.

Zhang, Shengxue; Yang, Xuewen; Chen, Rongrong; Zhang, Yuwen; Lu, Wei; Liu, Yan; Wang, Jianhua; Lin, Min; Wang, Guoying

2012-01-01

161

Getting a head start: the importance of personal genetics education in high schools.  

PubMed

With advances in sequencing technology, widespread and affordable genome sequencing will soon be a reality. However, studies suggest that "genetic literacy" of the general public is inadequate to prepare our society for this unprecedented access to our genetic information. As the current generation of high school students will come of age in an era when personal genetic information is increasingly utilized in health care, it is of vital importance to ensure these students understand the genetic concepts necessary to make informed medical decisions. These concepts include not only basic scientific knowledge, but also considerations of the ethical, legal, and social issues that will arise in the age of personal genomics. In this article, we review the current state of genetics education, highlight issues that we believe need to be addressed in a comprehensive genetics education curriculum, and describe our education efforts at the Harvard Medical School-based Personal Genetics Education Project. PMID:22461746

Kung, Johnny T; Gelbart, Marnie E

2012-03-01

162

genetics  

NSDL National Science Digital Library

learning about our genetic make up We've been learning about DNA. Go to each web site, read and follow the instructions of the activities provided. On a piece of paper write your answers to the following questions and submit your work. Put the site for each of the questions you are answering. The first site is, ...

Curran, Carolyn

2011-12-05

163

Genetic adaptation to high altitude in the Ethiopian highlands  

PubMed Central

Background Genomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high- and low-altitude populations living in Ethiopia, for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome-wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude. Results We have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high- and low-altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels. Conclusions We highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia.

2012-01-01

164

Transcriptome sequencing for high throughput SNP development and genetic mapping in Pea  

PubMed Central

Background Pea has a complex genome of 4.3 Gb for which only limited genomic resources are available to date. Although SNP markers are now highly valuable for research and modern breeding, only a few are described and used in pea for genetic diversity and linkage analysis. Results We developed a large resource by cDNA sequencing of 8 genotypes representative of modern breeding material using the Roche 454 technology, combining both long reads (400 bp) and high coverage (3.8 million reads, reaching a total of 1,369 megabases). Sequencing data were assembled and generated a 68 K unigene set, from which 41 K were annotated from their best blast hit against the model species Medicago truncatula. Annotated contigs showed an even distribution along M. truncatula pseudochromosomes, suggesting a good representation of the pea genome. 10 K pea contigs were found to be polymorphic among the genetic material surveyed, corresponding to 35 K SNPs. We validated a subset of 1538 SNPs through the GoldenGate assay, proving their ability to structure a diversity panel of breeding germplasm. Among them, 1340 were genetically mapped and used to build a new consensus map comprising a total of 2070 markers. Based on blast analysis, we could establish 1252 bridges between our pea consensus map and the pseudochromosomes of M. truncatula, which provides new insight on synteny between the two species. Conclusions Our approach created significant new resources in pea, i.e. the most comprehensive genetic map to date tightly linked to the model species M. truncatula and a large SNP resource for both academic research and breeding.

2014-01-01

165

High genetic diversity and structured populations of the oriental fruit moth in its range of origin.  

PubMed

The oriental fruit moth Grapholita (?=?Cydia) molesta is a key fruit pest globally. Despite its economic importance, little is known about its population genetics in its putative native range that includes China. We used five polymorphic microsatellite loci and two mitochondrial gene sequences to characterize the population genetic diversity and genetic structure of G. molesta from nine sublocations in three regions of a major fruit growing area of China. Larval samples were collected throughout the season from peach, and in late season, after host switch by the moth to pome fruit, also from apple and pear. We found high numbers of microsatellite alleles and mitochondrial DNA haplotypes in all regions, together with a high number of private alleles and of haplotypes at all sublocations, providing strong evidence that the sampled area belongs to the origin of this species. Samples collected from peach at all sublocations were geographically structured, and a significant albeit weak pattern of isolation-by-distance was found among populations, likely reflecting the low flight capacity of this moth. Interestingly, populations sampled from apple and pear in the late season showed a structure differing from that of populations sampled from peach throughout the season, indicating a selective host switch of a certain part of the population only. The recently detected various olfactory genotypes in G. molesta may underly this selective host switch. These genetic data yield, for the first time, an understanding of population dynamics of G. molesta in its native range, and of a selective host switch from peach to pome fruit, which may have a broad applicability to other global fruit production areas for designing suitable pest management strategies. PMID:24265692

Zheng, Yan; Peng, Xiong; Liu, Gaoming; Pan, Hongyan; Dorn, Silvia; Chen, Maohua

2013-01-01

166

Population Genetic Studies Revealed Local Adaptation in a High Gene-Flow Marine Fish, the Small Yellow Croaker (Larimichthys polyactis)  

PubMed Central

The genetic differentiation of many marine fish species is low. Yet local adaptation may be common in marine fish species as the vast and changing marine environment provides more chances for natural selection. Here, we used anonymous as well as known protein gene linked microsatellites and mitochondrial DNA to detect the population structure of the small yellow croaker (Larimichthys polyactis) in the Northwest Pacific marginal seas. Among these loci, we detected at least two microsatellites, anonymous H16 and HSP27 to be clearly under diversifying selection in outlier tests. Sequence cloning and analysis revealed that H16 was located in the intron of BAHCC1 gene. Landscape genetic analysis showed that H16 mutations were significantly associated with temperature, which further supported the diversifying selection at this locus. These marker types presented different patterns of population structure: (i) mitochondrial DNA phylogeny showed no evidence of genetic divergence and demonstrated only one glacial linage; (ii) population differentiation using putatively neutral microsatellites presented a pattern of high gene flow in the L. polyactis. In addition, several genetic barriers were identified; (iii) the population differentiation pattern revealed by loci under diversifying selection was rather different from that revealed by putatively neutral loci. The results above suggest local adaptation in the small yellow croaker. In summary, population genetic studies based on different marker types disentangle the effects of demographic history, migration, genetic drift and local adaptation on population structure and also provide valuable new insights for the design of management strategies in L. polyactis.

Wang, Le; Liu, Shufang; Zhuang, Zhimeng; Guo, Liang; Meng, Zining; Lin, Haoran

2013-01-01

167

Distinct and Diverse: Range-Wide Phylogeography Reveals Ancient Lineages and High Genetic Variation in the Endangered Okapi (Okapia johnstoni)  

PubMed Central

The okapi is an endangered, evolutionarily distinctive even-toed ungulate classified within the giraffidae family that is endemic to the Democratic Republic of Congo. The okapi is currently under major anthropogenic threat, yet to date nothing is known about its genetic structure and evolutionary history, information important for conservation management given the species' current plight. The distribution of the okapi, being confined to the Congo Basin and yet spanning the Congo River, also makes it an important species for testing general biogeographic hypotheses for Congo Basin fauna, a currently understudied area of research. Here we describe the evolutionary history and genetic structure of okapi, in the context of other African ungulates including the giraffe, and use this information to shed light on the biogeographic history of Congo Basin fauna in general. Using nuclear and mitochondrial DNA sequence analysis of mainly non-invasively collected samples, we show that the okapi is both highly genetically distinct and highly genetically diverse, an unusual combination of genetic traits for an endangered species, and feature a complex evolutionary history. Genetic data are consistent with repeated climatic cycles leading to multiple Plio-Pleistocene refugia in isolated forests in the Congo catchment but also imply historic gene flow across the Congo River.

Stanton, David W. G.; Hart, John; Galbusera, Peter; Helsen, Philippe; Shephard, Jill; Kumpel, Noelle F.; Wang, Jinliang; Ewen, John G.; Bruford, Michael W.

2014-01-01

168

Distinct and Diverse: Range-Wide Phylogeography Reveals Ancient Lineages and High Genetic Variation in the Endangered Okapi (Okapia johnstoni).  

PubMed

The okapi is an endangered, evolutionarily distinctive even-toed ungulate classified within the giraffidae family that is endemic to the Democratic Republic of Congo. The okapi is currently under major anthropogenic threat, yet to date nothing is known about its genetic structure and evolutionary history, information important for conservation management given the species' current plight. The distribution of the okapi, being confined to the Congo Basin and yet spanning the Congo River, also makes it an important species for testing general biogeographic hypotheses for Congo Basin fauna, a currently understudied area of research. Here we describe the evolutionary history and genetic structure of okapi, in the context of other African ungulates including the giraffe, and use this information to shed light on the biogeographic history of Congo Basin fauna in general. Using nuclear and mitochondrial DNA sequence analysis of mainly non-invasively collected samples, we show that the okapi is both highly genetically distinct and highly genetically diverse, an unusual combination of genetic traits for an endangered species, and feature a complex evolutionary history. Genetic data are consistent with repeated climatic cycles leading to multiple Plio-Pleistocene refugia in isolated forests in the Congo catchment but also imply historic gene flow across the Congo River. PMID:25007188

Stanton, David W G; Hart, John; Galbusera, Peter; Helsen, Philippe; Shephard, Jill; Kümpel, Noëlle F; Wang, Jinliang; Ewen, John G; Bruford, Michael W

2014-01-01

169

Complete Genome Sequence of Potato leafroll virus Isolates Infecting Potato in the Different Geographical Areas of India Shows Low Level Genetic Diversity.  

PubMed

Five Potato leafroll virus (PLRV) isolates were collected from five states representing different potato growing parts of India. The ssRNA genome sequences of these isolates were determined. The genome comprised of 5,883 nucleotides and deduced genome organization resembled other PLRV isolates. About 97.6-98.7 % similarities was observed within the Indian isolates and were more close to European, Canadian, African, American and Czech isolates (95.8-98.6 %) than to an Australian isolate (92.9-93.4 %). These isolates were 43.7-53.1 % similar to other poleroviruses and 29.1-29.3 % to Barley yellow dwarf virus, a luteovirus. Out of five isolates, the isolate PBI-6 was recombinant one as detected by RDP3 software. Multiple sequence alignment of nucleotide and amino acid sequences of different ORFs indicated that the ORF 3 and ORF 4, corresponding to coat protein and movement proteins are more conserved than other ORFs. Amino acid changes specific to Indian isolates were observed and it was more in ORF 2 than in ORF 0, ORF 3 and ORF 4. This is the first report of complete genome sequence of PLRV isolates from India, which reveals low level genetic diversity. PMID:24426276

Jeevalatha, A; Kaundal, Priyanka; Shandil, R K; Sharma, N N; Chakrabarti, S K; Singh, B P

2013-09-01

170

Awareness of Societal Issues Among High School Biology Teachers Teaching Genetics  

Microsoft Academic Search

The purpose of this study was to investigate how aware high school biology teachers are of societal issues (values, moral,\\u000a ethic, and legal issues) while teaching genetics, genetics engineering, molecular genetics, human heredity, and evolution.\\u000a The study includes a short historical review of World War II atrocities during the Holocaust when scientists from all the\\u000a above-mentioned disciplines had been involved

Reuven Lazarowitz; Ilit Bloch

2005-01-01

171

Baculovirus expression system and method for high throughput expression of genetic material  

DOEpatents

The present invention provides novel recombinant baculovirus expression systems for expressing foreign genetic material in a host cell. Such expression systems are readily adapted to an automated method for expression foreign genetic material in a high throughput manner. In other aspects, the present invention features a novel automated method for determining the function of foreign genetic material by transfecting the same into a host by way of the recombinant baculovirus expression systems according to the present invention.

Clark, Robin (Benecia, CA); Davies, Anthony (Mill Valley, CA)

2001-01-01

172

Similarity in Recombination Rate Estimates Highly Correlates with Genetic Differentiation in Humans  

PubMed Central

Recombination varies greatly among species, as illustrated by the poor conservation of the recombination landscape between humans and chimpanzees. Thus, shorter evolutionary time frames are needed to understand the evolution of recombination. Here, we analyze its recent evolution in humans. We calculated the recombination rates between adjacent pairs of 636,933 common single-nucleotide polymorphism loci in 28 worldwide human populations and analyzed them in relation to genetic distances between populations. We found a strong and highly significant correlation between similarity in the recombination rates corrected for effective population size and genetic differentiation between populations. This correlation is observed at the genome-wide level, but also for each chromosome and when genetic distances and recombination similarities are calculated independently from different parts of the genome. Moreover, and more relevant, this relationship is robustly maintained when considering presence/absence of recombination hotspots. Simulations show that this correlation cannot be explained by biases in the inference of recombination rates caused by haplotype sharing among similar populations. This result indicates a rapid pace of evolution of recombination, within the time span of differentiation of modern humans.

Laayouni, Hafid; Montanucci, Ludovica; Sikora, Martin; Mele, Marta; Dall'Olio, Giovanni Marco; Lorente-Galdos, Belen; McGee, Kate M.; Graffelman, Jan; Awadalla, Philip; Bosch, Elena; Comas, David; Navarro, Arcadi; Calafell, Francesc; Casals, Ferran; Bertranpetit, Jaume

2011-01-01

173

A high precision comprehensive evaluation method for flood disaster loss based on improved genetic programming  

NASA Astrophysics Data System (ADS)

Precise comprehensive evaluation of flood disaster loss is significant for the prevention and mitigation of flood disasters. Here, one of the difficulties involved is how to establish a model capable of describing the complex relation between the input and output data of the system of flood disaster loss. Genetic programming (GP) solves problems by using ideas from genetic algorithm and generates computer programs automatically. In this study a new method named the evaluation of the grade of flood disaster loss (EGFD) on the basis of improved genetic programming (IGP) is presented (IGP-EGFD). The flood disaster area and the direct economic loss are taken as the evaluation indexes of flood disaster loss. Obviously that the larger the evaluation index value, the larger the corresponding value of the grade of flood disaster loss is. Consequently the IGP code is designed to make the value of the grade of flood disaster be an increasing function of the index value. The result of the application of the IGP-EGFD model to Henan Province shows that a good function expression can be obtained within a bigger searched function space; and the model is of high precision and considerable practical significance. Thus, IGP-EGFD can be widely used in automatic modeling and other evaluation systems.

Zhou, Yuliang; Lu, Guihua; Jin, Juliang; Tong, Fang; Zhou, Ping

2006-10-01

174

Constitutive expression of high-affinity sulfate transporter (HAST) gene in Indian mustard showed enhanced sulfur uptake and assimilation.  

PubMed

Lycopersicon esculantum sulfate transporter gene (LeST 1.1) encodes a high-affinity sulfate transporter (HAST) located in root epidermis. In this study, the LeST 1.1 gene was constitutively expressed in Indian mustard (Brassica juncea cv. Pusa Jai Kisan). Transgenic as well as untransformed plants were grown in sulfur-insufficient (25 and 50 ?M) and sulfur-sufficient (1,000 ?M) conditions for 30 days. Two-fold increase was noticed in the sulfate uptake rate of transgenic plants grown in both sulfur-insufficient and -sufficient conditions as compared to untransformed plants. The transgenic B. juncea plants were able to accumulate higher biomass and showed improved sulfur status even in sulfur-insufficient conditions when compared with untransformed plants. Chlorophyll content, ATP sulfurylase activity and protein content were also higher in transgenic plants than untranformed plants under sulfur-insufficient conditions. Our results, thus, clearly indicate that constitutive expression of LeST 1.1 gene in B. juncea had led to enhanced capacity of sulfur uptake and assimilation even in sulfur-insufficient conditions. This approach can also be used in other crops to enhance their sulfate uptake and assimilation potential under S-insufficient conditions. PMID:20938698

Abdin, M Z; Akmal, M; Ram, M; Nafis, T; Alam, P; Nadeem, M; Khan, M A; Ahmad, A

2011-07-01

175

Population genetics of the understory fishtail palm Chamaedorea ernesti-augusti in Belize: high genetic connectivity with local differentiation  

PubMed Central

Background Developing a greater understanding of population genetic structure in lowland tropical plant species is highly relevant to our knowledge of increasingly fragmented forests and to the conservation of threatened species. Specific studies are particularly needed for taxa whose population dynamics are further impacted by human harvesting practices. One such case is the fishtail or xaté palm (Chamaedorea ernesti-augusti) of Central America, whose wild-collected leaves are becoming progressively more important to the global ornamental industry. We use microsatellite markers to describe the population genetics of this species in Belize and test the effects of climate change and deforestation on its recent and historical effective population size. Results We found high levels of inbreeding coupled with moderate or high allelic diversity within populations. Overall high gene flow was observed, with a north and south gradient and ongoing differentiation at smaller spatial scales. Immigration rates among populations were more difficult to discern, with minimal evidence for isolation by distance. We infer a tenfold reduction in effective population size ca. 10,000 years ago, but fail to detect changes attributable to Mayan or contemporary deforestation. Conclusion Populations of C. ernesti-augusti are genetically heterogeneous demes at a local spatial scale, but are widely connected at a regional level in Belize. We suggest that the inferred patterns in population genetic structure are the result of the colonization of this species into Belize following expansion of humid forests in combination with demographic and mating patterns. Within populations, we hypothesize that low aggregated population density over large areas, short distance pollen dispersal via thrips, low adult survival, and low fruiting combined with early flowering may contribute towards local inbreeding via genetic drift. Relatively high levels of regional connectivity are likely the result of animal-mediated long-distance seed dispersal. The greatest present threat to the species is the potential onset of inbreeding depression as the result of increased human harvesting activities. Future genetic studies in understory palms should focus on both fine-scale and landscape-level genetic structure.

Cibrian-Jaramillo, Angelica; Bacon, Christine D; Garwood, Nancy C; Bateman, Richard M; Thomas, Meredith M; Russell, Steve; Bailey, C Donovan; Hahn, William J; Bridgewater, Samuel GM; DeSalle, Rob

2009-01-01

176

Colorectal cancers show distinct mutation spectra in members of the canonical WNT signaling pathway according to their anatomical location and type of genetic instability.  

PubMed

It is unclear whether the mutation spectra in WNT genes vary among distinct types of colorectal tumors. We have analyzed mutations in specific WNT genes in a cohort of 52 colorectal tumors and performed a meta-analysis of previous studies. Notably, significant differences were found among the mutation spectra. We have previously shown that in familial adenomatous polyposis, APC somatic mutations are selected to provide the "just-right" level of WNT signaling for tumor formation. Here, we found that APC mutations encompassing at least two beta-catenin down-regulating motifs (20 a.a. repeats) are significantly more frequent in microsatellite unstable (MSI-H) than in microsatellite stable (MSS) tumors where truncations retaining less than two repeats are more frequent (P = 0.0009). Moreover, in cases where both APC hits are detected, selection for mutations retaining a cumulative number of two 20 a.a. repeats became apparent in MSI-H tumors (P = 0.001). This type of mutations were also more frequent in proximal versus distal colonic tumors, regardless of MSI status (P = 0.0008). Among MSI-H tumors, CTNNB1 mutations were significantly more frequent in HNPCC than in sporadic lesions (28% versus 6%, P < 10-6) and were preferentially detected in the proximal colon, independently of MSI status (P = 0.017). In conclusion, the observed spectra of WNT gene mutations in colorectal tumors are likely the result from selection of specific levels of beta-catenin signaling, optimal for tumor formation in the context of specific anatomical locations and forms of genetic instability. We suggest that this may underlie the preferential location of MMR deficient tumors in the proximal colon. PMID:20544848

Albuquerque, Cristina; Baltazar, Célia; Filipe, Bruno; Penha, Filipa; Pereira, Teresa; Smits, Ron; Cravo, Marília; Lage, Pedro; Fidalgo, Paulo; Claro, Isabel; Rodrigues, Paula; Veiga, Isabel; Ramos, José Silva; Fonseca, Isabel; Leitão, Carlos Nobre; Fodde, Riccardo

2010-08-01

177

High Resolution Synchronisation Of Climate Archives Shows Evidence For A Time-Transgressive Abrupt Climate Change During The Younger Dryas  

NASA Astrophysics Data System (ADS)

Understanding regional variations in climatic changes is critical the understanding of the dynamics of the atmospheric climate system. One key tool is the past record of climatic oscillations, which provide evidence of large abrupt shifts. The last major reorganisation of the North Atlantic realm took place during the Younger Dryas (YD), a ~1100 year long cold period at the end of the last glaciation, thought to be induced through increased meltwater and a reduction in North Atlantic overturning. Within this region, the YD had at least two phases an earlier cold phase followed by a second phase of climatic amelioration related to a resumption of North Atlantic overturning and reorganisation of the atmospheric system. Previously studies suggest this shift between climate states occurred at the same time across the North Atlantic, however often the available chronological resolution is insufficient to determine synchroneity of this transition between records. We now show that this transition was locally abrupt, but time-transgressive across the region through the direct synchronisation of high resolution continental records. This observation has become possible through the correlation of independent annually resolved records using isochronous volcanic ash layers, we thus avoid any circularity involved in aligning records through palaeoclimate signals. This independent synchronisation also allows us to resolve differences between archives at an annual to decadal scale. As a result of this we can now infer that atmospheric response to the gradual resumption of North Atlantic overturning was very rapid at individual sites but was a-synchronous at a regional scale. This has significant implications for both palaeoclimate modelling and also our understanding of the dynamic nature of atmospheric response to climate change.

Lane, C. S.; Brauer, A.; Blockley, S.; Dulski, P.

2012-12-01

178

A DTI study of white matter microstructure in individuals at high genetic risk for schizophrenia  

Microsoft Academic Search

Structural brain developmental anomalies, particularly those in frontotemporal white matter pathways, may have a genetic component and place people at increased risk for schizophrenia. The current study employed Diffusion Tensor Imaging (DTI) to measure fractional anisotropy (FA) as a quantitative indicator of white matter integrity. We examined twenty-two participants at high genetic risk for schizophrenia (HR), 23 people with schizophrenia

Matthew J. Hoptman; Jay Nierenberg; Hilary C. Bertisch; Dean Catalano; Babak A. Ardekani; Craig A. Branch; Lynn E. DeLisi

2008-01-01

179

Effect of bead and illustrations models on high school students' achievement in molecular genetics  

Microsoft Academic Search

Our main goal in this study was to explore whether the use of models in molecular genetics instruction in high school can contribute to students' understanding of concepts and processes in genetics. Three comparable groups of 11th and 12th graders participated: The control group (116 students) was taught in the traditional lecture format, while the others received instructions which integrated

Yosi Rotbain; Gili Marbach-Ad; Ruth Stavy

2006-01-01

180

Temporal trends in gonococcal population genetics in a high prevalence urban community  

Microsoft Academic Search

Molecular evolutionary studies can provide insights into the spread of infectious diseases and inform infection control measures. We performed a population genetic analysis of gonococcal isolates obtained over a 15-year interval in Baltimore, MD, where gonorrhea is highly prevalent. Categorical analysis of genetic differentiation revealed temporal structuring of the gonococcal population. The use of a new method to determine the

Marcos Pérez-Losada; Keith A. Crandall; Jonathan Zenilman; Raphael P. Viscidi

2007-01-01

181

Mitochondrial DNA Markers Reveal High Genetic Diversity but Low Genetic Differentiation in the Black Fly Simulium tani Takaoka & Davies along an Elevational Gradient in Malaysia  

PubMed Central

The population genetic structure of Simulium tani was inferred from mitochondria-encoded sequences of cytochrome c oxidase subunits I (COI) and II (COII) along an elevational gradient in Cameron Highlands, Malaysia. A statistical parsimony network of 71 individuals revealed 71 haplotypes in the COI gene and 43 haplotypes in the COII gene; the concatenated sequences of the COI and COII genes revealed 71 haplotypes. High levels of genetic diversity but low levels of genetic differentiation were observed among populations of S. tani at five elevations. The degree of genetic diversity, however, was not in accordance with an altitudinal gradient, and a Mantel test indicated that elevation did not have a limiting effect on gene flow. No ancestral haplotype of S. tani was found among the populations. Pupae with unique structural characters at the highest elevation showed a tendency to form their own haplotype cluster, as revealed by the COII gene. Tajima’s D, Fu’s Fs, and mismatch distribution tests revealed population expansion of S. tani in Cameron Highlands. A strong correlation was found between nucleotide diversity and the levels of dissolved oxygen in the streams where S. tani was collected.

Low, Van Lun; Adler, Peter H.; Takaoka, Hiroyuki; Ya'cob, Zubaidah; Lim, Phaik Eem; Tan, Tiong Kai; Lim, Yvonne A. L.; Chen, Chee Dhang; Norma-Rashid, Yusoff; Sofian-Azirun, Mohd

2014-01-01

182

Mitochondrial DNA Markers Reveal High Genetic Diversity but Low Genetic Differentiation in the Black Fly Simulium tani Takaoka & Davies along an Elevational Gradient in Malaysia.  

PubMed

The population genetic structure of Simulium tani was inferred from mitochondria-encoded sequences of cytochrome c oxidase subunits I (COI) and II (COII) along an elevational gradient in Cameron Highlands, Malaysia. A statistical parsimony network of 71 individuals revealed 71 haplotypes in the COI gene and 43 haplotypes in the COII gene; the concatenated sequences of the COI and COII genes revealed 71 haplotypes. High levels of genetic diversity but low levels of genetic differentiation were observed among populations of S. tani at five elevations. The degree of genetic diversity, however, was not in accordance with an altitudinal gradient, and a Mantel test indicated that elevation did not have a limiting effect on gene flow. No ancestral haplotype of S. tani was found among the populations. Pupae with unique structural characters at the highest elevation showed a tendency to form their own haplotype cluster, as revealed by the COII gene. Tajima's D, Fu's Fs, and mismatch distribution tests revealed population expansion of S. tani in Cameron Highlands. A strong correlation was found between nucleotide diversity and the levels of dissolved oxygen in the streams where S. tani was collected. PMID:24941043

Low, Van Lun; Adler, Peter H; Takaoka, Hiroyuki; Ya'cob, Zubaidah; Lim, Phaik Eem; Tan, Tiong Kai; Lim, Yvonne A L; Chen, Chee Dhang; Norma-Rashid, Yusoff; Sofian-Azirun, Mohd

2014-01-01

183

Detecting genetic association of common human facial morphological variation using high density 3D image registration.  

PubMed

Human facial morphology is a combination of many complex traits. Little is known about the genetic basis of common facial morphological variation. Existing association studies have largely used simple landmark-distances as surrogates for the complex morphological phenotypes of the face. However, this can result in decreased statistical power and unclear inference of shape changes. In this study, we applied a new image registration approach that automatically identified the salient landmarks and aligned the sample faces using high density pixel points. Based on this high density registration, three different phenotype data schemes were used to test the association between the common facial morphological variation and 10 candidate SNPs, and their performances were compared. The first scheme used traditional landmark-distances; the second relied on the geometric analysis of 15 landmarks and the third used geometric analysis of a dense registration of ?30,000 3D points. We found that the two geometric approaches were highly consistent in their detection of morphological changes. The geometric method using dense registration further demonstrated superiority in the fine inference of shape changes and 3D face modeling. Several candidate SNPs showed potential associations with different facial features. In particular, one SNP, a known risk factor of non-syndromic cleft lips/palates, rs642961 in the IRF6 gene, was validated to strongly predict normal lip shape variation in female Han Chinese. This study further demonstrated that dense face registration may substantially improve the detection and characterization of genetic association in common facial variation. PMID:24339768

Peng, Shouneng; Tan, Jingze; Hu, Sile; Zhou, Hang; Guo, Jing; Jin, Li; Tang, Kun

2013-12-01

184

High Genetic Variability of Herbivore-Induced Volatile Emission within a Broad Range of Maize Inbred Lines1  

PubMed Central

Maize plants (Zea mays) attacked by caterpillars release a mixture of odorous compounds that attract parasitic wasps, natural enemies of the herbivores. We assessed the genetic variability of these induced volatile emissions among 31 maize inbred lines representing a broad range of genetic diversity used by breeders in Europe and North America. Odors were collected from young plants that had been induced by injecting them with caterpillar regurgitant. Significant variation among lines was found for all 23 volatile compounds included in the analysis: the lines differed enormously in the total amount of volatiles emitted and showed highly variable odor profiles distinctive of each genotype. Principal component analysis performed on the relative quantities of particular compounds within the blend revealed clusters of highly correlated volatiles, which may share common metabolic pathways. European and American lines belonging to established heterotic groups were loosely separated from each other, with the most clear-cut difference in the typical release of (E)-?-caryophyllene by European lines. There was no correlation between the distances among the lines based on their odor profiles and their respective genetic distances previously assessed by neutral RFLP markers. This most comprehensive study to date on intraspecific variation in induced odor emission by maize plants provides a further example of the remarkably high genetic diversity conserved within this important crop plant. A better understanding of the genetic control of induced odor emissions may help in the development of maize varieties particularly attractive to parasitoids and other biological control agents and perhaps more repellent for herbivores.

Degen, Thomas; Dillmann, Christine; Marion-Poll, Frederic; Turlings, Ted C.J.

2004-01-01

185

Genetic structure in a fragmented Northern Hemisphere rainforest: large effective sizes and high connectivity among populations of the epiphytic lichen Lobaria pulmonaria.  

PubMed

An extraordinary diversity of epiphytic lichens is found in the boreal rainforest of central Norway, the highest-latitude rainforest in the world. These rainforest relicts are located in ravine systems, and clear cutting has increased the distance between remaining patches. We hypothesized that the relatively small lichen populations in the remaining forest stands have suffered a depletion of genetic diversity through bottlenecks and founder events. To test this hypothesis, we assessed genetic diversity and structure in the populations of the tripartite lichen Lobaria pulmonaria using eight SSR loci. We sampled thalli growing on Picea abies branches and propagules deposited in snow at three localities. Contrary to expectations, we found high genetic diversity in lichen and snow samples, and high effective sizes of the studied populations. Also, limited genetic differentiation between populations, high historical migration rates, and a high proportion of first generation immigrants were estimated, implying high connectivity across distances <30km. Almost all genetic variation was attributed to variation within sites; spatial genetic structures within populations were absent or appeared on small scales (5-10m). The high genetic diversity in the remaining old boreal rainforests shows that even relict forest patches might be suitable for conservation of genetic diversity. PMID:22571538

Hilmo, Olga; Lundemo, Sverre; Holien, Håkon; Stengrundet, Kirsti; Stenøien, Hans K

2012-07-01

186

Bottlenecked but long-lived: high genetic diversity retained in white-tailed eagles upon recovery from population decline  

PubMed Central

Most of the white-tailed eagle (Haliaeetus albicilla) populations in Europe experienced dramatic declines during the twentieth century. However, owing to intense conservation actions and the ban of DDT and other persistent pollutants, populations are currently recovering. We show that despite passing through demographic bottlenecks, white-tailed eagle populations have retained significant levels of genetic diversity. Both genetic and ringing data indicate that migration between populations has not been a major factor for the maintenance of genetic variability. We argue that the long generation time of eagles has acted as an intrinsic buffer against loss of genetic diversity, leading to a shorter effective time of the experienced bottleneck. Notably, conservation actions taken in several small sub-populations have ensured the preservation of a larger proportion of the total genetic diversity than if conservation had focused on the population stronghold in Norway. For conservation programmes targeting other endangered, long-lived species, our results highlight the possibility for local retention of high genetic diversity in isolated remnant populations.

Hailer, Frank; Helander, Bjorn; Folkestad, Alv O; Ganusevich, Sergei A; Garstad, Steinar; Hauff, Peter; Koren, Christian; Nygard, Torgeir; Volke, Veljo; Vila, Carles; Ellegren, Hans

2006-01-01

187

An advantage of magnetic index nu to show high local disturbances in ionosphere during quiet day conditions  

Microsoft Academic Search

We analysed data of ionospheric characteristics (foE, foEs, foF2, h'E, h'F2) during 30-day long quiet day conditions (Kp = 0-2) in 2004. We found correlations between high local disturbances in ionosphere during very quiet days and high values of magnetic index nu. The coexistence of E sporadic layer or high local disturbances of the foE during magnetically very quiet days

Beata Dziak-Jankowska; Iwona Stanislawska; Dalia Buresova; Tomasz Ernst; Lukasz Tomasik

2010-01-01

188

Field, Genetic, and Modeling Approaches Show Strong Positive Selection Acting upon an Insecticide Resistance Mutation in Anopheles gambiae s.s.  

