Population genetic structure and direct observations reveal sex-reversed patterns of dispersal in a cooperative bird.

PubMed

Harrison, Xavier A; York, Jennifer E; Young, Andrew J

2014-12-01

Sex-biased dispersal is pervasive and has diverse evolutionary implications, but the fundamental drivers of dispersal sex biases remain unresolved. This is due in part to limited diversity within taxonomic groups in the direction of dispersal sex biases, which leaves hypothesis testing critically dependent upon identifying rare reversals of taxonomic norms. Here, we use a combination of observational and genetic data to demonstrate a rare reversal of the avian sex bias in dispersal in the cooperatively breeding white-browed sparrow weaver (Plocepasser mahali). Direct observations revealed that (i) natal philopatry was rare, with both sexes typically dispersing locally to breed, and (ii), unusually for birds, males bred at significantly greater distances from their natal group than females. Population genetic analyses confirmed these patterns, as (i) corrected Assignment index (AIc), FST tests and isolation-by-distance metrics were all indicative of longer dispersal distances among males than females, and (ii) spatial autocorrelation analysis indicated stronger within-group genetic structure among females than males. Examining the spatial scale of extra-group mating highlighted that the resulting 'sperm dispersal' could have acted in concert with individual dispersal to generate these genetic patterns, but gamete dispersal alone cannot account entirely for the sex differences in genetic structure observed. That leading hypotheses for the evolution of dispersal sex biases cannot readily account for these sex-reversed patterns of dispersal in white-browed sparrow weavers highlights the continued need for attention to alternative explanations for this enigmatic phenomenon. We highlight the potential importance of sex differences in the distances over which dispersal opportunities can be detected. © 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus

PubMed Central

Poon, Art F. Y; Kosakovsky Pond, Sergei L.; Bennett, Phil; Richman, Douglas D; Leigh Brown, Andrew J.; Frost, Simon D. W

2007-01-01

CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design. PMID:17397261

Effects of Large-Scale Releases on the Genetic Structure of Red Sea Bream (Pagrus major, Temminck et Schlegel) Populations in Japan.

PubMed

Blanco Gonzalez, Enrique; Aritaki, Masato; Knutsen, Halvor; Taniguchi, Nobuhiko

2015-01-01

Large-scale hatchery releases are carried out for many marine fish species worldwide; nevertheless, the long-term effects of this practice on the genetic structure of natural populations remains unclear. The lack of knowledge is especially evident when independent stock enhancement programs are conducted simultaneously on the same species at different geographical locations, as occurs with red sea bream (Pagrus major, Temminck et Schlegel) in Japan. In this study, we examined the putative effects of intensive offspring releases on the genetic structure of red sea bream populations along the Japanese archipelago by genotyping 848 fish at fifteen microsatellite loci. Our results suggests weak but consistent patterns of genetic divergence (F(ST) = 0.002, p < 0.001). Red sea bream in Japan appeared spatially structured with several patches of distinct allelic composition, which corresponded to areas receiving an important influx of fish of hatchery origin, either released intentionally or from unintentional escapees from aquaculture operations. In addition to impacts upon local populations inhabiting semi-enclosed embayments, large-scale releases (either intentionally or from unintentional escapes) appeared also to have perturbed genetic structure in open areas. Hence, results of the present study suggest that independent large-scale marine stock enhancement programs conducted simultaneously on one species at different geographical locations may compromise native genetic structure and lead to patchy patterns in population genetic structure.

CRISPR: a Versatile Tool for Both Forward and Reverse Genetics Research

PubMed Central

Gurumurthy, Channabasavaiah B.; Grati, M'hamed; Ohtsuka, Masato; Schilit, Samantha L.P.; Quadros, Rolen M.; Liu, Xue Zhong

2016-01-01

Human genetics research employs the two opposing approaches of forward and reverse genetics. While forward genetics identifies and links a mutation to an observed disease etiology, reverse genetics induces mutations in model organisms to study their role in disease. In most cases, causality for mutations identified by forward genetics is confirmed by reverse genetics through the development of genetically engineered animal models and an assessment of whether the model can recapitulate the disease. While many technological advances have helped improve these approaches, some gaps still remain. CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) system, which has emerged as a revolutionary genetic engineering tool, holds great promise for closing such gaps. By combining the benefits of forward and reverse genetics, it has dramatically expedited human genetics research. We provide a perspective on the power of CRISPR-based forward and reverse genetics tools in human genetics and discuss its applications using some disease examples. PMID:27384229

European Invasion of North American Pinus strobus at Large and Fine Scales: High Genetic Diversity and Fine-Scale Genetic Clustering over Time in the Adventive Range

PubMed Central

Mandák, Bohumil; Hadincová, Věroslava; Mahelka, Václav; Wildová, Radka

2013-01-01

Background North American Pinus strobus is a highly invasive tree species in Central Europe. Using ten polymorphic microsatellite loci we compared various aspects of the large-scale genetic diversity of individuals from 30 sites in the native distribution range with those from 30 sites in the European adventive distribution range. To investigate the ascertained pattern of genetic diversity of this intercontinental comparison further, we surveyed fine-scale genetic diversity patterns and changes over time within four highly invasive populations in the adventive range. Results Our data show that at the large scale the genetic diversity found within the relatively small adventive range in Central Europe, surprisingly, equals the diversity found within the sampled area in the native range, which is about thirty times larger. Bayesian assignment grouped individuals into two genetic clusters separating North American native populations from the European, non-native populations, without any strong genetic structure shown over either range. In the case of the fine scale, our comparison of genetic diversity parameters among the localities and age classes yielded no evidence of genetic diversity increase over time. We found that SGS differed across age classes within the populations under study. Old trees in general completely lacked any SGS, which increased over time and reached its maximum in the sapling stage. Conclusions Based on (1) the absence of difference in genetic diversity between the native and adventive ranges, together with the lack of structure in the native range, and (2) the lack of any evidence of any temporal increase in genetic diversity at four highly invasive populations in the adventive range, we conclude that population amalgamation probably first happened in the native range, prior to introduction. In such case, there would have been no need for multiple introductions from previously isolated populations, but only several introductions from genetically diverse populations. PMID:23874648

A Reverse Taxonomic Approach to Assess Macrofaunal Distribution Patterns in Abyssal Pacific Polymetallic Nodule Fields

PubMed Central

Janssen, Annika; Kaiser, Stefanie; Meißner, Karin; Brenke, Nils; Menot, Lenaick; Martínez Arbizu, Pedro

2015-01-01

Heightened interest in the exploitation of deep seafloor minerals is raising questions on the consequences for the resident fauna. Assessing species ranges and determination of processes underlying current species distributions are prerequisites to conservation planning and predicting faunal responses to changing environmental conditions. The abyssal central Pacific nodule belt, located between the Clarion and Clipperton Fracture Zones (CCZ), is an area prospected for mining of polymetallic nodules. We examined variations in genetic diversity and broad-scale connectivity of isopods and polychaetes across the CCZ. Faunal assemblages were studied from two mining claims (the eastern German and French license areas) located 1300 km apart and influenced by different productivity regimes. Using a reverse taxonomy approach based on DNA barcoding, we tested to what extent distance and large-scale changes in environmental parameters lead to differentiation in two macrofaunal taxa exhibiting different functions and life-history patterns. A fragment of the mitochondrial gene Cytochrome Oxidase Subunit 1 (COI) was analyzed. At a 97% threshold the molecular operational taxonomic units (MOTUs) corresponded well to morphological species. Molecular analyses indicated high local and regional diversity mostly because of large numbers of singletons in the samples. Consequently, variation in composition of genotypic clusters between sites was exceedingly large partly due to paucity of deep-sea sampling and faunal patchiness. A higher proportion of wide-ranging species in polychaetes was contrasted with mostly restricted distributions in isopods. Remarkably, several cryptic lineages appeared to be sympatric and occurred in taxa with putatively good dispersal abilities, whereas some brooding lineages revealed broad distributions across the CCZ. Geographic distance could explain variation in faunal connectivity between regions and sites to some extent, while assumed dispersal capabilities were not as important. PMID:25671322

copia-like retrotransposons are ubiquitous among plants.

PubMed Central

Voytas, D F; Cummings, M P; Koniczny, A; Ausubel, F M; Rodermel, S R

1992-01-01

Transposable genetic elements are assumed to be a feature of all eukaryotic genomes. Their identification, however, has largely been haphazard, limited principally to organisms subjected to molecular or genetic scrutiny. We assessed the phylogenetic distribution of copia-like retrotransposons, a class of transposable element that proliferates by reverse transcription, using a polymerase chain reaction assay designed to detect copia-like element reverse transcriptase sequences. copia-like retrotransposons were identified in 64 plant species as well as the photosynthetic protist Volvox carteri. The plant species included representatives from 9 of 10 plant divisions, including bryophytes, lycopods, ferns, gymnosperms, and angiosperms. DNA sequence analysis of 29 cloned PCR products and of a maize retrotransposon cDNA confirmed the identity of these sequences as copia-like reverse transcriptase sequences, thereby demonstrating that this class of retrotransposons is a ubiquitous component of plant genomes. Images PMID:1379734

Achieving online consent to participation in large-scale gene-environment studies: a tangible destination.

PubMed

Wood, Fiona; Kowalczuk, Jenny; Elwyn, Glyn; Mitchell, Clive; Gallacher, John

2011-08-01

Population based genetics studies are dependent on large numbers of individuals in the pursuit of small effect sizes. Recruiting and consenting a large number of participants is both costly and time consuming. We explored whether an online consent process for large-scale genetics studies is acceptable for prospective participants using an example online genetics study. We conducted semi-structured interviews with 42 members of the public stratified by age group, gender and newspaper readership (a measure of social status). Respondents were asked to use a website designed to recruit for a large-scale genetic study. After using the website a semi-structured interview was conducted to explore opinions and any issues they would have. Responses were analysed using thematic content analysis. The majority of respondents said they would take part in the research (32/42). Those who said they would decline to participate saw fewer benefits from the research, wanted more information and expressed a greater number of concerns about the study. Younger respondents had concerns over time commitment. Middle aged respondents were concerned about privacy and security. Older respondents were more altruistic in their motivation to participate. Common themes included trust in the authenticity of the website, security of personal data, curiosity about their own genetic profile, operational concerns and a desire for more information about the research. Online consent to large-scale genetic studies is likely to be acceptable to the public. The online consent process must establish trust quickly and effectively by asserting authenticity and credentials, and provide access to a range of information to suit different information preferences.

A Multi-Stage Reverse Logistics Network Problem by Using Hybrid Priority-Based Genetic Algorithm

NASA Astrophysics Data System (ADS)

Lee, Jeong-Eun; Gen, Mitsuo; Rhee, Kyong-Gu

Today remanufacturing problem is one of the most important problems regarding to the environmental aspects of the recovery of used products and materials. Therefore, the reverse logistics is gaining become power and great potential for winning consumers in a more competitive context in the future. This paper considers the multi-stage reverse Logistics Network Problem (m-rLNP) while minimizing the total cost, which involves reverse logistics shipping cost and fixed cost of opening the disassembly centers and processing centers. In this study, we first formulate the m-rLNP model as a three-stage logistics network model. Following for solving this problem, we propose a Genetic Algorithm pri (GA) with priority-based encoding method consisting of two stages, and introduce a new crossover operator called Weight Mapping Crossover (WMX). Additionally also a heuristic approach is applied in the 3rd stage to ship of materials from processing center to manufacturer. Finally numerical experiments with various scales of the m-rLNP models demonstrate the effectiveness and efficiency of our approach by comparing with the recent researches.

An assessment of heavy ion irradiation mutagenesis for reverse genetics in wheat (Triticum aestivum L.).

PubMed

Fitzgerald, Timothy L; Powell, Jonathan J; Stiller, Jiri; Weese, Terri L; Abe, Tomoko; Zhao, Guangyao; Jia, Jizeng; McIntyre, C Lynne; Li, Zhongyi; Manners, John M; Kazan, Kemal

2015-01-01

Reverse genetic techniques harnessing mutational approaches are powerful tools that can provide substantial insight into gene function in plants. However, as compared to diploid species, reverse genetic analyses in polyploid plants such as bread wheat can present substantial challenges associated with high levels of sequence and functional similarity amongst homoeologous loci. We previously developed a high-throughput method to identify deletions of genes within a physically mutagenized wheat population. Here we describe our efforts to combine multiple homoeologous deletions of three candidate disease susceptibility genes (TaWRKY11, TaPFT1 and TaPLDß1). We were able to produce lines featuring homozygous deletions at two of the three homoeoloci for all genes, but this was dependent on the individual mutants used in crossing. Intriguingly, despite extensive efforts, viable lines possessing homozygous deletions at all three homoeoloci could not be produced for any of the candidate genes. To investigate deletion size as a possible reason for this phenomenon, we developed an amplicon sequencing approach based on synteny to Brachypodium distachyon to assess the size of the deletions removing one candidate gene (TaPFT1) in our mutants. These analyses revealed that genomic deletions removing the locus are relatively large, resulting in the loss of multiple additional genes. The implications of this work for the use of heavy ion mutagenesis for reverse genetic analyses in wheat are discussed.

An Assessment of Heavy Ion Irradiation Mutagenesis for Reverse Genetics in Wheat (Triticum aestivum L.)