PubMed Central

Alleles subject to strong, recent positive selection will be swept toward fixation together with contiguous sections of the genome. Whether the genomic signatures of such selection will be readily detectable in outbred wild populations is unclear. In this study, we employ haplotype diversity analysis to examine evidence for selective sweeps around knockdown resistance (kdr) mutations associated with resistance to dichlorodiphenyltrichloroethane and pyrethroid insecticides in the mosquito Anopheles gambiae. Both kdr mutations have significantly lower haplotype diversity than the wild-type (nonresistant) allele, with kdr L1014F showing the most pronounced footprint of selection. We complement these data with a time series of collections showing that the L1014F allele has increased in frequency from 0.05 to 0.54 in 5 years, consistent with a maximum likelihood–fitted selection coefficient of 0.16 and a dominance coefficient of 0.25. Our data show that strong, recent positive selective events, such as those caused by insecticide resistance, can be identified in wild insect populations.

Lynd, Amy; Weetman, David; Barbosa, Susana; Egyir Yawson, Alexander; Mitchell, Sara; Pinto, Joao; Hastings, Ian; Donnelly, Martin J.

2010-01-01

189

New Center Aims to Help Motivate California High Schoolers: Related Poll Shows Student Support for Career-Related Schools  

ERIC Educational Resources Information Center

Hoping to motivate more California students to finish high school and find future success, the James Irvine Foundation last week announced a new center aimed at expanding work-based learning programs that integrate high-level academics. Called ConnectEd: The California Center for College and Career, the new project will seek to provide solutions…

Jacobson, Linda

2006-01-01

190

Analysis of codon usage patterns and predicted highly expressed genes for six phytopathogenic Xanthomonas genomes shows a high degree of conservation.  

PubMed

Members of the genus Xanthomonas are significant phytopathogens, which cause diseases in several economically important crops including rice, canola, tomato, citrus, etc. We have analyzed the genomes of six recently sequenced Xanthomonas strains for their synonymous codon usage patterns for all of protein coding genes and specific genes associated with pathogenesis, and determined the predicted highly expressed (PHX) genes by the use of the codon adaptation index (CAI). Our results show considerable heterogeneity among the genes of these moderately G+C rich genomes. Most of the genes were moderate to highly biased in their codon usage. However, unlike ribosomal protein genes, which were governed by translational selection, those genes associated with pathogenesis (GAP) were affected by mutational pressure and were predicted to have moderate to low expression levels. Only two out of 339 GAP genes were in the PHX category. PHX genes present in clusters of orthologous groups of proteins (COGs) were identified. Genes in the plasmids present in two strains showed moderate to low expression level and only a couple of genes featured in the PHX list. Common genes present in the top-20 PHX gene-list were identified and their possible functions are discussed. Correspondence analysis showed that genes are highly confined to a core in the plot. PMID:18391244

Sen, Gargi; Sur, Saubashya; Bose, Debadin; Mondal, Uttam; Furnholm, Teal; Bothra, Asim; Tisa, Louis; Sen, Arnab

2007-01-01

191

Phenacetin O-deethylase: an activity of a cytochrome P-450 showing genetic linkage with that catalysing the 4-hydroxylation of debrisoquine?  

PubMed Central

Phenacetin O-deethylase activity was impaired, both in vivo and in vitro, in poor metabolisers of debrisoquine, consistent with the work of others. No impairment was observed in the oxidation of acetanilide, amylobarbitone or antipyrine in the PM phenotype. There was a good correlation (r = 0.804) between the high affinity component of phenacetin O-deethylase and debrisoquine 4-hydroxylase activities. No such correlation was observed with the low affinity component of phenacetin O-deethylase activity. Although debrisoquine was a competitive inhibitor of phenacetin O-deethylase activity, phenacetin was without effect on debrisoquine 4-hydroxylation. There was also marked differences in the effects of sparteine, guanoxan and alpha-naphthoflavone on the two activities. Cigarette smoking was associated with a significant, two-fold, increase in phenacetin O-deethylase activity whilst debrisoquine 4-hydroxylase activity was not affected. It is concluded that the high affinity component of phenacetin O-deethylase and debrisoquine 4-hydroxylase activities are catalysed by different isozymes of cytochrome P-450 but that these are most probably regulated by closely linked genes.

Kahn, G C; Boobis, A R; Brodie, M J; Toverud, E L; Murray, S; Davies, D S

1985-01-01

192

Genetic structure in striped skunks (Mephitis mephitis) on the southern high plains of Texas  

USGS Publications Warehouse

Genetic variation within populations reflects population-level social and demographic processes and influences how a population behaves as an evolutionary unit. We examined partitioning of genetic variation in striped skunks (Mephitis mephitis) from the Southern High Plains of Texas during 1994-1995. Sixty-nine male and 35 female skunks were sampled on four 12.8-km2 study plots. Plot centers ranged from 17.6 to 61.6 km apart. We used multi-locus DNA fingerprinting with 2 probes, pV47 and CTTxAGG, to test 3 hypotheses: (1) females are more genetically similar to other females than males are to other males on the same plot (indicating greater female philopatry than male philopatry), (2) genetic similarity is greater within plots than among plots (indicating partitioning of genetic variation in space), and (3) genetic similarity of males decreases as the distance separating males increases (indicating geographic distance affects rates of gene flow). In general, males on a plot had lower average genetic similarity than females. Genetic similarity within plots was not different from genetic similarity among plots for males or for females. Genetic similarity of males did not decrease with increasing distance among plots. The lack of geographical genetic structure in striped skunks suggests at the scale of this study (<60 km) that gene flow of biparentally inherited genes is not distance-mediated. However, the higher similarity values for females than for males on the same plot supports an effect of male-biased dispersal and female philopatry on partitioning of genetic variation between sexes.

Hansen, L. A.; Mathews, N. E.; Hansen, R. W.; Vander Lee, B. A.; Scott, Lutz, R.

2003-01-01

193

High Genetic Diversity among Community-Associated Staphylococcus aureus in Europe: Results from a Multicenter Study  

PubMed Central

Background Several studies have addressed the epidemiology of community-associated Staphylococcus aureus (CA-SA) in Europe; nonetheless, a comprehensive perspective remains unclear. In this study, we aimed to describe the population structure of CA-SA and to shed light on the origin of methicillin-resistant S. aureus (MRSA) in this continent. Methods and Findings A total of 568 colonization and infection isolates, comprising both MRSA and methicillin-susceptible S. aureus (MSSA), were recovered in 16 European countries, from community and community-onset infections. The genetic background of isolates was characterized by molecular typing techniques (spa typing, pulsed-field gel electrophoresis and multilocus sequence typing) and the presence of PVL and ACME was tested by PCR. MRSA were further characterized by SCCmec typing. We found that 59% of all isolates were associated with community-associated clones. Most MRSA were related with USA300 (ST8-IVa and variants) (40%), followed by the European clone (ST80-IVc and derivatives) (28%) and the Taiwan clone (ST59-IVa and related clonal types) (15%). A total of 83% of MRSA carried Panton-Valentine leukocidin (PVL) and 14% carried the arginine catabolic mobile element (ACME). Surprisingly, we found a high genetic diversity among MRSA clonal types (ST-SCCmec), Simpson’s index of diversity?=?0.852 (0.788–0.916). Specifically, about half of the isolates carried novel associations between genetic background and SCCmec. Analysis by BURP showed that some CA-MSSA and CA-MRSA isolates were highly related, suggesting a probable local acquisition/loss of SCCmec. Conclusions Our results imply that CA-MRSA origin, epidemiology and population structure in Europe is very dissimilar from that of USA.

Rolo, Joana; Miragaia, Maria; Turlej-Rogacka, Agata; Empel, Joanna; Bouchami, Ons; Faria, Nuno A.; Tavares, Ana; Hryniewicz, Waleria; Fluit, Ad C.; de Lencastre, Herminia

2012-01-01

194

High Genetic Diversity among Stenotrophomonas maltophilia Strains Despite Their Originating at a Single Hospital  

PubMed Central

The levels of genetic relatedness of 139 Stenotrophomonas maltophilia strains recovered from 105 hospitalized non-cystic fibrosis patients (51% from medical wards, 35% from intensive care units, and 14% from surgical wards) and 7 environmental sources in the same hospital setting during a 4-year period were typed by the pulsed-field gel electrophoresis (PFGE) technique. A total of 99 well-defined distinct XbaI PFGE patterns were identified (Simpson's discrimination index, 0.996). The dendrogram showed a Dice similarity coefficient ranging from 28 to 80%. Two major clusters (I and II), three minor clusters (III, IV, and V), and two independent branches were observed when using a 36% Dice coefficient, indicating a high diversity of genetic relatedness. It is of note that 84% of strains were grouped within two major clonal lineages. No special cluster gathering was found among strains belonging to the same sample type specimen, patients' infection or colonization status, and ward of precedence. Despite this fact, three different clones (A, B, and C) recovered from respiratory samples from six, three, and two patients, respectively, and two clones, D and E, in two bacteremic patients each, were identified. Isolation of an S. maltophilia strain belonging to the clone A profile in a bronchoscope demonstrated a common source from this clone. This study revealed a high genetic diversity of S. maltophilia isolates despite their origin from a single hospital, which may be related to the wide environmental distribution of this pathogen. However, few clones could be transmitted among different patients, yielding outbreak situations.

Valdezate, Sylvia; Vindel, Ana; Martin-Davila, Pilar; Del Saz, Begona Sanchez; Baquero, Fernando; Canton, Rafael

2004-01-01

195

High genetic diversity among Stenotrophomonas maltophilia strains despite their originating at a single hospital.  

PubMed

The levels of genetic relatedness of 139 Stenotrophomonas maltophilia strains recovered from 105 hospitalized non-cystic fibrosis patients (51% from medical wards, 35% from intensive care units, and 14% from surgical wards) and 7 environmental sources in the same hospital setting during a 4-year period were typed by the pulsed-field gel electrophoresis (PFGE) technique. A total of 99 well-defined distinct XbaI PFGE patterns were identified (Simpson's discrimination index, 0.996). The dendrogram showed a Dice similarity coefficient ranging from 28 to 80%. Two major clusters (I and II), three minor clusters (III, IV, and V), and two independent branches were observed when using a 36% Dice coefficient, indicating a high diversity of genetic relatedness. It is of note that 84% of strains were grouped within two major clonal lineages. No special cluster gathering was found among strains belonging to the same sample type specimen, patients' infection or colonization status, and ward of precedence. Despite this fact, three different clones (A, B, and C) recovered from respiratory samples from six, three, and two patients, respectively, and two clones, D and E, in two bacteremic patients each, were identified. Isolation of an S. maltophilia strain belonging to the clone A profile in a bronchoscope demonstrated a common source from this clone. This study revealed a high genetic diversity of S. maltophilia isolates despite their origin from a single hospital, which may be related to the wide environmental distribution of this pathogen. However, few clones could be transmitted among different patients, yielding outbreak situations. PMID:14766838

Valdezate, Sylvia; Vindel, Ana; Martín-Dávila, Pilar; Del Saz, Begoña Sánchez; Baquero, Fernando; Cantón, Rafael

2004-02-01

196

High genome heterozygosity and endemic genetic recombination in the wheat stripe rust fungus.  

PubMed

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive diseases of wheat. Here we report a 110-Mb draft sequence of Pst isolate CY32, obtained using a 'fosmid-to-fosmid' strategy, to better understand its race evolution and pathogenesis. The Pst genome is highly heterozygous and contains 25,288 protein-coding genes. Compared with non-obligate fungal pathogens, Pst has a more diverse gene composition and more genes encoding secreted proteins. Re-sequencing analysis indicates significant genetic variation among six isolates collected from different continents. Approximately 35% of SNPs are in the coding sequence regions, and half of them are non-synonymous. High genetic diversity in Pst suggests that sexual reproduction has an important role in the origin of different regional races. Our results show the effectiveness of the 'fosmid-to-fosmid' strategy for sequencing dikaryotic genomes and the feasibility of genome analysis to understand race evolution in Pst and other obligate pathogens. PMID:24150273

Zheng, Wenming; Huang, Lili; Huang, Jinqun; Wang, Xiaojie; Chen, Xianming; Zhao, Jie; Guo, Jun; Zhuang, Hua; Qiu, Chuangzhao; Liu, Jie; Liu, Huiquan; Huang, Xueling; Pei, Guoliang; Zhan, Gangming; Tang, Chunlei; Cheng, Yulin; Liu, Minjie; Zhang, Jinshan; Zhao, Zhongtao; Zhang, Shijie; Han, Qingmei; Han, Dejun; Zhang, Hongchang; Zhao, Jing; Gao, Xiaoning; Wang, Jianfeng; Ni, Peixiang; Dong, Wei; Yang, Linfeng; Yang, Huanming; Xu, Jin-Rong; Zhang, Gengyun; Kang, Zhensheng

2013-01-01

197

A highly sensitive and genetically encoded fluorescent reporter for ratiometric monitoring of quinones in living cells.  

PubMed

The transcriptional regulator QsrR is converted into a genetically encoded fluorescent probe capable of ratiometric monitoring of quinones in living cells with high sensitivity and selectivity. PMID:23903292

Ji, Quanjiang; Zhao, Boxuan Simen; He, Chuan

2013-09-21

198

Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals  

PubMed Central

Background A high-fat diet promotes postprandial systemic inflammation and metabolic endotoxemia. We investigated the effects of three consecutive high-fat meals on endotoxemia, inflammation, vascular function, and postprandial lipid metabolism in patients with type 1 diabetes. Methods Non-diabetic controls (n?=?34) and patients with type 1 diabetes (n?=?37) were given three high-caloric, fat-containing meals during one day. Blood samples were drawn at fasting (8:00) and every two hours thereafter until 18:00. Applanation tonometry was used to assess changes in the augmentation index during the investigation day. Results Three consecutive high-fat meals had only a modest effect on serum LPS-activity levels and inflammatory markers throughout the day in both groups. Of note, patients with type 1 diabetes were unable to decrease the augmentation index in response to the high-fat meals. The most profound effects of the consecutive fat loads were seen in chylomicron and HDL-metabolism. The triglyceride-rich lipoprotein remnant marker, apoB-48, was elevated in patients compared to controls both at fasting (p?=?0.014) and postprandially (p?=?0.035). The activities of the HDL-associated enzymes PLTP (p?high-fat meals, early signs of vascular dysfunction alongside accumulation of chylomicron remnants, higher augmentation index, and decreased PON-1 activity were observed in patients with type 1 diabetes. The high-fat meals had no significant impact on postprandial LPS-activity in non-diabetic subjects or patients with type 1 diabetes suggesting that metabolic endotoxemia may be more central in patients with chronic metabolic disturbances such as obesity, type 2 diabetes, or diabetic kidney disease.

2014-01-01

199

Parameter Estimation of High-Voltage Circuit Breaker Based on Genetic Algorithms  

Microsoft Academic Search

\\u000a A method of parameter estimation of High-Voltage circuit break based on genetic algorithms is proposed in order to estimate\\u000a the parameters of capacitance, inductance and resistance in oscillation circuit DC circuit breaker and then properly assess\\u000a the performance of DC circuit breaker. In this paper A genetic algorithm is introduced and applied in parameter estimation\\u000a of High-Voltage circuit breaker and

Tao Jin; Wei Chen; Tao Ning; Zhihua Li

200

Biodegradable polymeric nanoparticles show high efficacy and specificity at DNA delivery to human glioblastoma in vitro and in vivo.  

PubMed

Current glioblastoma therapies are insufficient to prevent tumor recurrence and eventual death. Here, we describe a method to treat malignant glioma by nonviral DNA delivery using biodegradable poly(?-amino ester)s (PBAEs), with a focus on the brain tumor initiating cells (BTICs), the tumor cell population believed to be responsible for the formation of new tumors and resistance to many conventional therapies. We show transfection efficacy of >60% and low biomaterial-mediated cytotoxicity in primary human BTICs in vitro even when the BTICs are grown as 3-D oncospheres. Intriguingly, we find that these polymeric nanoparticles show intrinsic specificity for nonviral transfection of primary human BTICs over primary healthy human neural progenitor cells and that this specificity is not due to differences in cellular growth rate or total cellular uptake of nanoparticles. Moreover, we demonstrate that biodegradable PBAE/DNA nanoparticles can be fabricated, lyophilized, and then stored for at least 2 years without losing efficacy, increasing the translational relevance of this technology. Using lyophilized nanoparticles, we show transgene expression by tumor cells after intratumoral injection into an orthotopic murine model of human glioblastoma. PBAE/DNA nanoparticles were more effective than naked DNA at exogenous gene expression in vivo, and tumor cells were transfected more effectively than noninvaded brain parenchyma in vivo. This work shows the potential of nonviral gene delivery tools to target human brain tumors. PMID:24766032

Guerrero-Cázares, Hugo; Tzeng, Stephany Y; Young, Noah P; Abutaleb, Ameer O; Quiñones-Hinojosa, Alfredo; Green, Jordan J

2014-05-27

201

Metabolic characterization of a strain (BM90) of Delftia tsuruhatensis showing highly diversified capacity to degrade low molecular weight phenols  

Microsoft Academic Search

A novel bacterium, strain BM90, previously isolated from Tyrrhenian Sea, was metabolically characterized testing its ability\\u000a to use 95 different carbon sources by the Biolog system. The bacterium showed a broad capacity to use fatty-, organic- and\\u000a amino-acids; on the contrary, its ability to use carbohydrates was extremely scarce. Strain BM90 was identified and affiliated\\u000a to Delftia tsuruhatensis by molecular

Belén Juárez-Jiménez; Maximino Manzanera; Belén Rodelas; Maria Victoria Martínez-Toledo; Jesus Gonzalez-López; Silvia Crognale; Chiara Pesciaroli; Massimiliano Fenice

2010-01-01

202

Ultrastructural characterization of cationic liposome-DNA complexes showing enhanced stability in serum and high transfection activity in vivo  

Microsoft Academic Search

We have investigated the morphology and transfection activity of cationic liposome-DNA complexes (CLDC) under conditions relevant to both in vivo and in vitro studies. Moreover we have attempted to establish structure-function relationships relevant for high transfection activities under both conditions. CLDC were composed of dimethyldioctadecylammonium bromide with either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol) interacting either with pre-condensed DNA or with

Brigitte Sternberg; Keelung Hong; Weiwen Zheng; Demetrios Papahadjopoulos

1998-01-01

203

Highly resolved early Eocene food webs show development of modern trophic structure after the end-Cretaceous extinction  

PubMed Central

Generalities of food web structure have been identified for extant ecosystems. However, the trophic organization of ancient ecosystems is unresolved, as prior studies of fossil webs have been limited by low-resolution, high-uncertainty data. We compiled highly resolved, well-documented feeding interaction data for 700 taxa from the 48 million-year-old latest early Eocene Messel Shale, which contains a species assemblage that developed after an interval of protracted environmental and biotal change during and following the end-Cretaceous extinction. We compared the network structure of Messel lake and forest food webs to extant webs using analyses that account for scale dependence of structure with diversity and complexity. The Messel lake web, with 94 taxa, displays unambiguous similarities in structure to extant webs. While the Messel forest web, with 630 taxa, displays differences compared to extant webs, they appear to result from high diversity and resolution of insect–plant interactions, rather than substantive differences in structure. The evidence presented here suggests that modern trophic organization developed along with the modern Messel biota during an 18 Myr interval of dramatic post-extinction change. Our study also has methodological implications, as the Messel forest web analysis highlights limitations of current food web data and models.

Dunne, Jennifer A.; Labandeira, Conrad C.; Williams, Richard J.

2014-01-01

204

Adaptive Color Polymorphism and Unusually High Local Genetic Diversity in the Side-Blotched Lizard, Uta stansburiana  

PubMed Central

Recently, studies of adaptive color variation have become popular as models for examining the genetics of natural selection. We examined color pattern polymorphism and genetic variation in a population of side-blotched lizards (Uta stansburiana) that is found in habitats with both dark (lava) and light colored (granite) substrates. We conducted a limited experiment for adult phenotypic plasticity in laboratory conditions. We recorded both substrate and lizard color patterns in the field to determine whether lizards tended to match their substrate. Finally we examined genetic variation in a gene (melanocortin 1 receptor) that has been shown to affect lizard color in other species and in a presumably neutral gene (mitochondrial cytochrome b). Populations were sampled in the immediate area of the lava flows as well as from a more distant site to examine the role of population structure. Our captive Uta did not change color to match their background. We show that side-blotched lizards tend to match the substrate on which it was caught in the field and that variation in the melanocortin 1 receptor gene does not correlate well with color pattern in this population. Perhaps the most remarkable result is that this population of side-blotched lizards shows extremely high levels of variation at both genetic markers, in the sense of allele numbers, with relatively low levels of between-allele sequence variation. Genetic variation across this small region was as great or greater than that seen in samples of pelagic fish species collected worldwide. Statistical analysis of genetic variation suggests rapid population expansion may be responsible for the high levels of variation.

Micheletti, Steven; Parra, Eliseo; Routman, Eric J.

2012-01-01

205

Dana-Farber study shows promise of hormone-depleting drug against localized high-risk prostate tumors  

Cancer.gov

A hormone-depleting drug approved last year for the treatment of metastatic prostate cancer can help eliminate or nearly eliminate tumors in many patients with aggressive cancers that have yet to spread beyond the prostate, according to a clinical study to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO), June 1-5 in Chicago. The phase II clinical trial, led by investigators at Dana-Farber Cancer Institute and other research centers, examined the use of the drug abiraterone acetate (Zytiga) in combination with prednisone and surgery in 58 men with high-risk prostate cancer isolated to the prostate gland.

206

Next generation sequencing shows high variation of the intestinal microbial species composition in Atlantic cod caught at a single location  

PubMed Central

Background The observation that specific members of the microbial intestinal community can be shared among vertebrate hosts has promoted the concept of a core microbiota whose composition is determined by host-specific selection. Most studies investigating this concept in individual hosts have focused on mammals, yet the diversity of fish lineages provides unique comparative opportunities from an evolutionary, immunological and environmental perspective. Here we describe microbial intestinal communities of eleven individual Atlantic cod (Gadus morhua) caught at a single location based on an extensively 454 sequenced 16S rRNA library of the V3 region. Results We obtained a total of 280447 sequences and identify 573 Operational Taxonomic Units (OTUs) at 97% sequence similarity level, ranging from 40 to 228 OTUs per individual. We find that ten OTUs are shared, though the number of reads of these OTUs is highly variable. This variation is further illustrated by community diversity estimates that fluctuate several orders of magnitude among specimens. The shared OTUs belong to the orders of Vibrionales, which quantitatively dominate the Atlantic cod intestinal microbiota, followed by variable numbers of Bacteroidales, Erysipelotrichales, Clostridiales, Alteromonadales and Deferribacterales. Conclusions The microbial intestinal community composition varies significantly in individual Atlantic cod specimens caught at a single location. This high variation among specimens suggests that a complex combination of factors influence the species distribution of these intestinal communities.

2013-01-01

207

High genetic diversity in Sarracenia leucophylla(Sarraceniaceae), a carnivorous wetland herb.  

PubMed

Eighteen allozyme loci were used to examine genetic diversity in 10 natural populations of Sarracenia leucophylla Raf., a pitcher plant restricted to the southeastern United States. One ex situ population propagated for restoration in Georgia was also analyzed. S. leucophylla is an insect-pollinated, outcrossing perennial wetland herb that is threatened over much of its geographic range. Fifteen loci (83.3%) were polymorphic, with a mean number of alleles of 3.33. Compared to species having similar life-history traits and to previously analyzed Sarracenia species, S. leucophylla displayed unexpectedly high genetic diversity. For example, genetic diversity within the species (Hes) was 0.224 and mean population genetic diversity (Hep) was 0.183. Although small S. leucophylla populations maintained less genetic diversity than larger ones, these differences were not statistically significant. Nonetheless, this suggests that small populations may have lost rare alleles. Statistically significant genetic differentiation among populations was found (theta = 0.192, P < .01), although it was not atypical considering the species' life-history characteristics. A significant correlation (P < .01) between genetic and geographic distance was found, indicating an isolation-by-distance effect. However, the correlation coefficient for this relationship was low (r = 0.46), suggesting that factors other than gene flow play a prominent role in the geographic distribution of genetic diversity within the species. The ex situ population captured most of the allozyme variation found in its source population. PMID:15220390

Wang, Z-F; Hamrick, J L; Godt, M J W

2004-01-01

208

Awareness of Societal Issues Among High School Biology Teachers Teaching Genetics  

NASA Astrophysics Data System (ADS)

The purpose of this study was to investigate how aware high school biology teachers are of societal issues (values, moral, ethic, and legal issues) while teaching genetics, genetics engineering, molecular genetics, human heredity, and evolution. The study includes a short historical review of World War II atrocities during the Holocaust when scientists from all the above-mentioned disciplines had been involved in trying to support and develop the eugenics theories. It investigates pre- and postwar theories of the eugenics movement in the United States which were implemented successfully in Germany and a literature survey of the studies of societal issues related to these subjects. The sample consisted of 30 male and female biology teachers. Enclosed are teachers' answers in favor or against including debates about societal issues in their classrooms while teaching the disciplines mentioned above. Teachers' answers were analyzed in relation to three variables: years of teaching experience, gender, and religion faith. Data were collected from questionnaires and personal interviews and analyzed according to qualitative and quantitative methods. The results show that amongst the teachers there is a medium to low level of awareness of societal issues, while mainly emphasizing scientific subjects in preparation of matriculation examinations. The majority of the teachers do not include societal issues in their teaching, but if students raise these issues, teachers claimed to address them. No differences in teachers' opinions to societal issues were found in relation to gender or religious faith. Teachers with more years of teaching experience tend to teach with a more Science, Technology, and Society (STS) approach than novice teachers. The results are discussed in relation to teachers' professional development and teaching strategies are suggested to be used in their classrooms based on a STS approach, which includes the societal issues as a main goal.

Lazarowitz, Reuven; Bloch, Ilit

2005-12-01

209

I(h) channels prevent overexcitability of early developmental CA1 neurons showing high input resistance in rats.  

PubMed

Immature hippocampal neurons with high input resistances (R(in)) are vulnerable to hyperexcitable or epileptogenic conditions. This phenomenon has been suggested to explain the neuroprotective roles of hyperpolarization-activated cation channels (I(h) channels) to regulate membrane R(in). In the present study, we tried to electrophysiologically clarify the relationship between membrane R(in) and I(h) channels and determine the neuroprotective roles of these channels in development. The CA1 neurons from rats (within 3 postnatal weeks) were classified into two groups based on the onset time (shorter or longer than 20 ms) to fire the first action potential (AP) in response to a current injection (100 pA, 800 ms). Neurons with a shorter onset time (Short-OsT), exhibited higher R(in), while neurons with longer onset times (Long-OsT) revealed lower R(in). Unexpectedly, Short-OsT neurons with higher R(in) exhibited larger amplitudes of I(h) compared with Long-OsT neurons. Furthermore, the application of temporal depolarization stimulus (TDS, -14 mV holding for 150 s) significantly enhanced suprathreshold excitabilities of repetitive APs in Long-OsT but not Short-OsT neurons, suggesting a protective role of I(h) channels under high R(in) conditions. In the presence of the specific hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288, TDS also enhanced the excitability of Short-OsT neurons, suggesting that young CA1 neurons regulate I(h) channel expression for neuroprotective modulation against epileptogenic conditions. PMID:23219935

Yang, Yoon-Sil; Kang, Moon-Seok; Kim, Seon-Hee; Kim, Se-Jae; Eun, Su-Yong; Kwon, Oh-Bin; Jung, Sung-Cherl

2013-02-01

210

High urban breeding densities do not disrupt genetic monogamy in a bird species.  

PubMed

Urbanization causes widespread endangerment of biodiversity worldwide. However, some species successfully colonize cities reaching higher densities than in their rural habitats. In these cases, although urban city dwellers may apparently be taking advantage of these new environments, they also face new ecological conditions that may induce behavioural changes. For example, the frequency of alternative reproductive behaviours such as extra-pair paternity and intraspecific brood parasitism might increase with breeding densities. Here, using a panel of 17 microsatellites, we tested whether increments in breeding densities such as those associated with urban invasion processes alter genetic monogamy in the burrowing owl Athene cunicularia. Our results show low rates of extra-pair paternity (1.47%), but relatively high levels of intraspecific brood parasitism (8.82%). However, we were not able to detect differences in the frequency at which either alternative reproductive behaviour occurs along a strong breeding density gradient. Further research is needed to properly ascertain the role of other social and ecological factors in the frequency at which this species presents alternative reproductive strategies. Meanwhile, our results suggest that genetic monogamy is maintained despite the increment in conspecific density associated with a recent urban invasion process. PMID:24614308

Rodriguez-Martínez, Sol; Carrete, Martina; Roques, Séverine; Rebolo-Ifrán, Natalia; Tella, José L

2014-01-01

211

Predicted HIV-1 coreceptor usage among Kenya patients shows a high tendency for subtype d to be cxcr4 tropic  

PubMed Central

Background CCR5 antagonists have clinically been approved for prevention or treatment of HIV/AIDS. Countries in Sub-Saharan Africa with the highest burden of HIV/AIDS are due to adopt these regimens. However, HIV-1 can also use CXCR4 as a co-receptor. There is hence an urgent need to map out cellular tropism of a country’s circulating HIV strains to guide the impending use of CCR5 antagonists. Objectives To determine HIV-1 coreceptor usage among patients attending a comprehensive care centre in Nairobi, Kenya. Methods Blood samples were obtained from HIV infected patients attending the comprehensive care centre, Kenyatta National Hospital in years 2008 and 2009. The samples were separated into plasma and peripheral blood mononuclear cells (PBMCs). Proviral DNA was extracted from PBMCs and Polymerase Chain reaction (PCR) done to amplify the HIV env fragment spanning the C2-V3 region. The resultant fragment was directly sequenced on an automated sequencer (ABI, 3100). Co-receptor prediction of the env sequences was done using Geno2pheno [co-receptor], and phylogenetic relationships determined using CLUSTALW and Neighbor Joining method. Results A total of 67 samples (46 treatment experienced and 21 treatment naive) were successfully amplified and sequenced. Forty nine (73%) sequences showed a prediction for R5 tropism while 18(27%) were X4 tropic. Phylogenetic analysis showed that 46(69%) were subtype A, 11(16%) subtype C, and 10(15%) subtype D. No statistical significant associations were observed between cell tropism and CD4+ status, patient gender, age, or treatment option. There was a tendency for more X4 tropic strains being in the treatment experienced group than the naive group: Of 46 treatment experiencing participants, 14(30%) harboured X4, compared with 4(19%) of 21 of the treatment-naïve participants, the association is however not statistically significant (p?=?0.31). However, a strong association was observed between subtype D and CXCR4 co- receptor usage (p?=?0.015) with 6(60%) of the 10 subtype D being X4 tropic and 4(40%) R5 tropic. Conclusion HIV-1 R5 tropic strains were the most prevalent in the study population and HIV infected patients in Kenya may benefit from CCR5 antagonists. However, there is need for caution where subtype D infection is suspected or where antiretroviral salvage therapy is indicated.

2012-01-01

212

Genetic score based on high-risk genetic polymorphisms and early onset of ischemic heart disease in an Italian cohort of ischemic patients.  

PubMed

Several single-nucleotide polymorphisms (SNPs) have been recognized as associated with ischemic heart disease (IHD) although the optimal set of risk genotypes has not be identified. This study aimed to examine whether identified high-risk SNPs are associated with early onset of IHD. In the GENOCOR study, 44 high-risk SNPs were genotyped in 114 patients with early onset of IHD (46.2±5.1years) and 384 patients with late onset of IHD (60.7±5.9years). The associations between individual SNPs and early onset IHD were assessed. A multilocus genetic risk score (GRS) for each associated risk genetic markers was constructed by summing the number of risk alleles. The SNPs significantly associated with IHD were: -482C>T of Apolipoprotein C III gene (ApoC3, p=0.02); 1171 5A>6A of Matrix metalloproteinase 3 stromelisine I gene (p=0.01); G98T of Selectin E gene (p=0.05); C/G of 9p21.3 locus (p=0.01). Likelihood ratio test showed a strong interaction for increasing risk of early IHD between the presence of ApoC3 and 9p21.3 locus with hypertriglyceridemia (p=0.0008, 0.0011) as well as between 9p21.3 locus and smoking (p=0.0010) after correction for multiple testing. The OR for premature IHD for GRS unit was 1.3 (95% CI 1.1-1.6, p=0.001). Patients in the top tertile of GRS were estimated to have a 3.2-fold (95% CI 1.5-6.8; p=0.001) increased risk of early IHD compared with those in the bottom tertile. The results show that currently identified high-risk SNPs confer an additive biomarker for cardiovascular events. GRS may provide important incremental information on the genetic component of IHD. PMID:24656450

Vecoli, Cecilia; Adlerstein, Daniel; Shehi, Erlet; Bigazzi, Federico; Sampietro, Tiziana; Foffa, Ilenia; Carpeggiani, Clara; L'abbate, Antonio; Andreassi, Maria Grazia

2014-05-01

213

Genetic structure is correlated with phenotypic divergence rather than geographic isolation in the highly polymorphic strawberry poison-dart frog.  

PubMed

Phenotypic and genetic divergence can be influenced by a variety of factors, including sexual and natural selection, genetic drift and geographic isolation. Investigating the roles of these factors in natural systems can provide insight into the relative influences of allopatric and ecological modes of biological diversification in nature. The strawberry poison frog, Dendrobates pumilio, presents an excellent opportunity for this kind of research, displaying a diverse array of colour morphs and inhabiting a heterogeneous landscape that includes oceanic islands, fragmented rainforest patches and wide expanses of suitable habitat. In this study, we use 15 highly polymorphic microsatellite loci to estimate population structure and gene flow among populations from across the range of D. pumilio and a causal modelling framework to statistically test 12 hypotheses regarding the geographic and phenotypic variables that explain genetic differentiation within this system. Our results demonstrate that the genetic distance between populations is most strongly associated with differences in dorsal coloration. Previous experimental studies have shown that phenotypic differences can result in sexual and natural selection against non-native phenotypes, and our results now show that these forces lead to genetic isolation between different colour morphs in the wild, presenting a potential case of incipient speciation through selection. PMID:20025652

Wang, Ian J; Summers, Kyle

2010-02-01

214

A High Throughput Genotyping Approach Reveals Distinctive Autosomal Genetic Signatures for European and Near Eastern Wild Boar  

PubMed Central

The lack of a Near Eastern genetic signature in modern European porcine breeds indicates that, although domestic pigs from the Fertile Crescent entered Europe during the Neolithic, they were completely replaced by their European counterparts in a short window of time. Whilst the absence of such genetic signature has been convincingly demonstrated at the mitochondrial level, variation at the autosomal genomes of European and Near Eastern Sus scrofa has not been compared yet. Herewith, we have explored the genetic relationships among 43 wild boar from Europe (N?=?21), Near East (N?=?19) and Korea (N?=?3), and 40 Iberian (N?=?16), Canarian (N?=?4) and Mangalitza (N?=?20) pigs by using a high throughput SNP genotyping platform. After data filtering, 37,167 autosomal SNPs were used to perform population genetics analyses. A multidimensional scaling plot based on genome-wide identity-by-state pairwise distances inferred with PLINK showed that Near Eastern and European wild boar populations are genetically differentiated. Maximum likelihood trees built with TreeMix supported this conclusion i.e. an early population split between Near Eastern and European Sus scrofa was observed. Moreover, analysis of the data with Structure evidenced that the sampled Iberian, Canarian and Mangalitza pigs did not carry any autosomal signature compatible with a Near Eastern ancestry, a finding that agrees well with previous mitochondrial studies.

Yeghoyan, Seryozha; Balteanu, Valentin Adrian; Carsai, Teodora Crina; Scherbakov, Oleg; Ramirez, Oscar; Eghbalsaied, Shahin; Castello, Anna; Mercade, Anna; Amills, Marcel

2013-01-01

215

[Lidamycin inhibits the proliferation of HERG K+ channel highly expressing cancer cells and shows synergy with anticancer drugs].  

PubMed

This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs. PMID:22260022

Shang, Bo-yang; Shang, Yue; Zhen, Yong-su; Chen, Shu-zhen

2011-11-01

216

Thermostable trypsin conjugates immobilized to biogenic magnetite show a high operational stability and remarkable reusability for protein digestion.  

PubMed

In this work, magnetosomes produced by microorganisms were chosen as a suitable magnetic carrier for covalent immobilization of thermostable trypsin conjugates with an expected applicability for efficient and rapid digestion of proteins at elevated temperatures. First, a biogenic magnetite was isolated from Magnetospirillum gryphiswaldense and its free surface was coated with the natural polysaccharide chitosan containing free amino and hydroxy groups. Prior to covalent immobilization, bovine trypsin was modified by conjugating with ?-, ?- and ?-cyclodextrin. Modified trypsin was bound to the magnetic carriers via amino groups using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysulfosuccinimide as coupling reagents. The magnetic biomaterial was characterized by magnetometric analysis and electron microscopy. With regard to their biochemical properties, the immobilized trypsin conjugates showed an increased resistance to elevated temperatures, eliminated autolysis, had an unchanged pH optimum and a significant storage stability and reusability. Considering these parameters, the presented enzymatic system exhibits properties that are superior to those of trypsin forms obtained by other frequently used approaches. The proteolytic performance was demonstrated during in-solution digestion of model proteins (horseradish peroxidase, bovine serum albumin and hen egg white lysozyme) followed by mass spectrometry. It is shown that both magnetic immobilization and chemical modification enhance the characteristics of trypsin making it a promising tool for protein digestion. PMID:23466477

Pe?ová, M; Šebela, M; Marková, Z; Poláková, K; ?uda, J; Šafá?ová, K; Zbo?il, R

2013-03-29

217

Thermostable trypsin conjugates immobilized to biogenic magnetite show a high operational stability and remarkable reusability for protein digestion  

NASA Astrophysics Data System (ADS)

In this work, magnetosomes produced by microorganisms were chosen as a suitable magnetic carrier for covalent immobilization of thermostable trypsin conjugates with an expected applicability for efficient and rapid digestion of proteins at elevated temperatures. First, a biogenic magnetite was isolated from Magnetospirillum gryphiswaldense and its free surface was coated with the natural polysaccharide chitosan containing free amino and hydroxy groups. Prior to covalent immobilization, bovine trypsin was modified by conjugating with ?-, ?- and ?-cyclodextrin. Modified trypsin was bound to the magnetic carriers via amino groups using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysulfosuccinimide as coupling reagents. The magnetic biomaterial was characterized by magnetometric analysis and electron microscopy. With regard to their biochemical properties, the immobilized trypsin conjugates showed an increased resistance to elevated temperatures, eliminated autolysis, had an unchanged pH optimum and a significant storage stability and reusability. Considering these parameters, the presented enzymatic system exhibits properties that are superior to those of trypsin forms obtained by other frequently used approaches. The proteolytic performance was demonstrated during in-solution digestion of model proteins (horseradish peroxidase, bovine serum albumin and hen egg white lysozyme) followed by mass spectrometry. It is shown that both magnetic immobilization and chemical modification enhance the characteristics of trypsin making it a promising tool for protein digestion.

Pe?ová, M.; Šebela, M.; Marková, Z.; Poláková, K.; ?uda, J.; Šafá?ová, K.; Zbo?il, R.

2013-03-01

218

Abnormal Mammary Adipose Tissue Environment of Brca1 Mutant Mice Show a Persistent Deposition of Highly Vascularized Multilocular Adipocytes  

PubMed Central

A major challenge to breast cancer research is the identification of alterations in the architecture and composition of the breast that are associated with breast cancer progression. The aim of the present investigation was to characterize the mammary adipose phenotype from Brca1 mutant mice in the expectation that this would shed light on the role of the mammary tissue environment in the early stages of breast tumorigenesis. We observed that histological sections of mammary tissue from adult Brca1 mutant mice abnormally display small, multilocular adipocytes that are reminiscent of brown adipose tissue (BAT) as compared to wildtype mice. Using a marker for BAT, the uncoupling protein 1 (UCP1), we demonstrated that these multilocular adipose regions in Brca1 mutant mice stain positive for UCP1. Transcriptionally, UCP1 mRNA levels in the Brca1 mutant mice were elevated greater than 50-fold compared to age-matched mammary glands from wildtype mice. Indeed, BAT has characteristics that are favorable for tumor growth, including high vascularity. Therefore, we also demonstrated that the multilocular brown adipose phenotype in the mammary fat pad of Brca1 mutant mice displayed regions of increased vascularity as evidenced by a significant increase in the protein expression of CD31, a marker for angiogenesis. This Brca1 mutant mouse model should provide a physiologically relevant context to determine whether brown adipose tissue can play a role in breast cancer development.

Jones, Laundette P.; Buelto, Destiney; Tago, Elaine; Owusu-Boaitey, Kwadwo E.

2013-01-01

219

Remotely sensed forest cover loss shows high spatial and temporal variation across Sumatera and Kalimantan, Indonesia 2000-2008  

NASA Astrophysics Data System (ADS)

The Indonesian islands of Sumatera and Kalimantan (the Indonesian part of the island of Borneo) are a center of significant and rapid forest cover loss in the humid tropics with implications for carbon dynamics, biodiversity conservation, and local livelihoods. The aim of our research was to analyze and interpret annual trends of forest cover loss for different sub-regions of the study area. We mapped forest cover loss for 2000-2008 using multi-resolution remote sensing data from the Landsat enhanced thematic mapper plus (ETM +) and moderate resolution imaging spectroradiometer (MODIS) sensors and analyzed annual trends per island, province, and official land allocation zone. The total forest cover loss for Sumatera and Kalimantan 2000-2008 was 5.39 Mha, which represents 5.3% of the land area and 9.2% of the year 2000 forest cover of these two islands. At least 6.5% of all mapped forest cover loss occurred in land allocation zones prohibiting clearing. An additional 13.6% of forest cover loss occurred where clearing is legally restricted. The overall trend of forest cover loss increased until 2006 and decreased thereafter. The trends for Sumatera and Kalimantan were distinctly different, driven primarily by the trends of Riau and Central Kalimantan provinces, respectively. This analysis shows that annual mapping of forest cover change yields a clearer picture than a one-time overall national estimate. Monitoring forest dynamics is important for national policy makers, especially given the commitment of Indonesia to reducing greenhouse gas emissions as part of the reducing emissions from deforestation and forest degradation in developing countries initiative (REDD +). The improved spatio-temporal detail of forest change monitoring products will make it possible to target policies and projects in meeting this commitment. Accurate, annual forest cover loss maps will be integral to many REDD + objectives, including policy formulation, definition of baselines, detection of displacement, and the evaluation of the permanence of emission reduction.

Broich, Mark; Hansen, Matthew; Stolle, Fred; Potapov, Peter; Arunarwati Margono, Belinda; Adusei, Bernard

2011-01-01

220

Genetic algorithms  

NASA Technical Reports Server (NTRS)

Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

Wang, Lui; Bayer, Steven E.

1991-01-01

221

Genetic determinants of on-clopidogrel high platelet reactivity.  

PubMed

Clopidogrel has been used (alone or in association with aspirin) to prevent vascular complications in atherothrombotic patients, to prevent stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) and as a long-term prevention of cardiovascular and cerebrovascular events. Unfortunately, it is important to note that there are a number of patients who, during clopidogrel therapy, show and maintain a high platelet reactivity (PR), similar to that observed before the start of antiplatelet therapy. Clopidogrel pro-drug is absorbed in the intestine and this process is influenced by P-glycoprotein-1 (P-GP). Its conversion into 2-oxo clopidogrel is regulated by cytochromes (CYP) called CYP2C19, CYP2B6 and CYP1A2. Whereas, the final transformation into the active metabolite is regulated by CYP called CYP2C19, CYP2C9, CYP2B6, CYP3A4, CYP3A5 and, as recently emerged, by the glycoprotein paraoxonase-1 (PON1). The genes encoding these enzymes are characterized by several polymorphisms. Some of these are able to modify the activity of proteins, reducing the concentration of active metabolite and the values of on-clopidogrel PR. Only one gene polymorphism (CYP2C19*17) increases the clopidogrel metabolization and so the clopidogrel-induced platelet inhibition. Several studies have clearly associated these gene polymorphisms to both ischemic and bleeding complications in patients receiving dual antiplatelet therapy. The aim of this review is to describe the principal gene polymorphisms influencing on-clopidogrel PR and their relationship with long-term clinical outcome. PMID:21627411

Campo, Gianluca; Miccoli, Matteo; Tebaldi, Matteo; Marchesini, Jlenia; Fileti, Luca; Monti, Monia; Valgimigli, Marco; Ferrari, Roberto

2011-01-01

222

Microsatellites and the Genetics of Highly Selfing Populations in the Freshwater Snail Bulinus Truncatus  

PubMed Central

Hermaphrodite tropical freshwater snails provide a good opportunity to study the effects of mating system and genetic drift on population genetic structure because they are self-fertile and they occupy transient patchily distributed habitats (ponds). Up to now the lack of detectable allozyme polymorphism prevented any intrapopulation studies. In this paper, we examine the consequences of selfing and bottlenecks on genetic polymorphism using microsatellite markers in 14 natural populations (under a hierarchical sampling design) of the hermaphrodite freshwater snail Bulinus truncatus. These population genetics data allowed us to discuss the currently available mutation models for microsatellite sequences. Microsatellite markers revealed an unexpectedly high levels of genetic variation with <=41 alleles for one locus and gene diversity of 0.20-0.75 among populations. The values of any estimator of F(is) indicate high selfing rates in all populations. Linkage disequilibria observed at all loci for some populations may also indicate high levels of inbreeding. The large extent of genetic differentiation measured by F(st), R(st) or by a test for homogeneity between genic distributions is explained by both selfing and bottlenecks. Despite a limited gene flow, migration events could be detected when comparing different populations within ponds.

Viard, F.; Bremond, P.; Labbo, R.; Justy, F.; Delay, B.; Jarne, P.

1996-01-01

223

Pediatric High-grade Glioma: Molecular Genetic Clues for Innovative Therapeutic Approaches  

Microsoft Academic Search

High grade glioma remains the most intractable childhood tumor of the central nervous system. The molecular genetics of childhood high grade glioma remain largely unknown in comparison to that of their adult counterparts. In an era of molecularly targeted therapies, this dearth of knowledge will present particular challenges to those who must design and implement the next generation of therapeutic

Brian R. Rood; Tobey J. MacDonald

2005-01-01

224

High-density genetic linkage maps of Phytophthora infestans reveal trisomic progeny and chromosomal rearrangements.  

PubMed Central

Detailed analysis of the inheritance of molecular markers was performed in the oomycete plant pathogen Phytophthora infestans. Linkage analysis in the sexual progeny of two Dutch field isolates (cross 71) resulted in a high-density map containing 508 markers on 13 major and 10 minor linkage groups. The map showed strong clustering of markers, particularly of markers originating from one parent, and dissimilarity between the parental isolates on linkage group III in the vicinity of the mating-type locus, indicating a chromosomal translocation. A second genetic map, constructed by linkage analysis in sexual progeny of two Mexican isolates (cross 68), contained 363 markers and is thus less dense than the cross 71 map. For some linkage groups the two independent linkage maps could be aligned, but sometimes markers appeared to be in a different order, or not linked at all, indicating chromosomal rearrangements between genotypes. Graphical genotyping showed that some progeny contained three copies of a homologous linkage group. This trisomy was found for several linkage groups in both crosses. Together, these analyses suggest a genome with a high degree of flexibility, which may have implications for evolution of new races and resistance development to crop protection agents.

van der Lee, Theo; Testa, Antonino; Robold, Andrea; van 't Klooster, John; Govers, Francine

2004-01-01

225

High-throughput Genetic Screen for Synaptogenic Factors: Identification of LRP6 as Critical for Excitatory Synapse Development  

PubMed Central

SUMMARY Genetic screens in invertebrates have discovered many synaptogenic genes and pathways. However, similar genetic studies have not been possible in mammals. We have optimized an automated high-throughput platform that employs automated liquid handling and imaging of primary mammalian neurons. Using this platform we have screened 3200 shRNAs targeting 800 proteins. One of the hits identified was LRP6, a co-receptor for canonical Wnt ligands. LRP6 regulates excitatory synaptogenesis, and is selectively localized to excitatory synapses. In vivo knockdown of LRP6 leads to a reduction in the number of functional synapses. Moreover, we show that the canonical Wnt ligand, Wnt8A, promotes synaptogenesis via LRP6. These results provide a proof of principle for using a high content approach to screen for synaptogenic factors in the mammalian nervous system, and identify and characterize a Wnt ligand receptor complex that is critical for development of functional synapses in vivo.

Sharma, Kamal; Choi, Se-Young; Zhang, Yong; Nieland, Thomas J.F.; Long, Shunyou; Li, Min; Huganir, Richard

2014-01-01

226

Dissecting High-Dimensional Phenotypes with Bayesian Sparse Factor Analysis of Genetic Covariance Matrices  

PubMed Central

Quantitative genetic studies that model complex, multivariate phenotypes are important for both evolutionary prediction and artificial selection. For example, changes in gene expression can provide insight into developmental and physiological mechanisms that link genotype and phenotype. However, classical analytical techniques are poorly suited to quantitative genetic studies of gene expression where the number of traits assayed per individual can reach many thousand. Here, we derive a Bayesian genetic sparse factor model for estimating the genetic covariance matrix (G-matrix) of high-dimensional traits, such as gene expression, in a mixed-effects model. The key idea of our model is that we need consider only G-matrices that are biologically plausible. An organism’s entire phenotype is the result of processes that are modular and have limited complexity. This implies that the G-matrix will be highly structured. In particular, we assume that a limited number of intermediate traits (or factors, e.g., variations in development or physiology) control the variation in the high-dimensional phenotype, and that each of these intermediate traits is sparse – affecting only a few observed traits. The advantages of this approach are twofold. First, sparse factors are interpretable and provide biological insight into mechanisms underlying the genetic architecture. Second, enforcing sparsity helps prevent sampling errors from swamping out the true signal in high-dimensional data. We demonstrate the advantages of our model on simulated data and in an analysis of a published Drosophila melanogaster gene expression data set.

Runcie, Daniel E.; Mukherjee, Sayan

2013-01-01

227

Combined analyses of kinship and FST suggest potential drivers of chaotic genetic patchiness in high gene-flow populations  

PubMed Central

We combine kinship estimates with traditional F-statistics to explain contemporary drivers of population genetic differentiation despite high gene flow. We investigate range-wide population genetic structure of the California spiny (or red rock) lobster (Panulirus interruptus) and find slight, but significant global population differentiation in mtDNA (?ST = 0.006, P = 0.001; Dest_Chao = 0.025) and seven nuclear microsatellites (FST = 0.004, P < 0.001; Dest_Chao = 0.03), despite the species’ 240- to 330-day pelagic larval duration. Significant population structure does not correlate with distance between sampling locations, and pairwise FST between adjacent sites often exceeds that among geographically distant locations. This result would typically be interpreted as unexplainable, chaotic genetic patchiness. However, kinship levels differ significantly among sites (pseudo-F16,988 = 1.39, P = 0.001), and ten of 17 sample sites have significantly greater numbers of kin than expected by chance (P < 0.05). Moreover, a higher proportion of kin within sites strongly correlates with greater genetic differentiation among sites (Dest_Chao, R2 = 0.66, P < 0.005). Sites with elevated mean kinship were geographically proximate to regions of high upwelling intensity (R2 = 0.41, P = 0.0009). These results indicate that P. interruptus does not maintain a single homogenous population, despite extreme dispersal potential. Instead, these lobsters appear to either have substantial localized recruitment or maintain planktonic larval cohesiveness whereby siblings more likely settle together than disperse across sites. More broadly, our results contribute to a growing number of studies showing that low FST and high family structure across populations can coexist, illuminating the foundations of cryptic genetic patterns and the nature of marine dispersal.

Iacchei, Matthew; Ben-Horin, Tal; Selkoe, Kimberly A; Bird, Christopher E; Garcia-Rodriguez, Francisco J; Toonen, Robert J

2013-01-01

228

Genetic basis of unstable expression of high gamma-tocopherol content in sunflower seeds  

PubMed Central

Background Tocopherols are natural antioxidants with both in vivo (vitamin E) and in vitro activity. Sunflower seeds contain predominantly alpha-tocopherol (>90% of total tocopherols), with maximum vitamin E effect but lower in vitro antioxidant action than other tocopherol forms such as gamma-tocopherol. Sunflower germplasm with stable high levels of gamma-tocopherol (>85%) has been developed. The trait is controlled by recessive alleles at a single locus Tph2 underlying a gamma-tocopherol methyltransferase (gamma-TMT). Additionally, unstable expression of increased gamma-tocopherol content in the range from 5 to 85% has been reported. The objective of this research was to determine the genetic basis of unstable expression of high gamma-tocopherol content in sunflower seeds. Results Male sterile plants of nuclear male sterile line nmsT2100, with stable high gamma-tocopherol content, were crossed with plants of line IAST-1, with stable high gamma-tocopherol content but derived from a population that exhibited unstable expression of the trait. F2 seeds showed continuous segregation for gamma-tocopherol content from 1.0 to 99.7%. Gamma-tocopherol content in F2 plants (average of 24 individual F3 seeds) segregated from 59.4 to 99.4%. A genetic linkage map comprising 17 linkage groups (LGs) was constructed from this population using 109 SSR and 20 INDEL marker loci, including INDEL markers for tocopherol biosynthesis genes. QTL analysis revealed a major QTL on LG 8 that corresponded to the gamma-TMT Tph2 locus, which suggested that high gamma-tocopherol lines nmsT2100 and IAST-1 possess different alleles at this locus. Modifying genes were identified at LGs 1, 9, 14 and 16, corresponding in most cases with gamma-TMT duplicated loci. Conclusions Unstable expression of high gamma-tocopherol content is produced by the effect of modifying genes on tph2a allele at the gamma-TMT Tph2 gene. This allele is present in line IAST-1 and is different to allele tph2 present in line nmsT2100, which is not affected by modifying genes. No sequence differences at the gamma-TMT gene were found associated to allelic unstability. Our results suggested that modifying genes are mostly epistatically interacting gamma-TMT duplicated loci.

2012-01-01

229

High-seas Biodiversity and Genetic Resources: Science and Policy Questions  

NSDL National Science Digital Library

Global efforts to protect marine genetic resources and high-seas biodiversity peak in 2010, a very eventful year for the conservation and study of high-seas biodiversity, with developments that put relevant policy and scientific directions at a significant crossroads. With these timely developments come important conservation, equity, and research questions: How do we protect deep-seas biodiversity against irresponsible exploitation in hard-to-monitor areas? How do we equitably govern the use of marine genetic resources while also fostering advanced scientific research?

Richard Blaustein (freelance writer;)

2010-06-01

230

Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report  

Microsoft Academic Search

The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of

Duster

1998-01-01

231

A High-Throughput Arabidopsis Reverse Genetics System  

Microsoft Academic Search

A collection of Arabidopsis lines with T-DNA insertions in known sites was generated to increase the efficiency of func- tional genomics. A high-throughput modified thermal asymetric interlaced (TAIL)-PCR protocol was developed and used to amplify DNA fragments flanking the T-DNA left borders from ? 100,000 transformed lines. A total of 85,108 TAIL-PCR products from 52,964 T-DNA lines were sequenced and

Allen Sessions; Ellen Burke; Gernot Presting; John McElver; David Patton; Bob Dietrich; Patrick Ho; Johana Bacwaden; Cynthia Ko; Joseph D. Clarke; David Cotton; David Bullis; Jennifer Snell; Trini Miguel; Theresa Mitzel; Fumiaki Katagiri; Jane Glazebrook; Marc Law; Stephen A. Goff

2002-01-01

232

Optimization of high harmonic generation by genetic algorithm  

Microsoft Academic Search

In order to develop an intense Extreme Ultra-Violet source based on High Harmonics Generation (HHG) for many applications,\\u000a we have performed HHG signal optimization experiments. It has been shown that HHG is very sensitive to temporal fundamental\\u000a pulse shape. For these experiments, we have used an acousto-optical programmable dispersive filter (Dazzler) in order to modify\\u000a the spectral phase of the

Constance Valentin; Olga Boyko; Evaggelos Papalazarou; Gilles Rey; Brigitte Mercier; Laura Antonucci; Philippe Balcou

2006-01-01

233

High genetic diversity at the regional scale and possible speciation in Sebacina epigaea and S. incrustans  

PubMed Central

Background Phylogenetic studies, particularly those based on rDNA sequences from plant roots and basidiomata, have revealed a strikingly high genetic diversity in the Sebacinales. However, the factors determining this genetic diversity at higher and lower taxonomic levels within this order are still unknown. In this study, we analysed patterns of genetic variation within two morphological species, Sebacina epigaea and S. incrustans, based on 340 DNA haplotype sequences of independent genetic markers from the nuclear (ITS?+?5.8S?+?D1/D2, RPB2) and mitochondrial (ATP6) genomes for 98 population samples. By characterising the genetic population structure within these species, we provide insights into species boundaries and the possible factors responsible for genetic diversity at a regional geographic scale. Results We found that recombination events are relatively common between natural populations within Sebacina epigaea and S. incrustans, and play a significant role in generating intraspecific genetic diversity. Furthermore, we also found that RPB2 and ATP6 genes display higher levels of intraspecific synonymous polymorphism. Phylogenetic and demographic analyses based on nuclear and mitochondrial loci revealed three distinct phylogenetic lineages within of each of the morphospecies S. epigaea and S. incrustans: one major and widely distributed lineage, and two geographically restricted lineages, respectively. We found almost no differential morphological or ecological characteristics that could be used to discriminate between these lineages. Conclusions Our results suggest that recombination and negative selection have played significant roles in generating genetic diversity within these morphological species at small geographical scales. Concordance between gene genealogies identified lineages/cryptic species that have evolved independently for a relatively long period of time. These putative species were not associated with geographic provenance, geographic barrier, host preference or distinct phenotypic innovations.

2013-01-01

234

A high-density rice genetic linkage map with 2275 markers using a single F2 population.  

PubMed

A 2275-marker genetic map of rice (Oryza sativa L.) covering 1521.6 cM in the Kosambi function has been constructed using 186 F2 plants from a single cross between the japonica variety Nipponbare and the indica variety Kasalath. The map provides the most detailed and informative genetic map of any plant. Centromere locations on 12 linkage groups were determined by dosage analysis of secondary and telotrisomics using > 130 DNA markers located on respective chromosome arms. A limited influence on meiotic recombination inhibition by the centromere in the genetic map was discussed. The main sources of the markers in this map were expressed sequence tag (EST) clones from Nipponbare callus, root, and shoot libraries. We mapped 1455 loci using ESTs; 615 of these loci showed significant similarities to known genes, including single-copy genes, family genes, and isozyme genes. The high-resolution genetic map permitted us to characterize meiotic recombinations in the whole genome. Positive interference of meiotic recombination was detected both by the distribution of recombination number per each chromosome and by the distribution of double crossover interval lengths. PMID:9475757

Harushima, Y; Yano, M; Shomura, A; Sato, M; Shimano, T; Kuboki, Y; Yamamoto, T; Lin, S Y; Antonio, B A; Parco, A; Kajiya, H; Huang, N; Yamamoto, K; Nagamura, Y; Kurata, N; Khush, G S; Sasaki, T

1998-01-01

235

Utilizing high-fidelity crucial conversation simulation in genetic counseling training.  

PubMed

Genetics professionals are often required to deliver difficult news to patients and families. This is a challenging task, but one that many genetics trainees have limited opportunity to master during training. This is true for several reasons, including relative scarcity of these events and an understandable hesitation of supervisors allowing a trainee to provide such high stakes information. Medical simulation is effective in other health care disciplines giving trainees opportunities of "hands on" education in similar high stakes situations. We hypothesized that crucial conversations simulation would be effective for genetics trainees to gain experience in communication and counseling skills in a realistic clinical scenario. To test this hypothesis, we designed a prenatal counseling scenario requiring disclosure of an abnormal amniocentesis result and discussion of pregnancy management options; we challenged participants to address common counseling questions. Three medical genetics resident physicians and five genetic counseling students participated. Genetics and simulation experts observed the session via live video feed from a different room. A behavioral checklist was completed in real time assessing trainee's performance and documenting medical information discussed. Debriefing immediately followed the session and included simulation and genetics experts and the actor parents. Participants completed open-ended post evaluations. There was a trend towards participants being more likely to discuss issues the child could have while an infant/toddler rather than issues that could emerge as the child with Down Syndrome transitions to adulthood and end of life (P=.069). All participants found the simulation helpful, notably that it was more realistic than role-playing with colleagues. PMID:23633180

Holt, R Lynn; Tofil, Nancy M; Hurst, Christina; Youngblood, Amber Q; Peterson, Dawn Taylor; Zinkan, J Lynn; White, Marjorie Lee; Clemons, Jason L; Robin, Nathaniel H

2013-06-01

236

Showing What They Know  

ERIC Educational Resources Information Center

Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

Cech, Scott J.

2008-01-01

237

Assessment of genetic diversity in a highly valuable medicinal plant Catharanthus roseus using molecular  

Microsoft Academic Search

Genetic diversity was evaluated among 14 cultivars of Catharanthus roseus using RAPD and ISSR markers. The RAPD primers resulted in the amplification of 56 bands, among which 46 (82%) bands were polymorphic Four ISSR primers amplified 31 loci out of which 17 were polymorphic and 14 are monomorphic. The Jaccard's similarity derived from the combined marker system showed that the

Ranjan Kumar Shaw; Laxmikanta Acharya; Arup Kumar Mukherjee

238

High-gain nonlinear observer for simple genetic regulation process  

NASA Astrophysics Data System (ADS)

High-gain nonlinear observers occur in the nonlinear automatic control theory and are in standard usage in chemical engineering processes. We apply such a type of analysis in the context of a very simple one-gene regulation circuit. In general, an observer combines an analytical differential-equation-based model with partial measurement of the system in order to estimate the non-measured state variables. We use one of the simplest observers, that of Gauthier et al., which is a copy of the original system plus a correction term which is easy to calculate. For the illustration of this procedure, we employ a biological model, recently adapted from Goodwin's old book by De Jong, in which one plays with the dynamics of the concentrations of the messenger RNA coding for a given protein, the protein itself, and a single metabolite. Using the observer instead of the metabolite, it is possible to rebuild the non-measured concentrations of the mRNA and the protein.

Torres, L. A.; Ibarra-Junquera, V.; Escalante-Minakata, P.; Rosu, H. C.