PubMed Central

Fitzgerald, Timothy L.; Powell, Jonathan J.; Stiller, Jiri; Weese, Terri L.; Abe, Tomoko; Zhao, Guangyao; Jia, Jizeng; McIntyre, C. Lynne; Li, Zhongyi; Manners, John M.; Kazan, Kemal

2015-01-01

Reverse genetic techniques harnessing mutational approaches are powerful tools that can provide substantial insight into gene function in plants. However, as compared to diploid species, reverse genetic analyses in polyploid plants such as bread wheat can present substantial challenges associated with high levels of sequence and functional similarity amongst homoeologous loci. We previously developed a high-throughput method to identify deletions of genes within a physically mutagenized wheat population. Here we describe our efforts to combine multiple homoeologous deletions of three candidate disease susceptibility genes (TaWRKY11, TaPFT1 and TaPLDß1). We were able to produce lines featuring homozygous deletions at two of the three homoeoloci for all genes, but this was dependent on the individual mutants used in crossing. Intriguingly, despite extensive efforts, viable lines possessing homozygous deletions at all three homoeoloci could not be produced for any of the candidate genes. To investigate deletion size as a possible reason for this phenomenon, we developed an amplicon sequencing approach based on synteny to Brachypodium distachyon to assess the size of the deletions removing one candidate gene (TaPFT1) in our mutants. These analyses revealed that genomic deletions removing the locus are relatively large, resulting in the loss of multiple additional genes. The implications of this work for the use of heavy ion mutagenesis for reverse genetic analyses in wheat are discussed. PMID:25719507

EPI-743 reverses the progression of the pediatric mitochondrial disease--genetically defined Leigh Syndrome.

PubMed

Martinelli, Diego; Catteruccia, Michela; Piemonte, Fiorella; Pastore, Anna; Tozzi, Giulia; Dionisi-Vici, Carlo; Pontrelli, Giuseppe; Corsetti, Tiziana; Livadiotti, Susanna; Kheifets, Viktoria; Hinman, Andrew; Shrader, William D; Thoolen, Martin; Klein, Matthew B; Bertini, Enrico; Miller, Guy

2012-11-01

Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases. In compassionate use cases and in an FDA Expanded Access protocol, children with Leigh syndrome treated with EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement. To confirm these initial findings, a phase 2A open label trial of EPI-743 for children with genetically-confirmed Leigh syndrome was conducted and herein we report the results. A single arm clinical trial was performed in children with genetically defined Leigh syndrome. Subjects were treated for 6 months with EPI-743 three times daily and all were eligible for a treatment extension phase. The primary objective of the trial was to arrest disease progression as assessed by neuromuscular and quality of life metrics. Results were compared to the reported natural history of the disease. Ten consecutive children, ages 1-13 years, were enrolled; they possessed seven different genetic defects. All children exhibited reversal of disease progression regardless of genetic determinant or disease severity. The primary endpoints--Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function Measure, and PedsQL Neuromuscular Module--demonstrated statistically significant improvement (p<0.05). In addition, all children had an improvement of one class on the Movement Disorder-Childhood Rating Scale. No significant drug-related adverse events were recorded. In comparison to the natural history of Leigh syndrome, EPI-743 improves clinical outcomes in children with genetically confirmed Leigh syndrome. Copyright © 2012 Elsevier Inc. All rights reserved.

Compromising genetic diversity in the wild: Unmonitored large-scale release of plants and animals

Treesearch

Linda Laikre; Michael K. Schwartz; Robin S. Waples; Nils Ryman; F. W. Allendorf; C. S. Baker; D. P. Gregovich; M. M. Hansen; J. A. Jackson; K. C. Kendall; K. McKelvey; M. C. Neel; I. Olivieri; R. Short Bull; J. B. Stetz; D. A. Tallmon; C. D. Vojta; D. M. Waller

2010-01-01

Large-scale exploitation of wild animals and plants through fishing, hunting and logging often depends on augmentation through releases of translocated or captively raised individuals. Such releases are performed worldwide in vast numbers. Augmentation can be demographically and economically beneficial but can also cause four types of adverse genetic change to wild...

More Reasons to be Straightforward: Findings and Norms for Two Scales Relevant to Social Anxiety

PubMed Central

Rodebaugh, Thomas L.; Heimberg, Richard G.; Brown, Patrick J.; Fernandez, Katya C.; Blanco, Carlos; Schneier, Franklin R.; Liebowitz, Michael R.

2011-01-01

The validity of both the Social Interaction Anxiety Scale and Brief Fear of Negative Evaluation scale has been well-supported, yet the scales have a small number of reverse-scored items that may detract from the validity of their total scores. The current study investigates two characteristics of participants that may be associated with compromised validity of these items: higher age and lower levels of education. In community and clinical samples, the validity of each scale's reverse-scored items was moderated by age, years of education, or both. The straightforward items did not show this pattern. To encourage the use of the straightforward items of these scales, we provide normative data from the same samples as well as two large student samples. We contend that although response bias can be a substantial problem, the reverse-scored questions of these scales do not solve that problem and instead decrease overall validity. PMID:21388781

Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

PubMed Central

2012-01-01

Background Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus. Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China. PMID:22591597

Imaging spectroscopy links aspen genotype with below-ground processes at landscape scales

PubMed Central

Madritch, Michael D.; Kingdon, Clayton C.; Singh, Aditya; Mock, Karen E.; Lindroth, Richard L.; Townsend, Philip A.

2014-01-01

Fine-scale biodiversity is increasingly recognized as important to ecosystem-level processes. Remote sensing technologies have great potential to estimate both biodiversity and ecosystem function over large spatial scales. Here, we demonstrate the capacity of imaging spectroscopy to discriminate among genotypes of Populus tremuloides (trembling aspen), one of the most genetically diverse and widespread forest species in North America. We combine imaging spectroscopy (AVIRIS) data with genetic, phytochemical, microbial and biogeochemical data to determine how intraspecific plant genetic variation influences below-ground processes at landscape scales. We demonstrate that both canopy chemistry and below-ground processes vary over large spatial scales (continental) according to aspen genotype. Imaging spectrometer data distinguish aspen genotypes through variation in canopy spectral signature. In addition, foliar spectral variation correlates well with variation in canopy chemistry, especially condensed tannins. Variation in aspen canopy chemistry, in turn, is correlated with variation in below-ground processes. Variation in spectra also correlates well with variation in soil traits. These findings indicate that forest tree species can create spatial mosaics of ecosystem functioning across large spatial scales and that these patterns can be quantified via remote sensing techniques. Moreover, they demonstrate the utility of using optical properties as proxies for fine-scale measurements of biodiversity over large spatial scales. PMID:24733949

Culture rather than genes provides greater scope for the evolution of large-scale human prosociality

PubMed Central

Bell, Adrian V.; Richerson, Peter J.; McElreath, Richard

2009-01-01

Whether competition among large groups played an important role in human social evolution is dependent on how variation, whether cultural or genetic, is maintained between groups. Comparisons between genetic and cultural differentiation between neighboring groups show how natural selection on large groups is more plausible on cultural rather than genetic variation. PMID:19822753

Virus fitness differences observed between two naturally occurring isolates of Ebola virus Makona variant using a reverse genetics approach.

PubMed

Albariño, César G; Guerrero, Lisa Wiggleton; Chakrabarti, Ayan K; Kainulainen, Markus H; Whitmer, Shannon L M; Welch, Stephen R; Nichol, Stuart T

2016-09-01

During the large outbreak of Ebola virus disease that occurred in Western Africa from late 2013 to early 2016, several hundred Ebola virus (EBOV) genomes have been sequenced and the virus genetic drift analyzed. In a previous report, we described an efficient reverse genetics system designed to generate recombinant EBOV based on a Makona variant isolate obtained in 2014. Using this system, we characterized the replication and fitness of 2 isolates of the Makona variant. These virus isolates are nearly identical at the genetic level, but have single amino acid differences in the VP30 and L proteins. The potential effects of these differences were tested using minigenomes and recombinant viruses. The results obtained with this approach are consistent with the role of VP30 and L as components of the EBOV RNA replication machinery. Moreover, the 2 isolates exhibited clear fitness differences in competitive growth assays. Published by Elsevier Inc.

A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity

USGS Publications Warehouse

Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M.; Vakharia, Vikram N.

2011-01-01

Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-ΔNV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-ΔNV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-ΔNV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines.

Landscape-scale genetic variation in a forest outbreak species, the mountain pine beetle (Dendroctonus ponderosae)

Treesearch

K. E. Mock; B. J. Bentz; E. M. O' Neill; J. P. Chong; J. Orwin; M. E. Pfrender

2007-01-01

The mountain pine beetle Dendroctonus ponderosae is a native species currently experiencing large-scale outbreaks in western North American pine forests. We sought to describe the pattern of genetic variation across the range of this species, to determine whether there were detectable genetic differences between D. ponderosae...

'Fracking', Induced Seismicity and the Critical Earth

NASA Astrophysics Data System (ADS)

Leary, P.; Malin, P. E.

2012-12-01

Issues of 'fracking' and induced seismicity are reverse-analogous to the equally complex issues of well productivity in hydrocarbon, geothermal and ore reservoirs. In low hazard reservoir economics, poorly producing wells and low grade ore bodies are many while highly producing wells and high grade ores are rare but high pay. With induced seismicity factored in, however, the same distribution physics reverses the high/low pay economics: large fracture-connectivity systems are hazardous hence low pay, while high probability small fracture-connectivity systems are non-hazardous hence high pay. Put differently, an economic risk abatement tactic for well productivity and ore body pay is to encounter large-scale fracture systems, while an economic risk abatement tactic for 'fracking'-induced seismicity is to avoid large-scale fracture systems. Well productivity and ore body grade distributions arise from three empirical rules for fluid flow in crustal rock: (i) power-law scaling of grain-scale fracture density fluctuations; (ii) spatial correlation between spatial fluctuations in well-core porosity and the logarithm of well-core permeability; (iii) frequency distributions of permeability governed by a lognormality skewness parameter. The physical origin of rules (i)-(iii) is the universal existence of a critical-state-percolation grain-scale fracture-density threshold for crustal rock. Crustal fractures are effectively long-range spatially-correlated distributions of grain-scale defects permitting fluid percolation on mm to km scales. The rule is, the larger the fracture system the more intense the percolation throughput. As percolation pathways are spatially erratic and unpredictable on all scales, they are difficult to model with sparsely sampled well data. Phenomena such as well productivity, induced seismicity, and ore body fossil fracture distributions are collectively extremely difficult to predict. Risk associated with unpredictable reservoir well productivity and ore body distributions can be managed by operating in a context which affords many small failures for a few large successes. In reverse view, 'fracking' and induced seismicity could be rationally managed in a context in which many small successes can afford a few large failures. However, just as there is every incentive to acquire information leading to higher rates of productive well drilling and ore body exploration, there are equal incentives for acquiring information leading to lower rates of 'fracking'-induced seismicity. Current industry practice of using an effective medium approach to reservoir rock creates an uncritical sense that property distributions in rock are essentially uniform. Well-log data show that the reverse is true: the larger the length scale the greater the deviation from uniformity. Applying the effective medium approach to large-scale rock formations thus appears to be unnecessarily hazardous. It promotes the notion that large scale fluid pressurization acts against weakly cohesive but essentially uniform rock to produce large-scale quasi-uniform tensile discontinuities. Indiscriminate hydrofacturing appears to be vastly more problematic in reality than as pictured by the effective medium hypothesis. The spatial complexity of rock, especially at large scales, provides ample reason to find more controlled pressurization strategies for enhancing in situ flow.

Reverse Genetics for Mammalian Orthoreovirus.

PubMed

Stuart, Johnasha D; Phillips, Matthew B; Boehme, Karl W

2017-01-01

Reverse genetics allows introduction of specific alterations into a viral genome. Studies performed with mutant viruses generated using reverse genetics approaches have contributed immeasurably to our understanding of viral replication and pathogenesis, and also have led to development of novel vaccines and virus-based vectors. Here, we describe the reverse genetics system that allows for production and recovery of mammalian orthoreovirus, a double-stranded (ds) RNA virus, from plasmids that encode the viral genome.

Reverse engineering and analysis of large genome-scale gene networks

PubMed Central

Aluru, Maneesha; Zola, Jaroslaw; Nettleton, Dan; Aluru, Srinivas

2013-01-01

Reverse engineering the whole-genome networks of complex multicellular organisms continues to remain a challenge. While simpler models easily scale to large number of genes and gene expression datasets, more accurate models are compute intensive limiting their scale of applicability. To enable fast and accurate reconstruction of large networks, we developed Tool for Inferring Network of Genes (TINGe), a parallel mutual information (MI)-based program. The novel features of our approach include: (i) B-spline-based formulation for linear-time computation of MI, (ii) a novel algorithm for direct permutation testing and (iii) development of parallel algorithms to reduce run-time and facilitate construction of large networks. We assess the quality of our method by comparison with ARACNe (Algorithm for the Reconstruction of Accurate Cellular Networks) and GeneNet and demonstrate its unique capability by reverse engineering the whole-genome network of Arabidopsis thaliana from 3137 Affymetrix ATH1 GeneChips in just 9 min on a 1024-core cluster. We further report on the development of a new software Gene Network Analyzer (GeNA) for extracting context-specific subnetworks from a given set of seed genes. Using TINGe and GeNA, we performed analysis of 241 Arabidopsis AraCyc 8.0 pathways, and the results are made available through the web. PMID:23042249

Reversible Self-Actuated Thermo-Responsive Pore Membrane

PubMed Central

Park, Younggeun; Gutierrez, Maria Paz; Lee, Luke P.