2007-07-01

239

HIGH LEVELS OF GENETIC VARIABILITY IN THE HAPLOID MOSS PLAGIOMNIUM CILIARE  

Microsoft Academic Search

Horizontal starch-gel electrophoresis was used to measure variability at 14 enzyme loci from 13 natural populations of the dioecious moss Plagiomniwn ciliare. Overall levels of genetic polymorphism were unexpectedly high for a haploid organism. Using a 1% frequency criterion, 71% of the loci surveyed were polymorphic for the species as a whole. The number of alleles per polymorphic locus for

ROBERT WYATT; IRENEUSZ J. ODRZYKOSKI; ANN STONEBURNER

1989-01-01

240

Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence  

Microsoft Academic Search

Several studies have reported an inverse relation- ship between hepatic lipase activity and plasma high density lipoprotein (HDL) cholesterol concentrations. The purpose of the present study was to determine whether genetic and pharmacological variation in hepatic lipase activity alters the distribution of HDL subclasses. Two independent ana- lytical methods (nuclear magnetic resonance and gradient gel electrophoresis) were used to compare

Scott M. Grundy; Gloria L. Vega; James D. Otvos; David L. Rainwater

241

Principles underlying genetic improvement for high and stable crop yield potential  

Microsoft Academic Search

This paper explores the genetic basis of high and stable crop yield, and delineates the conditions that provide the link between genotypic and phenotypic superiority and, consequently, improve selection efficiency in plant breeding. Response to selection is viewed as the result of the conversion, through intralocus recombination, of two heterotic nonadditive allelic loci into a single super additive locus, and

Vasilia A. Fasoula; Dionysia A. Fasoula

2002-01-01

242

Unusually high genetic diversity in COI sequences of Chimarra obscura (Trichoptera: Philopotamidae)  

EPA Science Inventory

Chimarra obscura (Walker 1852) is a philopotamid caddisfly found throughout much of North America. Using the COI DNA barcode locus, we have found unexpectedly high amounts of genetic diversity and distances within C. obscura. Of the approximately 150 specimens sampled, we have fo...

243

Range-wide analysis of genetic structure in a widespread, highly mobile species (Odocoileus hemionus) reveals the importance of historical biogeography.  

PubMed

Highly mobile species that thrive in a wide range of habitats are expected to show little genetic differentiation across their range. A limited but growing number of studies have revealed that patterns of broad-scale genetic differentiation can and do emerge in vagile, continuously distributed species. However, these patterns are complex and often shaped by both historical and ecological factors. Comprehensive surveys of genetic variation at a broad scale and at high resolution are useful for detecting cryptic spatial genetic structure and for investigating the relative roles of historical and ecological processes in structuring widespread, highly mobile species. In this study, we analysed 10 microsatellite loci from over 1900 samples collected across the full range of mule deer (Odocoileus hemionus), one of the most widely distributed and abundant of all large mammal species in North America. Through both individual- and population-based analyses, we found evidence for three main genetic lineages, one corresponding to the 'mule deer' morphological type and two to the 'black-tailed deer' type. Historical biogeographic events likely are the primary drivers of genetic divergence in this species; boundaries of the three lineages correspond well with predictions based on Pleistocene glacial cycles, and substructure within each lineage demonstrates island vicariance. However, across large geographic areas, including the entire mule deer lineage, we found that genetic variation fit an isolation-by-distance pattern rather than discrete clusters. A lack of genetic structure across wide geographic areas of the continental west indicates that ecological processes have not resulted in restrictions to gene flow sufficient for spatial genetic structure to emerge. Our results have important implications for our understanding of evolutionary mechanisms of divergence, as well as for taxonomy, conservation and management. PMID:24863151

Latch, Emily K; Reding, Dawn M; Heffelfinger, James R; Alcalá-Galván, Carlos H; Rhodes, Olin E

2014-07-01

244

Genetic Diversity Analysis of Highly Incomplete SNP Genotype Data with Imputations: An Empirical Assessment  

PubMed Central

Genotyping by sequencing (GBS) recently has emerged as a promising genomic approach for assessing genetic diversity on a genome-wide scale. However, concerns are not lacking about the uniquely large unbalance in GBS genotype data. Although some genotype imputation has been proposed to infer missing observations, little is known about the reliability of a genetic diversity analysis of GBS data, with up to 90% of observations missing. Here we performed an empirical assessment of accuracy in genetic diversity analysis of highly incomplete single nucleotide polymorphism genotypes with imputations. Three large single-nucleotide polymorphism genotype data sets for corn, wheat, and rice were acquired, and missing data with up to 90% of missing observations were randomly generated and then imputed for missing genotypes with three map-independent imputation methods. Estimating heterozygosity and inbreeding coefficient from original, missing, and imputed data revealed variable patterns of bias from assessed levels of missingness and genotype imputation, but the estimation biases were smaller for missing data without genotype imputation. The estimates of genetic differentiation were rather robust up to 90% of missing observations but became substantially biased when missing genotypes were imputed. The estimates of topology accuracy for four representative samples of interested groups generally were reduced with increased levels of missing genotypes. Probabilistic principal component analysis based imputation performed better in terms of topology accuracy than those analyses of missing data without genotype imputation. These findings are not only significant for understanding the reliability of the genetic diversity analysis with respect to large missing data and genotype imputation but also are instructive for performing a proper genetic diversity analysis of highly incomplete GBS or other genotype data.

Fu, Yong-Bi

2014-01-01

245

Unexpected genetic differentiation between recently recolonized populations of a long-lived and highly vagile marine mammal  

PubMed Central

Many species have been heavily exploited by man leading to local extirpations, yet few studies have attempted to unravel subsequent recolonization histories. This has led to a significant gap in our knowledge of the long-term effects of exploitation on the amount and structure of contemporary genetic variation, with important implications for conservation. The Antarctic fur seal provides an interesting case in point, having been virtually exterminated in the nineteenth century but subsequently staged a dramatic recovery to recolonize much of its original range. Consequently, we evaluated the hypothesis that South Georgia (SG), where a few million seals currently breed, was the main source of immigrants to other locations including Livingston Island (LI), by genotyping 366 individuals from these two populations at 17 microsatellite loci and sequencing a 263 bp fragment of the mitochondrial hypervariable region 1. Contrary to expectations, we found highly significant genetic differences at both types of marker, with 51% of LI individuals carrying haplotypes that were not observed in 246 animals from SG. Moreover, the youngest of three sequentially founded colonies at LI showed greater similarity to SG at mitochondrial DNA than microsatellites, implying temporal and sex-specific variation in recolonization. Our findings emphasize the importance of relict populations and provide insights into the mechanisms by which severely depleted populations can recover while maintaining surprisingly high levels of genetic diversity.

Bonin, Carolina A; Goebel, Michael E; Forcada, Jaume; Burton, Ronald S; Hoffman, Joseph I

2013-01-01

246

High Genetic Diversity and Insignificant Interspecific Differentiation in Opisthopappus Shih, an Endangered Cliff Genus Endemic to the Taihang Mountains of China  

PubMed Central

Opisthopappus Shih is endemic to the Taihang Mountains, China. It grows in the crevice of cliffs and is in fragmented distribution. This genus consists of two species, namely, O. taihangensis (Ling) Shih and O. longilobus Shih, which are both endangered plants in China. This study adopted intersimple sequence repeat markers (ISSR) to analyze the genetic diversity and genetic structure from different levels (genus, species, and population) in this genus. A total of 253 loci were obtained from 27 primers, 230 of which were polymorphic loci with a proportion of polymorphic bands (PPB) of up to 90.91% at genus level. At species level, both O. taihangensis (PPB = 90.12%, H = 0.1842, and I = 0.289) and O. longilobus (PPB = 95.21%, H = 0.2226, and I = 0.3542) have high genetic diversity. Their respective genetic variation mostly existed within the population. And genetic variation in O. longilobus (84.95%) was higher than that in O. taihangensis (80.45%). A certain genetic differentiation among populations in O. taihangensis was found (Gst = 0.2740, ?st = 0.196) and genetic differentiation in O. longilobus was very small (Gst = 0.1034, ?st = 0.151). Gene flow in different degrees (Nm = 1.325 and 4.336, resp.) and mating system can form the existing genetic structures of these two species. Furthermore, genetic differentiation coefficient (Gst = 0.0453) between species and the clustering result based on the genetic distance showed that interspecific differentiation between O. taihangensis and O. longilobus was not significant and could occur lately.

Guo, Rongmin; Zhou, Lihua; Zhao, Hongbo

2013-01-01

247

AFLP polymorphisms allow high resolution genetic analysis of American Tegumentary Leishmaniasis agents circulating in Panama and other members of the Leishmania genus.  

PubMed

American Tegumentary Leishmaniasis is caused by parasites of the genus Leishmania, and causes significant health problems throughout the Americas. In Panama, Leishmania parasites are endemic, causing thousands of new cases every year, mostly of the cutaneous form. In the last years, the burden of the disease has increased, coincident with increasing disturbances in its natural sylvatic environments. The study of genetic variation in parasites is important for a better understanding of the biology, population genetics, and ultimately the evolution and epidemiology of these organisms. Very few attempts have been made to characterize genetic polymorphisms of parasites isolated from Panamanian patients of cutaneous leishmaniasis. Here we present data on the genetic variability of local isolates of Leishmania, as well as specimens from several other species, by means of Amplified Fragment Length Polymorphisms (AFLP), a technique seldom used to study genetic makeup of parasites. We demonstrate that this technique allows detection of very high levels of genetic variability in local isolates of Leishmania panamensis in a highly reproducible manner. The analysis of AFLP fingerprints generated by unique selective primer combinations in L. panamensis suggests a predominant clonal mode of reproduction. Using fluorescently labeled primers, many taxon-specific fragments were identified which may show potential as species diagnostic fragments. The AFLP permitted a high resolution genetic analysis of the Leishmania genus, clearly separating certain groups among L. panamensis specimens and highly related species such as L. panamensis and L. guyanensis. The phylogenetic networks reconstructed from our AFLP data are congruent with established taxonomy for the genus Leishmania, even when using single selective primer combinations. Results of this study demonstrate that AFLP polymorphisms can be informative for genetic characterization in Leishmania parasites, at both intra and inter-specific levels. PMID:24039881

Restrepo, Carlos M; De La Guardia, Carolina; Sousa, Octavio E; Calzada, José E; Fernández, Patricia L; Lleonart, Ricardo

2013-01-01

248

High-Throughput Automated Phenotyping of Two Genetic Mouse Models of Huntington's Disease  

PubMed Central

Phenotyping with traditional behavioral assays constitutes a major bottleneck in the primary screening, characterization, and validation of genetic mouse models of disease, leading to downstream delays in drug discovery efforts. We present a novel and comprehensive one-stop approach to phenotyping, the PhenoCube™. This system simultaneously captures the cognitive performance, motor activity, and circadian patterns of group-housed mice by use of home-cage operant conditioning modules (IntelliCage) and custom-built computer vision software. We evaluated two different mouse models of Huntington’s Disease (HD), the R6/2 and the BACHD in the PhenoCube™ system. Our results demonstrated that this system can efficiently capture and track alterations in both cognitive performance and locomotor activity patterns associated with these disease models. This work extends our prior demonstration that PhenoCube™ can characterize circadian dysfunction in BACHD mice and shows that this system, with the experimental protocols used, is a sensitive and efficient tool for a first pass high-throughput screening of mouse disease models in general and mouse models of neurodegeneration in particular.

Balci, Fuat; Oakeshott, Stephen; Shamy, Jul Lea; El-Khodor, Bassem F.; Filippov, Igor; Mushlin, Richard; Port, Russell; Connor, David; Paintdakhi, Ahmad; Menalled, Liliana; Ramboz, Sylvie; Howland, David; Kwak, Seung; Brunner, Dani

2013-01-01

249

A fully simultaneously optimizing genetic approach to the highly excited coupled-cluster factorization problem  

NASA Astrophysics Data System (ADS)

In this article we report on the coupled-cluster factorization problem. We describe the first implementation that optimizes (i) the contraction order for each term, (ii) the identification of reusable intermediates, (iii) the selection and factoring out of common factors simultaneously, considering all projection levels in a single step. The optimization is achieved by means of a genetic algorithm. Taking a one-term-at-a-time strategy as reference our factorization yields speedups of up to 4 (for intermediate excitation levels, smaller basis sets). We derive a theoretical lower bound for the highest order scaling cost and show that it is met by our implementation. Additionally, we report on the performance of the resulting highly excited coupled-cluster algorithms and find significant improvements with respect to the implementation of Kállay and Surján [J. Chem. Phys. 115, 2945 (2001)] and comparable performance with respect to MOLPRO's handwritten and dedicated open shell coupled cluster with singles and doubles substitutions implementation [P. J. Knowles, C. Hampel, and H.-J. Werner, J. Chem. Phys. 99, 5219 (1993)].

Engels-Putzka, Anna; Hanrath, Michael

2011-03-01

250

Generation of high-affinity DNA aptamers using an expanded genetic alphabet.  

PubMed

DNA aptamers produced with natural or modified natural nucleotides often lack the desired binding affinity and specificity to target proteins. Here we describe a method for selecting DNA aptamers containing the four natural nucleotides and an unnatural nucleotide with the hydrophobic base 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds). We incorporated up to three Ds nucleotides in a random sequence library, which is expected to increase the chemical and structural diversity of the DNA molecules. Selection experiments against two human target proteins, vascular endothelial cell growth factor-165 (VEGF-165) and interferon-? (IFN-?), yielded DNA aptamers that bind with KD values of 0.65 pM and 0.038 nM, respectively, affinities that are >100-fold improved over those of aptamers containing only natural bases. These results show that incorporation of unnatural bases can yield aptamers with greatly augmented affinities, suggesting the potential of genetic alphabet expansion as a powerful tool for creating highly functional nucleic acids. PMID:23563318

Kimoto, Michiko; Yamashige, Rie; Matsunaga, Ken-ichiro; Yokoyama, Shigeyuki; Hirao, Ichiro

2013-05-01

251

High-dimensional variance partitioning reveals the modular genetic basis of adaptive divergence in gene expression during reproductive character displacement.  

PubMed

Although adaptive change is usually associated with complex changes in phenotype, few genetic investigations have been conducted on adaptations that involve sets of high-dimensional traits. Microarrays have supplied high-dimensional descriptions of gene expression, and phenotypic change resulting from adaptation often results in large-scale changes in gene expression. We demonstrate how genetic analysis of large-scale changes in gene expression generated during adaptation can be accomplished by determining high-dimensional variance partitioning within classical genetic experimental designs. A microarray experiment conducted on a panel of recombinant inbred lines (RILs) generated from two populations of Drosophila serrata that have diverged in response to natural selection, revealed genetic divergence in 10.6% of 3762 gene products examined. Over 97% of the genetic divergence in transcript abundance was explained by only 12 genetic modules. The two most important modules, explaining 50% of the genetic variance in transcript abundance, were genetically correlated with the morphological traits that are known to be under selection. The expression of three candidate genes from these two important genetic modules was assessed in an independent experiment using qRT-PCR on 430 individuals from the panel of RILs, and confirmed the genetic association between transcript abundance and morphological traits under selection. PMID:22023580

McGraw, Elizabeth A; Ye, Yixin H; Foley, Brad; Chenoweth, Stephen F; Higgie, Megan; Hine, Emma; Blows, Mark W

2011-11-01

252

A High Resolution Genetic Map Anchoring Scaffolds of the Sequenced Watermelon Genome  

PubMed Central

As part of our ongoing efforts to sequence and map the watermelon (Citrullus spp.) genome, we have constructed a high density genetic linkage map. The map positioned 234 watermelon genome sequence scaffolds (an average size of 1.41 Mb) that cover about 330 Mb and account for 93.5% of the 353 Mb of the assembled genomic sequences of the elite Chinese watermelon line 97103 (Citrullus lanatus var. lanatus). The genetic map was constructed using an F8 population of 103 recombinant inbred lines (RILs). The RILs are derived from a cross between the line 97103 and the United States Plant Introduction (PI) 296341-FR (C. lanatus var. citroides) that contains resistance to fusarium wilt (races 0, 1, and 2). The genetic map consists of eleven linkage groups that include 698 simple sequence repeat (SSR), 219 insertion-deletion (InDel) and 36 structure variation (SV) markers and spans ?800 cM with a mean marker interval of 0.8 cM. Using fluorescent in situ hybridization (FISH) with 11 BACs that produced chromosome-specifc signals, we have depicted watermelon chromosomes that correspond to the eleven linkage groups constructed in this study. The high resolution genetic map developed here should be a useful platform for the assembly of the watermelon genome, for the development of sequence-based markers used in breeding programs, and for the identification of genes associated with important agricultural traits.

Kou, Qinghe; Jiang, Jiao; Guo, Shaogui; Zhang, Haiying; Hou, Wenju; Zou, Xiaohua; Sun, Honghe; Gong, Guoyi; Levi, Amnon; Xu, Yong

2012-01-01

253

Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report  

SciTech Connect

The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

Duster, T.

1998-11-01

254

Phase-Specific Brain Change of Spatial Working Memory Processing in Genetic and Ultra-High Risk Groups of Schizophrenia  

PubMed Central

Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable patients with schizophrenia and 16 healthy controls, while subjects were performing a spatial delayed-response task. During the encoding phase, the GHR group showed increased activation in the fronto-parietal regions, whereas the UHR and schizophrenia groups showed significantly less activation in these regions than did the healthy control group. Especially, frontal activation was strongest in GHR subjects, followed by healthy controls, and occurred to a lesser degree in the UHR group, with the least activation occurring in the schizophrenia group. During the maintenance phase, the thalamus showed a differential activation, similar to frontal activation pattern during the encoding phase. During the retrieval phase, no prominent differential activations were found. Increased activations were observed in the superior temporal gyrus during the encoding and maintenance phases in the GHR, UHR, and schizophrenia groups relative to healthy controls. Our findings suggest that functional deficits associated with spatial WM processing emerge in the UHR before the onset of schizophrenia and compensatory neural processes exist in the GHR with genetic liability to schizophrenia.

Choi, Jung-Seok; Park, Ji-Young; Jung, Myung Hun; Jang, Joon Hwan; Kang, Do-Hyung; Jung, Wi Hoon; Han, Ji Yeon; Choi, Chi-Hoon; Hong, Kyung Sue; Kwon, Jun Soo

2012-01-01

255

High-performance genetically targetable optical neural silencing by light-driven proton pumps.  

PubMed

The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations. PMID:20054397

Chow, Brian Y; Han, Xue; Dobry, Allison S; Qian, Xiaofeng; Chuong, Amy S; Li, Mingjie; Henninger, Michael A; Belfort, Gabriel M; Lin, Yingxi; Monahan, Patrick E; Boyden, Edward S

2010-01-01

256

Automatic Compilation from High-Level Biologically-Oriented Programming Language to Genetic Regulatory Networks  

PubMed Central

Background The field of synthetic biology promises to revolutionize our ability to engineer biological systems, providing important benefits for a variety of applications. Recent advances in DNA synthesis and automated DNA assembly technologies suggest that it is now possible to construct synthetic systems of significant complexity. However, while a variety of novel genetic devices and small engineered gene networks have been successfully demonstrated, the regulatory complexity of synthetic systems that have been reported recently has somewhat plateaued due to a variety of factors, including the complexity of biology itself and the lag in our ability to design and optimize sophisticated biological circuitry. Methodology/Principal Findings To address the gap between DNA synthesis and circuit design capabilities, we present a platform that enables synthetic biologists to express desired behavior using a convenient high-level biologically-oriented programming language, Proto. The high level specification is compiled, using a regulatory motif based mechanism, to a gene network, optimized, and then converted to a computational simulation for numerical verification. Through several example programs we illustrate the automated process of biological system design with our platform, and show that our compiler optimizations can yield significant reductions in the number of genes () and latency of the optimized engineered gene networks. Conclusions/Significance Our platform provides a convenient and accessible tool for the automated design of sophisticated synthetic biological systems, bridging an important gap between DNA synthesis and circuit design capabilities. Our platform is user-friendly and features biologically relevant compiler optimizations, providing an important foundation for the development of sophisticated biological systems.

Beal, Jacob; Lu, Ting; Weiss, Ron

2011-01-01

257

High-performance genetically targetable optical neural silencing by light-driven proton pumps  

Microsoft Academic Search

The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch)

Brian Y. Chow; Xue Han; Allison S. Dobry; Xiaofeng Qian; Amy S. Chuong; Mingjie Li; Michael A. Henninger; Gabriel M. Belfort; Yingxi Lin; Patrick E. Monahan; Edward S. Boyden

2010-01-01

258

The large plasmids of Shiga-toxin-producing Escherichia coli (STEC) are highly variable genetic elements  

Microsoft Academic Search

Shiga-toxin-producing Escherichia coli (STEC) of different serotypes are known to harbour large plasmids. The aim of this study was to investigate, using the example of the plasmid-encoded serine protease EspP, whether these plasmids are a uniform genetic element present in STEC. Examination of 201 diarrhoeagenic E. coli strains using a newly developed espP-specific PCR showed that espP is specific for

Werner Brunder; Herbert Schmidt; Matthias Frosch; Helge Karch

1999-01-01

259

A high-capacity cell macroencapsulation system supporting the long-term survival of genetically engineered allogeneic cells.  

PubMed

The rapid increase in the number of approved therapeutic proteins, including recombinant antibodies, for diseases necessitating chronic treatments raises the question of the overall costs imposed on healthcare systems. It is therefore important to investigate alternative methods for recombinant protein administration. The implantation of genetically engineered cells is an attractive strategy for the chronic long-term delivery of recombinant proteins. Here, we have developed a high-capacity cell encapsulation system for the implantation of allogeneic myoblasts, which survive at high density for at least one year. This flat sheet device is based on permeable polypropylene membranes sealed to a mechanically resistant frame which confine cells seeded in a tailored biomimetic poly(ethylene glycol) (PEG)-based hydrogel matrix. In order to quantitate the number of cells surviving in the device and optimize initial conditions leading to high-density survival, we implant devices containing C2C12 mouse myoblasts expressing a luciferase reporter in the mouse subcutaneous tissue. We show that initial cell load, hydrogel stiffness and permeable membrane porosity are critical parameters to achieve long-term implant survival and efficacy. Optimization of these parameters leads to the survival of encapsulated myogenic cells at high density for several months, with minimal inflammatory response and dense neovascularization in the adjacent host tissue. Therefore, this encapsulation system is an effective platform for the implantation of genetically engineered cells in allogeneic conditions, which could be adapted to the chronic administration of recombinant proteins. PMID:24103654

Lathuilière, Aurélien; Cosson, Steffen; Lutolf, Matthias P; Schneider, Bernard L; Aebischer, Patrick

2014-01-01

260

Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction  

PubMed Central

Background When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown. Results We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya). Conclusion We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs.

Tengs, Torstein; Zhang, Haibo; Holst-Jensen, Arne; Bohlin, Jon; Butenko, Melinka A; Kristoffersen, Anja Brathen; Sorteberg, Hilde-Gunn Opsahl; Berdal, Knut G

2009-01-01

261

High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography  

PubMed Central

Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

Small, Peter M; Sheffer, Hadar; Niemann, Stefan; Homolka, Susanne; Roach, Jared C; Kremer, Kristin; Petrov, Dmitri A; Feldman, Marcus W; Gagneux, Sebastien

2008-01-01

262

High genetic variation among Aschersonia placenta (Clavicipitaceae) isolates from citrus orchards in China.  

PubMed

Aschersonia placenta had been recognized as an important fungal pathogen of whiteflies. In recent years, natural occurrence of Aschersonia in whitefly populations was observed in many citrus orchards in the southern regions of China. We analyzed 60 A. placenta isolates obtained from Chinese citrus orchards, using inter-simple sequence repeats to examine the genetic diversity and to determine whether intraspecific variation is correlated with geographic origin. One hundred and fourteen fragments were generated from these isolates; 97% were polymorphic. The Nei's gene diversity (H) was estimated to be 0.1748 within the populations (range 0.0974-0.2179) and 0.3057 at the species level. Analysis of molecular variance showed that the genetic variation was found mainly within populations (74.9%). The coefficient of gene differentiation (GST = 0.4315) indicated that 56.85% of the genetic diversity resided within populations. The Mantel test revealed no significant correlation between the genetic distance and the corresponding geographical distance (r = 0.142 and P = 0.887); the unweighted pair-group method using arithmetic average clustering gave similar results. PMID:24338414

Wang, P P; Song, X H; Zhang, H Y

2013-01-01

263

Genetic diversity of European cattle breeds highlights the conservation value of traditional unselected breeds with high effective population size.  

PubMed

In times of rapid global and unforeseeable environmental changes, there is an urgent need for a sustainable cattle breeding policy, based on a global view. Most of the indigenous breeds are specialized in a particular habitat or production system but are rapidly disappearing. Thus, they represent an important resource to meet present and future breeding objectives. Based on 105 microsatellites, we obtained thorough information on genetic diversity and population structure of 16 cattle breeds that cover a geographical area from the domestication centre near Anatolia, through the Balkan and alpine regions, to the North-West of Europe. Breeds under strict artificial selection and indigenous breeds under traditional breeding schemes were included. The overall results showed that the genetic diversity is widespread in Busa breeds in the Anatolian and Balkan areas, when compared with the alpine and north-western European breeds. Our results reflect long-term evolutionary and short-term breeding events very well. The regular pattern of allele frequency distribution in the entire cattle population studied clearly suggests conservation of rare alleles by conservation of preferably unselected traditional breeds with large effective population sizes. From a global and long-term conservation genetics point of view, the native and highly variable breeds closer to the domestication centre could serve as valuable sources of genes for future needs, not only for cattle but also for other farm animals. PMID:19659482

Medugorac, Ivica; Medugorac, Ana; Russ, Ingolf; Veit-Kensch, Claudia E; Taberlet, Pierre; Luntz, Bernhard; Mix, Henry M; Förster, Martin

2009-08-01

264

Agents That Cause a High Frequency of Genetic Change from [psi+] to [psi-] in SACCHAROMYCES CEREVISIAE  

PubMed Central

The [psi] factor of yeast is cytoplasmically inherited. Singh, Helms and Sherman (1979) reported that high concentrations of KCl and of ethylene glycol induce the genetic change from [psi+] to [psi-]. In this study, the following agents have been shown to induce the same genetic change: guanidine hydrochloride at 1 mm, dimethyl sulfoxide at 2.5% v/v and ethanol or methanol at 10% v/v. It is likely that a number of other agents also cause the change, namely 2 m glycerol, m succinate, m glutamate and m MgCl2. Most of these agents induce the change at very high frequencies; with some, the frequency is 100%. Although the observed phenotypic change can also occur as a result of chromosomal gene mutation, no changes of this type were identified. Some of the agents also cause mutation from [rho+] to [rho-] and from killer to sensitive.

Tuite, M. F.; Mundy, C. R.; Cox, B. S.

1981-01-01

265

Rapid anti-pathogen response in ant societies relies on high genetic diversity  

PubMed Central

Social organisms are constantly exposed to infectious agents via physical contact with conspecifics. While previous work has shown that disease susceptibility at the individual and group level is influenced by genetic diversity within and between group members, it remains poorly understood how group-level resistance to pathogens relates directly to individual physiology, defence behaviour and social interactions. We investigated the effects of high versus low genetic diversity on both the individual and collective disease defences in the ant Cardiocondyla obscurior. We compared the antiseptic behaviours (grooming and hygienic behaviour) of workers from genetically homogeneous and diverse colonies after exposure of their brood to the entomopathogenic fungus Metarhizium anisopliae. While workers from diverse colonies performed intensive allogrooming and quickly removed larvae covered with live fungal spores from the nest, workers from homogeneous colonies only removed sick larvae late after infection. This difference was not caused by a reduced repertoire of antiseptic behaviours or a generally decreased brood care activity in ants from homogeneous colonies. Our data instead suggest that reduced genetic diversity compromises the ability of Cardiocondyla colonies to quickly detect or react to the presence of pathogenic fungal spores before an infection is established, thereby affecting the dynamics of social immunity in the colony.

Ugelvig, Line V.; Kronauer, Daniel J. C.; Schrempf, Alexandra; Heinze, Jurgen; Cremer, Sylvia

2010-01-01

266

High genetic polymorphism of relapsing P. vivax isolates in northwest Colombia  

PubMed Central

Genetic diversity of Plasmodium populations has been more extensively documented in Colombia for Plasmodium falciparum than for Plasmodium vivax. Recently, highly variable microsatellite markers have been described and used in population-level studies of genetic variation of P. vivax throughout the world. We applied this approach to understand the genetic structure of P. vivax populations and to identify recurrence-associated haplotypes. In this, three microsatellite markers of P. vivax were amplified and the combined size of the fragments was used to establish genotypes. Patients from an ongoing treatment efficacy trial who were kept either in endemic or non-endemic regions in the northwest of Colombia were included in the study. In total 58 paired clinical isolates, were amplified. A total of 54 haplotypes were observed among the two regions. Some haplotypes were exclusive to the endemic region where the highest degree of polymorphism was detected. In addition, we confirmed the different genotypes of recurrent-relapsing and primary infection isolates suggesting the activation of heterologous hypnozoite populations. We conclude that analysis of the three microsatellites is a valuable tool to establish the genetic characteristics of P. vivax populations in Colombia.

Restrepo, Eliana; Imwong, Mallika; Rojas, Winston; Carmona-Fonseca, Jaime; Maestre, Amanda

2011-01-01

267

Exploration of genetically determined resistance against hepatitis C infection in high-risk injecting drug users.  

PubMed

Genetic resistance to specific infections is well recognized. In hepatitis C virus (HCV) infection, genetic polymorphisms in IL-28B and the killer cell immunoglobulin-like receptors (KIR) and their HLA class I ligands have been shown to affect clearance of the virus following infection. There are limited data regarding resistance to established HCV infection. Reliable quantification of repeated exposure in high-risk populations, such as injecting drug users (IDU), is a key limitation of previous studies of resistance. Behavioural data and DNA from IDU (n = 210) in the Hepatitis C Incidence and Transmission Study in prisons (HITS-p) cohort were genotyped for polymorphisms in: IL-28B, peptidyl-prolyl isomerase A (PPIA), HLA-C and KIR2. To quantify risk, a composite risk index based on factors predictive of incident HCV infection was derived. Logistic regression analysis revealed the risk index was strongly associated with incident HCV infection (P < 0.0001). The upper tertile of the uninfected individuals had risk indices comparable to the incident cases, but remained uninfected. There were no significant differences in the frequencies of IL-28B or PPIA polymorphisms between these exposed-uninfected cases, or in the frequencies of KIR2-DL3, HLA-C1, or their combination. A framework for the investigation of genetic determinants of resistance to HCV infection has been developed. Several candidate gene associations were investigated and excluded. Further investigation of genetic determinants of resistance to HCV infection is warranted. PMID:24612442

Sugden, P B; Cameron, B; Luciani, F; Lloyd, A R

2014-08-01

268

Effect of bead and illustrations models on high school students' achievement in molecular genetics  

NASA Astrophysics Data System (ADS)

Our main goal in this study was to explore whether the use of models in molecular genetics instruction in high school can contribute to students' understanding of concepts and processes in genetics. Three comparable groups of 11th and 12th graders participated: The control group (116 students) was taught in the traditional lecture format, while the others received instructions which integrated a bead model (71 students), or an illustration model (71 students). Similar instructions and the same guiding questions accompanied the two models. We used three instruments: a multiple-choice and an open-ended written questionnaire, as well as personal interviews. Five of the multiple-choice questions were also given to students before receiving their genetics instruction (pretest). We found that students who used one of the two types of models improved their knowledge in molecular genetics compared to the control group. However, the open-ended questions revealed that bead model activity was significantly more effective than illustration activity. On the basis of these findings we conclude that, though it is advisable to use a three-dimensional model, such as the bead model, engaging students in activities with illustrations can still improve their achievement in comparison to traditional instruction.

Rotbain, Yosi; Marbach-Ad, Gili; Stavy, Ruth

2006-05-01

269

High Genetic Diversity and Low Differentiation of Michelia coriacea (Magnoliaceae), a Critically Endangered Endemic in Southeast Yunnan, China  

PubMed Central

Michelia coriacea, a critically endangered tree, has a restricted and fragmented distribution in Southeast Yunnan Province, China. The genetic diversity, genetic structure and gene flow in the three extant populations of this species were detected by 10 inter-simple sequence repeat (ISSR) markers and 11 simple sequence repeat (SSR) markers. Examination of genetic diversity revealed that the species maintained a relatively high level of genetic diversity at the species level (percentage of polymorphic bands) PPB = 96.36% from ISSRs; PPL (percentage of polymorphic loci) = 95.56% from SSRs, despite several fragmental populations. Low levels of genetic differentiation among the populations of M. coriacea were detected by Nei’s Gst = 0.187 for ISSR and Wright’s Fst = 0.090 for SSR markers, which is further confirmed by Bayesian model-based STRUCTURE and PCoA analysis that could not reveal a clear separation between populations, although YKP was differentiated to other two populations by ISSR markers. Meanwhile, AMOVA analysis also indicated that 22.84% and 13.90% of genetic variation existed among populations for ISSRs and SSRs, respectively. The high level of genetic diversity, low genetic differentiation, and the population, structure imply that the fragmented habitat and the isolated population of M. coriacea may be due to recent over-exploitation. Conservation and management of M. coriacea should concentrate on maintaining the high level of genetic variability through both in and ex-situ conservation actions.