2016-01-01

Smart membranes, which can selectively control the transfer of light, air, humidity and temperature, are important to achieve indoor climate regulation. Even though reversible self-actuation of smart membranes is desirable in large-scale, reversible self-regulation remains challenging. Specifically, reversible 100% opening/closing of pore actuation showing accurate responsiveness, reproducibility and structural flexibility, including uniform structure assembly, is currently very difficult. Here, we report a reversible, thermo-responsive self-activated pore membrane that achieves opening and closing of pores. The reversible, self-actuated thermo-responsive pore membrane was fabricated with hybrid materials of poly (N-isopropylacrylamide), (PNIPAM) within polytetrafluoroethylene (PTFE) to form a multi-dimensional pore array. Using Multiphysics simulation of heat transfer and structural mechanics based on finite element analysis, we demonstrated that pore opening and closing dynamics can be self-activated at environmentally relevant temperatures. Temperature cycle characterizations of the pore structure revealed 100% opening ratio at T = 40 °C and 0% opening ratio at T = 20 °C. The flexibility of the membrane showed an accurate temperature-responsive function at a maximum bending angle of 45°. Addressing the importance of self-regulation, this reversible self-actuated thermo-responsive pore membrane will advance the development of future large-scale smart membranes needed for sustainable indoor climate control. PMID:27991563

Reversible Self-Actuated Thermo-Responsive Pore Membrane

NASA Astrophysics Data System (ADS)

Park, Younggeun; Gutierrez, Maria Paz; Lee, Luke P.

2016-12-01

Smart membranes, which can selectively control the transfer of light, air, humidity and temperature, are important to achieve indoor climate regulation. Even though reversible self-actuation of smart membranes is desirable in large-scale, reversible self-regulation remains challenging. Specifically, reversible 100% opening/closing of pore actuation showing accurate responsiveness, reproducibility and structural flexibility, including uniform structure assembly, is currently very difficult. Here, we report a reversible, thermo-responsive self-activated pore membrane that achieves opening and closing of pores. The reversible, self-actuated thermo-responsive pore membrane was fabricated with hybrid materials of poly (N-isopropylacrylamide), (PNIPAM) within polytetrafluoroethylene (PTFE) to form a multi-dimensional pore array. Using Multiphysics simulation of heat transfer and structural mechanics based on finite element analysis, we demonstrated that pore opening and closing dynamics can be self-activated at environmentally relevant temperatures. Temperature cycle characterizations of the pore structure revealed 100% opening ratio at T = 40 °C and 0% opening ratio at T = 20 °C. The flexibility of the membrane showed an accurate temperature-responsive function at a maximum bending angle of 45°. Addressing the importance of self-regulation, this reversible self-actuated thermo-responsive pore membrane will advance the development of future large-scale smart membranes needed for sustainable indoor climate control.

Querying Large Biological Network Datasets

ERIC Educational Resources Information Center

Gulsoy, Gunhan

2013-01-01

New experimental methods has resulted in increasing amount of genetic interaction data to be generated every day. Biological networks are used to store genetic interaction data gathered. Increasing amount of data available requires fast large scale analysis methods. Therefore, we address the problem of querying large biological network datasets.…

MGIS: Managing banana (Musa spp.) genetic resources information and high-throughput genotyping data

USDA-ARS?s Scientific Manuscript database

Unraveling genetic diversity held in genebanks on a large scale is underway, due to the advances in Next-generation sequence-based technologies that produce high-density genetic markers for a large number of samples at low cost. Genebank users should be in a position to identify and select germplasm...

More reasons to be straightforward: findings and norms for two scales relevant to social anxiety.

PubMed

Rodebaugh, Thomas L; Heimberg, Richard G; Brown, Patrick J; Fernandez, Katya C; Blanco, Carlos; Schneier, Franklin R; Liebowitz, Michael R

2011-06-01

The validity of both the Social Interaction Anxiety Scale and Brief Fear of Negative Evaluation scale has been well-supported, yet the scales have a small number of reverse-scored items that may detract from the validity of their total scores. The current study investigates two characteristics of participants that may be associated with compromised validity of these items: higher age and lower levels of education. In community and clinical samples, the validity of each scale's reverse-scored items was moderated by age, years of education, or both. The straightforward items did not show this pattern. To encourage the use of the straightforward items of these scales, we provide normative data from the same samples as well as two large student samples. We contend that although response bias can be a substantial problem, the reverse-scored questions of these scales do not solve that problem and instead decrease overall validity. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effect of the solar field reversal on the modulation of galactic cosmic rays

NASA Technical Reports Server (NTRS)

Thomas, B. T.; Goldstein, B. E.

1983-01-01

There is now a growing awareness that solar cycle related changes in the large-scale structure of the interplanetary magnetic field (IMF) may play an important role in the modulation of galactic cosmic rays. To date, attention focussed on two aspects of the magnetic field structure: large scale compression regions produced by fast solar wind streams and solar flares, both of which are known to vary in intensity and number over the solar cycle, and the variable warp of the heliospheric current sheet. It is suggested that another feature of the solar cycle is worthy of consideration: the field reversal itself. If the Sun reverses its polarity by simply overturning the heliospheric current sheet (northern fields migrating southward and vice-versa) then there may well be an effect on cosmic ray intensity. However, such a simple picture of solar reversal seems improbable. Observations of the solar corona suggest the existence of not one but several current sheets in the heliosphere at solar maximum. The results of a simple calculation to demonstrate that the variation in cosmic ray intensities that will result can be as large as is actually observed over the solar cycle are given.

Exploiting the Brachypodium Tool Box in cereal and grass research

USDA-ARS?s Scientific Manuscript database

It is now a decade since Brachypodium distachyon was suggested as a model species for temperate grasses and cereals. Since then transformation protocols, large expressed sequence tag (EST) populations, tools for forward and reverse genetic screens, highly refined cytogenetic probes, germplasm coll...

National Science Foundation-sponsored workshop report. Draft plan for soybean genomics.

PubMed

Stacey, Gary; Vodkin, Lila; Parrott, Wayne A; Shoemaker, Randy C

2004-05-01

Recent efforts to coordinate and define a research strategy for soybean (Glycine max) genomics began with the establishment of a Soybean Genetics Executive Committee, which will serve as a communication focal point between the soybean research community and granting agencies. Secondly, a workshop was held to define a strategy to incorporate existing tools into a framework for advancing soybean genomics research. This workshop identified and ranked research priorities essential to making more informed decisions as to how to proceed with large scale sequencing and other genomics efforts. Most critical among these was the need to finalize a physical map and to obtain a better understanding of genome microstructure. Addressing these research needs will require pilot work on new technologies to demonstrate an ability to discriminate between recently duplicated regions in the soybean genome and pilot projects to analyze an adequate amount of random genome sequence to identify and catalog common repeats. The development of additional markers, reverse genetics tools, and bioinformatics is also necessary. Successful implementation of these goals will require close coordination among various working groups.

Stream Flow Prediction by Remote Sensing and Genetic Programming

NASA Technical Reports Server (NTRS)

Chang, Ni-Bin

2009-01-01

A genetic programming (GP)-based, nonlinear modeling structure relates soil moisture with synthetic-aperture-radar (SAR) images to present representative soil moisture estimates at the watershed scale. Surface soil moisture measurement is difficult to obtain over a large area due to a variety of soil permeability values and soil textures. Point measurements can be used on a small-scale area, but it is impossible to acquire such information effectively in large-scale watersheds. This model exhibits the capacity to assimilate SAR images and relevant geoenvironmental parameters to measure soil moisture.

[Genetically modified organisms: a new threat to food safety].

PubMed

Spendeler, Liliane

2005-01-01

This article analyzes all of the food safety-related aspects related to the use of genetically modified organisms into agriculture and food. A discussion is provided as to the uncertainties related to the insertion of foreign genes into organisms, providing examples of unforeseen, undesirable effects and of instabilities of the organisms thus artificially fabricated. Data is then provided from both official agencies as well as existing literature questioning the accuracy and reliability of the risk analyses as to these organisms being harmless to health and discusses the almost total lack of scientific studies analyzing the health safety/dangerousness of transgenic foods. Given all these unknowns, other factors must be taken into account, particularly genetic contamination of the non-genetically modified crops, which is now starting to become widespread in some parts of the world. Not being able of reversing the situation in the even of problems is irresponsible. Other major aspects are the impacts on the environment (such as insects building up resistances, the loss of biodiversity, the increase in chemical products employed) with indirect repercussions on health and/or future food production. Lastly, thoughts for discussion are added concerning food safety in terms of food availability and food sovereignty, given that the transgenic seed and related agrochemicals market is currently cornered by five large-scale transnational companies. The conclusion entails an analysis of biotechnological agriculture's contribution to sustainability.

Variation in the population structure of Yukon River chum and coho salmon: Evaluating the potential impact of localized habitat degradation

USGS Publications Warehouse

Olsen, J.B.; Spearman, William J.; Sage, G.K.; Miller, S.J.; Flannery, B.G.; Wenburg, J.K.

2004-01-01

We used microsatellite and mitochondrial DNA-restriction fragment length polymorphism (mtDNA-RFLP) analyses to test the hypothesis that chum salmon Oncorhynchus keta and coho salmon O. kisutch in the Yukon River, Alaska, exhibit population structure at differing spatial scales. If the hypothesis is true, then the risk of losing genetic diversity because of habitat degradation from a gold mine near a Yukon River tributary could differ between the two species. For each species, collections were made from two tributaries in both the Innoko and Tanana rivers, which are tributaries to the lower and middle Yukon River. The results revealed a large difference in the degree and spatial distribution of population structure between the two species. For chum salmon, the microsatellite loci (F-statistic [FST] = 0.021) and mtDNA (F ST = -0.008) revealed a low degree of interpopulation genetic diversity on a relatively large geographic scale. This large-scale population structure should minimize, although not eliminate, the risk of genetic diversity loss due to localized habitat degradation. For coho salmon, the microsatellites (FST = 0.091) and mtDNA (FST = 0.586) revealed a high degree of interpopulation genetic diversity on a relatively small geographic scale. This small-scale population structure suggests that coho salmon are at a relatively high risk of losing genetic diversity due to lo-calized habitat degradation. Our study underscores the importance of a multispecies approach for evaluating the potential impact of land-use activities on the genetic diversity of Pacific salmon.

Rescue of a Plant Negative-Strand RNA Virus from Cloned cDNA: Insights into Enveloped Plant Virus Movement and Morphogenesis.

PubMed

Wang, Qiang; Ma, Xiaonan; Qian, ShaSha; Zhou, Xin; Sun, Kai; Chen, Xiaolan; Zhou, Xueping; Jackson, Andrew O; Li, Zhenghe

2015-10-01

Reverse genetics systems have been established for all major groups of plant DNA and positive-strand RNA viruses, and our understanding of their infection cycles and pathogenesis has benefitted enormously from use of these approaches. However, technical difficulties have heretofore hampered applications of reverse genetics to plant negative-strand RNA (NSR) viruses. Here, we report recovery of infectious virus from cloned cDNAs of a model plant NSR, Sonchus yellow net rhabdovirus (SYNV). The procedure involves Agrobacterium-mediated transcription of full-length SYNV antigenomic RNA and co-expression of the nucleoprotein (N), phosphoprotein (P), large polymerase core proteins and viral suppressors of RNA silencing in Nicotiana benthamiana plants. Optimization of core protein expression resulted in up to 26% recombinant SYNV (rSYNV) infections of agroinfiltrated plants. A reporter virus, rSYNV-GFP, engineered by inserting a green fluorescence protein (GFP) gene between the N and P genes was able to express GFP during systemic infections and after repeated plant-to-plant mechanical passages. Deletion analyses with rSYNV-GFP demonstrated that SYNV cell-to-cell movement requires the sc4 protein and suggested that uncoiled nucleocapsids are infectious movement entities. Deletion analyses also showed that the glycoprotein is not required for systemic infection, although the glycoprotein mutant was defective in virion morphogenesis. Taken together, we have developed a robust reverse genetics system for SYNV that provides key insights into morphogenesis and movement of an enveloped plant virus. Our study also provides a template for developing analogous systems for reverse genetic analysis of other plant NSR viruses.

Rescue of a Plant Negative-Strand RNA Virus from Cloned cDNA: Insights into Enveloped Plant Virus Movement and Morphogenesis

PubMed Central

Zhou, Xin; Sun, Kai; Chen, Xiaolan; Zhou, Xueping; Jackson, Andrew O.; Li, Zhenghe

2015-01-01

Reverse genetics systems have been established for all major groups of plant DNA and positive-strand RNA viruses, and our understanding of their infection cycles and pathogenesis has benefitted enormously from use of these approaches. However, technical difficulties have heretofore hampered applications of reverse genetics to plant negative-strand RNA (NSR) viruses. Here, we report recovery of infectious virus from cloned cDNAs of a model plant NSR, Sonchus yellow net rhabdovirus (SYNV). The procedure involves Agrobacterium-mediated transcription of full-length SYNV antigenomic RNA and co-expression of the nucleoprotein (N), phosphoprotein (P), large polymerase core proteins and viral suppressors of RNA silencing in Nicotiana benthamiana plants. Optimization of core protein expression resulted in up to 26% recombinant SYNV (rSYNV) infections of agroinfiltrated plants. A reporter virus, rSYNV-GFP, engineered by inserting a green fluorescence protein (GFP) gene between the N and P genes was able to express GFP during systemic infections and after repeated plant-to-plant mechanical passages. Deletion analyses with rSYNV-GFP demonstrated that SYNV cell-to-cell movement requires the sc4 protein and suggested that uncoiled nucleocapsids are infectious movement entities. Deletion analyses also showed that the glycoprotein is not required for systemic infection, although the glycoprotein mutant was defective in virion morphogenesis. Taken together, we have developed a robust reverse genetics system for SYNV that provides key insights into morphogenesis and movement of an enveloped plant virus. Our study also provides a template for developing analogous systems for reverse genetic analysis of other plant NSR viruses. PMID:26484673

Next-generation sequencing for targeted discovery of rare mutations in rice

USDA-ARS?s Scientific Manuscript database

Advances in DNA sequencing (i.e., next-generation sequencing, NGS) have greatly increased the power and efficiency of detecting rare mutations in large mutant populations. Targeting Induced Local Lesions in Genomes (TILLING) is a reverse genetics approach for identifying gene mutations resulting fro...

Time irreversibility in reversible shell models of turbulence.

PubMed

De Pietro, Massimo; Biferale, Luca; Boffetta, Guido; Cencini, Massimo

2018-04-06

Turbulent flows governed by the Navier-Stokes equations (NSE) generate an out-of-equilibrium time irreversible energy cascade from large to small scales. In the NSE, the energy transfer is due to the nonlinear terms that are formally symmetric under time reversal. As for the dissipative term: first, it explicitly breaks time reversibility; second, it produces a small-scale sink for the energy transfer that remains effective even in the limit of vanishing viscosity. As a result, it is not clear how to disentangle the time irreversibility originating from the non-equilibrium energy cascade from the explicit time-reversal symmetry breaking due to the viscous term. To this aim, in this paper we investigate the properties of the energy transfer in turbulent shell models by using a reversible viscous mechanism, avoiding any explicit breaking of the [Formula: see text] symmetry. We probe time irreversibility by studying the statistics of Lagrangian power, which is found to be asymmetric under time reversal also in the time-reversible model. This suggests that the turbulent dynamics converges to a strange attractor where time reversibility is spontaneously broken and whose properties are robust for what concerns purely inertial degrees of freedoms, as verified by the anomalous scaling behavior of the velocity structure functions.

The stability and change of etiological influences on depression, anxiety symptoms and their co-occurrence across adolescence and young adulthood.

PubMed

Waszczuk, M A; Zavos, H M S; Gregory, A M; Eley, T C

2016-01-01

Depression and anxiety persist within and across diagnostic boundaries. The manner in which common v. disorder-specific genetic and environmental influences operate across development to maintain internalizing disorders and their co-morbidity is unclear. This paper investigates the stability and change of etiological influences on depression, panic, generalized, separation and social anxiety symptoms, and their co-occurrence, across adolescence and young adulthood. A total of 2619 twins/siblings prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and 20 years. Each symptom scale showed a similar pattern of moderate continuity across development, largely underpinned by genetic stability. New genetic influences contributing to change in the developmental course of the symptoms emerged at each time point. All symptom scales correlated moderately with one another over time. Genetic influences, both stable and time-specific, overlapped considerably between the scales. Non-shared environmental influences were largely time- and symptom-specific, but some contributed moderately to the stability of depression and anxiety symptom scales. These stable, longitudinal environmental influences were highly correlated between the symptoms. The results highlight both stable and dynamic etiology of depression and anxiety symptom scales. They provide preliminary evidence that stable as well as newly emerging genes contribute to the co-morbidity between depression and anxiety across adolescence and young adulthood. Conversely, environmental influences are largely time-specific and contribute to change in symptoms over time. The results inform molecular genetics research and transdiagnostic treatment and prevention approaches.

Spatial extent of analysis influences observed patterns of population genetic structure in a widespread darter species (Percidae)

USGS Publications Warehouse

Argentina, Jane E.; Angermeier, Paul L.; Hallerman, Eric M.; Welsh, Stuart A.

2018-01-01

Connectivity among stream fish populations allows for exchange of genetic material and helps maintain genetic diversity, adaptive potential and population stability over time. Changes in species demographics and population connectivity have the potential to permanently alter the genetic patterns of stream fish, although these changes through space and time are variable and understudied in small‐bodied freshwater fish.As a spatially widespread, common species of benthic freshwater fish, the variegate darter (Etheostoma variatum) is a model species for documenting how patterns of genetic structure and diversity respond to increasing isolation due to large dams and how scale of study may shape our understanding of these patterns. We sampled variegate darters from 34 sites across their range in the North American Ohio River basin and examined how patterns of genetic structure and diversity within and between populations responded to historical population changes and dams within and between populations.Spatial scale and configuration of genetic structure varied across the eight identified populations, from tributaries within a watershed, to a single watershed, to multiple watersheds that encompass Ohio River mainstem habitats. This multiwatershed pattern of population structuring suggests genetic dispersal across large distances was and may continue to be common, although some populations remain isolated despite no apparent structural dispersal barriers. Populations with low effective population sizes and evidence of past population bottlenecks showed low allelic richness, but diversity patterns were not related to watershed size, a surrogate for habitat availability. Pairwise genetic differentiation (FST) increased with fluvial distance and was related to both historic and contemporary processes. Genetic diversity changes were influenced by underlying population size and stability, and while instream barriers were not strong determinants of genetic structuring or loss of genetic diversity, they reduce population connectivity and may impact long‐term population persistence.The broad spatial scale of this study demonstrated the large spatial extent of some variegate darter populations and indicated that dispersal is more extensive than expected given the movement patterns typically observed for small‐bodied, benthic fish. Dam impacts depended on underlying population size and stability, with larger populations more resilient to genetic drift and allelic richness loss than smaller populations.Other darters that inhabit large river habitats may show similar patterns in landscape‐scale studies, and large river barriers may impact populations of small‐bodied fish more than previously expected. Estimation of dispersal rates and behaviours is critical to conservation of imperilled riverine species such as darters.

Harnessing quantitative genetics and genomics for understanding and improving complex traits in crops

USDA-ARS?s Scientific Manuscript database

Classical quantitative genetics aids crop improvement by providing the means to estimate heritability, genetic correlations, and predicted responses to various selection schemes. Genomics has the potential to aid quantitative genetics and applied crop improvement programs via large-scale, high-thro...

Stochastic dynamics of genetic broadcasting networks

NASA Astrophysics Data System (ADS)

Potoyan, Davit A.; Wolynes, Peter G.

2017-11-01

The complex genetic programs of eukaryotic cells are often regulated by key transcription factors occupying or clearing out of a large number of genomic locations. Orchestrating the residence times of these factors is therefore important for the well organized functioning of a large network. The classic models of genetic switches sidestep this timing issue by assuming the binding of transcription factors to be governed entirely by thermodynamic protein-DNA affinities. Here we show that relying on passive thermodynamics and random release times can lead to a "time-scale crisis" for master genes that broadcast their signals to a large number of binding sites. We demonstrate that this time-scale crisis for clearance in a large broadcasting network can be resolved by actively regulating residence times through molecular stripping. We illustrate these ideas by studying a model of the stochastic dynamics of the genetic network of the central eukaryotic master regulator NFκ B which broadcasts its signals to many downstream genes that regulate immune response, apoptosis, etc.

Stochastic dynamics of genetic broadcasting networks

NASA Astrophysics Data System (ADS)

Potoyan, Davit; Wolynes, Peter

The complex genetic programs of eukaryotic cells are often regulated by key transcription factors occupying or clearing out of a large number of genomic locations. Orchestrating the residence times of these factors is therefore important for the well organized functioning of a large network. The classic models of genetic switches sidestep this timing issue by assuming the binding of transcription factors to be governed entirely by thermodynamic protein-DNA affinities. Here we show that relying on passive thermodynamics and random release times can lead to a ''time-scale crisis'' of master genes that broadcast their signals to large number of binding sites. We demonstrate that this ''time-scale crisis'' can be resolved by actively regulating residence times through molecular stripping. We illustrate these ideas by studying the stochastic dynamics of the genetic network of the central eukaryotic master regulator NFκB which broadcasts its signals to many downstream genes that regulate immune response, apoptosis etc.

Large-scale coupling dynamics of instructed reversal learning.

PubMed

Mohr, Holger; Wolfensteller, Uta; Ruge, Hannes

2018-02-15

The ability to rapidly learn from others by instruction is an important characteristic of human cognition. A recent study found that the rapid transfer from initial instructions to fluid behavior is supported by changes of functional connectivity between and within several large-scale brain networks, and particularly by the coupling of the dorsal attention network (DAN) with the cingulo-opercular network (CON). In the present study, we extended this approach to investigate how these brain networks interact when stimulus-response mappings are altered by novel instructions. We hypothesized that residual stimulus-response associations from initial practice might negatively impact the ability to implement novel instructions. Using functional imaging and large-scale connectivity analysis, we found that functional coupling between the CON and DAN was generally at a higher level during initial than reversal learning. Examining the learning-related connectivity dynamics between the CON and DAN in more detail by means of multivariate patterns analyses, we identified a specific subset of connections which showed a particularly high increase in connectivity during initial learning compared to reversal learning. This finding suggests that the CON-DAN connections can be separated into two functionally dissociable yet spatially intertwined subsystems supporting different aspects of short-term task automatization. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic structuring of northern myotis (Myotis septentrionalis) at multiple spatial scales

USGS Publications Warehouse

Johnson, Joshua B.; Roberts, James H.; King, Timothy L.; Edwards, John W.; Ford, W. Mark; Ray, David A.

2014-01-01

Although groups of bats may be genetically distinguishable at large spatial scales, the effects of forest disturbances, particularly permanent land use conversions on fine-scale population structure and gene flow of summer aggregations of philopatric bat species are less clear. We genotyped and analyzed variation at 10 nuclear DNA microsatellite markers in 182 individuals of the forest-dwelling northern myotis (Myotis septentrionalis) at multiple spatial scales, from within first-order watersheds scaling up to larger regional areas in West Virginia and New York. Our results indicate that groups of northern myotis were genetically indistinguishable at any spatial scale we considered, and the collective population maintained high genetic diversity. It is likely that the ability to migrate, exploit small forest patches, and use networks of mating sites located throughout the Appalachian Mountains, Interior Highlands, and elsewhere in the hibernation range have allowed northern myotis to maintain high genetic diversity and gene flow regardless of forest disturbances at local and regional spatial scales. A consequence of maintaining high gene flow might be the potential to minimize genetic founder effects following population declines caused currently by the enzootic White-nose Syndrome.

Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next-generation human artificial chromosomes for Duchenne muscular dystrophy.

PubMed

Benedetti, Sara; Uno, Narumi; Hoshiya, Hidetoshi; Ragazzi, Martina; Ferrari, Giulia; Kazuki, Yasuhiro; Moyle, Louise Anne; Tonlorenzi, Rossana; Lombardo, Angelo; Chaouch, Soraya; Mouly, Vincent; Moore, Marc; Popplewell, Linda; Kazuki, Kanako; Katoh, Motonobu; Naldini, Luigi; Dickson, George; Messina, Graziella; Oshimura, Mitsuo; Cossu, Giulio; Tedesco, Francesco Saverio

2018-02-01

Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation. We previously reported amelioration of the dystrophic phenotype in mice transplanted with murine muscle progenitors containing a HAC with the entire dystrophin locus (DYS-HAC). However, translation of this strategy to human muscle progenitors requires extension of their proliferative potential to withstand clonal cell expansion after HAC transfer. Here, we show that reversible cell immortalisation mediated by lentivirally delivered excisable hTERT and Bmi1 transgenes extended cell proliferation, enabling transfer of a novel DYS-HAC into DMD satellite cell-derived myoblasts and perivascular cell-derived mesoangioblasts. Genetically corrected cells maintained a stable karyotype, did not undergo tumorigenic transformation and retained their migration ability. Cells remained myogenic in vitro (spontaneously or upon MyoD induction) and engrafted murine skeletal muscle upon transplantation. Finally, we combined the aforementioned functions into a next-generation HAC capable of delivering reversible immortalisation, complete genetic correction, additional dystrophin expression, inducible differentiation and controllable cell death. This work establishes a novel platform for complex gene transfer into clinically relevant human muscle progenitors for DMD gene therapy. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Wind reversals in turbulent Rayleigh-Bénard convection.

PubMed

Araujo, Francisco Fontenele; Grossmann, Siegfried; Lohse, Detlef

2005-08-19

The phenomenon of irregular cessation and subsequent reversal of the large-scale circulation in turbulent Rayleigh-Bénard convection is theoretically analyzed. The force and thermal balance on a single plume detached from the thermal boundary layer yields a set of coupled nonlinear equations, whose dynamics is related to the Lorenz equations. For Prandtl and Rayleigh numbers in the range 10(-2) < or = Pr < or = 10(3) and 10(7) < or = Ra < or = 10(12), the model has the following features: (i) chaotic reversals may be exhibited at Ra > or = 10(7); (ii) the Reynolds number based on the root mean square velocity scales as Re(rms) approximately Ra([0.41...0.47]) (depending on Pr), and as Re(rms) approximately Pr(-[0.66...0.76]) (depending on Ra); and (iii) the mean reversal frequency follows an effective scaling law omega/(nu L(-2)) approximately Pr(-(0.64 +/- 0.01))Ra(0.44 +/- 0.01). The phase diagram of the model is sketched, and the observed transitions are discussed.

Microfluidic approach of Sickled Cell Anemia

NASA Astrophysics Data System (ADS)

Abkarian, Manouk; Loiseau, Etienne; Massiera, Gladys

2012-11-01

Sickle Cell Anemia is a disorder of the microcirculation caused by a genetic point mutation that produces an altered hemoglobin protein called HbS. HbS self-assembles reversibly into long rope like fibers inside the red blood cells. The resulting distorded sickled red blood cells are believed to block the smallest capillaries of the tissues producing anemia. Despite the large amount of work that provided a thorough understanding of HbS polymerization in bulk as well as in intact red blood cells at rest, no consequent cellular scale approaches of the study of polymerization and its link to the capillary obstruction have been proposed in microflow, although the problem of obstruction is in essence a circulatory problem. Here, we use microfluidic channels, designed to mimic physiological conditions (flow velocity, oxygen concentration, hematocrit...) of the microcirculation to carry out a biomimetic study at the cellular scale of sickled cell vaso-occlusion. We show that flow geometry, oxygen concentration, white blood cells and free hemoglobin S are essential in the formation of original cell aggregates which could play a role in the vaso-occlusion events.