Zhao, Xingfeng; Ma, Yongpeng; Sun, Weibang; Wen, Xiangying; Milne, Richard

2012-01-01

270

GENETICS Serotonergic Mediation of Aggression in High and Low Aggressive Chicken Strains  

Microsoft Academic Search

Serotonin (5-HT) regulates aggressive be- havior via binding to its receptors, such as 5-HT1A and 1B, in humans and rodents. Here we investigate the heri- table components of 5-HT regulation of aggressiveness in chickens, utilizing 3 distinct genetic strains. In this study, we used 2 divergently selected strains (high and low group productivity and survivability, respectively; HGPS and LGPS) and

R. L. Dennis; Z. Q. Chen; H. W. Cheng

271

Smoking habit and genetic factors associated with lung cancer in a population highly exposed to arsenic  

Microsoft Academic Search

In order to find some relationship between genetic differences in metabolic activation and detoxification of environmental carcinogens and host susceptibility to chemically induced cancers, we have investigated the distribution of the GSTM1 null genotype and CYP450 *1A1 MspI polymorphism in lung cancer patients and healthy volunteers of the second region in the north of Chile highly exposed to arsenic. The

M. Adonis; V. Martínez; P. Marín; D. Berrios; L. Gil

2005-01-01

272

Particle size analysis of high density lipoproteins in patients with genetic cholesteryl ester transfer protein deficiency  

Microsoft Academic Search

We investigated the detailed distribution of high-density lipoproteins (HDL) particle size in patients with cholesteryl ester transfer protein (CETP) deficiency. Serum samples pre-stained with Sudan black B were electrophoresed using 4–30% polyacrylamide gradient gels, and the Stokes diameter of HDL particles was determined in 23 patients with genetic CETP deficiency, nine patients with hyperalphalipoproteinemia and seven subjects with normal HDL

Tomoko Arai; Toshihiko Tsukada; Toshio Murase; Kojiro Matsumoto

2000-01-01

273

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates  

PubMed Central

High-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high- and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

Storz, Jay F.; Scott, Graham R.; Cheviron, Zachary A.

2010-01-01

274

Genetic Requirements for High Constitutive SOS Expression in recA730 Mutants of Escherichia coli ?  

PubMed Central

The RecA protein in its functional state is in complex with single-stranded DNA, i.e., in the form of a RecA filament. In SOS induction, the RecA filament functions as a coprotease, enabling the autodigestion of the LexA repressor. The RecA filament can be formed by different mechanisms, but all of them require three enzymatic activities essential for the processing of DNA double-stranded ends. These are helicase, 5?–3? exonuclease, and RecA loading onto single-stranded DNA (ssDNA). In some mutants, the SOS response can be expressed constitutively during the process of normal DNA metabolism. The RecA730 mutant protein is able to form the RecA filament without the help of RecBCD and RecFOR mediators since it better competes with the single-strand binding (SSB) protein for ssDNA. As a consequence, the recA730 mutants show high constitutive SOS expression. In the study described in this paper, we studied the genetic requirements for constitutive SOS expression in recA730 mutants. Using a ?-galactosidase assay, we showed that the constitutive SOS response in recA730 mutants exhibits different requirements in different backgrounds. In a wild-type background, the constitutive SOS response is partially dependent on RecBCD function. In a recB1080 background (the recB1080 mutation retains only helicase), constitutive SOS expression is partially dependent on RecBCD helicase function and is strongly dependent on RecJ nuclease. Finally, in a recB-null background, the constitutive SOS expression of the recA730 mutant is dependent on the RecJ nuclease. Our results emphasize the importance of the 5?–3? exonuclease for high constitutive SOS expression in recA730 mutants and show that RecBCD function can further enhance the excellent intrinsic abilities of the RecA730 protein in vivo.

Vlasic, Ignacija; Simatovic, Ana; Brcic-Kostic, Krunoslav

2011-01-01

275

Artificially created stimuli produced by a genetic algorithm using a saliency model as its fitness function show that Inattentional Blindness modulates performance in a pop-out visual search paradigm.  

PubMed

Salient stimuli are more readily detected than less salient stimuli, and individual differences in such detection may be relevant to why some people fail to notice an unexpected stimulus that appears in their visual field whereas others do notice it. This failure to notice unexpected stimuli is termed 'Inattentional Blindness' and is more likely to occur when we are engaged in a resource-consuming task. A genetic algorithm is described in which artificial stimuli are created using a saliency model as its fitness function. These generated stimuli, which vary in their saliency level, are used in two studies that implement a pop-out visual search task to evaluate the power of the model to discriminate the performance of people who were and were not Inattentionally Blind (IB). In one study the number of orientational filters in the model was increased to check if discriminatory power and the saliency estimation for low-level images could be improved. Results show that the performance of the model does improve when additional filters are included, leading to the conclusion that low-level images may require a higher number of orientational filters for the model to better predict participants' performance. In both studies we found that given the same target patch image (i.e. same saliency value) IB individuals take longer to identify a target compared to non-IB individuals. This suggests that IB individuals require a higher level of saliency for low-level visual features in order to identify target patches. PMID:24508072

Papera, Massimiliano; Cooper, Richard P; Richards, Anne

2014-04-01

276

High-Confidence Discovery of Genetic Network Regulators in Expression Quantitative Trait Loci Data  

PubMed Central

Expression QTL (eQTL) studies involve the collection of microarray gene expression data and genetic marker data from segregating individuals in a population to search for genetic determinants of differential gene expression. Previous studies have found large numbers of trans-regulated genes (regulated by unlinked genetic loci) that link to a single locus or eQTL “hotspot,” and it would be desirable to find the mechanism of coregulation for these gene groups. However, many difficulties exist with current network reconstruction algorithms such as low power and high computational cost. A common observation for biological networks is that they have a scale-free or power-law architecture. In such an architecture, highly influential nodes exist that have many connections to other nodes. If we assume that this type of architecture applies to genetic networks, then we can simplify the problem of genetic network reconstruction by focusing on discovery of the key regulatory genes at the top of the network. We introduce the concept of “shielding” in which a specific gene expression variable (the shielder) renders a set of other gene expression variables (the shielded genes) independent of the eQTL. We iteratively build networks from the eQTL to the shielder down using tests of conditional independence. We have proposed a novel test for controlling the shielder false-positive rate at a predetermined level by requiring a threshold number of shielded genes per shielder. Using simulation, we have demonstrated that we can control the shielder false-positive rate as well as obtain high shielder and edge specificity. In addition, we have shown our method to be robust to violation of the latent variable assumption, an important feature in the practical application of our method. We have applied our method to a yeast expression QTL data set in which microarray and marker data were collected from the progeny of a backcross of two species of Saccharomyces cerevisiae (Brem et al. 2002). Seven genetic networks have been discovered, and bioinformatic analysis of the discovered regulators and corresponding regulated genes has generated plausible hypotheses for mechanisms of regulation that can be tested in future experiments.

Duarte, Christine W.; Zeng, Zhao-Bang

2011-01-01

277

High genetic diversity in a small population: the case of Chilean blue whales.  

PubMed

It is generally assumed that species with low population sizes have lower genetic diversities than larger populations and vice versa. However, this would not be the case for long-lived species with long generation times, and which populations have declined due to anthropogenic effects, such as the blue whale (Balaenoptera musculus). This species was intensively decimated globally to near extinction during the 20th century. Along the Chilean coast, it is estimated that at least 4288 blue whales were hunted from an apparently pre-exploitation population size (k) of a maximum of 6200 individuals (Southeastern Pacific). Thus, here, we describe the mtDNA (control region) and nDNA (microsatellites) diversities of the Chilean blue whale aggregation site in order to verify the expectation of low genetic diversity in small populations. We then compare our findings with other blue whale aggregations in the Southern Hemisphere. Interestingly, although the estimated population size is small compared with the pre-whaling era, there is still considerable genetic diversity, even after the population crash, both in mitochondrial (N = 46) and nuclear (N = 52) markers (Hd = 0.890 and Ho = 0.692, respectively). Our results suggest that this diversity could be a consequence of the long generation times and the relatively short period of time elapsed since the end of whaling, which has been observed in other heavily-exploited whale populations. The genetic variability of blue whales on their southern Chile feeding grounds was similar to that found in other Southern Hemisphere blue whale feeding grounds. Our phylogenetic analysis of mtDNA haplotypes does not show extensive differentiation of populations among Southern Hemisphere blue whale feeding grounds. The present study suggests that although levels of genetic diversity are frequently used as estimators of population health, these parameters depend on the biology of the species and should be taken into account in a monitoring framework study to obtain a more complete picture of the conservation status of a population. PMID:24834336

Torres-Florez, Juan P; Hucke-Gaete, Rodrigo; Rosenbaum, Howard; Figueroa, Christian C

2014-04-01

278

High genetic diversity in a small population: the case of Chilean blue whales  

PubMed Central

It is generally assumed that species with low population sizes have lower genetic diversities than larger populations and vice versa. However, this would not be the case for long-lived species with long generation times, and which populations have declined due to anthropogenic effects, such as the blue whale (Balaenoptera musculus). This species was intensively decimated globally to near extinction during the 20th century. Along the Chilean coast, it is estimated that at least 4288 blue whales were hunted from an apparently pre-exploitation population size (k) of a maximum of 6200 individuals (Southeastern Pacific). Thus, here, we describe the mtDNA (control region) and nDNA (microsatellites) diversities of the Chilean blue whale aggregation site in order to verify the expectation of low genetic diversity in small populations. We then compare our findings with other blue whale aggregations in the Southern Hemisphere. Interestingly, although the estimated population size is small compared with the pre-whaling era, there is still considerable genetic diversity, even after the population crash, both in mitochondrial (N = 46) and nuclear (N = 52) markers (Hd = 0.890 and Ho = 0.692, respectively). Our results suggest that this diversity could be a consequence of the long generation times and the relatively short period of time elapsed since the end of whaling, which has been observed in other heavily-exploited whale populations. The genetic variability of blue whales on their southern Chile feeding grounds was similar to that found in other Southern Hemisphere blue whale feeding grounds. Our phylogenetic analysis of mtDNA haplotypes does not show extensive differentiation of populations among Southern Hemisphere blue whale feeding grounds. The present study suggests that although levels of genetic diversity are frequently used as estimators of population health, these parameters depend on the biology of the species and should be taken into account in a monitoring framework study to obtain a more complete picture of the conservation status of a population.

Torres-Florez, Juan P; Hucke-Gaete, Rodrigo; Rosenbaum, Howard; Figueroa, Christian C

2014-01-01

279

Genotype-Phenotype Correlations in a Mountain Population Community with High Prevalence of Wilson's Disease: Genetic and Clinical Homogeneity  

PubMed Central

Wilson’s disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson’s disease ever reported of 1?1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18±1 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson’s disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson’s disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

Cocos, Relu; Sendroiu, Alina; Schipor, Sorina; Bohiltea, Laurentiu Camil; Sendroiu, Ionut; Raicu, Florina

2014-01-01

280

Genotype-Phenotype Correlations in a Mountain Population Community with High Prevalence of Wilson's Disease: Genetic and Cinical Homogeneity.  

PubMed

Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1?1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18±1 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities. PMID:24897373

Coco?, Relu; Sendroiu, Alina; Schipor, Sorina; Bohîl?ea, Lauren?iu Camil; Sendroiu, Ionu?; Raicu, Florina

2014-01-01

281

How Not to Be a BlackBox: Evolution and Genetic-Engineering of High-Level Behaviours  

Microsoft Academic Search

In spite of many success stories in various do- mains, Genetic Algorithm and Genetic Program- ming still suffer from some significant pitfalls. Those evolved programs often lack of some im- portant properties such as robustness, compre- hensibility, transparency, modifiability and us- ability of domain knowledge easily available. We attempt to resolve these problems, at least in evolving high-level behaviours, by

Ik Soo Lim; Daniel Thalmann

282

High-throughput genomic technology in research and clinical management of breast cancer. Evolving landscape of genetic epidemiological studies.  

PubMed

Candidate polymorphism-based genetic epidemiological studies have yielded little success in the search for low-penetrance breast cancer susceptibility genes. The lack of progress is partially due to insufficient coverage of genomic regions with genetic markers, as well as economic constraints, limiting both the number of genetic targets and the number of individuals being studied. Recent rapid advances in high-throughput genotyping technology and our understanding of genetic variation patterns across the human genome are now revolutionizing the way in which genetic epidemiological studies are being designed and conducted. Genetic epidemiological studies are quickly progressing from candidate gene studies to comprehensive pathway investigation and, further, to genomic epidemiological studies where the whole human genome is being interrogated to identify susceptibility alleles. This paper reviews the evolving approaches in the search for low-penetrance breast cancer susceptibility gene variants and discusses their potential promises and pitfalls. PMID:16834767

Low, Yen-Ling; Wedrén, Sara; Liu, Jianjun

2006-01-01

283

High genetic diversity and adaptive potential of two simian hemorrhagic fever viruses in a wild primate population.  

PubMed

Key biological properties such as high genetic diversity and high evolutionary rate enhance the potential of certain RNA viruses to adapt and emerge. Identifying viruses with these properties in their natural hosts could dramatically improve disease forecasting and surveillance. Recently, we discovered two novel members of the viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 and SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. Nearly nothing is known about the biological properties of SHFVs in nature, although the SHFV type strain, SHFV-LVR, has caused devastating outbreaks of viral hemorrhagic fever in captive macaques. Here we detected SHFV-krc1 and SHFV-krc2 in 40% and 47% of 60 wild red colobus tested, respectively. We found viral loads in excess of 10(6)-10(7) RNA copies per milliliter of blood plasma for each of these viruses. SHFV-krc1 and SHFV-krc2 also showed high genetic diversity at both the inter- and intra-host levels. Analyses of synonymous and non-synonymous nucleotide diversity across viral genomes revealed patterns suggestive of positive selection in SHFV open reading frames (ORF) 5 (SHFV-krc2 only) and 7 (SHFV-krc1 and SHFV-krc2). Thus, these viruses share several important properties with some of the most rapidly evolving, emergent RNA viruses. PMID:24651479

Bailey, Adam L; Lauck, Michael; Weiler, Andrea; Sibley, Samuel D; Dinis, Jorge M; Bergman, Zachary; Nelson, Chase W; Correll, Michael; Gleicher, Michael; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Chapman, Colin; Kuhn, Jens H; Hughes, Austin L; Friedrich, Thomas C; Goldberg, Tony L; O'Connor, David H

2014-01-01

284

Discordant distribution of populations and genetic variation in a sea star with high dispersal potential.  

PubMed

Patiria miniata, a broadcast-spawning sea star species with high dispersal potential, has a geographic range in the intertidal zone of the northeast Pacific Ocean from Alaska to California that is characterized by a large range gap in Washington and Oregon. We analyzed spatial genetic variation across the P. miniata range using multilocus sequence data (mtDNA, nuclear introns) and multilocus genotype data (microsatellites). We found a strong phylogeographic break at Queen Charlotte Sound in British Columbia that was not in the location predicted by the geographical distribution of the populations. However, this population genetic discontinuity does correspond to previously described phylogeographic breaks in other species. Northern populations from Alaska and Haida Gwaii were strongly differentiated from all southern populations from Vancouver Island and California. Populations from Vancouver Island and California were undifferentiated with evidence of high gene flow or very recent separation across the range disjunction between them. The surprising and discordant spatial distribution of populations and alleles suggests that historical vicariance (possibly caused by glaciations) and contemporary dispersal barriers (possibly caused by oceanographic conditions) both shape population genetic structure in this species. PMID:19663996

Keever, Carson C; Sunday, Jennifer; Puritz, Jonathan B; Addison, Jason A; Toonen, Robert J; Grosberg, Richard K; Hart, Michael W

2009-12-01

285

High school students' problem-solving performance on realistic genetics problems  

NASA Astrophysics Data System (ADS)

Problem solving is recognized as a valuable educational experience in science. Thus genetics, essentially a problem-solving science included in almost all high school biology courses, offers a fruitful area for studying student problem-solving performance. The research reported in this article describes the performance of 30 high school students solving 119 problems generated by the computer program GENETICS CONSTRUCTION KIT (Jungck & Calley, 1985). Solving GCK problems requires students to plan experiments, generate and interpret data, and reason from effects (phenotypic data) to causes (genotypic data). Research data consisted of transcribed audiotapes of students thinking aloud as they solved problems and computer printouts of initial data and sequence of crosses. Transcripts were analyzed for common actions and comments made during the problem-solving process in terms of initial data redescription and interpretation, hypothesis generation, cross data redescription and interpretation, solution synthesis, and solution confirmation. This study was done in an effort to add to the understanding of student problem-solving strategies and to develop a model of student performance - a model that when combined with a model of expert performance may serve as a basis for improving genetics instruction.

Slack, Susie Johnston; Stewart, Jim

286

Determining Signalling Nodes for Apoptosis by a Genetic High-Throughput Screen  

PubMed Central

Background With the ever-increasing information emerging from the various sequencing and gene annotation projects, there is an urgent need to elucidate the cellular functions of the newly discovered genes. The genetically regulated cell suicide of apoptosis is especially suitable for such endeavours as it is governed by a vast number of factors. Methodology/Principal Findings We have set up a high-throughput screen in 96-well microtiter plates for genes that induce apoptosis upon their individual transfection into human cells. Upon screening approximately 100,000 cDNA clones we determined 74 genes that initiate this cellular suicide programme. A thorough bioinformatics analysis of these genes revealed that 91% are novel apoptosis regulators. Careful sequence analysis and functional annotation showed that the apoptosis factors exhibit a distinct functional distribution that distinguishes the cell death process from other signalling pathways. While only a minority of classic signal transducers were determined, a substantial number of the genes fall into the transporter- and enzyme-category. The apoptosis factors are distributed throughout all cellular organelles and many signalling circuits, but one distinct signalling pathway connects at least some of the isolated genes. Comparisons with microarray data suggest that several genes are dysregulated in specific types of cancers and degenerative diseases. Conclusions/Significance Many unknown genes for cell death were revealed through our screen, supporting the enormous complexity of cell death regulation. Our results will serve as a repository for other researchers working with genomics data related to apoptosis or for those seeking to reveal novel signalling pathways for cell suicide.

Lin, Bevan; Huntley, Derek; AbuAli, Ghada; Langley, Sarah R.; Sindelar, George; Petretto, Enrico; Butcher, Sarah; Grimm, Stefan

2011-01-01

287

High-resolution mapping reveals hundreds of genetic incompatibilities in hybridizing fish species  

PubMed Central

Hybridization is increasingly being recognized as a common process in both animal and plant species. Negative epistatic interactions between genes from different parental genomes decrease the fitness of hybrids and can limit gene flow between species. However, little is known about the number and genome-wide distribution of genetic incompatibilities separating species. To detect interacting genes, we perform a high-resolution genome scan for linkage disequilibrium between unlinked genomic regions in naturally occurring hybrid populations of swordtail fish. We estimate that hundreds of pairs of genomic regions contribute to reproductive isolation between these species, despite them being recently diverged. Many of these incompatibilities are likely the result of natural or sexual selection on hybrids, since intrinsic isolation is known to be weak. Patterns of genomic divergence at these regions imply that genetic incompatibilities play a significant role in limiting gene flow even in young species. DOI: http://dx.doi.org/10.7554/eLife.02535.001

Schumer, Molly; Cui, Rongfeng; Powell, Daniel L; Dresner, Rebecca; Rosenthal, Gil G; Andolfatto, Peter

2014-01-01

288

Genetic dissection of Al tolerance QTLs in the maize genome by high density SNP scan  

PubMed Central

Background Aluminum (Al) toxicity is an important limitation to food security in tropical and subtropical regions. High Al saturation on acid soils limits root development, reducing water and nutrient uptake. In addition to naturally occurring acid soils, agricultural practices may decrease soil pH, leading to yield losses due to Al toxicity. Elucidating the genetic and molecular mechanisms underlying maize Al tolerance is expected to accelerate the development of Al-tolerant cultivars. Results Five genomic regions were significantly associated with Al tolerance, using 54,455 SNP markers in a recombinant inbred line population derived from Cateto Al237. Candidate genes co-localized with Al tolerance QTLs were further investigated. Near-isogenic lines (NILs) developed for ZmMATE2 were as Al-sensitive as the recurrent line, indicating that this candidate gene was not responsible for the Al tolerance QTL on chromosome 5, qALT5. However, ZmNrat1, a maize homolog to OsNrat1, which encodes an Al3+ specific transporter previously implicated in rice Al tolerance, was mapped at ~40 Mbp from qALT5. We demonstrate for the first time that ZmNrat1 is preferentially expressed in maize root tips and is up-regulated by Al, similarly to OsNrat1 in rice, suggesting a role of this gene in maize Al tolerance. The strongest-effect QTL was mapped on chromosome 6 (qALT6), within a 0.5 Mbp region where three copies of the Al tolerance gene, ZmMATE1, were found in tandem configuration. qALT6 was shown to increase Al tolerance in maize; the qALT6-NILs carrying three copies of ZmMATE1 exhibited a two-fold increase in Al tolerance, and higher expression of ZmMATE1 compared to the Al sensitive recurrent parent. Interestingly, a new source of Al tolerance via ZmMATE1 was identified in a Brazilian elite line that showed high expression of ZmMATE1 but carries a single copy of ZmMATE1. Conclusions High ZmMATE1 expression, controlled either by three copies of the target gene or by an unknown molecular mechanism, is responsible for Al tolerance mediated by qALT6. As Al tolerant alleles at qALT6 are rare in maize, marker-assisted introgression of this QTL is an important strategy to improve maize adaptation to acid soils worldwide.

2014-01-01

289

X-ray photoelectron spectroscopy of negative electrodes from high-power lithium-ion cells showing various levels of power fade  

SciTech Connect

High-power lithium-ion cells for transportation applications are being developed and studied at Argonne National Laboratory. The current generation of cells containing LiNi{sub 0.8}Co{sub 0.15}Al{sub 0.05}O{sub 2}-based cathodes, graphite-based anodes, and LiPF6-based electrolytes show loss of capacity and power during accelerated testing at elevated temperatures. Negative electrode samples harvested from some cells that showed varying degrees of power and capacity fade were examined by X-ray photoelectron spectroscopy (XPS). The samples exhibited a surface film on the graphite, which was thicker on samples from cells that showed higher fade. Furthermore, solvent-based compounds were dominant on samples from low power fade cells, whereas LiPF{sub 6}-based products were dominant on samples from high power fade cells. The effect of sample rinsing and air exposure is discussed. Mechanisms are proposed to explain the formation of compounds suggested by the XPS data.

Herstedt, Marie; Abraham, Daniel P.; Kerr, John B.

2004-02-28

290

Wavelets meet genetic imaging  

NASA Astrophysics Data System (ADS)

Genetic image analysis is an interdisciplinary area, which combines microscope image processing techniques with the use of biochemical probes for the detection of genetic aberrations responsible for cancers and genetic diseases. Recent years have witnessed parallel and significant progress in both image processing and genetics. On one hand, revolutionary multiscale wavelet techniques have been developed in signal processing and applied mathematics in the last decade, providing sophisticated tools for genetic image analysis. On the other hand, reaping the fruit of genome sequencing, high resolution genetic probes have been developed to facilitate accurate detection of subtle and cryptic genetic aberrations. In the meantime, however, they bring about computational challenges for image analysis. In this paper, we review the fruitful interaction between wavelets and genetic imaging. We show how wavelets offer a perfect tool to address a variety of chromosome image analysis problems. In fact, the same word "subband" has been used in the nomenclature of cytogenetics to describe the multiresolution banding structure of the chromosome, even before its appearance in the wavelet literature. The application of wavelets to chromosome analysis holds great promise in addressing several computational challenges in genetics. A variety of real world examples such as the chromosome image enhancement, compression, registration and classification will be demonstrated. These examples are drawn from fluorescence in situ hybridization (FISH) and microarray (gene chip) imaging experiments, which indicate the impact of wavelets on the diagnosis, treatments and prognosis of cancers and genetic diseases.

Wang, Yu-Ping

2005-08-01

291

Construction of a genetic map based on high-throughput SNP genotyping and genetic mapping of a TuMV resistance locus in Brassica rapa.  

PubMed

Brassica rapa is a member of the Brassicaceae family and includes vegetables and oil crops that are cultivated worldwide. The introduction of durable resistance against turnip mosaic virus (TuMV) into agronomically important cultivars has been a significant challenge for genetic and horticultural breeding studies of B. rapa. Based on our previous genome-wide analysis of DNA polymorphisms between the TuMV-resistant doubled haploid (DH) line VC40 and the TuMV-susceptible DH line SR5, we constructed a core genetic map of the VCS-13M DH population, which is composed of 83 individuals derived from microspore cultures of a F1 cross between VC40 and SR5, by analyzing the segregation of 314 sequence-characterized genetic markers. The genetic markers correspond to 221 SNPs and 31 InDels of genes as well as 62 SSRs, covering 1,115.9 cM with an average distance of 3.6 cM between the adjacent marker loci. The alignment and orientation of the constructed map showed good agreement with the draft genome sequence of Chiifu, thus providing an efficient strategy to map genic sequences. Using the genetic map, a novel dominant TuMV resistance locus (TuMV-R) in the VCS-13M DH population was identified as a 0.34 Mb region in the short arm of chromosome A6 in which four CC-NBS-LRR resistance genes and two pathogenesis-related-1 genes reside. The genetic map developed in this study can play an important role in the genetic study of TuMV resistance and the molecular breeding of B. rapa. PMID:24326528

Chung, Hee; Jeong, Young-Min; Mun, Jeong-Hwan; Lee, Soo-Seong; Chung, Won-Hyong; Yu, Hee-Ju

2014-04-01

292

High-Level Genetic Diversity and Complex Population Structure of Siberian Apricot (Prunus sibirica L.) in China as Revealed by Nuclear SSR Markers  

PubMed Central

Siberian apricot (Prunus sibirica L.), an ecologically and economically important tree species with a high degree of tolerance to a variety of extreme environmental conditions, is widely distributed across the mountains of northeastern and northern China, eastern and southeastern regions of Mongolia, Eastern Siberia, and the Maritime Territory of Russia. However, few studies have examined the genetic diversity and population structure of this species. Using 31 nuclear microsatellites, we investigated the level of genetic diversity and population structure of Siberian apricot sampled from 22 populations across China. The number of alleles per locus ranged from 5 to 33, with an average of 19.323 alleles. The observed heterozygosity and expected heterozygosity ranged from 0.037 to 0.874 and 0.040 to 0.924 with average values of 0.639 and 0.774, respectively. A STRUCTURE-based analysis clustered all of the populations into four genetic clusters. Significant genetic differentiation was observed between all population pairs. A hierarchical analysis of molecular variance attributed about 94% of the variation to within populations. No significant difference was detected between the wild and semi-wild groups, indicating that recent cultivation practices have had little impact on the genetic diversity of Siberian apricot. The Mantel test showed that the genetic distance among the populations was not significantly correlated with geographic distance (r?=?0.4651, p?=?0.9940). Our study represents the most comprehensive investigation of the genetic diversity and population structure of Siberian apricot in China to date, and it provides valuable information for the collection of genetic resources for the breeding of Siberian apricot and related species.

Wang, Zhe; Kang, Ming; Liu, Huabo; Gao, Jiao; Zhang, Zhengdong; Li, Yingyue; Wu, Rongling; Pang, Xiaoming

2014-01-01

293

High efficiency and reliability of inter-simple sequence repeats (ISSR) markers for evaluation of genetic diversity in Brazilian cultivated Jatropha curcas L. accessions.  

PubMed

Jatropha curcas L. is found in all tropical regions and has garnered lot of attention for its potential as a source of biodiesel. As J. curcas is a plant that is still in the process of being domesticated, interest in improving its agronomic traits has increased in an attempt to select more productive varieties, aiming at sustainable utilization of this plant for biodiesel production. Therefore, the study of genetic diversity in different accessions of J. curcas in Brazil constitutes a necessary first step in genetic programs designed to improve this species. In this study we have used ISSR markers to assess the genetic variability of 332 accessions from eight states in Brazil that produce J. curcas seeds for commercialization. Seven ISSR primers amplified a total of 21,253 bands, of which 19,472 bands (91%) showed polymorphism. Among the polymorphic bands 275 rare bands were identified (present in fewer than 15% of the accessions). Polymorphic information content (PIC), marker index (MI) and resolving power (RP) averaged 0.26, 17.86 and 19.87 per primer, respectively, showing the high efficiency and reliability of the markers used. ISSR markers analyses as number of polymorphic loci, genetic diversity and accession relationships through UPGMA-phenogram and MDS showed that Brazilian accessions are closely related but have a higher level of genetic diversity than accessions from other countries, and the accessions from Natal (RN) are the most diverse, having high value as a source of genetic diversity for breeding programs of J. curcas in the world. PMID:21113672

Grativol, Clícia; da Fonseca Lira-Medeiros, Catarina; Hemerly, Adriana Silva; Ferreira, Paulo Cavalcanti Gomes

2011-10-01

294

Rats perinatally exposed to food restriction and high-fat diet show differences in adipose tissue gene expression under chronic caloric restriction  

PubMed Central

The aim of this study is to analyze how maternal diet during the lactational period influences the adipose tissue response to chronic caloric restriction in offspring. Lactating dams were subjected to one of three treatments: 50% food restriction (FR), ad lib standard chow (AL), or ad lib high-fat diet (HF). Juveniles were first weaned onto standard chow, then in adulthood 50% calorically restricted and maintained at 90% of normal body weight for 60 d. HF animals showed increased percent body fat compared with AL and FR animals despite equivalent body weights. HF animals showed alterations in the balance of adipose tissue lipogenic (FAS, LPL) and lipolytic (HSL) gene expression that may underlie their propensity to maintain fat stores under caloric restriction.

MacKay, Harry; Khazall, Rim; Patterson, Zachary R; Wellman, Martin; Abizaid, Alfonso

2013-01-01

295

Post Genome-Wide Association Studies of Novel Genes Associated with Type 2 Diabetes Show Gene-Gene Interaction and High Predictive Value  

PubMed Central

Background Recently, several Genome Wide Association (GWA) studies in populations of European descent have identified and validated novel single nucleotide polymorphisms (SNPs), highly associated with type 2 diabetes (T2D). Our aims were to validate these markers in other European and non-European populations, then to assess their combined effect in a large French study comparing T2D and normal glucose tolerant (NGT) individuals. Methodology/Principal Findings In the same French population analyzed in our previous GWA study (3,295 T2D and 3,595 NGT), strong associations with T2D were found for CDKAL1 (ORrs7756992?=?1.30[1.19–1.42], P?=?2.3×10?9), CDKN2A/2B (ORrs10811661?=?0.74[0.66–0.82], P?=?3.5×10?8) and more modestly for IGFBP2 (ORrs1470579?=?1.17[1.07–1.27], P?=?0.0003) SNPs. These results were replicated in both Israeli Ashkenazi (577 T2D and 552 NGT) and Austrian (504 T2D and 753 NGT) populations (except for CDKAL1) but not in the Moroccan population (521 T2D and 423 NGT). In the overall group of French subjects (4,232 T2D and 4,595 NGT), IGFBP2 and CXCR4 synergistically interacted with (LOC38776, SLC30A8, HHEX) and (NGN3, CDKN2A/2B), respectively, encoding for proteins presumably regulating pancreatic endocrine cell development and function. The T2D risk increased strongly when risk alleles, including the previously discovered T2D-associated TCF7L2 rs7903146 SNP, were combined (8.68-fold for the 14% of French individuals carrying 18 to 30 risk alleles with an allelic OR of 1.24). With an area under the ROC curve of 0.86, only 15 novel loci were necessary to discriminate French individuals susceptible to develop T2D. Conclusions/Significance In addition to TCF7L2, SLC30A8 and HHEX, initially identified by the French GWA scan, CDKAL1, IGFBP2 and CDKN2A/2B strongly associate with T2D in French individuals, and mostly in populations of Central European descent but not in Moroccan subjects. Genes expressed in the pancreas interact together and their combined effect dramatically increases the risk for T2D, opening avenues for the development of genetic prediction tests.