An efficient and rapid influenza gene cloning strategy for reverse genetics system.

PubMed

Shao, Hongxia; Fan, Zhonglei; Wan, Zhimin; Tian, Xiaoyan; Chen, Hongjun; Perez, Daniel R; Qin, Aijian; Ye, Jianqiang

2015-09-15

Influenza reverse genetics plays vital roles in understanding influenza molecular characteristics and vaccine development. However, current influenza reverse genetics heavily depends on restriction enzyme and ligation for gene cloning. The traditional cloning process of influenza eight fragments for virus rescuing generally requires considerable work. To simplify and increase the pace of gene cloning for influenza reverse genetics system, we developed a rapid restriction enzyme-free ExnaseTM II-based in vitro recombination approach for influenza gene cloning. We used this strategy rapidly and successfully to clone influenza eight genes both from viruses PR8 and H9N2 for virus rescuing. Our data demonstrate that the strategy developed here can accelerate the process of influenza gene cloning into reverse genetics system, and shows high potential for applications in both influenza basic and applied research. Copyright © 2015 Elsevier B.V. All rights reserved.

Next Generation Analytic Tools for Large Scale Genetic Epidemiology Studies of Complex Diseases

PubMed Central

Mechanic, Leah E.; Chen, Huann-Sheng; Amos, Christopher I.; Chatterjee, Nilanjan; Cox, Nancy J.; Divi, Rao L.; Fan, Ruzong; Harris, Emily L.; Jacobs, Kevin; Kraft, Peter; Leal, Suzanne M.; McAllister, Kimberly; Moore, Jason H.; Paltoo, Dina N.; Province, Michael A.; Ramos, Erin M.; Ritchie, Marylyn D.; Roeder, Kathryn; Schaid, Daniel J.; Stephens, Matthew; Thomas, Duncan C.; Weinberg, Clarice R.; Witte, John S.; Zhang, Shunpu; Zöllner, Sebastian; Feuer, Eric J.; Gillanders, Elizabeth M.

2012-01-01

Over the past several years, genome-wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To identify obstacles to future progress in genetic epidemiology research and provide recommendations to NIH for overcoming these barriers, the National Cancer Institute sponsored a workshop entitled “Next Generation Analytic Tools for Large-Scale Genetic Epidemiology Studies of Complex Diseases” on September 15–16, 2010. The goal of the workshop was to facilitate discussions on (1) statistical strategies and methods to efficiently identify genetic and environmental factors contributing to the risk of complex disease; and (2) how to develop, apply, and evaluate these strategies for the design, analysis, and interpretation of large-scale complex disease association studies in order to guide NIH in setting the future agenda in this area of research. The workshop was organized as a series of short presentations covering scientific (gene-gene and gene-environment interaction, complex phenotypes, and rare variants and next generation sequencing) and methodological (simulation modeling and computational resources and data management) topic areas. Specific needs to advance the field were identified during each session and are summarized. PMID:22147673

Molecular inversion probe assay.

PubMed

Absalan, Farnaz; Ronaghi, Mostafa

2007-01-01

We have described molecular inversion probe technologies for large-scale genetic analyses. This technique provides a comprehensive and powerful tool for the analysis of genetic variation and enables affordable, large-scale studies that will help uncover the genetic basis of complex disease and explain the individual variation in response to therapeutics. Major applications of the molecular inversion probes (MIP) technologies include targeted genotyping from focused regions to whole-genome studies, and allele quantification of genomic rearrangements. The MIP technology (used in the HapMap project) provides an efficient, scalable, and affordable way to score polymorphisms in case/control populations for genetic studies. The MIP technology provides the highest commercially available multiplexing levels and assay conversion rates for targeted genotyping. This enables more informative, genome-wide studies with either the functional (direct detection) approach or the indirect detection approach.

PhOBF1, a petunia OCS element binding factor, plays an important role in antiviral RNA silencing

USDA-ARS?s Scientific Manuscript database

Virus-induced gene silencing (VIGS) is a common strategy of reverse genetics for characterizing function of genes in plant. The detailed mechanism governing RNA silencing efficiency triggered by virus is largely unclear. Here, we revealed that a petunia (Petunia hybrida) ocs element binding factor, ...

Synthetically chemical-electrical mechanism for controlling large scale reversible deformation of liquid metal objects

PubMed Central

Zhang, Jie; Sheng, Lei; Liu, Jing

2014-01-01

Reversible deformation of a machine holds enormous promise across many scientific areas ranging from mechanical engineering to applied physics. So far, such capabilities are still hard to achieve through conventional rigid materials or depending mainly on elastomeric materials, which however own rather limited performances and require complicated manipulations. Here, we show a basic strategy which is fundamentally different from the existing ones to realize large scale reversible deformation through controlling the working materials via the synthetically chemical-electrical mechanism (SCHEME). Such activity incorporates an object of liquid metal gallium whose surface area could spread up to five times of its original size and vice versa under low energy consumption. Particularly, the alterable surface tension based on combination of chemical dissolution and electrochemical oxidation is ascribed to the reversible shape transformation, which works much more flexible than many former deformation principles through converting electrical energy into mechanical movement. A series of very unusual phenomena regarding the reversible configurational shifts are disclosed with dominant factors clarified. This study opens a generalized way to combine the liquid metal serving as shape-variable element with the SCHEME to compose functional soft machines, which implies huge potential for developing future smart robots to fulfill various complicated tasks. PMID:25408295

Synthetically chemical-electrical mechanism for controlling large scale reversible deformation of liquid metal objects.

PubMed

Zhang, Jie; Sheng, Lei; Liu, Jing

2014-11-19

Reversible deformation of a machine holds enormous promise across many scientific areas ranging from mechanical engineering to applied physics. So far, such capabilities are still hard to achieve through conventional rigid materials or depending mainly on elastomeric materials, which however own rather limited performances and require complicated manipulations. Here, we show a basic strategy which is fundamentally different from the existing ones to realize large scale reversible deformation through controlling the working materials via the synthetically chemical-electrical mechanism (SCHEME). Such activity incorporates an object of liquid metal gallium whose surface area could spread up to five times of its original size and vice versa under low energy consumption. Particularly, the alterable surface tension based on combination of chemical dissolution and electrochemical oxidation is ascribed to the reversible shape transformation, which works much more flexible than many former deformation principles through converting electrical energy into mechanical movement. A series of very unusual phenomena regarding the reversible configurational shifts are disclosed with dominant factors clarified. This study opens a generalized way to combine the liquid metal serving as shape-variable element with the SCHEME to compose functional soft machines, which implies huge potential for developing future smart robots to fulfill various complicated tasks.

Synthetically chemical-electrical mechanism for controlling large scale reversible deformation of liquid metal objects

NASA Astrophysics Data System (ADS)

Zhang, Jie; Sheng, Lei; Liu, Jing

2014-11-01

Reversible deformation of a machine holds enormous promise across many scientific areas ranging from mechanical engineering to applied physics. So far, such capabilities are still hard to achieve through conventional rigid materials or depending mainly on elastomeric materials, which however own rather limited performances and require complicated manipulations. Here, we show a basic strategy which is fundamentally different from the existing ones to realize large scale reversible deformation through controlling the working materials via the synthetically chemical-electrical mechanism (SCHEME). Such activity incorporates an object of liquid metal gallium whose surface area could spread up to five times of its original size and vice versa under low energy consumption. Particularly, the alterable surface tension based on combination of chemical dissolution and electrochemical oxidation is ascribed to the reversible shape transformation, which works much more flexible than many former deformation principles through converting electrical energy into mechanical movement. A series of very unusual phenomena regarding the reversible configurational shifts are disclosed with dominant factors clarified. This study opens a generalized way to combine the liquid metal serving as shape-variable element with the SCHEME to compose functional soft machines, which implies huge potential for developing future smart robots to fulfill various complicated tasks.

Genes mirror geography in Daphnia magna.

PubMed

Fields, Peter D; Reisser, Céline; Dukić, Marinela; Haag, Christoph R; Ebert, Dieter

2015-09-01

Identifying the presence and magnitude of population genetic structure remains a major consideration in evolutionary biology as doing so allows one to understand the demographic history of a species as well as make predictions of how the evolutionary process will proceed. Next-generation sequencing methods allow us to reconsider previous ideas and conclusions concerning the distribution of genetic variation, and what this distribution implies about a given species evolutionary history. A previous phylogeographic study of the crustacean Daphnia magna suggested that, despite strong genetic differentiation among populations at a local scale, the species shows only moderate genetic structure across its European range, with a spatially patchy occurrence of individual lineages. We apply RAD sequencing to a sample of D. magna collected across a wide swath of the species' Eurasian range and analyse the data using principle component analysis (PCA) of genetic variation and Procrustes analytical approaches, to quantify spatial genetic structure. We find remarkable consistency between the first two PCA axes and the geographic coordinates of individual sampling points, suggesting that, on a continent-wide scale, genetic differentiation is driven to a large extent by geographic distance. The observed pattern is consistent with unimpeded (i.e. no barriers, landscape or otherwise) migration at large spatial scales, despite the fragmented and patchy nature of favourable habitats at local scales. With high-resolution genetic data similar patterns may be uncovered for other species with wide geographic distributions, allowing an increased understanding of how genetic drift and selection have shaped their evolutionary history. © 2015 John Wiley & Sons Ltd.

Large-Scale Discovery of Induced Point Mutations With High-Throughput TILLING

PubMed Central

Till, Bradley J.; Reynolds, Steven H.; Greene, Elizabeth A.; Codomo, Christine A.; Enns, Linda C.; Johnson, Jessica E.; Burtner, Chris; Odden, Anthony R.; Young, Kim; Taylor, Nicholas E.; Henikoff, Jorja G.; Comai, Luca; Henikoff, Steven

2003-01-01

TILLING (Targeting Induced Local Lesions in Genomes) is a general reverse-genetic strategy that provides an allelic series of induced point mutations in genes of interest. High-throughput TILLING allows the rapid and low-cost discovery of induced point mutations in populations of chemically mutagenized individuals. As chemical mutagenesis is widely applicable and mutation detection for TILLING is dependent only on sufficient yield of PCR products, TILLING can be applied to most organisms. We have developed TILLING as a service to the Arabidopsis community known as the Arabidopsis TILLING Project (ATP). Our goal is to rapidly deliver allelic series of ethylmethanesulfonate-induced mutations in target 1-kb loci requested by the international research community. In the first year of public operation, ATP has discovered, sequenced, and delivered >1000 mutations in >100 genes ordered by Arabidopsis researchers. The tools and methodologies described here can be adapted to create similar facilities for other organisms. PMID:12618384

NR-code: Nonlinear reconstruction code

NASA Astrophysics Data System (ADS)

Yu, Yu; Pen, Ue-Li; Zhu, Hong-Ming

2018-04-01

NR-code applies nonlinear reconstruction to the dark matter density field in redshift space and solves for the nonlinear mapping from the initial Lagrangian positions to the final redshift space positions; this reverses the large-scale bulk flows and improves the precision measurement of the baryon acoustic oscillations (BAO) scale.

Random codon re-encoding induces stable reduction of replicative fitness of Chikungunya virus in primate and mosquito cells.

PubMed

Nougairede, Antoine; De Fabritus, Lauriane; Aubry, Fabien; Gould, Ernest A; Holmes, Edward C; de Lamballerie, Xavier

2013-02-01

Large-scale codon re-encoding represents a powerful method of attenuating viruses to generate safe and cost-effective vaccines. In contrast to specific approaches of codon re-encoding which modify genome-scale properties, we evaluated the effects of random codon re-encoding on the re-emerging human pathogen Chikungunya virus (CHIKV), and assessed the stability of the resultant viruses during serial in cellulo passage. Using different combinations of three 1.4 kb randomly re-encoded regions located throughout the CHIKV genome six codon re-encoded viruses were obtained. Introducing a large number of slightly deleterious synonymous mutations reduced the replicative fitness of CHIKV in both primate and arthropod cells, demonstrating the impact of synonymous mutations on fitness. Decrease of replicative fitness correlated with the extent of re-encoding, an observation that may assist in the modulation of viral attenuation. The wild-type and two re-encoded viruses were passaged 50 times either in primate or insect cells, or in each cell line alternately. These viruses were analyzed using detailed fitness assays, complete genome sequences and the analysis of intra-population genetic diversity. The response to codon re-encoding and adaptation to culture conditions occurred simultaneously, resulting in significant replicative fitness increases for both re-encoded and wild type viruses. Importantly, however, the most re-encoded virus failed to recover its replicative fitness. Evolution of these viruses in response to codon re-encoding was largely characterized by the emergence of both synonymous and non-synonymous mutations, sometimes located in genomic regions other than those involving re-encoding, and multiple convergent and compensatory mutations. However, there was a striking absence of codon reversion (<0.4%). Finally, multiple mutations were rapidly fixed in primate cells, whereas mosquito cells acted as a brake on evolution. In conclusion, random codon re-encoding provides important information on the evolution and genetic stability of CHIKV viruses and could be exploited to develop a safe, live attenuated CHIKV vaccine.

Nocturnal Reversed Flows Above Parallel Ridges in Perdigão, Portugal

NASA Astrophysics Data System (ADS)

Krishnamurthy, R.; Fernando, H. J.; Leo, L. S.; Vassallo, D.; Hocut, C. M.; Creegan, E.; Rodriguez, C. V.; Palma, J. L.

2017-12-01

Prediction of topographically forced or induced wind events is extremely important for dispersion modeling and wind energy studies in complex terrain. To improve the current understanding of micro-scale processes over complex terrain, a large-scale field experiment was conducted in Perdigão, Portugal from May 1st, 2017 to June 15th, 2017. Measurements over a periodic valley were performed using 52 meteorological met-masts, 30 Doppler Lidars (scanning & vertical profilers), 2 tethered lifting systems and other remote sensing instruments (Sodar-rass, wind profilers & radiometer), and radiosondes were released every 6 hours over the period of study. The observations showed several cases of flow reversals confined to a thin layer of 70 - 100 m above the ridge under stably stratified conditions. These flow reversals were mostly observed during the lee wave formation over the periodic valley. It was observed that the flow reversal occurs predominantly under two atmospheric conditions: a) presence of large recirculation zones on the lee side of the hill causing a pressure gradient between the lee-side floor and the mountain ridge, and b) local change in the horizontal pressure gradient due to differential heating rates of the neighboring valley atmospheres. Microscale flow simulations could capture these observed flow reversals. Based on the network of tower instruments and remote sensing devices, the development, structure and occurrences of the flow reversals are being analyzed and quantified. Since these flow reversals are observed within the rotor swept area of modern wind turbines, they would drastically increase the fatigue loads on wind turbine blades. This presentation will include reversed flow observations from several synchronized scanning Doppler Lidars and meteorological towers and a theoretical framework for reverse flow over parallel valleys.

Genetically distinct populations of northern shrimp, Pandalus borealis, in the North Atlantic: adaptation to different temperatures as an isolation factor.

PubMed

Jorde, Per Erik; Søvik, Guldborg; Westgaard, Jon-Ivar; Albretsen, Jon; André, Carl; Hvingel, Carsten; Johansen, Torild; Sandvik, Anne Dagrun; Kingsley, Michael; Jørstad, Knut Eirik

2015-04-01

The large-scale population genetic structure of northern shrimp, Pandalus borealis, was investigated over the species' range in the North Atlantic, identifying multiple genetically distinct groups. Genetic divergence among sample localities varied among 10 microsatellite loci (range: FST = -0.0002 to 0.0475) with a highly significant average (FST = 0.0149; P < 0.0001). In contrast, little or no genetic differences were observed among temporal replicates from the same localities (FST = 0.0004; P = 0.33). Spatial genetic patterns were compared to geographic distances, patterns of larval drift obtained through oceanographic modelling, and temperature differences, within a multiple linear regression framework. The best-fit model included all three factors and explained approximately 29% of all spatial genetic divergence. However, geographic distance and larval drift alone had only minor effects (2.5-4.7%) on large-scale genetic differentiation patterns, whereas bottom temperature differences explained most (26%). Larval drift was found to promote genetic homogeneity in parts of the study area with strong currents, but appeared ineffective across large temperature gradients. These findings highlight the breakdown of gene flow in a species with a long pelagic larval phase (up to 3 months) and indicate a role for local adaptation to temperature conditions in promoting evolutionary diversification and speciation in the marine environment. © 2015 John Wiley & Sons Ltd.

How Large Scale Flows in the Solar Convection Zone may Influence Solar Activity

NASA Technical Reports Server (NTRS)

Hathaway, D. H.

2004-01-01

Large scale flows within the solar convection zone are the primary drivers of the Sun s magnetic activity cycle. Differential rotation can amplify the magnetic field and convert poloidal fields into toroidal fields. Poleward meridional flow near the surface can carry magnetic flux that reverses the magnetic poles and can convert toroidal fields into poloidal fields. The deeper, equatorward meridional flow can carry magnetic flux toward the equator where it can reconnect with oppositely directed fields in the other hemisphere. These axisymmetric flows are themselves driven by large scale convective motions. The effects of the Sun s rotation on convection produce velocity correlations that can maintain the differential rotation and meridional circulation. These convective motions can influence solar activity themselves by shaping the large-scale magnetic field pattern. While considerable theoretical advances have been made toward understanding these large scale flows, outstanding problems in matching theory to observations still remain.

Methanol production from Eucalyptus wood chips. Working Document 2. Vegetative propagation of Eucalypts

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

Fishkind, H.H.

1982-04-01

The feasibility of large-scale plantation establishment by various methods was examined, and the following conclusions were reached: seedling plantations are limited in potential yield due to genetic variation among the planting stock and often inadequate supplies of appropriate seed; vegetative propagation by rooted cuttings can provide good genetic uniformity of select hybrid planting stock; however, large-scale production requires establishment and maintenance of extensive cutting orchards. The collection of shoots and preparation of cuttings, although successfully implemented in the Congo and Brazil, would not be economically feasible in Florida for large-scale plantations; tissue culture propagation of select hybrid eucalypts offers themore » only opportunity to produce the very large number of trees required to establish the energy plantation. The cost of tissue culture propagation, although higher than seedling production, is more than off-set by the increased productivity of vegetative plantations established from select hybrid Eucalyptus.« less

Generation of recombinant rotaviruses expressing fluorescent proteins using an optimized reverse genetics system.

PubMed

Komoto, Satoshi; Fukuda, Saori; Ide, Tomihiko; Ito, Naoto; Sugiyama, Makoto; Yoshikawa, Tetsushi; Murata, Takayuki; Taniguchi, Koki

2018-04-18

An entirely plasmid-based reverse genetics system for rotaviruses was established very recently. We improved the reverse genetics system to generate recombinant rotavirus by transfecting only 11 cDNA plasmids for its 11 gene segments under the condition of increasing the ratio of the cDNA plasmids for NSP2 and NSP5 genes. Utilizing this highly efficient system, we then engineered infectious recombinant rotaviruses expressing bioluminescent (NanoLuc luciferase) and fluorescent (EGFP and mCherry) reporters. These recombinant rotaviruses expressing reporters remained genetically stable during serial passages. Our reverse genetics approach and recombinant rotaviruses carrying reporter genes will be great additions to the tool kit for studying the molecular virology of rotavirus, and for developing future next-generation vaccines and expression vectors. IMPORTANCE Rotavirus is one of the most important pathogens causing severe gastroenteritis in young children worldwide. In this paper, we describe a robust and simple reverse genetics system based on only rotavirus cDNAs, and its application for engineering infectious recombinant rotaviruses harboring bioluminescent (NanoLuc) and fluorescent (EGFP and mCherry) protein genes. This highly efficient reverse genetics system and recombinant RVAs expressing reporters could be powerful tools for the study of different aspects of rotavirus replication. Furthermore, they may be useful for next-generation vaccine production for this medically important virus. Copyright © 2018 American Society for Microbiology.

Polygamy and an absence of fine-scale structure in Dendroctonus ponderosae (Hopk.) (Coleoptera: Curcilionidae) confirmed using molecular markers

PubMed Central

Janes, J K; Roe, A D; Rice, A V; Gorrell, J C; Coltman, D W; Langor, D W; Sperling, F A H

2016-01-01

An understanding of mating systems and fine-scale spatial genetic structure is required to effectively manage forest pest species such as Dendroctonus ponderosae (mountain pine beetle). Here we used genome-wide single-nucleotide polymorphisms to assess the fine-scale genetic structure and mating system of D. ponderosae collected from a single stand in Alberta, Canada. Fine-scale spatial genetic structure was absent within the stand and the majority of genetic variation was best explained at the individual level. Relatedness estimates support previous reports of pre-emergence mating. Parentage assignment tests indicate that a polygamous mating system better explains the relationships among individuals within a gallery than the previously reported female monogamous/male polygynous system. Furthermore, there is some evidence to suggest that females may exploit the galleries of other females, at least under epidemic conditions. Our results suggest that current management models are likely to be effective across large geographic areas based on the absence of fine-scale genetic structure. PMID:26286666

Reverse genetics of Newcastle disease virus

USDA-ARS?s Scientific Manuscript database

Reverse genetics allows the generation of recombinant viruses or vectors used in functional studies, vaccine development, and gene therapy. This technique allows genetic manipulation and cloning of viral genomes, mutation through site-directed mutagenesis, and gene insertion or deletion, among othe...

Reversing storm hotspots on sandy beaches: Spatial and temporal characteristics

USGS Publications Warehouse

List, J.H.; Farris, A.S.; Sullivan, C.

2006-01-01

Coastal erosion hotspots are defined as sections of coast that exhibit significantly higher rates of erosion than adjacent areas. This paper describes the spatial and temporal characteristics of a recently identified type of coastal erosion hotspot, which forms in response to storms on uninterrupted sandy coasts largely free from human intervention. These are referred to here as reversing storm hotspots because the erosion is reversed by accretion of a similar magnitude to the storm-induced erosion. The accretion occurs within a few days or weeks of fair weather after the storm. Reversing storm hotspots observed here, on two US east coast beaches, have a longshore length averaging 3.86 km, a cross-shore excursion (magnitude of erosion or accretion) averaging 15.4 m, and a time scale of days to weeks associated with individual storm events. These spatial and temporal scales clearly distinguish reversing storm hotspots from previously described forms of longshore variability in erosion, including those attributed to several types of shoreline undulations and hotspots associated with long-term shoreline change. 

RNA Virus Reverse Genetics and Vaccine Design

PubMed Central

Stobart, Christopher C.; Moore, Martin L.

2014-01-01

RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines. PMID:24967693

Diffuse pollution of soil and water: Long term trends at large scales?

NASA Astrophysics Data System (ADS)

Grathwohl, P.

2012-04-01

Industrialization and urbanization, which consequently increased pressure on the environment to cause degradation of soil and water quality over more than a century, is still ongoing. The number of potential environmental contaminants detected in surface and groundwater is continuously increasing; from classical industrial and agricultural chemicals, to flame retardants, pharmaceuticals, and personal care products. While point sources of pollution can be managed in principle, diffuse pollution is only reversible at very long time scales if at all. Compounds which were phased out many decades ago such as PCBs or DDT are still abundant in soils, sediments and biota. How diffuse pollution is processed at large scales in space (e.g. catchments) and time (centuries) is unknown. The relevance to the field of processes well investigated at the laboratory scale (e.g. sorption/desorption and (bio)degradation kinetics) is not clear. Transport of compounds is often coupled to the water cycle and in order to assess trends in diffuse pollution, detailed knowledge about the hydrology and the solute fluxes at the catchment scale is required (e.g. input/output fluxes, transformation rates at the field scale). This is also a prerequisite in assessing management options for reversal of adverse trends.

DNA barcoding at riverscape scales: Assessing biodiversity among fishes of the genus Cottus (Teleostei) in northern Rocky Mountain streams

Treesearch

Michael K. Young; Kevin S. McKelvey; Kristine L. Pilgrim; Michael K. Schwartz

2013-01-01

There is growing interest in broad-scale biodiversity assessments that can serve as benchmarks for identifying ecological change. Genetic tools have been used for such assessments for decades, but spatial sampling considerations have largely been ignored. Here, we demonstrate how intensive sampling efforts across a large geographical scale can influence identification...

Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses

PubMed Central

Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nuntawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

2012-01-01

Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate (A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby Canine Kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 29 HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. PMID:22230579

Small organic molecule based flow battery

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

Huskinson, Brian; Marshak, Michael; Aziz, Michael J.

The invention provides an electrochemical cell based on a new chemistry for a flow battery for large scale, e.g., gridscale, electrical energy storage. Electrical energy is stored chemically at an electrochemical electrode by the protonation of small organic molecules called quinones to hydroquinones. The proton is provided by a complementary electrochemical reaction at the other electrode. These reactions are reversed to deliver electrical energy. A flow battery based on this concept can operate as a closed system. The flow battery architecture has scaling advantages over solid electrode batteries for large scale energy storage.

Mendelian randomization in nutritional epidemiology

PubMed Central

Qi, Lu

2013-01-01

Nutritional epidemiology aims to identify dietary and lifestyle causes for human diseases. Causality inference in nutritional epidemiology is largely based on evidence from studies of observational design, and may be distorted by unmeasured or residual confounding and reverse causation. Mendelian randomization is a recently developed methodology that combines genetic and classical epidemiological analysis to infer causality for environmental exposures, based on the principle of Mendel’s law of independent assortment. Mendelian randomization uses genetic variants as proxiesforenvironmentalexposuresofinterest.AssociationsderivedfromMendelian randomization analysis are less likely to be affected by confounding and reverse causation. During the past 5 years, a body of studies examined the causal effects of diet/lifestyle factors and biomarkers on a variety of diseases. The Mendelian randomization approach also holds considerable promise in the study of intrauterine influences on offspring health outcomes. However, the application of Mendelian randomization in nutritional epidemiology has some limitations. PMID:19674341

Generation of EMS-Mutagenized Populations of Arabidopsis thaliana for Polyamine Genetics.

PubMed

Atanasov, Kostadin E; Liu, Changxin; Tiburcio, Antonio F; Alcázar, Rubén

2018-01-01

In the recent years, genetic engineering of polyamine biosynthetic genes has provided evidence for their involvement in plant stress responses and different aspects of plant development. Such approaches are being complemented with the use of reverse genetics, in which mutants affected on a particular trait, tightly associated with polyamines, are isolated and the causal genes mapped. Reverse genetics enables the identification of novel genes in the polyamine pathway, which may be involved in downstream signaling, transport, homeostasis, or perception. Here, we describe a basic protocol for the generation of ethyl methanesulfonate (EMS) mutagenized populations of Arabidopsis thaliana for its use in reverse genetics applied to polyamines.

The genetic architecture of coronary artery disease: current knowledge and future opportunities

USDA-ARS?s Scientific Manuscript database

Recent Findings Large-scale studies in human populations, coupled with rapid advances in genetic technologies over the last decade, have clearly established the association of common genetic variation with risk of CAD. However, the effect sizes of the susceptibility alleles are for the most part mod...