Cauchi, Stephane; Meyre, David; Durand, Emmanuelle; Proenca, Christine; Marre, Michel; Hadjadj, Samy; Choquet, Helene; De Graeve, Franck; Gaget, Stefan; Allegaert, Frederic; Delplanque, Jerome; Permutt, Marshall Alan; Wasson, Jon; Blech, Ilana; Charpentier, Guillaume; Balkau, Beverley; Vergnaud, Anne-Claire; Czernichow, Sebastien; Patsch, Wolfgang; Chikri, Mohamed; Glaser, Benjamin; Sladek, Robert; Froguel, Philippe

2008-01-01

296

High-Voltage Electroporation of Bacteria: Genetic Transformation of Campylobacter jejuni with Plasmid DNA  

NASA Astrophysics Data System (ADS)

Electroporation permits the uptake of DNA by mammalian cells and plant protoplasts because it induces transient permeability of the cell membrane. We investigated the utility of high-voltage electroporation as a method for genetic transformation of intact bacterial cells by using the enteric pathogen Campylobacter jejuni as a model system. This report demonstrates that the application of high-voltage discharges to bacterial cells permits genetic transformation. Our method involves exposure of a Campylobacter cell suspension to a high-voltage exponential decay discharge (5-13 kV/cm) for a brief period of time (resistance-capacitance time constant = 2.4-26 msec) in the presence of plasmid DNA. Electrical transformation of C. jejuni results in frequencies as high as 1.2 × 106 transformants per ? g of DNA. We have investigated the effects of pulse amplitude and duration, cell growth conditions, divalent cations, and DNA concentration on the efficiency of transformation. Transformants of C. jejuni obtained by electroporation contained structurally intact plasmid molecules. In addition, evidence is presented that indicates that C. jejuni possesses DNA restriction and modification systems. The use of electroporation as a method for transforming other bacterial species and guidelines for its implementation are also discussed.

Miller, Jeff F.; Dower, William J.; Tompkins, Lucy S.

1988-02-01

297

Rapid Recombination Mapping for High-Throughput Genetic Screens in Drosophila  

PubMed Central

Mutagenesis screens are a staple of classical genetics. Chemical-induced mutations, however, are often difficult and time-consuming to identify. Here, we report that recombination analysis with pairs of dominant visible markers provides a rapid and reliable strategy to map mutations in Drosophila melanogaster. This method requires only two generations and a total of six crosses in vials to estimate the genetic map position of the responsible lesion with high accuracy. This genetic map position can then be reliably used to identify the mutated gene through complementation testing with an average of nine deficiencies and Sanger sequencing. We have used this approach to successfully map a collection of mutations from an ethyl methanesulfonate?based mutagenesis screen on the third chromosome. We propose that this method also may be used in conjunction with whole-genome sequencing, particularly when multiple independent alleles of the mutated locus are not available. By facilitating the rapid identification of mutated genes, our mapping strategy removes a primary obstacle to the widespread use of powerful chemical mutagenesis screens to understand fundamental biological phenomena.

Sapiro, Anne L.; Ihry, Robert J.; Buhr, Derek L.; Konieczko, Kevin M.; Ives, Sarah M.; Engstrom, Anna K.; Wleklinski, Nicholas P.; Kopish, Kristin J.; Bashirullah, Arash

2013-01-01

298

High-density SNP-based genetic map development and linkage disequilibrium assessment in Brassica napus L  

PubMed Central

Background High density genetic maps built with SNP markers that are polymorphic in various genetic backgrounds are very useful for studying the genetics of agronomical traits as well as genome organization and evolution. Simultaneous dense SNP genotyping of segregating populations and variety collections was applied to oilseed rape (Brassica napus L.) to obtain a high density genetic map for this species and to study the linkage disequilibrium pattern. Results We developed an integrated genetic map for oilseed rape by high throughput SNP genotyping of four segregating doubled haploid populations. A very high level of collinearity was observed between the four individual maps and a large number of markers (>59%) was common to more than two maps. The precise integrated map comprises 5764 SNP and 1603 PCR markers. With a total genetic length of 2250 cM, the integrated map contains a density of 3.27 markers (2.56 SNP) per cM. Genotyping of these mapped SNP markers in oilseed rape collections allowed polymorphism level and linkage disequilibrium (LD) to be studied across the different collections (winter vs spring, different seed quality types) and along the linkage groups. Overall, polymorphism level was higher and LD decayed faster in spring than in “00” winter oilseed rape types but this was shown to vary greatly along the linkage groups. Conclusions Our study provides a valuable resource for further genetic studies using linkage or association mapping, for marker assisted breeding and for Brassica napus sequence assembly and genome organization analyses.

2013-01-01

299

Genetic Pool Information Reflects Highly Suitable Areas: The Case of Two Parapatric Endangered Species of Tuco-tucos (Rodentia: Ctenomiydae).  

PubMed

Conservation of small mammals requires knowledge of the genetically and ecologically meaningful spatial scales at which species respond to habitat modifications. Conservation strategies can be improved through the use of ecological niche models and genetic data to classify areas of high environmental suitability. In this study, we applied a Maxent model integrated with genetic information (nucleotide diversity, haplotype diversity and Fu's Fs neutrality tests) to evaluate potential genetic pool populations with highly suitable areas for two parapatric endangered species of tuco-tucos (Ctenomys minutus and C. lami). Our results demonstrated that both species were largely influenced by vegetation and soil variables at a landscape scale and inhabit a highly specific niche. Ctenomys minutus was also influenced by the variable altitude; the species was associated with low altitudes (sea level). Our model of genetic data associated with environmental suitability indicate that the genetic pool data were associated with highly suitable areas for C. minutus. This pattern was not evident for C. lami, but this outcome could be a consequence of the restricted range of the species. The preservation of species requires not only detailed knowledge of their natural history and genetic structure but also information on the availability of suitable areas where species can survive, and such knowledge can aid significantly in conservation planning. This finding reinforces the use of these two techniques for planning conservation actions. PMID:24819251

Galiano, Daniel; Bernardo-Silva, Jorge; Freitas, Thales R O de

2014-01-01

300

Genetic Pool Information Reflects Highly Suitable Areas: The Case of Two Parapatric Endangered Species of Tuco-tucos (Rodentia: Ctenomiydae)  

PubMed Central

Conservation of small mammals requires knowledge of the genetically and ecologically meaningful spatial scales at which species respond to habitat modifications. Conservation strategies can be improved through the use of ecological niche models and genetic data to classify areas of high environmental suitability. In this study, we applied a Maxent model integrated with genetic information (nucleotide diversity, haplotype diversity and Fu's Fs neutrality tests) to evaluate potential genetic pool populations with highly suitable areas for two parapatric endangered species of tuco-tucos (Ctenomys minutus and C. lami). Our results demonstrated that both species were largely influenced by vegetation and soil variables at a landscape scale and inhabit a highly specific niche. Ctenomys minutus was also influenced by the variable altitude; the species was associated with low altitudes (sea level). Our model of genetic data associated with environmental suitability indicate that the genetic pool data were associated with highly suitable areas for C. minutus. This pattern was not evident for C. lami, but this outcome could be a consequence of the restricted range of the species. The preservation of species requires not only detailed knowledge of their natural history and genetic structure but also information on the availability of suitable areas where species can survive, and such knowledge can aid significantly in conservation planning. This finding reinforces the use of these two techniques for planning conservation actions.

Galiano, Daniel; Bernardo-Silva, Jorge; de Freitas, Thales R. O.

2014-01-01

301

Microsatellites reveal genetic differentiation among populations in an insect species with high genetic variability in dispersal, the codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae).  

PubMed

Little is known about genetic differentiation and gene flow in populations of insect species that have a high genetic variability in dispersal but lack morphologically visible morphs that disperse. These characteristics apply to the codling moth, Cydia pomonella L. (Lepidoptera: Tortricidae), a major pest of fruits and nuts. Larvae were collected from three orchards each of pome fruits, stone fruits and nut trees in a major fruit growing area of Switzerland (Valais) and from six further (mainly apple) orchards throughout this country. Nine microsatellite loci were used to investigate genetic differentiation and the amount of gene flow among the sampled populations. All the loci were shown to be polymorphic in all populations. The number of alleles ranged from five to 15 over nine loci for the 15 populations. Significant genetic differentiation was noted among the populations from apple, apricot and walnut in the Valais region. Furthermore, among the eight populations sampled from apple in different geographic regions throughout Switzerland, AMOVA and pairwise FST analysis revealed significant population genetic differentiation even between populations collected from orchards 10 km apart. These results indicate that a distinct prevailing characteristic, in the present case the sedentary behaviour of the moth, can shape population architecture. PMID:19366473

Chen, M H; Dorn, S

2010-02-01

302

Long-term isolation and stability explain high genetic diversity in the Eastern Himalaya.  

PubMed

China's Southwest Mountainous Region in Eastern Himalaya is a ‘biodiversity hotspot’ of global interest for conservation. Yet little is known about what has driven this unique diversity. The dramatic topography of the Southwest Mountainous Region resulting from the tectonic uplift during the late Pliocene leads to dramatic ecological stratification, which creates physical barriers to migration and isolates organisms into different subregions and mountain systems. This agrees with the observation that the phylogeographical patterns found in four species of birds (Alcippe morrisonia, Stachyridopsis ruficeps, Parus monticolus and Aegithalos concinnus) distributed in this region are characterized by deep splits between lineages that coalesce between 0.8 and 2.1 Ma. Unlike other regions at this latitude, the Southwest Mountainous Region was largely unaffected by the Pleistocene glaciations. Genetically isolated populations of these birds could thus be maintained throughout the Pleistocene in these rather stable montane environments. In comparison, we found radically different phylogeographical patterns in populations of the same four species distributed in the adjacent lowland, the Central China region. This region has a distinctly different geological history with dramatic, climate-induced shifts in vegetation during the Pleistocene. Here, we found a considerably less geographical structure in the genetic variation and a much younger coalescence time (0.3-0.7 Ma). We also found evidence of genetic bottlenecks during the glacial periods and gene flow during the interglacial expansions. We conclude that the high genetic diversity in the Southwest Mountainous Region results from a long-term in situ diversification within these evolutionary isolated and environment stable montane habitats. PMID:24600707

Qu, Yanhua; Ericson, Per G P; Quan, Qing; Song, Gang; Zhang, Ruiying; Gao, Bin; Lei, Fumin

2014-02-01

303

High genetic variation in leopards indicates large and long-term stable effective population size.  

PubMed

In this paper we employ recently developed statistical and molecular tools to analyse the population history of the Tanzanian leopard (Panthera pardus), a large solitary felid. Because of their solitary lifestyle little is known of their past or present population dynamics. Eighty-one individuals were scored at 18 microsatellite loci. Overall, levels of heterozygosity were high (0.77 +/- 0.03), with a small heterozygote deficiency (0.06 +/- 0.03). Effective population size (Ne) was calculated to be 38 000-48 000. A Ne:N ratio of 0.42 (average from four cat studies) gives a present population size of about 100 000 leopards in Tanzania. Four different bottleneck tests indicated that this population has been large and stable for a minimum of several thousand years. FST values were low and no significant genetic structuring of the population could be detected. This concurs well with the large migration values (Nm) obtained (>3.3 individuals/generation). Our analysis reveals that ecological factors (e.g. disease), which are known to have had major impact on other carnivore populations, are unlikely to have impacted strongly on the population dynamics of Tanzanian leopards. The explanation may be found in their solitary life-style, their often nonconfrontational behaviour toward interspecific competitors, or that any bottlenecks have been of limited size, localized, or too short to have affected genetic variation to any measurable degree. Since the genetic structuring is weak, gene flow is not restricted to within protected areas. Local loss of genetic variation is therefore not of immediate concern. PMID:11091313

Spong, G; Johansson, M; Björklund, M

2000-11-01

304

Population analysis of Vibrio parahaemolyticus originating from different geographical regions demonstrates a high genetic diversity  

PubMed Central

Background Vibrio parahaemolyticus is frequently isolated from environmental and seafood samples and associated with gastroenteritis outbreakes in American, European, Asian and African countries. To distinguish between different lineages of V. parahaemolyticus various genotyping techniques have been used, incl. multilocus sequence typing (MLST). Even though some studies have already applied MLST analysis to characterize V. parahaemolyticus strain sets, these studies have been restricted to specific geographical areas (e.g. U.S. coast, Thailand and Peru), have focused exclusively on pandemic or non-pandemic pathogenic isolates or have been based on a limited strain number. Results To generate a global picture of V. parahaemolyticus genotype distribution, a collection of 130 environmental and seafood related V. parahaemolyticus isolates of different geographical origins (Sri Lanka, Ecuador, North Sea and Baltic Sea as well as German retail) was subjected to MLST analysis after modification of gyrB and recA PCRs. The V. parahaemolyticus population was composed of 82 unique Sequence Types (STs), of which 68 (82.9%) were new to the pubMLST database. After translating the in-frame nucleotide sequences into amino acid sequences, less diversity was detectable: a total of 31 different peptide Sequence Types (pSTs) with 19 (61.3%) new pSTs were generated from the analyzed isolates. Most STs did not show a global dissemination, but some were supra-regionally distributed and clusters of STs were dependent on geographical origin. On peptide level no general clustering of strains from specific geographical regions was observed, thereby the most common pSTs were found on all continents (Asia, South America and Europe) and rare pSTs were restricted to distinct countries or even geographical regions. One lineage of pSTs associated only with strains from North and Baltic Sea strains was identified. Conclusions Our study reveals a high genetic diversity in the analyzed V. parahaemolyticus strain set as well as for geographical strain subsets, with a high proportion of newly discovered alleles and STs. Differences between the subsets were identified. Our data support the postulated population structure of V. parahaemolyticus which follows the ‘epidemic’ model of clonal expansion. Application of peptide based AA-MLST allowed the identification of reliable relationships between strains.

2014-01-01

305

Molecular Evidence For High Levels of Intrapopulation Genetic Diversity in Woodrats (Neotoma Micropus)  

PubMed Central

Nucleotide sequences from the mitochondrial control region and genotypes from 5 nuclear microsatellite loci were used to examine genetic structure and infer recent (within approximately the last 3,000 years) evolutionary history of a population (549 individuals) of the southern plains woodrat (Neotoma micropus). Observed heterozygosity values ranged from 0.61 to 0.89 across microsatellite loci and systematically were lower than expected heterozygosity values (0.66–0.95). Probability of unique identity using microsatellite data was high (1 individual in 66,005,424). Fifty-three mitochondrial haplotypes were obtained from 150 individuals. FST values estimated from sequence and microsatellite data were 0.061 and 0.011, respectively, and the RST for microsatellite data was 0.007. Within-group genetic variation ranged from 93.90% to 99.99% depending on whether sequence or microsatellite data were examined. Analyses of microsatellite data suggested that all sampled individuals belonged to a single population, albeit genetically diverse. However, combined data analyses suggested the presence of low levels of substructure attributable to maternal lineages within the population. Low nucleotide-diversity values (0.007–0.010) in addition to high haplotype-diversity values (0.915–0.933) indicate a high number of closely related haplotypes, and suggest that this population may have undergone a recent expansion. However, Fu's FS statistic did not fully support this finding, because it did not reveal a significant excess of recent mutations. A phylogenetic approach using the haplotype sequence data and a combined set including both haplotype and genotype data was used to test for evolutionary patterns and history.

Mendez-Harclerode, Francisca M.; Strauss, Richard E.; Fulhorst, Charles F.; Milazzo, Mary L.; Ruthven, Donald C.; Bradley, Robert D.

2009-01-01

306

Mutational breeding and genetic engineering in the development of high grain protein content.  

PubMed

Cereals are the most important crops in the world for both human consumption and animal feed. Improving their nutritional values, such as high protein content, will have significant implications, from establishing healthy lifestyles to helping remediate malnutrition problems worldwide. Besides providing a source of carbohydrate, grain is also a natural source of dietary fiber, vitamins, minerals, specific oils, and other disease-fighting phytocompounds. Even though cereal grains contain relatively little protein compared to legume seeds, they provide protein for the nutrition of humans and livestock that is about 3 times that of legumes. Most cereal seeds lack a few essential amino acids; therefore, they have imbalanced amino acid profiles. Lysine (Lys), threonine (Thr), methionine (Met), and tryptophan (Trp) are among the most critical and are a limiting factor in many grain crops for human nutrition. Tremendous research has been put into the efforts to improve these essential amino acids. Development of high protein content can be outlined in four different approaches through manipulating seed protein bodies, modulating certain biosynthetic pathways to overproduce essential and limiting amino acids, increasing nitrogen relocation to the grain through the introduction of transgenes, and exploiting new genetic variance. Various technologies have been employed to improve protein content including conventional and mutational breeding, genetic engineering, marker-assisted selection, and genomic analysis. Each approach involves a combination of these technologies. Advancements in nutrigenomics and nutrigenetics continue to improve public knowledge at a rapid pace on the importance of specific aspects of food nutrition for optimum fitness and health. An understanding of the molecular basis for human health and genetic predisposition to certain diseases through human genomes enables individuals to personalize their nutritional requirements. It is critically important, therefore, to improve grain protein quality. Highly nutritious grain can be tailored to functional foods to meet the needs for both specific individuals and human populations as a whole. PMID:23869957

Wenefrida, Ida; Utomo, Herry S; Linscombe, Steve D

2013-12-01

307

The Sri Lankan paradox: high genetic diversity in Plasmodium vivax populations despite decreasing levels of malaria transmission.  

PubMed

SUMMARY Here we examined whether the recent dramatic decline in malaria transmission in Sri Lanka led to a major bottleneck in the local Plasmodium vivax population, with a substantial decrease in the effective population size. To this end, we typed 14 highly polymorphic microsatellite markers in 185 P. vivax patient isolates collected from 13 districts in Sri Lanka over a period of 5 years (2003-2007). Overall, we found a high degree of polymorphism, with 184 unique haplotypes (12-46 alleles per locus) and average genetic diversity (expected heterozygosity) of 0·8744. Almost 69% (n = 127) isolates had multiple-clone infections (MCI). Significant spatial and temporal differentiation (F ST  = 0·04-0·25; P?0·0009) between populations was observed. The effective population size was relatively high but showed a decline from 2003-4 to 2006-7 periods (estimated as 45 661 to 22 896 or 10 513 to 7057, depending on the underlying model used). We used three approaches - namely, mode-shift in allele frequency distribution, detection of heterozygote excess and the M-ratio statistics - to test for evidence of a recent population bottleneck but only the low values of M-ratio statistics (ranging between 0·15-0·33, mean 0·26) were suggestive of such a bottleneck. The persistence of high genetic diversity and high proportion of MCI, with little change in effective population size, despite the collapse in demographic population size of P. vivax in Sri Lanka indicates the importance of maintaining stringent control and surveillance measures to prevent resurgence. PMID:24533989

Gunawardena, Sharmini; Ferreira, Marcelo U; Kapilananda, G M G; Wirth, Dyann F; Karunaweera, Nadira D

2014-06-01

308

Viremic HIV Infected Individuals with High CD4 T Cells and Functional Envelope Proteins Show Anti-gp41 Antibodies with Unique Specificity and Function  

PubMed Central

Background CD4 T-cell decay is variable among HIV-infected individuals. In exceptional cases, CD4 T-cell counts remain stable despite high plasma viremia. HIV envelope glycoprotein (Env) properties, namely tropism, fusion or the ability to induce the NK ligand NKp44L, or host factors that modulate Env cytopathic mechanisms may be modified in such situation. Methods We identified untreated HIV-infected individuals showing non-cytopathic replication (VL>10,000 copies/mL and CD4 T-cell decay<50 cells/µL/year, Viremic Non Progressors, VNP) or rapid progression (CD4 T-cells<350 cells/µL within three years post-infection, RP). We isolated full-length Env clones and analyzed their functions (tropism, fusion activity and capacity to induce NKp44L expression on CD4 cells). Anti-Env humoral responses were also analyzed. Results Env clones isolated from VNP or RP individuals showed no major phenotypic differences. The percentage of functional clones was similar in both groups. All clones tested were CCR5-tropic and showed comparable expression and fusogenic activity. Moreover, no differences were observed in their capacity to induce NKp44L expression on CD4 T cells from healthy donors through the 3S epitope of gp41. In contrast, anti- Env antibodies showed clear functional differences: plasma from VNPs had significantly higher capacity than RPs to block NKp44L induction by autologous viruses. Consistently, CD4 T-cells isolated from VNPs showed undetectable NKp44L expression and specific antibodies against a variable region flanking the highly conserved 3S epitope were identified in plasma samples from these patients. Conversely, despite continuous antigen stimulation, VNPs were unable to mount a broad neutralizing response against HIV. Conclusions Env functions (fusion and induction of NKp44L) were similar in viremic patients with slow or rapid progression to AIDS. However, differences in humoral responses against gp41 epitopes nearby 3S sequence may contribute to the lack of CD4 T cell decay in VNPs by blocking the induction of NKp44L by gp41.

Curriu, Marta; Fausther-Bovendo, Hughes; Pernas, Maria; Massanella, Marta; Carrillo, Jorge; Cabrera, Cecilia; Lopez-Galindez, Cecilio; Clotet, Bonaventura; Debre, Patrice; Vieillard, Vincent; Blanco, Julia

2012-01-01

309

Radiation-induced meningiomas in multiple regions, showing rapid recurrence and a high MIB 1 labeling index: a case report and review of the literature  

PubMed Central

Combined chemotherapy and prophylactic cranial irradiation has improved the prognosis of children with acute leukemia. However cranial irradiation carries a latent risk of the induction of secondary intracranial tumors. We encountered a patient who developed multiple intracranial radiation-induced meningiomas (RIMs) 25 years after prophylactic cranial irradiation for the treatment of acute leukemia in childhood. The patient had 3 intracranial lesions, 1 of which showed rapid growth within 6 months; another of the tumors also enlarged within a short period. All of the tumors were surgically treated, and immunohistochemistry indicated a high MIB-1 labeling index in each of the multiple lesions. In the literature, the MIB-1 labeling indices of 27 tumors from 21 patients were examined. Among them, 12 recurrent tumors showed higher MIB-1 labeling indices compared to the MIB-1 labeling indices of the non-recurrent tumors. Overall, 11 of the patients with RIM had multiple lesions and 8 cases developed recurrence (72.7%). RIM cases with multiple lesions had higher MIB-1 labeling indices compared to the MIB-1 labeling indices of cases with single lesions. Collectively, these data showed that the MIB-1 labeling index is as important for predicting RIM recurrences, as it is for predicting sporadic meningioma (SM) recurrences. RIMs should be treated more aggressively than SMs because of their greater malignant potential.

2014-01-01

310

Characterization of oil exhibiting high ?-linolenic acid from a genetically transformed canola strain  

Microsoft Academic Search

The seed oil from a genetically transformed canola (Brassica napus) containing 43% (w\\/w) of ?-linolenic acid (G, 18?3n?6), 22% linoleic acid (L, 18?2n?6), and 16% oleic acid (O, 18?1n?9) was\\u000a evaluated. In this high ?-linolenic acid canola oil (HGCO), the predominant 18?3n?6-containing triacylglycerol (TG) molecular\\u000a species were GGL (23%), GLO (20%), and GGG (11%). In the total TG, approximately 75%

Jim-Wen Liu; Stephen DeMichele; Marti Bergana; Emil Bobik; Christine Hastilow; Lu-Te Chuang; Pradip Mukerji; Yung-Sheng Huang

2001-01-01

311

Direct 2-Arm Comparison Shows Benefit of High-Dose-Rate Brachytherapy Boost vs External Beam Radiation Therapy Alone for Prostate Cancer  

SciTech Connect

Purpose: To evaluate the outcomes of patients treated for intermediate- and high-risk prostate cancer with a single schedule of either external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDRB) boost or EBRT alone. Methods and Materials: From 2001-2006, 344 patients received EBRT with HDRB boost for definitive treatment of intermediate- or high-risk prostate cancer. The prescribed EBRT dose was 46 Gy in 23 fractions, with a HDR boost of 19.5 Gy in 3 fractions. This cohort was compared to a contemporaneously treated cohort who received EBRT to 74 Gy in 37 fractions, using a matched pair analysis. Three-dimensional conformal EBRT was used. Matching was performed using a propensity score matching technique. High-risk patients constituted 41% of the matched cohorts. Five-year clinical and biochemical outcomes were analyzed. Results: Initial significant differences in prognostic indicators between the unmatched treatment cohorts were rendered negligible after matching, providing a total of 688 patients. Median biochemical follow-up was 60.5 months. The 5-year freedom from biochemical failure was 79.8% (95% confidence interval [CI], 74.3%-85.0%) and 70.9% (95% CI, 65.4%-76.0%) for the HDRB and EBRT groups, respectively, equating to a hazard ratio of 0.59 (95% CI, 0.43-0.81, P=.0011). Interaction analyses showed no alteration in HDR efficacy when planned androgen deprivation therapy was administered (P=.95), but a strong trend toward reduced efficacy was shown compared to EBRT in high-risk cases (P=.06). Rates of grade 3 urethral stricture were 0.3% (95% CI, 0%-0.9%) and 11.8% (95% CI, 8.1%-16.5%) for EBRT and HDRB, respectively (P<.0001). No differences in clinical outcomes were observed. Conclusions: This comparison of 2 individual contemporaneously treated HDRB and EBRT approaches showed improved freedom from biochemical progression with the HDR approach. The benefit was more pronounced in intermediate- risk patients but needs to be weighed against an increased risk of urethral toxicity.

Khor, Richard [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne (Australia)] [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne (Australia); Duchesne, Gillian [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne (Australia) [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne (Australia); Monash University, Melbourne (Australia); Tai, Keen-Hun; Foroudi, Farshad; Chander, Sarat; Van Dyk, Sylvia; Garth, Margaret [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne (Australia)] [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne (Australia); Williams, Scott, E-mail: Scott.Williams@petermac.org [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne (Australia)] [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne (Australia)

2013-03-01

312

Expression of genes controlling fat deposition in two genetically diverse beef cattle breeds fed high or low silage diets  

PubMed Central

Background Both genetic background and finishing system can alter fat deposition, thus indicating their influence on adipogenic and lipogenic factors. However, the molecular mechanisms underlying fat deposition and fatty acid composition in beef cattle are not fully understood. This study aimed to assess the effect of breed and dietary silage level on the expression patterns of key genes controlling lipid metabolism in subcutaneous adipose tissue (SAT) and longissimus lumborum (LL) muscle of cattle. To that purpose, forty bulls from two genetically diverse Portuguese bovine breeds with distinct maturity rates, Alentejana and Barrosã, were selected and fed either low (30% maize silage/70% concentrate) or high silage (70% maize silage/30% concentrate) diets. Results The results suggested that enhanced deposition of fatty acids in the SAT from Barrosã bulls, when compared to Alentejana, could be due to higher expression levels of lipogenesis (SCD and LPL) and ?-oxidation (CRAT) related genes. Our results also indicated that SREBF1 expression in the SAT is increased by feeding the low silage diet. Together, these results point out to a higher lipid turnover in the SAT of Barrosã bulls when compared to Alentejana. In turn, lipid deposition in the LL muscle is related to the expression of adipogenic (PPARG and FABP4) and lipogenic (ACACA and SCD) genes. The positive correlation between ACACA expression levels and total lipids, as well trans fatty acids, points to ACACA as a major player in intramuscular deposition in ruminants. Moreover, results reinforce the role of FABP4 in intramuscular fat development and the SAT as the major site for lipid metabolism in ruminants. Conclusions Overall, the results showed that SAT and LL muscle fatty acid composition are mostly dependent on the genetic background. In addition, dietary silage level impacted on muscle lipid metabolism to a greater extent than on that of SAT, as evaluated by gene expression levels of adipogenic and lipogenic factors. Moreover, the response to diet composition evaluated through mRNA levels and fatty acid composition showed interesting differences between Alentejana and Barrosã bulls. These findings provide evidence that the genetic background should be taken into account while devising diet-based strategies to manipulate fatty acid composition of beef cattle tissues.

2013-01-01

313

Effects of the aspartic protease inhibitor from Lupinus bogotensis seeds on the growth and development of Hypothenemus hampei: an inhibitor showing high homology with storage proteins.  

PubMed

The coffee berry borer Hypothenemus hampei is a pest that causes great economic damage to coffee grains worldwide. Because the proteins consumed are digested by aspartic proteases in the insect's midgut, the inhibition of these proteases by transferring a gene encoding an aspartic protease inhibitor from Lupinus bogotensis Benth. to coffee plants could provide a promising strategy to control this pest. Five aspartic protease inhibitors from L. bogotensis (LbAPI) were accordingly purified and characterized. The gene encoding the L. bogotensis aspartic protease inhibitor (LbAPI), with the highest inhibitory activity against H. hampei, was expressed in Escherichia coli and the purified recombinant protein (rLbAPI), with a molecular mass of 15 kDa, was subsequently assessed for its ability to inhibit the aspartic protease activity present in the H. hampei midgut in vitro, as well as its effects on the growth and development of H. hampei in vivo. The in vitro experiments showed that rLbAPI was highly effective against aspartic proteases from H. hampei guts, with a half maximal inhibitory concentration (IC50) of 2.9 ?g. The in vivo experiments showed that the concentration of rLbAPI (w/w) in the artificial diet necessary to cause 50% mortality (LD50) of the larvae was 0.91%. The amino acid sequence of LbAPI had high homology (52-80%) to the seed storage proteins, vicilin and ?-conglutin, suggesting that this protein was generated by evolutionary events from a ?-conglutin precursor. Based on these results, LbAPI may have a dual function as storage protein, and as defense protein against H. hampei. These results provide a promising alternative to obtain a coffee plant resistant to H. hampei. PMID:24314849

Molina, Diana; Patiño, Luisa; Quintero, Mónica; Cortes, José; Bastos, Sara

2014-02-01

314

Two Different High Throughput Sequencing Approaches Identify Thousands of De Novo Genomic Markers for the Genetically Depleted Bornean Elephant  

PubMed Central

High throughput sequencing technologies are being applied to an increasing number of model species with a high-quality reference genome. The application and analyses of whole-genome sequence data in non-model species with no prior genomic information are currently under way. Recent sequencing technologies provide new opportunities for gathering genomic data in natural populations, laying the empirical foundation for future research in the field of conservation and population genomics. Here we present the case study of the Bornean elephant, which is the most endangered subspecies of Asian elephant and exhibits very low genetic diversity. We used two different sequencing platforms, the Roche 454 FLX (shotgun) and Illumina, GAIIx (Restriction site associated DNA, RAD) to evaluate the feasibility of the two methodologies for the discovery of de novo markers (single nucleotide polymorphism, SNPs and microsatellites) using low coverage data. Approximately, 6,683 (shotgun) and 14,724 (RAD) SNPs were detected within our elephant sequence dataset. Genotyping of a representative sample of 194 SNPs resulted in a SNP validation rate of ? 83 to 94% and 17% of the loci were polymorphic with a low diversity (Ho?=?0.057). Different numbers of microsatellites were identified through shotgun (27,226) and RAD (868) techniques. Out of all di-, tri-, and tetra-microsatellite loci, 1,706 loci had sufficient flanking regions (shotgun) while only 7 were found with RAD. All microsatellites were monomorphic in the Bornean but polymorphic in another elephant subspecies. Despite using different sample sizes, and the well known differences in the two platforms used regarding sequence length and throughput, the two approaches showed high validation rate. The approaches used here for marker development in a threatened species demonstrate the utility of high throughput sequencing technologies as a starting point for the development of genomic tools in a non-model species and in particular for a species with low genetic diversity.