Frequently Asked Questions about Genetic and Genomic Science

MedlinePlus

... of the new genetic and genomic techniques and technologies? Proteomics The suffix "-ome" comes from the Greek ... pharmacogenomics is one of the large-scale "omic" technologies, it can examine the entirety of the genome, ...

Molecular Genetic Analysis of Chlamydia Species.

PubMed

Sixt, Barbara S; Valdivia, Raphael H

2016-09-08

Species of Chlamydia are the etiologic agent of endemic blinding trachoma, the leading cause of bacterial sexually transmitted diseases, significant respiratory pathogens, and a zoonotic threat. Their dependence on an intracellular growth niche and their peculiar developmental cycle are major challenges to elucidating their biology and virulence traits. The last decade has seen tremendous advances in our ability to perform a molecular genetic analysis of Chlamydia species. Major achievements include the generation of large collections of mutant strains, now available for forward- and reverse-genetic applications, and the introduction of a system for plasmid-based transformation enabling complementation of mutations; expression of foreign, modified, or reporter genes; and even targeted gene disruptions. This review summarizes the current status of the molecular genetic toolbox for Chlamydia species and highlights new insights into their biology and new challenges in the nascent field of Chlamydia genetics.

TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network

PubMed Central

Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L.; Costanzo, Michael; Andrews, Brenda; Boone, Charles

2017-01-01

Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae. In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. PMID:28325812

TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network.

PubMed

Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L; Costanzo, Michael; Andrews, Brenda; Boone, Charles

2017-05-05

Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. Copyright © 2017 Usaj et al.

Improving Disease Prediction by Incorporating Family Disease History in Risk Prediction Models with Large-Scale Genetic Data.

PubMed

Gim, Jungsoo; Kim, Wonji; Kwak, Soo Heon; Choi, Hosik; Park, Changyi; Park, Kyong Soo; Kwon, Sunghoon; Park, Taesung; Won, Sungho

2017-11-01

Despite the many successes of genome-wide association studies (GWAS), the known susceptibility variants identified by GWAS have modest effect sizes, leading to notable skepticism about the effectiveness of building a risk prediction model from large-scale genetic data. However, in contrast to genetic variants, the family history of diseases has been largely accepted as an important risk factor in clinical diagnosis and risk prediction. Nevertheless, the complicated structures of the family history of diseases have limited their application in clinical practice. Here, we developed a new method that enables incorporation of the general family history of diseases with a liability threshold model, and propose a new analysis strategy for risk prediction with penalized regression analysis that incorporates both large numbers of genetic variants and clinical risk factors. Application of our model to type 2 diabetes in the Korean population (1846 cases and 1846 controls) demonstrated that single-nucleotide polymorphisms accounted for 32.5% of the variation explained by the predicted risk scores in the test data set, and incorporation of family history led to an additional 6.3% improvement in prediction. Our results illustrate that family medical history provides valuable information on the variation of complex diseases and improves prediction performance. Copyright © 2017 by the Genetics Society of America.

New insights into Kilauea's volcano dynamics brought by large-scale relative relocation of microearthquakes

USGS Publications Warehouse

Got, J.-L.; Okubo, P.

2003-01-01

We investigated the microseismicity recorded in an active volcano to infer information concerning the volcano structure and long-term dynamics, by using relative relocations and focal mechanisms of microearthquakes. There were 32,000 earthquakes of the Mauna Loa and Kilauea volcanoes recorded by more than eight stations of the Hawaiian Volcano Observatory seismic network between 1988 and 1999. We studied 17,000 of these events and relocated more than 70%, with an accuracy ranging from 10 to 500 m. About 75% of these relocated events are located in the vicinity of subhorizontal decollement planes, at a depth of 8-11 km. However, the striking features revealed by these relocation results are steep southeast dipping fault planes working as reverse faults, clearly located below the decollement plane and which intersect it. If this decollement plane coincides with the pre-Mauna Loa seafloor, as hypothesized by numerous authors, such reverse faults rupture the pre-Mauna Loa oceanic crust. The weight of the volcano and pressure in the magma storage system are possible causes of these ruptures, fully compatible with the local stress tensor computed by Gillard et al. [1996]. Reverse faults are suspected of producing scarps revealed by kilometer-long horizontal slip-perpendicular lineations along the decollement surface and therefore large-scale roughness, asperities, and normal stress variations. These are capable of generating stick-slip, large-magnitude earthquakes, the spatial microseismic pattern observed in the south flank of Kilauea volcano, and Hilina-type instabilities. Rupture intersecting the decollement surface, causing its large-scale roughness, may be an important parameter controlling the growth of Hawaiian volcanoes.

Accurate population genetic measurements require cryptic species identification in corals

NASA Astrophysics Data System (ADS)

Sheets, Elizabeth A.; Warner, Patricia A.; Palumbi, Stephen R.

2018-06-01

Correct identification of closely related species is important for reliable measures of gene flow. Incorrectly lumping individuals of different species together has been shown to over- or underestimate population differentiation, but examples highlighting when these different results are observed in empirical datasets are rare. Using 199 single nucleotide polymorphisms, we assigned 768 individuals in the Acropora hyacinthus and A. cytherea morphospecies complexes to each of eight previously identified cryptic genetic species and measured intraspecific genetic differentiation across three geographic scales (within reefs, among reefs within an archipelago, and among Pacific archipelagos). We then compared these calculations to estimated genetic differentiation at each scale with all cryptic genetic species mixed as if we could not tell them apart. At the reef scale, correct genetic species identification yielded lower F ST estimates and fewer significant comparisons than when species were mixed, raising estimates of short-scale gene flow. In contrast, correct genetic species identification at large spatial scales yielded higher F ST measurements than mixed-species comparisons, lowering estimates of long-term gene flow among archipelagos. A meta-analysis of published population genetic studies in corals found similar results: F ST estimates at small spatial scales were lower and significance was found less often in studies that controlled for cryptic species. Our results and these prior datasets controlling for cryptic species suggest that genetic differentiation among local reefs may be lower than what has generally been reported in the literature. Not properly controlling for cryptic species structure can bias population genetic analyses in different directions across spatial scales, and this has important implications for conservation strategies that rely on these estimates.

Evaluation of Penalized and Nonpenalized Methods for Disease Prediction with Large-Scale Genetic Data.

PubMed

Won, Sungho; Choi, Hosik; Park, Suyeon; Lee, Juyoung; Park, Changyi; Kwon, Sunghoon

2015-01-01

Owing to recent improvement of genotyping technology, large-scale genetic data can be utilized to identify disease susceptibility loci and this successful finding has substantially improved our understanding of complex diseases. However, in spite of these successes, most of the genetic effects for many complex diseases were found to be very small, which have been a big hurdle to build disease prediction model. Recently, many statistical methods based on penalized regressions have been proposed to tackle the so-called "large P and small N" problem. Penalized regressions including least absolute selection and shrinkage operator (LASSO) and ridge regression limit the space of parameters, and this constraint enables the estimation of effects for very large number of SNPs. Various extensions have been suggested, and, in this report, we compare their accuracy by applying them to several complex diseases. Our results show that penalized regressions are usually robust and provide better accuracy than the existing methods for at least diseases under consideration.

A new model for extinction and recolonization in two dimensions: quantifying phylogeography.

PubMed

Barton, Nicholas H; Kelleher, Jerome; Etheridge, Alison M

2010-09-01

Classical models of gene flow fail in three ways: they cannot explain large-scale patterns; they predict much more genetic diversity than is observed; and they assume that loosely linked genetic loci evolve independently. We propose a new model that deals with these problems. Extinction events kill some fraction of individuals in a region. These are replaced by offspring from a small number of parents, drawn from the preexisting population. This model of evolution forwards in time corresponds to a backwards model, in which ancestral lineages jump to a new location if they are hit by an event, and may coalesce with other lineages that are hit by the same event. We derive an expression for the identity in allelic state, and show that, over scales much larger than the largest event, this converges to the classical value derived by Wright and Malécot. However, rare events that cover large areas cause low genetic diversity, large-scale patterns, and correlations in ancestry between unlinked loci. © 2010 The Author(s). Journal compilation © 2010 The Society for the Study of Evolution.

A new way to protect privacy in large-scale genome-wide association studies.

PubMed

Kamm, Liina; Bogdanov, Dan; Laur, Sven; Vilo, Jaak

2013-04-01

Increased availability of various genotyping techniques has initiated a race for finding genetic markers that can be used in diagnostics and personalized medicine. Although many genetic risk factors are known, key causes of common diseases with complex heritage patterns are still unknown. Identification of such complex traits requires a targeted study over a large collection of data. Ideally, such studies bring together data from many biobanks. However, data aggregation on such a large scale raises many privacy issues. We show how to conduct such studies without violating privacy of individual donors and without leaking the data to third parties. The presented solution has provable security guarantees. Supplementary data are available at Bioinformatics online.

From drug to protein: using yeast genetics for high-throughput target discovery.

PubMed

Armour, Christopher D; Lum, Pek Yee

2005-02-01

The budding yeast Saccharomyces cerevisiae has long been an effective eukaryotic model system for understanding basic cellular processes. The genetic tractability and ease of manipulation in the laboratory make yeast well suited for large-scale chemical and genetic screens. Several recent studies describing the use of yeast genetics for high-throughput drug target identification are discussed in this review.

A novel reverse genetics system for production of infectious West Nile virus using homologous recombination in mammalian cells.

PubMed

Kobayashi, Shintaro; Yoshii, Kentaro; Hirano, Minato; Muto, Memi; Kariwa, Hiroaki

2017-02-01

Reverse genetics systems facilitate investigation of many aspects of the life cycle and pathogenesis of viruses. However, genetic instability in Escherichia coli has hampered development of a reverse genetics system for West Nile virus (WNV). In this study, we developed a novel reverse genetics system for WNV based on homologous recombination in mammalian cells. Introduction of the DNA fragment coding for the WNV structural protein together with a DNA-based replicon resulted in the release of infectious WNV. The growth rate and plaque size of the recombinant virus were almost identical to those of the parent WNV. Furthermore, chimeric WNV was produced by introducing the DNA fragment coding for the structural protein and replicon plasmid derived from various strains. Here, we report development of a novel system that will facilitate research into WNV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Virus-Induced Gene Silencing in Cultivated Cotton (Gossypium spp.) Using Tobacco Rattle Virus.

PubMed

Mustafa, Roma; Shafiq, Muhammad; Mansoor, Shahid; Briddon, Rob W; Scheffler, Brian E; Scheffler, Jodi; Amin, Imran

2016-01-01

The study described here has optimized the conditions for virus-induced gene silencing (VIGS) in three cultivated cotton species (Gossypium hirsutum, G. arboreum, and G. herbaceum) using a Tobacco rattle virus (TRV) vector. The system was used to silence the homolog of the Arabidopsis thaliana chloroplastos alterados 1 (AtCLA1) gene, involved in chloroplast development, in G. herbaceum, G. arboreum, and six commercial G. hirsutum cultivars. All plants inoculated with the TRV vector to silence CLA1 developed a typical albino phenotype indicative of silencing this gene. Although silencing in G. herbaceum and G. arboreum was complete, silencing efficiency differed for each G. hirsutum cultivar. Reverse transcriptase polymerase chain reaction (PCR) and real-time quantitative PCR showed a reduction in mRNA levels of the CLA1 homolog in all three species, with the highest efficiency (lowest CLA1 mRNA levels) in G. arboreum followed by G. herbaceum and G. hirsutum. The results indicate that TRV is a useful vector for VIGS in Gossypium species. However, selection of host cultivar is important. With the genome sequences of several cotton species recently becoming publicly available, this system has the potential to provide a very powerful tool for the rapid, large-scale reverse-genetic analysis of genes in Gossypium spp.

Challenges in the management of the blood supply.

PubMed

Williamson, Lorna M; Devine, Dana V

2013-05-25

Although blood suppliers are seeing short-term reductions in blood demand as a result of initiatives in patient blood management, modelling suggests that during the next 5-10 years, blood availability in developed countries will need to increase again to meet the demands of ageing populations. Increasing of the blood supply raises many challenges; new approaches to recruitment and retainment of future generations of blood donors will be needed, and care will be necessary to avoid taking too much blood from these donors. Integrated approaches in blood stock management between transfusion services and hospitals will be important to minimise wastage--eg, by use of supply chain solutions from industry. Cross-disciplinary systems for patient blood management need to be developed to lessen the need for transfusion--eg, by early identification and reversal of anaemia with haematinics or by reversal of the underlying cause. Personalised medicine could be applied to match donors to patients, not only with extended blood typing, but also by using genetically determined storage characteristics of blood components. Growing of red cells or platelets in large quantities from stem cells is a possibility in the future, but challenges of cost, scaling up, and reproducibility remain to be solved. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pleistocene and ecological effects on continental-scale genetic differentiation in the bobcat (Lynx rufus).

PubMed

Reding, Dawn M; Bronikowski, Anne M; Johnson, Warren E; Clark, William R

2012-06-01

The potential for widespread, mobile species to exhibit genetic structure without clear geographic barriers is a topic of growing interest. Yet the patterns and mechanisms of structure--particularly over broad spatial scales--remain largely unexplored for these species. Bobcats occur across North America and possess many characteristics expected to promote gene flow. To test whether historical, topographic or ecological factors have influenced genetic differentiation in this species, we analysed 1 kb mtDNA sequence and 15 microsatellite loci from over 1700 samples collected across its range. The primary signature in both marker types involved a longitudinal cline with a sharp transition, or suture zone, occurring along the Great Plains. Thus, the data distinguished bobcats in the eastern USA from those in the western half, with no obvious physical barrier to gene flow. Demographic analyses supported a scenario of expansion from separate Pleistocene refugia, with the Great Plains representing a zone of secondary contact. Substructure within the two main lineages likely reflected founder effects, ecological factors, anthropogenic/topographic effects or a combination of these forces. Two prominent topographic features, the Mississippi River and Rocky Mountains, were not supported as significant genetic barriers. Ecological regions and environmental correlates explained a small but significant proportion of genetic variation. Overall, results implicate historical processes as the primary cause of broad-scale genetic differentiation, but contemporary forces seem to also play a role in promoting and maintaining structure. Despite the bobcat's mobility and broad niche, large-scale landscape changes have contributed to significant and complex patterns of genetic structure. © 2012 Blackwell Publishing Ltd.