Sharma, Reeta; Goossens, Benoit; Kun-Rodrigues, Celia; Teixeira, Tatiana; Othman, Nurzhafarina; Boone, Jason Q.; Jue, Nathaniel K.; Obergfell, Craig; O'Neill, Rachel J.; Chikhi, Lounes

2012-01-01

315

Pyrogallol[4]arenes show highly variable amphiphilic behavior at the air-water interface dependent upon side chain length and branching.  

PubMed

The behavior of pyrogallol[4]arenes (Pgs) substituted with normal and branched alkyl side chains at the air-water interface was examined on a Langmuir trough. The amphiphilic systems studied form stable monolayers when the straight chains are as short as n-propyl. Remarkably, n-propylpyrogallol[4]arene shows a behavior at the air-water interface that is indistinguishable from that of pyrogallolarenes bearing n-hexyl, n-nonyl, and n-dodecyl side chains. There is no report of amphiphilic side-chain-length dependence or Langmuir trough behavior for families of branched alkyl chain calixarenes or resorcinarenes. In the Pg family reported here, Pgs with straight chains (except for methyl and ethyl) behave very similarly to each other and very differently from symmetrical branched chain analogues having the same total number of carbon atoms. For example, the shortest possible branched side chain of a Pg, isopropyl-Pg, forms stable monolayers by a unique molecular subduction mechanism. Isopropyl-Pg (dimethylmethyl side chain, iPrPg) and 3-pentyl-Pg (diethylmethyl side chain, 3-pentylPg) both show high levels of organization, albeit by quite different mechanisms, at the air-water interface. Both iPrPg and 3-pentylPg differ in behavior from 4-heptylPg. Brewster angle microscopy revealed differences in organization of the Pgs that supports the mechanistic suggestions offered herein. PMID:21688332

Daschbach, Megan M; Kulikov, Oleg V; Long, Elizabeth F; Gokel, George W

2011-08-01

316

First-degree relatives of early-onset gastric cancer patients show a high risk for gastric cancer: phenotype and genotype profile.  

PubMed

First-degree relatives (FDR) of early-onset gastric cancer (EOGC) is presumed to be a population with a distinct molecular and phenotypic profile, regarding the prevalence of gastric premalignant conditions and the association with Helicobacter pylori infection and host proinflammatory gene polymorphisms. A case-control study was conducted with FDR of EOGC patients (n?=?103) and age and gender matched controls (n?=?101; ranging from spouses to neighbors and dyspeptics). Upper endoscopy was performed, Operative Link on Gastritis Assessment (OLGA) system used for staging and H. pylori (cagA and vacA) and host IL1B-511, IL1RN intron2 VNTR and IFNGR1-56 genotyping. Seventy percent of cases showed atrophy, while 19 % presented with high-stage gastritis (OLGA stage III or IV) (p?high-risk OLGA stages and dysplasia that seem to be associated with high virulence H. pylori strains and pro-inflammatory host genotypes, including a possible population-specific risk marker. FDR of EOGC patients may merit specific management through endoscopic and histopathological adequate assessment of gastric mucosa and surveillance. PMID:23887584

Marcos-Pinto, Ricardo; Dinis-Ribeiro, Mário; Carneiro, Fátima; Wen, Xiaogang; Lopes, Carlos; Figueiredo, Céu; Machado, José Carlos; Ferreira, Rui M; Reis, Celso A; Canedo, Paulo; Durães, Cecília; Ferreira, José; Pedroto, Isabel; Areias, Jorge

2013-09-01

317

Exploring the genetic and environmental etiology of high general cognitive ability in fourteen- to thirty-six-month-old twins  

Microsoft Academic Search

Although numerous theories have attempted to explain the origins of high general cognitive ability (g), the genetic and environmental etiology of high g during infancy and early childhood has not previously been investigated. We report results of a twin study of high cognitive ability at 14, 20, 24, and 36 months using twins from the more than 600 children participating

S. A. Petrill; K. Saudino; S. S. Cherny; R. N. Emde; D. W. Fulker; J. K. Hewitt; R. Plomin

1998-01-01

318

Toward a more Uniform Sampling of Human Genetic Diversity: A Survey of Worldwide Populations by High-density Genotyping  

PubMed Central

High-throughput genotyping data are useful for making inferences about human evolutionary history. However, the populations sampled to date are unevenly distributed, and some areas (e.g., South and Central Asia) have rarely been sampled in large-scale studies. To assess human genetic variation more evenly, we sampled 296 individuals from 13 worldwide populations that are not covered by previous studies. By combining these samples with a data set from our laboratory and the HapMap II samples, we assembled a final dataset of ~250,000 SNPs in 850 individuals from 40 populations. With more uniform sampling, the estimate of global genetic differentiation (FST) substantially decreases from ~16% with the HapMap II samples to ~11%. A panel of copy number variations typed in the same populations shows patterns of diversity similar to the SNP data, with highest diversity in African populations. This unique sample collection also permits new inferences about human evolutionary history. The comparison of haplotype variation among populations supports a single out-of-Africa migration event and suggests that the founding population of Eurasia may have been relatively large but isolated from Africans for a period of time. We also found a substantial affinity between populations from central Asia (Kyrgyzstani and Mongolian Buryat) and America, suggesting a central Asian contribution to New World founder populations.

Xing, Jinchuan; Watkins, W. Scott; Shlien, Adam; Walker, Erin; Huff, Chad D.; Witherspoon, David J.; Zhang, Yuhua; Simonson, Tatum S.; Weiss, Robert B.; Schiffman, Joshua D.; Malkin, David; Woodward, Scott R.; Jorde, Lynn B.

2010-01-01

319

Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutations.  

PubMed

The genetic basis for fluoroquinolone resistance was examined in 30 high-level fluoroquinolone-resistant Escherichia coli clinical isolates from Beijing, China. Each strain also demonstrated resistance to a variety of other antibiotics. PCR sequence analysis of the quinolone resistance-determining region of the topoisomerase genes (gyrA/B, parC) revealed three to five mutations known to be associated with fluoroquinolone resistance. Western blot analysis failed to demonstrate overexpression of MarA, and Northern blot analysis did not detect overexpression of soxS RNA in any of the clinical strains. The AcrA protein of the AcrAB multidrug efflux pump was overexpressed in 19 of 30 strains of E. coli tested, and all 19 strains were tolerant to organic solvents. PCR amplification of the complete acrR (regulator/repressor) gene of eight isolates revealed amino acid changes in four isolates, a 9-bp deletion in another, and a 22-bp duplication in a sixth strain. Complementation with a plasmid-borne wild-type acrR gene reduced the level of AcrA in the mutants and partially restored antibiotic susceptibility 1.5- to 6-fold. This study shows that mutations in acrR are an additional genetic basis for fluoroquinolone resistance. PMID:11302820

Wang, H; Dzink-Fox, J L; Chen, M; Levy, S B

2001-05-01

320

High prevalence of genetically diverse Borrelia bavariensis-like strains in Ixodes persulcatus from Selenge Aimag, Mongolia.  

PubMed

In Mongolia, Lyme borreliosis was first reported in 2003. To determine which Borrelia species may contribute to the occurrence of Lyme borreliosis in Mongolia, real-time PCR was conducted on 372 adult Ixodes persulcatus ticks collected in Selenge Aimag, the province with the highest incidence of human Lyme borreliosis. 24.5% of ticks were identified to be positive for Borrelia burgdorferi sensu lato DNA. Species differentiation using an SNP-based real-time PCR and multi-locus sequence analysis revealed that strains phylogenetically closely related to B. bavariensis (previously known as B. garinii OspA serotype 4) is the most prevalent species, showing an unexpectedly high genetic diversity. PMID:23084366

Scholz, Holger C; Margos, G; Derschum, H; Speck, S; Tserennorov, D; Erdenebat, N; Undraa, B; Enkhtuja, M; Battsetseg, J; Otgonchimeg, C; Otgonsuren, G; Nymadulam, B; Römer, A; Thomas, A; Essbauer, S; Wölfel, R; Kiefer, D; Zöller, L; Otgonbaatar, D; Fingerle, V

2013-02-01

321

Unique genetic profile of sporadic colorectal cancer liver metastasis versus primary tumors as defined by high-density single-nucleotide polymorphism arrays.  

PubMed

Most genetic studies in colorectal carcinomas have focused on those abnormalities that are acquired by primary tumors, particularly in the transition from adenoma to carcinoma, whereas few studies have compared the genetic abnormalities of primary versus paired metastatic samples. In this study, we used high-density 500K single-nucleotide polymorphism arrays to map the overall genetic changes present in liver metastases (n=20) from untreated colorectal carcinoma patients studied at diagnosis versus their paired primary tumors (n=20). MLH1, MSH2 and MSH6 gene expression was measured in parallel by immunohistochemistry. Overall, metastatic tumors systematically contained those genetic abnormalities observed in the primary tumor sample from the same subject. However, liver metastases from many cases (up to 8 out of 20) showed acquisition of genetic aberrations that were not found in their paired primary tumors. These new metastatic aberrations mainly consisted of (1) an increased frequency of genetic lesions of chromosomes that have been associated with metastatic colorectal carcinoma (1p, 7p, 8q, 13q, 17p, 18q, 20q) and, more interestingly, (2) acquisition of new chromosomal abnormalities (eg, losses of chromosomes 4 and 10q and gains of chromosomes 5p and 6p). These genetic changes acquired by metastatic tumors may be associated with either the metastatic process and/or adaption of metastatic cells to the liver microenvironment. Further studies in larger series of patients are necessary to dissect the specific role of each of the altered genes and chromosomal regions in the metastatic spread of colorectal tumors. PMID:22222638

Muñoz-Bellvis, Luís; Fontanillo, Celia; González-González, María; Garcia, Eva; Iglesias, Manuel; Esteban, Carmen; Gutierrez, M L; Abad, M M; Bengoechea, Oscar; De Las Rivas, Javier; Orfao, Alberto; Sayagués, J M

2012-04-01

322

High Genetic Diversity of Measles Virus, World Health Organization European Region, 2005-2006  

PubMed Central

During 2005–2006, nine measles virus (MV) genotypes were identified throughout the World Health Organization European Region. All major epidemics were associated with genotypes D4, D6, and B3. Other genotypes (B2, D5, D8, D9, G2, and H1) were only found in limited numbers of cases after importation from other continents. The genetic diversity of endemic D6 strains was low; genotypes C2 and D7, circulating in Europe until recent years, were no longer identified. The transmission chains of several indigenous MV strains may thus have been interrupted by enhanced vaccination. However, multiple importations from Africa and Asia and virus introduction into highly mobile and unvaccinated communities caused a massive spread of D4 and B3 strains throughout much of the region. Thus, despite the reduction of endemic MV circulation, importation of MV from other continents caused prolonged circulation and large outbreaks after their introduction into unvaccinated and highly mobile communities.

Brown, Kevin E.; Jin, Li; Santibanez, Sabine; Shulga, Sergey V.; Aboudy, Yair; Demchyshyna, Irina V.; Djemileva, Sultana; Echevarria, Juan E.; Featherstone, David F.; Hukic, Mirsada; Johansen, Kari; Litwinska, Bogumila; Lopareva, Elena; Lupulescu, Emilia; Mentis, Andreas; Mihneva, Zefira; Mosquera, Maria M.; Muscat, Mark; Naumova, M.A.; Nedeljkovic, Jasminka; Nekrasova, Ljubov S.; Magurano, Fabio; Fortuna, Claudia; Rebelo de Andrade, Helena; Richard, Jean-Luc; Robo, Alma; Rota, Paul A.; Samoilovich, Elena O.; Sarv, Inna; Semeiko, Galina V.; Shugayev, Nazim; Utegenova, Elmira S.; van Binnendijk, Rob; Vinner, Lasse; Waku-Kouomou, Diane; Wild, T. Fabian; Brown, David W.G.; Mankertz, Annette; Muller, Claude P.; Mulders, Mick N.

2008-01-01

323

Highly sensitive detection of organophosphorus insecticides using magnetic microbeads and genetically engineered acetylcholinesterase.  

PubMed

This work presents a biosensor for organophosphorus pesticides based on immobilisation of a highly sensitive genetically engineered acetylcholinesterase (B394) by affinity interactions on metal chelate-functionalised magnetic microbeads. The developed sensor has been compared with those based on the widely used Electric eel cholinesterase and a classical entrapment procedure in a polyvinylalcohol-based matrix. The use of the B394 enzyme allowed lowering both IC50 and LOD by a factor of 100 when compared with Electric eel enzyme sensor. The oriented and site-specific immobilisation combined with the high specificity of the B349 mutant allows a more sensitive detection of insecticides, concentrations as low as 1.31(-11)M (IC10) being detected for both pesticides chlorpyriphos-oxon and chlorfenvinphos. PMID:17826976

Istamboulie, Georges; Andreescu, Silvana; Marty, Jean-Louis; Noguer, Thierry

2007-11-30

324

Genetic Variants in EPAS1 Contribute to Adaptation to High-Altitude Hypoxia in Sherpas  

PubMed Central

Sherpas comprise a population of Tibetan ancestry in the Himalayan region that is renowned for its mountaineering prowess. The very small amount of available genetic information for Sherpas is insufficient to explain their physiological ability to adapt to high-altitude hypoxia. Recent genetic evidence has indicated that natural selection on the endothelial PAS domain protein 1 (EPAS1) gene was occurred in the Tibetan population during their occupation in the Tibetan Plateau for millennia. Tibetan-specific variations in EPAS1 may regulate the physiological responses to high-altitude hypoxia via a hypoxia-inducible transcription factor pathway. We examined three significant tag single-nucleotide polymorphisms (SNPs, rs13419896, rs4953354, and rs4953388) in the EPAS1 gene in Sherpas, and compared these variants with Tibetan highlanders on the Tibetan Plateau as well as with non-Sherpa lowlanders. We found that Sherpas and Tibetans on the Tibetan Plateau exhibit similar patterns in three EPAS1 significant tag SNPs, but these patterns are the reverse of those in non-Sherpa lowlanders. The three SNPs were in strong linkage in Sherpas, but in weak linkage in non-Sherpas. Importantly, the haplotype structured by the Sherpa-dominant alleles was present in Sherpas but rarely present in non-Sherpas. Surprisingly, the average level of serum erythropoietin in Sherpas at 3440 m was equal to that in non-Sherpas at 1300 m, indicating a resistant response of erythropoietin to high-altitude hypoxia in Sherpas. These observations strongly suggest that EPAS1 is under selection for adaptation to the high-altitude life of Tibetan populations, including Sherpas. Understanding of the mechanism of hypoxia tolerance in Tibetans is expected to provide lights to the therapeutic solutions of some hypoxia-related human diseases, such as cardiovascular disease and cancer.

Basnyat, Buddha; Ito, Michiko; Kobayashi, Nobumitsu; Katsuyama, Yoshihiko; Kubo, Keishi; Ota, Masao

2012-01-01

325

Foraging segregation and genetic divergence between geographically proximate colonies of a highly mobile seabird.  

PubMed

Foraging segregation may play an important role in the maintenance of animal diversity, and is a proposed mechanism for promoting genetic divergence within seabird species. However, little information exists regarding its presence among seabird populations. We investigated genetic and foraging divergence between two colonies of endangered Hawaiian petrels (Pterodroma sandwichensis) nesting on the islands of Hawaii and Kauai using the mitochondrial Cytochrome b gene and carbon, nitrogen and hydrogen isotope values (?(13)C, ?(15)N and ?D, respectively) of feathers. Genetic analyses revealed strong differentiation between colonies on Hawaii and Kauai, with ?(ST) = 0.50 (p < 0.0001). Coalescent-based analyses gave estimates of <1 migration event per 1,000 generations. Hatch-year birds from Kauai had significantly lower ?(13)C and ?(15)N values than those from Hawaii. This is consistent with Kauai birds provisioning chicks with prey derived from near or north of the Hawaiian Islands, and Hawaii birds provisioning young with prey from regions of the equatorial Pacific characterized by elevated ?(15)N values at the food web base. ?(15)N values of Kauai and Hawaii adults differed significantly, indicating additional foraging segregation during molt. Feather ?D varied from -69 to 53‰. This variation cannot be related solely to an isotopically homogeneous ocean water source or evaporative water loss. Instead, we propose the involvement of salt gland excretion. Our data demonstrate the presence of foraging segregation between proximately nesting seabird populations, despite high species mobility. This ecological diversity may facilitate population coexistence, and its preservation should be a focus of conservation strategies. PMID:21837410

Wiley, Anne E; Welch, Andreanna J; Ostrom, Peggy H; James, Helen F; Stricker, Craig A; Fleischer, Robert C; Gandhi, Hasand; Adams, Josh; Ainley, David G; Duvall, Fern; Holmes, Nick; Hu, Darcy; Judge, Seth; Penniman, Jay; Swindle, Keith A

2012-01-01

326

Application of somatic embryogenesis in high-value clonal forestry: Deployment, genetic control, and stability of cryopreserved clones  

Microsoft Academic Search

Summary  The most important advantage of cloning conifers by somatic embryogenesis (SE) is that the embryogenic tissue can be cryopreserved\\u000a without changing its genetic make-up and without loss of juvenility. This offers an opportunity to develop high-value clonal\\u000a varieties by defrosting and repropagating cryopreserved clones after genetic testing has shown which clones are the best performers.\\u000a In the current absence of

Y. S. Park; J. D. Barrett; J. M. Bonga

1998-01-01

327

Putative osmosensor - OsHK3b - a histidine kinase protein from rice shows high structural conservation with its ortholog AtHK1 from Arabidopsis  

PubMed Central

Prokaryotes and eukaryotes respond to various environmental stimuli using the two-component system (TCS). Essentially, it consists of membrane-bound histidine kinase (HK) which senses the stimuli and further transfers the signal to the response regulator, which in turn, regulates expression of various target genes. Recently, sequence-based genome wide analysis has been carried out in Arabidopsis and rice to identify all the putative members of TCS family. One of the members of this family i.e. AtHK1, (a putative osmosensor, hybrid-type sensory histidine kinase) is known to interact with AtHPt1 (phosphotransfer proteins) in Arabidopsis. Based on predicted rice interactome network (PRIN), the ortholog of AtHK1 in rice, OsHK3b, was found to be interacting with OsHPt2. The analysis of amino acid sequence of AtHK1 showed the presence of transmitter domain (TD) and receiver domain (RD), while OsHK3b showed presence of three conserved domains namely CHASE (signaling domain), TD, and RD. In order to elaborate on structural details of functional domains of hybrid-type HK and phosphotransfer proteins in both these genera, we have modeled them using homology modeling approach. The structural motifs present in various functional domains of the orthologous proteins were found to be highly conserved. Binding analysis of the RD domain of these sensory proteins in Arabidopsis and rice revealed the role of various residues such as histidine in HPt protein which are essential for their interaction.

Kushwaha, Hemant Ritturaj; Singla-Pareek, Sneh Lata; Pareek, Ashwani

2013-01-01

328

Putative osmosensor - OsHK3b - a histidine kinase protein from rice shows high structural conservation with its ortholog AtHK1 from Arabidopsis.  

PubMed

Prokaryotes and eukaryotes respond to various environmental stimuli using the two-component system (TCS). Essentially, it consists of membrane-bound histidine kinase (HK) which senses the stimuli and further transfers the signal to the response regulator, which in turn, regulates expression of various target genes. Recently, sequence-based genome wide analysis has been carried out in Arabidopsis and rice to identify all the putative members of TCS family. One of the members of this family i.e. AtHK1, (a putative osmosensor, hybrid-type sensory histidine kinase) is known to interact with AtHPt1 (phosphotransfer proteins) in Arabidopsis. Based on predicted rice interactome network (PRIN), the ortholog of AtHK1 in rice, OsHK3b, was found to be interacting with OsHPt2. The analysis of amino acid sequence of AtHK1 showed the presence of transmitter domain (TD) and receiver domain (RD), while OsHK3b showed presence of three conserved domains namely CHASE (signaling domain), TD, and RD. In order to elaborate on structural details of functional domains of hybrid-type HK and phosphotransfer proteins in both these genera, we have modeled them using homology modeling approach. The structural motifs present in various functional domains of the orthologous proteins were found to be highly conserved. Binding analysis of the RD domain of these sensory proteins in Arabidopsis and rice revealed the role of various residues such as histidine in HPt protein which are essential for their interaction. PMID:23869567

Kushwaha, Hemant Ritturaj; Singla-Pareek, Sneh Lata; Pareek, Ashwani

2014-08-01

329

Characterization of genetic lesions in rhabdomyosarcoma using a high-density single nucleotide polymorphism array.  

PubMed

Rhabdomyosarcoma (RMS) is a common solid tumor in childhood divided into two histological subtypes, embryonal (ERMS) and alveolar (ARMS). The ARMS subtype shows aggressive clinical behavior with poor prognosis, while the ERMS subtype has a more favorable outcome. Because of the rarity, diagnostic diversity and heterogeneity of this tumor, its etiology remains to be completely elucidated. Thus, to identify genetic alterations associated with RMS development, we performed single nucleotide polymorphism array analyses of 55 RMS samples including eight RMS-derived cell lines. The ERMS subtype was characterized by hyperploidy, significantly associated with gains of chromosomes 2, 8 and 12, whereas the majority of ARMS cases exhibited near-diploid copy number profiles. Loss of heterozygosity of 15q was detected in 45.5% of ARMS that had been unrecognized in RMS to date. Novel amplifications were also detected, including IRS2 locus in two fusion-positive tumors, and KRAS or NRAS loci in three ERMS cases. Of note, gain of 13q was significantly associated with good patient outcome in ERMS. We also identified possible application of an ALK inhibitor to RMS, as ALK amplification and frequent expression of ALK were detected in our RMS cohort. These findings enhance our understanding of the genetic mechanisms underlying RMS pathogenesis and support further studies for therapeutic development of RMS. PMID:23578105

Nishimura, Riki; Takita, Junko; Sato-Otsubo, Aiko; Kato, Motohiro; Koh, Katsuyoshi; Hanada, Ryoji; Tanaka, Yukichi; Kato, Keisuke; Maeda, Daichi; Fukayama, Masashi; Sanada, Masashi; Hayashi, Yasuhide; Ogawa, Seishi

2013-07-01

330

Chandra and XMM-Newton Observations of the Bimodal Planck-detected ClusterG345.40-39.34 showing High and Low Entropy Subcluster Cores  

NASA Astrophysics Data System (ADS)

The recent Sunyaev-Zel'dovich (SZ) surveys (from the Planck mission, the ground based SPT and ACT) have provided complete, nearly mass-limited samples of clusters of galaxies. Through extensive X-ray (Chandra and XMM-Newton) follow-up observations of these SZ cluster samples, one can characterize each cluster in terms of its total mass, X-ray luminosity, gas mass, gas temperature, entropy, central cooling time, and morphology. Here, we present results of Chandra and XMM-Newton observations of G345.40-39.34, a Planck detected cluster. We show that G345.40-39.34 is a nearby (z=0.045) double cluster with its southern subcluster presenting an interesting thermodynamical characteristic: low global gas temperature and very high central entropy. Because these two simultaneous conditions are rare, we selected clusters that exhibit similar properties to compare with G345. Finally, we present discussions of the physical processes that could lead to this unusual thermodynamic state.

Andrade-Santos, Felipe

2014-06-01

331

Mark-recapture using tetracycline and genetics reveal record-high bear density  

USGS Publications Warehouse

We used tetracycline biomarking, augmented with genetic methods to estimate the size of an American black bear (Ursus americanus) population on an island in Southeast Alaska. We marked 132 and 189 bears that consumed remote, tetracycline-laced baits in 2 different years, respectively, and observed 39 marks in 692 bone samples subsequently collected from hunters. We genetically analyzed hair samples from bait sites to determine the sex of marked bears, facilitating derivation of sex-specific population estimates. We obtained harvest samples from beyond the study area to correct for emigration. We estimated a density of 155 independent bears/100 km2, which is equivalent to the highest recorded for this species. This high density appears to be maintained by abundant, accessible natural food. Our population estimate (approx. 1,000 bears) could be used as a baseline and to set hunting quotas. The refined biomarking method for abundance estimation is a useful alternative where physical captures or DNA-based estimates are precluded by cost or logistics. Copyright ?? 2011 The Wildlife Society.

Peacock, E.; Titus, K.; Garshelis, D. L.; Peacock, M. M.; Kuc, M.

2011-01-01

332

Detection of genetic markers related to high pathogenicity in influenza by SERS.  

PubMed

We have developed a method for the detection of genetic markers associated with high pathogenicity in influenza. The assay consists of an array of 5'-thiolated ssDNA oligonucleotides immobilized on the surface of a Ag nanorod substrate that serve as capture probes for the detection of synthetic RNA sequences coding for a genetic mutation in the influenza PB1-F2 protein. Hybridization of the DNA probes to their complementary RNA sequences was detected using surface-enhanced Raman spectroscopy (SERS). Multivariate statistical analysis was used to differentiate the spectra of the complementary DNA probe-RNA target hybrids from those of the non-complementary DNA probes containing a single base pair polymorphism. Hierarchical cluster analysis (HCA) was able to distinguish with 100% accuracy the spectra of the complementary DNA probe-RNA target from the spectra of the immobilized DNA probes alone, or the DNA probes incubated with non-complementary RNA sequences. Linearity of response and limits of sensitivity of the SERS-based assays were determined using a partial least squares (PLS) regression model; detection limits computed by PLS was determined to be ~10 nM. The binding affinity of the DNA probes to their complementary RNA sequences was confirmed using enzyme-linked immunosorbent assay (ELISA); however, the detection limits observed using ELISA were approximately 10× higher (~100 nM) than those determined by PLS analysis of the SERS spectra. PMID:23833767

Negri, Pierre; Dluhy, Richard A

2013-09-01

333

Structured Parenting of Toddlers at High versus Low Genetic Risk: Two Pathways to Child Problems  

ERIC Educational Resources Information Center

Objective: Little is known about how parenting might offset genetic risk to prevent the onset of child problems during toddlerhood. We used a prospective adoption design to separate genetic and environmental influences and test whether associations between structured parenting and toddler behavior problems were conditioned by genetic risk for…

Leve, Leslie D.; Harold, Gordon T.; Ge, Xiaojia; Neiderhiser, Jenae M.; Shaw, Daniel; Scaramella, Laura V.; Reiss, David

2009-01-01

334

Television Quiz Show Simulation  

ERIC Educational Resources Information Center

This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

Hill, Jonnie Lynn

2007-01-01

335

Partnership to engage St. Louis high school students in investigative genetics.  

PubMed

The authors describe the Modern Genetics Project, based on a successful hands-on science implementation model that was developed and field-tested in St. Louis area high schools between 1992 and 1998. The project, begun in 1991, features a curriculum enhancement unit, "Modern Genetics for All Students," that combines strong scientific content, hands-on investigations, and human health applications, with reference to developing national and state science-teaching standards for this topic. The unit provides a significantly higher level of hands-on involvement throughout the school year for students than is found in traditional biology classrooms. This project aims to enhance scientific literacy among St. Louis high school students (all grades) of all learning levels and all socioeconomic, racial, and ethnic backgrounds; many of the students using the curriculum are from underrepresented minorities. This long-term project is carried out by a strong partnership among scientists at Washington University, implementation specialists from the Mathematics and Science Education Center of the Cooperating School Districts of St. Louis, project evaluators from Southern Illinois University at Edwardsville, and biology teachers at local high schools. Funding was originally from the National Institutes of Health and is now from the Howard Hughes Medical Institute. In 1998, there were 31 teachers and approximately 3,200 students participating in the project. Both quantitative and qualitative evaluations of the project during the 1995-96 and 1996-97 school years indicate that there were significant gains in knowledge and attitudes among the students of all racial, ethnic, and socioeconomic groups represented, and among both boys and girls. PMID:10219205

Moore, C J; May, V L; Abusharbain, E

1999-04-01

336

Isolation of Bacillus subtilis (chungkookjang), a poly-gamma-glutamate producer with high genetic competence.  

PubMed

A bacterium with high poly-gamma-glutamate (PGA) productivity was isolated from the traditional Korean seasoning, Chung-Kook-Jang. This bacterium could be classified as a Bacillus subtilis, but sporulation in culture was infrequent in the absence of Mn2+. It was judged to be a variety of B. subtilis and designated B. subtilis (chungkookjang). L-Glutamate significantly induced PGA production, and highly elongated PGAs were synthesized. The volumetric yield reached 13.5 mg ml(-1) in the presence of 2% L-glutamate. The D-glutamate content was over 50% in every PGA produced under the conditions used. During PGA production, glutamate racemase activity was found in the cells, suggesting that the enzyme is involved in the D-glutamate supply. Molecular sizes of PGAs were changed by the salt concentration in the medium; PGAs with comparatively low molecular masses were produced in culture media containing high concentrations of NaCl. B. subtilis (chungkookjang) harbors no plasmid and is the first B. subtilis strain reported with both naturally high PGA productivity and high genetic competence. PMID:11778891

Ashiuchi, M; Kamei, T; Baek, D H; Shin, S Y; Sung, M H; Soda, K; Yagi, T; Misono, H

2001-12-01

337

Phenotypic definition of Chiari type I malformation coupled with high-density SNP genome screen shows significant evidence for linkage to regions on chromosomes 9 and 15.  

PubMed

Chiari type I malformation (CMI; OMIM 118420) is narrowly defined when the tonsils of the cerebellum extend below the foramen magnum, leading to a variety of neurological symptoms. It is widely thought that a small posterior fossa (PF) volume, relative to the total cranial volume leads to a cramped cerebellum and herniation of the tonsils into the top of the spinal column. In a collection of magnetic resonance imagings (MRIs) from affected individuals and their family members, we measured correlations between ten cranial morphologies and estimated their heritability in these families. Correlations between bones delineating the PF and significant heritability of PF volume (0.955, P = 0.003) support the cramped PF theory and a genetic basis for this condition. In a collection of 23 families with 71 affected individuals, we performed a genome wide linkage screen of over 10,000 SNPs across the genome to identify regions of linkage to CMI. Two-point LOD scores on chromosome 15 reached 3.3 and multipoint scores in this region identified a 13 cM region with LOD scores over 1 (15q21.1-22.3). This region contains a biologically plausible gene for CMI, fibrillin-1, which is a major gene in Marfan syndrome and has been linked to Shprintzen-Goldberg syndrome, of which CMI is a distinguishing characteristic. Multipoint LOD scores on chromosome 9 maximized at 3.05, identifying a 40 cM region with LOD scores over 1 (9q21.33-33.1) and a tighter region with multipoint LOD scores over 2 that was only 8.5 cM. This linkage evidence supports a genetic role in Chiari malformation and justifies further exploration with fine mapping and investigation of candidate genes in these regions. PMID:17103432

Boyles, Abee L; Enterline, David S; Hammock, Preston H; Siegel, Deborah G; Slifer, Susan H; Mehltretter, Lorraine; Gilbert, John R; Hu-Lince, Diane; Stephan, Dietrich; Batzdorf, Ulrich; Benzel, Edward; Ellenbogen, Richard; Green, Barth A; Kula, Roger; Menezes, Arnold; Mueller, Diane; Oro', John J; Iskandar, Bermans J; George, Timothy M; Milhorat, Thomas H; Speer, Marcy C

2006-12-15

338

Impact of virtual learning environment (VLE): A technological approach to genetics teaching on high school students' content knowledge, self-efficacy and career goal aspirations  

NASA Astrophysics Data System (ADS)

This study examines the effect of a technology-based instructional tool 'Geniverse' on the content knowledge gains, Science Self-Efficacy, Technology Self-Efficacy, and Career Goal Aspirations among 283 high school learners. The study was conducted in four urban high schools, two of which have achieved Adequate Yearly Progress (AYP) and two have not. Students in both types of schools were taught genetics either through Geniverse, a virtual learning environment or Dragon genetics, a paper-pencil activity embedded in traditional instructional method. Results indicated that students in all schools increased their knowledge of genetics using either type of instructional approach. Students who were taught using Geniverse demonstrated an advantage for genetics knowledge although the effect was small. These increases were more pronounced in the schools that had been meeting the AYP goal. The other significant effect for Geniverse was that students in the technology-enhanced classrooms increased in science Self-Efficacy while students in the non-technology enhanced classrooms decreased. In addition, students from Non-AYP schools showed an improvement in Science and Technology Self-Efficacy; however the effects were small. The implications of these results for the future use of technology-enriched classrooms were discussed. Keywords: Technology-based instruction, Self-Efficacy, career goals and Adequate Yearly Progress (AYP).

Kandi, Kamala M.

339

Effects of recent and past climatic shifts on the genetic structure of the high mountain yellow-spotted ringlet butterfly Erebia manto (Lepidoptera, Satyrinae): a conservation problem.  

PubMed

Mountain species have evolved important genetic differentiation due to past climatic fluctuations. The genetic uniqueness of many of these lineages is now at risk due to global warming. Here, we analyse allozyme polymorphisms of 1306 individuals (36 populations) of the mountain butterfly Erebia manto and perform Species Distribution Models (SDMs). As a consensus of analyses, we obtained six most likely genetic clusters: (i) Pyrenees with Massif Central; (ii) Vosges; (iii-v) Alps including the Slovakian Carpathians; (vi) southern Carpathians. The Vosges population showed the strongest genetic split from all other populations, being almost as strong as the split between E. manto and its sister species Erebia eriphyle. The distinctiveness of the Pyrenees-Massif Central group and of the southern Carpathians group from all other groups is also quite high. All three groups are assumed to have survived more than one full glacial-interglacial cycle close to their current distributions with up-hill and down-slope shifts conforming climatic conditions. In contrast with these well-differentiated groups, the three groups present in the Alps and the Slovakian Carpathians show a much shallower genetic structure and thus also should be of a more recent origin. As predicted by our SDM projections, rising temperatures will strongly impact the distribution of E. manto. While the populations in the Alps are predicted to shrink, the survival of the three lineages present here should not be at risk. The situation of the three other lineages is quite different. All models predict the extinction of the Vosges lineage in the wake of global warming, and also the southern Carpathians and Pyrenees-Massif Central lineages might be at high risk to disappear. Thus, albeit global warming will therefore be unlikely to threaten E. manto as a species, an important proportion of the species' intraspecific differentiation and thus uniqueness might be lost. PMID:24753365

Schmitt, Thomas; Habel, Jan Christian; Rödder, Dennis; Louy, Dirk

2014-07-01

340

High levels of genetic differentiation and selfing in the Brazilian cerrado fruit tree Dipteryx alata Vog. (Fabaceae).  

PubMed

Dipteryx alata is a native fruit tree species of the cerrado (Brazilian savanna) that has great economic potential because of its multiple uses. Knowledge of how the genetic variability of this species is organized within and among populations would be useful for genetic conservation and breeding programs. We used nine simple sequence repeat (SSR) primers developed for Dipteryx odorata to evaluate the genetic structure of three populations of D. alata located in central Brazil based on a leaf sample analysis from 101 adults. The outcrossing rate was evaluated using 300 open-pollinated offspring from 25 seed-trees. Pollen dispersal was measured by parentage analysis. We used spatial genetic structure (SGS) to test the minimal distance for harvesting seeds in conservation and breeding programs. Our data indicate that the populations studied had a high degree of genetic diversity and population structure, as suggested by the high level of divergence among populations . The estimated outcrossing rate suggested a mixed mating system, and the intrapopulation fixation index was influenced by SGS. We conclude that seed harvesting for genetic conservation and breeding programs requires a minimum distance between trees of 196 m to avoid collecting seeds from related seed-trees. PMID:21637609

Tarazi, Roberto; Moreno, Maria Andréia; Gandara, Flávio Bertin; Ferraz, Elza Martins; Moraes, Mário Luiz Teixeira; Vinson, Christina Cleo; Ciampi, Ana Yamaguishi; Vencovsky, Roland; Kageyama, Paulo Yoshio

2010-01-01

341

High levels of genetic differentiation and selfing in the Brazilian cerrado fruit tree Dipteryx alata Vog. (Fabaceae)  

PubMed Central

Dipteryx alata is a native fruit tree species of the cerrado (Brazilian savanna) that has great economic potential because of its multiple uses. Knowledge of how the genetic variability of this species is organized within and among populations would be useful for genetic conservation and breeding programs. We used nine simple sequence repeat (SSR) primers developed for Dipteryx odorata to evaluate the genetic structure of three populations of D. alata located in central Brazil based on a leaf sample analysis from 101 adults. The outcrossing rate was evaluated using 300 open-pollinated offspring from 25 seed-trees. Pollen dispersal was measured by parentage analysis. We used spatial genetic structure (SGS) to test the minimal distance for harvesting seeds in conservation and breeding programs. Our data indicate that the populations studied had a high degree of genetic diversity and population structure, as suggested by the high level of divergence among populations . The estimated outcrossing rate suggested a mixed mating system, and the intrapopulation fixation index was influenced by SGS. We conclude that seed harvesting for genetic conservation and breeding programs requires a minimum distance between trees of 196 m to avoid collecting seeds from related seed-trees.

2010-01-01

342

Reduced genetic variance among high fitness individuals: inferring stabilizing selection on male sexual displays in Drosophila serrata.  

PubMed

Directional selection is prevalent in nature, yet phenotypes tend to remain relatively constant, suggesting a limit to trait evolution. However, the genetic basis of this limit is unresolved. Given widespread pleiotropy, opposing selection on a trait may arise from the effects of the underlying alleles on other traits under selection, generating net stabilizing selection on trait genetic variance. These pleiotropic costs of trait exaggeration may arise through any number of other traits, making them hard to detect in phenotypic analyses. Stabilizing selection can be inferred, however, if genetic variance is greater among low- compared to high-fitness individuals. We extend a recently suggested approach to provide a direct test of a difference in genetic variance for a suite of cuticular hydrocarbons (CHCs) in Drosophila serrata. Despite strong directional sexual selection on these traits, genetic variance differed between high- and low-fitness individuals and was greater among the low-fitness males for seven of eight CHCs, significantly more than expected by chance. Univariate tests of a difference in genetic variance were nonsignificant but likely have low power. Our results suggest that further CHC exaggeration in D. serrata in response to sexual selection is limited by pleiotropic costs mediated through other traits. PMID:23025601

Sztepanacz, Jacqueline L; Rundle, Howard D

2012-10-01

343

A novel esterase from Burkholderia gladioli which shows high deacetylation activity on cephalosporins is related to beta-lactamases and DD-peptidases.  

PubMed

The gene (estB) encoding for a novel esterase (EstB) from Burkholderia gladioli (formerly Pseudomonas marginata) NCPPB 1891 was cloned in Escherichia coli. Sequence analysis showed an open reading frame encoding a polypeptide of 392 amino acid residues, with a molecular mass of about 42 kDa. Comparison of the amino acid sequence with those of other homologous enzymes indicated homologies to beta-lactamases, penicillin binding proteins and DD-peptidases. The serine residue (Ser(75)) which is located within a present class A beta-lactamase motif ([F,Y]-X-[L,I,V,M,F,Y]-X-S-[T,V]-X-K-X-X-X-X-[A,G,L]-X-X-[L,C]) was identified by site-directed mutagenesis to represent the active nucleophile. A second serine residue (Ser(149)) which is located within a G-x-S-x-G motif which is typically found in esterases and lipases was demonstrated not to play a significant role in enzyme function. The estB gene was overexpressed in E. coli using a tac promoter-based expression system. Investigation of EstB protein with respect to the ability to hydrolyse beta-lactam substrates clearly demonstrated that this protein has no beta-lactamase activity. The recombinant enzyme is active on triglycerides and on nitrophenyl esters with acyl chain lengths up to C6. The preference for short chain length substrates indicated that EstB is a typical carboxylesterase. As a special feature EstB esterase was found to have high deacetylation activity on cephalosporin derivatives. PMID:11472796

Petersen, E I; Valinger, G; Sölkner, B; Stubenrauch, G; Schwab, H

2001-07-26

344

Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia  

PubMed Central

SUMMARY Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL, and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2 and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2 negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.

Roberts, Kathryn G.; Morin, Ryan D.; Zhang, Jinghui; Hirst, Martin; Zhao, Yongjun; Su, Xiaoping; Chen, Shann-Ching; Payne-Turner, Debbie; Churchman, Michelle; Harvey, Richard C.; Chen, Xiang; Kasap, Corynn; Yan, Chunhua; Becksfort, Jared; Finney, Richard P.; Teachey, David T.; Maude, Shannon L.; Tse, Kane; Moore, Richard; Jones, Steven; Mungall, Karen; Birol, Inanc; Edmonson, Michael N.; Hu, Ying; Buetow, Kenneth E.; Chen, I-Ming; Carroll, William L.; Wei, Lei; Ma, Jing; Kleppe, Maria; Levine, Ross L.; Garcia-Manero, Guillermo; Larsen, Eric; Shah, Neil P.; Devidas, Meenakshi; Reaman, Gregory; Smith, Malcolm; Paugh, Steven W.; Evans, William E.; Grupp, Stephan A.; Jeha, Sima; Pui, Ching-Hon; Gerhard, Daniela S.; Downing, James R.; Willman, Cheryl L.; Loh, Mignon; Hunger, Stephen P.; Marra, Marco; Mullighan, Charles G.

2012-01-01

345

Springback Control of Sheet Metal Forming Based on High Dimension Model Representation and Genetic Algorithm  

NASA Astrophysics Data System (ADS)

Springback is related to multi-factors in the process of metal forming. In order to construct an accurate metamodel between technical parameters and springback, a general set of quantitative model assessment and analysis tool, termed high dimension model representations (HDMR), is applied to building metamodel. Genetic algorithm is also integrated for optimization based on metamodel. Compared with widely used metamodeling techniques, the most remarkable advantage of this method is its capacity to dramatically reduce sampling effort for learning the input-output behavior from exponential growth to polynomial level. In this work, the blank holding forces (BHFs) and corresponding key time are design variables. The final springback is well controlled by the HDMR-based metamodeling technique.

Long, Tang; Hu, Wang; Yong, Cai; Lichen, Mao; Guangyao, Li

2011-08-01

346

Genetic data provide evidence for wind-mediated transmission of highly pathogenic avian influenza.  

PubMed

Outbreaks of highly pathogenic avian influenza in poultry can cause severe economic damage and represent a public health threat. Development of efficient containment measures requires an understanding of how these influenza viruses are transmitted between farms. However, the actual mechanisms of interfarm transmission are largely unknown. Dispersal of infectious material by wind has been suggested, but never demonstrated, as a possible cause of transmission between farms. Here we provide statistical evidence that the direction of spread of avian influenza A(H7N7) is correlated with the direction of wind at date of infection. Using detailed genetic and epidemiological data, we found the direction of spread by reconstructing the transmission tree for a large outbreak in the Netherlands in 2003. We conservatively estimate the contribution of a possible wind-mediated mechanism to the total amount of spread during this outbreak to be around 18%. PMID:23230058

Ypma, Rolf J F; Jonges, Marcel; Bataille, Arnaud; Stegeman, Arjan; Koch, Guus; van Boven, Michiel; Koopmans, Marion; van Ballegooijen, W Marijn; Wallinga, Jacco

2013-03-01

347

A High-Performance Genetic Algorithm: Using Traveling Salesman Problem as a Case  

PubMed Central

This paper presents a simple but efficient algorithm for reducing the computation time of genetic algorithm (GA) and its variants. The proposed algorithm is motivated by the observation that genes common to all the individuals of a GA have a high probability of surviving the evolution and ending up being part of the final solution; as such, they can be saved away to eliminate the redundant computations at the later generations of a GA. To evaluate the performance of the proposed algorithm, we use it not only to solve the traveling salesman problem but also to provide an extensive analysis on the impact it may have on the quality of the end result. Our experimental results indicate that the proposed algorithm can significantly reduce the computation time of GA and GA-based algorithms while limiting the degradation of the quality of the end result to a very small percentage compared to traditional GA.

Tsai, Chun-Wei; Tseng, Shih-Pang; Yang, Chu-Sing

2014-01-01

348

High-resolution raster scan optoacoustic mesoscopy of genetically modified drosophila pupae  

NASA Astrophysics Data System (ADS)

Optoacoutic mesoscopy aims to bridge the gap between optoacoustic microscopy and optoacoustic tomography. We have developed a setup for optoacoustic mesoscopy where we use a high frequency, high numerical aperture spherically focused ultrasound transducer, with a wide bandwidth of 25-125 MHz. The excitation is performed using a diode laser capable of >500 ?J/pulse, 1.8ns pulse width, 1.4 kHz pulse repetition rate, at 515 nm. The system is capable to penetrate more than 5 mm with a resolution of 7 ?m axially and 30 ?m transversally. Using high-speed stages and scanning the transducer in a quasi-continuous mode, a field of view of 2×2 mm2 is scanned in less than 2 minutes. The system is suitable for imaging biological samples that have a diameter of 1-5 mm; zebrafish, drosophila melanogaster, and thin biological samples such as the mouse ear and mouse extremities. We have used our mesoscopic setup to generate 3- dimensional images of genetically modified drosophila fly, and drosophila pupae expressing GFP from the wings, high resolution images were generated in both cases, in the fly we can see the wings, the legs, the eyes, and the shape of the body. In the pupae the outline of the pupae, the spiracles at both ends and a strong signal corresponding to the location of the future wings are observed.

Omar, Murad; Gateau, Jérôme; Ntziachristos, Vasilis

2014-03-01

349

Plasmid Metagenome Reveals High Levels of Antibiotic Resistance Genes and Mobile Genetic Elements in Activated Sludge  

PubMed Central

The overuse or misuse of antibiotics has accelerated antibiotic resistance, creating a major challenge for the public health in the world. Sewage treatment plants (STPs) are considered as important reservoirs for antibiotic resistance genes (ARGs) and activated sludge characterized with high microbial density and diversity facilitates ARG horizontal gene transfer (HGT) via mobile genetic elements (MGEs). However, little is known regarding the pool of ARGs and MGEs in sludge microbiome. In this study, the transposon aided capture (TRACA) system was employed to isolate novel plasmids from activated sludge of one STP in Hong Kong, China. We also used Illumina Hiseq 2000 high-throughput sequencing and metagenomics analysis to investigate the plasmid metagenome. Two novel plasmids were acquired from the sludge microbiome by using TRACA system and one novel plasmid was identified through metagenomics analysis. Our results revealed high levels of various ARGs as well as MGEs for HGT, including integrons, transposons and plasmids. The application of the TRACA system to isolate novel plasmids from the environmental metagenome, coupled with subsequent high-throughput sequencing and metagenomic analysis, highlighted the prevalence of ARGs and MGEs in microbial community of STPs.

Zhang, Tong; Zhang, Xu-Xiang; Ye, Lin

2011-01-01

350

Genetic Analysis of High Bone Mass Cases from the BARCOS Cohort of Spanish Postmenopausal Women.  

PubMed

The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM. PMID:24736728

Sarrión, Patricia; Mellibovsky, Leonardo; Urreizti, Roser; Civit, Sergi; Cols, Neus; García-Giralt, Natàlia; Yoskovitz, Guy; Aranguren, Alvaro; Malouf, Jorge; Di Gregorio, Silvana; Río, Luís Del; Güerri, Roberto; Nogués, Xavier; Díez-Pérez, Adolfo; Grinberg, Daniel; Balcells, Susana

2014-01-01

351

Homemade Laser Show  

NSDL National Science Digital Library

With a laser pointer and some household items, learners can create their own laser light show. They can explore diffuse reflection, refraction and diffraction. The webpage includes a video which shows how to set up the activity and also includes scientific explanation. Because this activity involves lasers, it requires adult supervision.

Houston, Children'S M.

2011-01-01

352

Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology  

PubMed Central

The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP)-arrays to define those chromosomal regions which most commonly harbour copy number (CN) alterations and loss of heterozygozity (LOH) in a series of 20 PDAC tumors and we correlated the corresponding genetic profiles with the most relevant clinical and histopathological features of the disease. Overall our results showed that primary PDAC frequently display (>70%) extensive gains of chromosomes 1q, 7q, 8q and 20q, together with losses of chromosomes 1p, 9p, 12q, 17p and 18q, such chromosomal regions harboring multiple cancer- and PDAC-associated genes. Interestingly, these alterations clustered into two distinct genetic profiles characterized by gains of the 2q14.2, 3q22.1, 5q32, 10q26.13, 10q26.3, 11q13.1, 11q13.3, 11q13.4, 16q24.1, 16q24.3, 22q13.1, 22q13.31 and 22q13.32 chromosomal regions (group 1; n?=?9) versus gains at 1q21.1 and losses of the 1p36.11, 6q25.2, 9p22.1, 9p24.3, 17p13.3 and Xp22.33 chromosomal regions (group 2; n?=?11). From the clinical and histopathological point of view, group 1 cases were associated with smaller and well/moderately-differentiated grade I/II PDAC tumors, whereas and group 2 PDAC displayed a larger size and they mainly consisted of poorly-differentiated grade III carcinomas. These findings confirm the cytogenetic complexity and heterogenity of PDAC and provide evidence for the association between tumor cytogenetics and its histopathological features. In addition, we also show that the altered regions identified harbor multiple cancer associate genes that deserve further investigation to determine their relevance in the pathogenesis of PDAC.

Gutierrez, Maria Laura; Munoz-Bellvis, Luis; Abad, Maria del Mar; Bengoechea, Oscar; Gonzalez-Gonzalez, Maria

2011-01-01

353

A combined proteomic and genetic analysis of the highly variable platelet proteome: from plasmatic proteins and SNPs.  

PubMed

High biological variation in protein expression represents a major challenge in clinical proteomics. In a study based on 2D-DIGE, we found that the standardised abundance of only a few proteins varied by more than 50%. While some of the highest variable proteins in platelets of 52 healthy elderly were of plasmatic origin, such as albumin or haptoglobin, absence of several other high-abundant plasma proteins strongly suggests that plasma-derived proteins represent an integral part of the platelet proteome. Amongst the highly variable platelet-derived proteins, two spots were both identified as GSTO1 and assigned to either the wild-type or mutant isoform of SNP A140D. Remarkably, when the spots were considered within the respective genotype groups, their CV decreased to about the median variation. Albeit 2D-DIGE allowed correct genotyping, two individuals seemed to be GSTO1*A140 deficient. Probing 2D-Western blots with novel mAb, however, detected A140 protein as additional spot at pH 8.1, caused by the SNPs E155del and E208K. In contrast to previous studies, we show that GSTO1 protein is expressed in vivo, despite the deletion E155. Our data indicate that incorporation of exogenous proteins and genetic polymorphisms of endogenous proteins represent the main source of extreme biological variation in the platelet proteome. PMID:22885077

Veitinger, Michael; Umlauf, Ellen; Baumgartner, Roland; Badrnya, Sigrun; Porter, Jonny; Lamont, John; Gerner, Christopher; Gruber, Christian W; Oehler, Rudolf; Zellner, Maria

2012-10-22

354

Antiviral resistance among highly pathogenic influenza A (H5N1) viruses isolated worldwide in 2002-2012 shows need for continued monitoring  

PubMed Central

Highly pathogenic (HP) H5N1 influenza viruses are evolving pathogens with the potential to cause sustained human-to-human transmission and pandemic virus spread. Specific antiviral drugs can play an important role in the early stages of a pandemic, but the emergence of drug-resistant variants can limit control options. The available data on the susceptibility of HP H5N1 influenza viruses to neuraminidase (NA) inhibitors and adamantanes is scarce, and there is no extensive analysis. Here, we systematically examined the prevalence of NA inhibitor and adamantane resistance among HP H5N1 influenza viruses that circulated worldwide during 2002–2012. The phenotypic fluorescence-based assay showed that both human and avian HP H5N1 viruses are susceptible to NA inhibitors oseltamivir and zanamivir with little variability over time and ~5.5-fold less susceptibility to oseltamivir of viruses of hemagglutinin (HA) clade 2 than of clade 1. Analysis of available sequence data revealed a low incidence of NA inhibitor–resistant variants. The established markers of NA inhibitor resistance (E119A, H274Y, and N294S, N2 numbering) were found in 2.4% of human and 0.8% of avian isolates, and the markers of reduced susceptibility (I117V, K150N, I222V/T/K, and S246N) were found in 0.8% of human and 2.9 % of avian isolates. The frequency of amantadine-resistant variants was higher among human (62.2%) than avian (31.6%) viruses with disproportionate distribution among different HA clades. As in human isolates, avian H5N1 viruses carry double L26I and S31N M2 mutations more often than a single S31N mutation. Overall, both human and avian HP H5N1 influenza viruses are susceptible to NA inhibitors; some proportion is still susceptible to amantadine in contrast to ~100% amantadine resistance among currently circulating seasonal human H1N1 and H3N2 viruses. Continued antiviral susceptibility monitoring of H5N1 viruses is needed to maintain therapeutic approaches for control of disease.

Govorkova, Elena A.; Baranovich, Tatiana; Seiler, Patrick; Armstrong, Jianling; Burnham, Andrew; Guan, Yi; Peiris, Malik; Webby, Richard J.; Webster, Robert G.

2013-01-01

355

“They Don’t Teach This in High School”: An Examination of the Portrayal of Teenage Pregnancy in the MTV Television Show 16 and Pregnant  

Microsoft Academic Search

This paper examines the depiction of teenage pregnancy on the MTV show 16 and Pregnant- a documentary style reality show. Using a qualitative textual analysis the author examines how he teen girls describe themselves, whether contraception was discussed and if it was how so, what options the teens discussed in regards to the pregnancy, the role of the father of

Elizabeth F. Smith

2012-01-01

356

High Genetic Diversity and Fine-Scale Spatial Structure in the Marine Flagellate Oxyrrhis marina (Dinophyceae) Uncovered by Microsatellite Loci  

PubMed Central

Free-living marine protists are often assumed to be broadly distributed and genetically homogeneous on large spatial scales. However, an increasing application of highly polymorphic genetic markers (e.g., microsatellites) has provided evidence for high genetic diversity and population structuring on small spatial scales in many free-living protists. Here we characterise a panel of new microsatellite markers for the common marine flagellate Oxyrrhis marina. Nine microsatellite loci were used to assess genotypic diversity at two spatial scales by genotyping 200 isolates of O. marina from 6 broad geographic regions around Great Britain and Ireland; in one region, a single 2 km shore line was sampled intensively to assess fine-scale genetic diversity. Microsatellite loci resolved between 1–6 and 7–23 distinct alleles per region in the least and most variable loci respectively, with corresponding variation in expected heterozygosities (He) of 0.00–0.30 and 0.81–0.93. Across the dataset, genotypic diversity was high with 183 genotypes detected from 200 isolates. Bayesian analysis of population structure supported two model populations. One population was distributed across all sampled regions; the other was confined to the intensively sampled shore, and thus two distinct populations co-occurred at this site. Whilst model-based analysis inferred a single UK-wide population, pairwise regional FST values indicated weak to moderate population sub-division (0.01–0.12), but no clear correlation between spatial and genetic distance was evident. Data presented in this study highlight extensive genetic diversity for O. marina; however, it remains a substantial challenge to uncover the mechanisms that drive genetic diversity in free-living microorganisms.

Lowe, Chris D.; Montagnes, David J. S.; Martin, Laura E.; Watts, Phillip C.

2010-01-01

357

A Holographic Road Show.  

ERIC Educational Resources Information Center

Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

Kirkpatrick, Larry D.; Rugheimer, Mac

1979-01-01

358

High altitude genetic adaptation in Tibetans: no role of increased hemoglobin-oxygen affinity.  

PubMed

High altitude exerts selective evolutionary pressure primarily due to its hypoxic environment, resulting in multiple adaptive responses. High hemoglobin-oxygen affinity is postulated to be one such adaptive change, which has been reported in Sherpas of the Himalayas. Tibetans have lived on the Qinghai-Tibetan plateau for thousands of years and have developed unique phenotypes, such as protection from polycythemia which has been linked to PDH2 mutation, resulting in the downregulation of the HIF pathway. In order to see if Tibetans also developed high hemoglobin-oxygen affinity as a part of their genetic adaptation, we conducted this study assessing hemoglobin-oxygen affinity and their fetal hemoglobin levels in Tibetan subjects from 3 different altitudes. We found normal hemoglobin-oxygen affinity in all subjects, fetal hemoglobin levels were normal in all except one and no hemoglobin variants in any of the subjects. We conclude that increased hemoglobin-oxygen affinity or increased fetal hemoglobin are not adaptive phenotypes of the Tibetan highlanders. PMID:24618341

Tashi, Tsewang; Feng, Tang; Koul, Parvaiz; Amaru, Ricardo; Hussey, Dottie; Lorenzo, Felipe R; RiLi, Ge; Prchal, Josef T

2014-01-01

359

Genetic Signatures Reveal High-Altitude Adaptation in a Set of Ethiopian Populations  

PubMed Central

The Tibetan and Andean Plateaus and Ethiopian highlands are the largest regions to have long-term high-altitude residents. Such populations are exposed to lower barometric pressures and hence atmospheric partial pressures of oxygen. Such “hypobaric hypoxia” may limit physical functional capacity, reproductive health, and even survival. As such, selection of genetic variants advantageous to hypoxic adaptation is likely to have occurred. Identifying signatures of such selection is likely to help understanding of hypoxic adaptive processes. Here, we seek evidence of such positive selection using five Ethiopian populations, three of which are from high-altitude areas in Ethiopia. As these populations may have been recipients of Eurasian gene flow, we correct for this admixture. Using single-nucleotide polymorphism genotype data from multiple populations, we find the strongest signal of selection in BHLHE41 (also known as DEC2 or SHARP1). Remarkably, a major role of this gene is regulation of the same hypoxia response pathway on which selection has most strikingly been observed in both Tibetan and Andean populations. Because it is also an important player in the circadian rhythm pathway, BHLHE41 might also provide insights into the mechanisms underlying the recognized impacts of hypoxia on the circadian clock. These results support the view that Ethiopian, Andean, and Tibetan populations living at high altitude have adapted to hypoxia differently, with convergent evolution affecting different genes from the same pathway.

Huerta-Sanchez, Emilia; DeGiorgio, Michael; Pagani, Luca; Tarekegn, Ayele; Ekong, Rosemary; Antao, Tiago; Cardona, Alexia; Montgomery, Hugh E.; Cavalleri, Gianpiero L.; Robbins, Peter A.; Weale, Michael E.; Bradman, Neil; Bekele, Endashaw; Kivisild, Toomas; Tyler-Smith, Chris; Nielsen, Rasmus

2013-01-01

360

Genetic signatures reveal high-altitude adaptation in a set of ethiopian populations.  

PubMed

The Tibetan and Andean Plateaus and Ethiopian highlands are the largest regions to have long-term high-altitude residents. Such populations are exposed to lower barometric pressures and hence atmospheric partial pressures of oxygen. Such "hypobaric hypoxia" may limit physical functional capacity, reproductive health, and even survival. As such, selection of genetic variants advantageous to hypoxic adaptation is likely to have occurred. Identifying signatures of such selection is likely to help understanding of hypoxic adaptive processes. Here, we seek evidence of such positive selection using five Ethiopian populations, three of which are from high-altitude areas in Ethiopia. As these populations may have been recipients of Eurasian gene flow, we correct for this admixture. Using single-nucleotide polymorphism genotype data from multiple populations, we find the strongest signal of selection in BHLHE41 (also known as DEC2 or SHARP1). Remarkably, a major role of this gene is regulation of the same hypoxia response pathway on which selection has most strikingly been observed in both Tibetan and Andean populations. Because it is also an important player in the circadian rhythm pathway, BHLHE41 might also provide insights into the mechanisms underlying the recognized impacts of hypoxia on the circadian clock. These results support the view that Ethiopian, Andean, and Tibetan populations living at high altitude have adapted to hypoxia differently, with convergent evolution affecting different genes from the same pathway. PMID:23666210

Huerta-Sánchez, Emilia; Degiorgio, Michael; Pagani, Luca; Tarekegn, Ayele; Ekong, Rosemary; Antao, Tiago; Cardona, Alexia; Montgomery, Hugh E; Cavalleri, Gianpiero L; Robbins, Peter A; Weale, Michael E; Bradman, Neil; Bekele, Endashaw; Kivisild, Toomas; Tyler-Smith, Chris; Nielsen, Rasmus

2013-08-01

361

Trade Show Managers  

Microsoft Academic Search

Trade show management is a multi-faceted field, requiring a breadth of skills on the part of those engaged in the craft. Whether they go by the title of Show Manager, Director of Marketing, Vice President of Meetings\\/Conventions, or Director of Meetings\\/Conventions, these professionals work with exhibitors, attendees, and service providers to produce their events. The managers of the 200 largest

Susan Gregory; Deborah Breiter

2001-01-01

362

High genetic diversity and connectivity in a common mesopelagic fish of the Southern Ocean: The myctophid Electrona antarctica  

NASA Astrophysics Data System (ADS)

Many marine pelagic fish species are characterized by subtle but complex genetic structures and dynamics, depending on the balance between current-mediated larval dispersal and adult active homing behavior. The circumantarctic continuous hydrodynamics of the Southern Ocean is a prime example of a system with a potentially great homogenizing effect among distant populations. We tested this hypothesis by analyzing the contemporary genetic relatedness among populations of a common and endemic mesopelagic fish of the Southern Ocean, Electrona antarctica. Seven newly developed species-specific microsatellite markers were used to investigate patterns of neutral genetic variation in 11 geographically widespread samples ( n=400) collected between 2006 and 2007. We detected a very high level of genetic diversity, but a striking lack of genetic differentiation on a circumantarctic scale, indicating large effective population sizes complemented with high levels of admixture. These findings underscore the large scale homogenizing effect of the Southern Coastal Current, leading to a high level of connectivity of our model species in the Southern Ocean, which is congruent with its huge biomass and central role in marine food webs. As an important Antarctic marine living resource this species may as such be managed on a circumantarctic level, although the demographic stability of this stock should be estimated urgently.

Van de Putte, A. P.; Van Houdt, J. K. J.; Maes, G. E.; Hellemans, B.; Collins, M. A.; Volckaert, F. A. M.

2012-01-01

363

Genome-wide genetic variations are highly correlated with proximal DNA methylation patterns  

PubMed Central

5-methyl-cytosines at CpG sites frequently mutate into thymines, accounting for a large proportion of spontaneous point mutations. The repair system would leave substantial numbers of errors in neighboring regions if the synthesis of erased gaps around deaminated 5-methyl-cytosines is error-prone. Indeed, we identified an unexpected genome-wide role of the CpG methylation state as a major determinant of proximal natural genetic variation. Specifically, 507 Mbp (?18%) of the human genome was within 10 bp of a CpG site; in these regions, the single nucleotide polymorphism (SNP) rate significantly increased by ?50% (P < 10?566 by a two-proportion z-test) if the neighboring CpG sites are methylated. To reconfirm this finding in another vertebrate, we compared six single-base resolution methylomes in two inbred medaka (Oryzias latipes) strains with sufficient genetic divergence (3.4%). We found that the SNP rate also increased by ?50% (P < 10?2170), and the substitution rates in all dinucleotides increased simultaneously (P < 10?441) around methylated CpG sites. In the hypomethylated regions, the “CGCG” motif was significantly enriched (P < 10?680) and evolutionarily conserved (P = ? 0.203%), and slow CpG deamination rather than fast CpG gain was seen, indicating a