DNA sequence variation of wild barley Hordeum spontaneum (L.) across environmental gradients in Israel

PubMed Central

Bedada, G; Westerbergh, A; Nevo, E; Korol, A; Schmid, K J

2014-01-01

Wild barley Hordeum spontaneum (L.) shows a wide geographic distribution and ecological diversity. A key question concerns the spatial scale at which genetic differentiation occurs and to what extent it is driven by natural selection. The Levant region exhibits a strong ecological gradient along the North–South axis, with numerous small canyons in an East–West direction and with small-scale environmental gradients on the opposing North- and South-facing slopes. We sequenced 34 short genomic regions in 54 accessions of wild barley collected throughout Israel and from the opposing slopes of two canyons. The nucleotide diversity of the total sample is 0.0042, which is about two-thirds of a sample from the whole species range (0.0060). Thirty accessions collected at ‘Evolution Canyon' (EC) at Nahal Oren, close to Haifa, have a nucleotide diversity of 0.0036, and therefore harbor a large proportion of the genetic diversity. There is a high level of genetic clustering throughout Israel and within EC, which roughly differentiates the slopes. Accessions from the hot and dry South-facing slope have significantly reduced genetic diversity and are genetically more distinct from accessions from the North-facing slope, which are more similar to accessions from other regions in Northern Israel. Statistical population models indicate that wild barley within the EC consist of three separate genetic clusters with substantial gene flow. The data indicate a high level of population structure at large and small geographic scales that shows isolation-by-distance, and is also consistent with ongoing natural selection contributing to genetic differentiation at a small geographic scale. PMID:24619177

Large-scale recovery of an endangered amphibian despite ongoing exposure to multiple stressors

USGS Publications Warehouse

Knapp, Roland A.; Fellers, Gary M.; Kleeman, Patrick M.; Miller, David A. W.; Vrendenburg, Vance T.; Rosenblum, Erica Bree; Briggs, Cheryl J.

2016-01-01

Amphibians are one of the most threatened animal groups, with 32% of species at risk for extinction. Given this imperiled status, is the disappearance of a large fraction of the Earth’s amphibians inevitable, or are some declining species more resilient than is generally assumed? We address this question in a species that is emblematic of many declining amphibians, the endangered Sierra Nevada yellow-legged frog (Rana sierrae). Based on >7,000 frog surveys conducted across Yosemite National Park over a 20-y period, we show that, after decades of decline and despite ongoing exposure to multiple stressors, including introduced fish, the recently emerged disease chytridiomycosis, and pesticides, R. sierrae abundance increased sevenfold during the study and at a rate of 11% per year. These increases occurred in hundreds of populations throughout Yosemite, providing a rare example of amphibian recovery at an ecologically relevant spatial scale. Results from a laboratory experiment indicate that these increases may be in part because of reduced frog susceptibility to chytridiomycosis. The disappearance of nonnative fish from numerous water bodies after cessation of stocking also contributed to the recovery. The large-scale increases in R. sierrae abundance that we document suggest that, when habitats are relatively intact and stressors are reduced in their importance by active management or species’ adaptive responses, declines of some amphibians may be partially reversible, at least at a regional scale. Other studies conducted over similarly large temporal and spatial scales are critically needed to provide insight and generality about the reversibility of amphibian declines at a global scale.

Large-scale recovery of an endangered amphibian despite ongoing exposure to multiple stressors.

PubMed

Knapp, Roland A; Fellers, Gary M; Kleeman, Patrick M; Miller, David A W; Vredenburg, Vance T; Rosenblum, Erica Bree; Briggs, Cheryl J

2016-10-18

Amphibians are one of the most threatened animal groups, with 32% of species at risk for extinction. Given this imperiled status, is the disappearance of a large fraction of the Earth's amphibians inevitable, or are some declining species more resilient than is generally assumed? We address this question in a species that is emblematic of many declining amphibians, the endangered Sierra Nevada yellow-legged frog (Rana sierrae). Based on >7,000 frog surveys conducted across Yosemite National Park over a 20-y period, we show that, after decades of decline and despite ongoing exposure to multiple stressors, including introduced fish, the recently emerged disease chytridiomycosis, and pesticides, R. sierrae abundance increased sevenfold during the study and at a rate of 11% per year. These increases occurred in hundreds of populations throughout Yosemite, providing a rare example of amphibian recovery at an ecologically relevant spatial scale. Results from a laboratory experiment indicate that these increases may be in part because of reduced frog susceptibility to chytridiomycosis. The disappearance of nonnative fish from numerous water bodies after cessation of stocking also contributed to the recovery. The large-scale increases in R. sierrae abundance that we document suggest that, when habitats are relatively intact and stressors are reduced in their importance by active management or species' adaptive responses, declines of some amphibians may be partially reversible, at least at a regional scale. Other studies conducted over similarly large temporal and spatial scales are critically needed to provide insight and generality about the reversibility of amphibian declines at a global scale.

Large-scale recovery of an endangered amphibian despite ongoing exposure to multiple stressors

PubMed Central

Knapp, Roland A.; Fellers, Gary M.; Kleeman, Patrick M.; Miller, David A. W.; Rosenblum, Erica Bree; Briggs, Cheryl J.

2016-01-01

Amphibians are one of the most threatened animal groups, with 32% of species at risk for extinction. Given this imperiled status, is the disappearance of a large fraction of the Earth’s amphibians inevitable, or are some declining species more resilient than is generally assumed? We address this question in a species that is emblematic of many declining amphibians, the endangered Sierra Nevada yellow-legged frog (Rana sierrae). Based on >7,000 frog surveys conducted across Yosemite National Park over a 20-y period, we show that, after decades of decline and despite ongoing exposure to multiple stressors, including introduced fish, the recently emerged disease chytridiomycosis, and pesticides, R. sierrae abundance increased sevenfold during the study and at a rate of 11% per year. These increases occurred in hundreds of populations throughout Yosemite, providing a rare example of amphibian recovery at an ecologically relevant spatial scale. Results from a laboratory experiment indicate that these increases may be in part because of reduced frog susceptibility to chytridiomycosis. The disappearance of nonnative fish from numerous water bodies after cessation of stocking also contributed to the recovery. The large-scale increases in R. sierrae abundance that we document suggest that, when habitats are relatively intact and stressors are reduced in their importance by active management or species’ adaptive responses, declines of some amphibians may be partially reversible, at least at a regional scale. Other studies conducted over similarly large temporal and spatial scales are critically needed to provide insight and generality about the reversibility of amphibian declines at a global scale. PMID:27698128

Analysis of efficiency of waste reverse logistics for recycling.

PubMed

Veiga, Marcelo M

2013-10-01

Brazil is an agricultural country with the highest pesticide consumption in the world. Historically, pesticide packaging has not been disposed of properly. A federal law requires the chemical industry to provide proper waste management for pesticide-related products. A reverse logistics program was implemented, which has been hailed a great success. This program was designed to target large rural communities, where economy of scale can take place. Over the last 10 years, the recovery rate has been very poor in most small rural communities. The objective of this study was to analyze the case of this compulsory reverse logistics program for pesticide packaging under the recent Brazilian Waste Management Policy, which enforces recycling as the main waste management solution. This results of this exploratory research indicate that despite its aggregate success, the reverse logistics program is not efficient for small rural communities. It is not possible to use the same logistic strategy for small and large communities. The results also indicate that recycling might not be the optimal solution, especially in developing countries with unsatisfactory recycling infrastructure and large transportation costs. Postponement and speculation strategies could be applied for improving reverse logistics performance. In most compulsory reverse logistics programs, there is no economical solution. Companies should comply with the law by ranking cost-effective alternatives.

Pregnancy rate and birth rate of calves from a large-scale IVF program using reverse-sorted semen in Bos indicus, Bos indicus-taurus, and Bos taurus cattle.

PubMed

Morotti, F; Sanches, B V; Pontes, J H F; Basso, A C; Siqueira, E R; Lisboa, L A; Seneda, M M

2014-03-15

Obtaining sexed sperm from previously frozen doses (reverse-sorted semen [RSS]) provides an important advantage because of the possibility of using the semen of bulls with desired genetic attributes that have died or have become infertile but from whom frozen semen is available. We report the efficiency of RSS on the pregnancy rate and birth rate of calves in a large-scale program using ovum pick-up and in vitro embryo production (IVEP) from Bos indicus, Bos indicus-taurus, and Bos taurus cattle. From 645 ovum pick-up procedures (Holstein, Gir, and Nelore), 9438 viable oocytes were recovered. A dose of frozen semen (Holstein, Nelore, Brahman, Gir, and Braford) was thawed, and the sperm were sex-sorted and cooled for use in IVF. Additionally, IVF with sperm from three Holstein bulls with freeze-thawed, sex-sorted (RSS) or sex-sorted, freeze-thawed (control) was tested. A total of 2729 embryos were produced, exhibiting a mean blastocyst rate of 29%. Heifers and cows selected for adequate body condition, estrus, and health received 2404 embryos, and 60 days later, a 41% average pregnancy rate was observed. A total of 966 calves were born, and 910 were of a predetermined sex, with an average of 94% accuracy in determining the sex. Despite the lower blastocyst rate with freeze-thawed, sex-sorted semen compared with sex-sorted semen, (P < 0.05), the pregnancy rate (bull I, 45% vs. 40%; II, 35% vs. 50%; and III, 47% vs. 48% for RSS and control, respectively; P > 0.05) and sex-sorted efficiency (bull I, 93% vs. 98%; II, 96% vs. 94%; and III, 96% vs. 97% for RSS and control, respectively; P > 0.05) were similar for each of the three bulls regardless of the sperm type used in the IVF. The sexing of previously frozen semen, associated with IVEP, produces viable embryos with a pregnancy rate of up to 40%, and calves of the desired sex are born even if the paternal bull has acquired some infertility, died, or is located a long distance from the sexing laboratory. Furthermore, these data show the feasibility of the process even when used in a large-scale IVEP program. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic structure of populations of whale sharks among ocean basins and evidence for their historic rise and recent decline.

PubMed

Vignaud, Thomas M; Maynard, Jeffrey A; Leblois, Raphael; Meekan, Mark G; Vázquez-Juárez, Ricardo; Ramírez-Macías, Dení; Pierce, Simon J; Rowat, David; Berumen, Michael L; Beeravolu, Champak; Baksay, Sandra; Planes, Serge

2014-05-01

This study presents genetic evidence that whale sharks, Rhincodon typus, are comprised of at least two populations that rarely mix and is the first to document a population expansion. Relatively high genetic structure is found when comparing sharks from the Gulf of Mexico with sharks from the Indo-Pacific. If mixing occurs between the Indian and Atlantic Oceans, it is not sufficient to counter genetic drift. This suggests whale sharks are not all part of a single global metapopulation. The significant population expansion we found was indicated by both microsatellite and mitochondrial DNA. The expansion may have happened during the Holocene, when tropical species could expand their range due to sea-level rise, eliminating dispersal barriers and increasing plankton productivity. However, the historic trend of population increase may have reversed recently. Declines in genetic diversity are found for 6 consecutive years at Ningaloo Reef in Australia. The declines in genetic diversity being seen now in Australia may be due to commercial-scale harvesting of whale sharks and collision with boats in past decades in other countries in the Indo-Pacific. The study findings have implications for models of population connectivity for whale sharks and advocate for continued focus on effective protection of the world's largest fish at multiple spatial scales. © 2014 John Wiley & Sons Ltd.

Characterizing dispersal patterns in a threatened seabird with limited genetic structure

Treesearch

Laurie A. Hall; Per J. Palsboll; Steven R. Beissinger; James T. Harvey; Martine Berube; Martin G. Raphael; Kim Nelson; Richard T. Golightly; Laura McFarlane-Tranquilla; Scott H. Newman; M. Zachariah Peery

2009-01-01

Genetic assignment methods provide an appealing approach for characterizing dispersal patterns on ecological time scales, but require sufficient genetic differentiation to accurately identify migrants and a large enough sample size of migrants to, for example, compare dispersal between sexes or age classes. We demonstrate that assignment methods can be rigorously used...

Coordinated phenotype switching with large-scale chromosome flip-flop inversion observed in bacteria.

PubMed

Cui, Longzhu; Neoh, Hui-min; Iwamoto, Akira; Hiramatsu, Keiichi

2012-06-19

Genome inversions are ubiquitous in organisms ranging from prokaryotes to eukaryotes. Typical examples can be identified by comparing the genomes of two or more closely related organisms, where genome inversion footprints are clearly visible. Although the evolutionary implications of this phenomenon are huge, little is known about the function and biological meaning of this process. Here, we report our findings on a bacterium that generates a reversible, large-scale inversion of its chromosome (about half of its total genome) at high frequencies of up to once every four generations. This inversion switches on or off bacterial phenotypes, including colony morphology, antibiotic susceptibility, hemolytic activity, and expression of dozens of genes. Quantitative measurements and mathematical analyses indicate that this reversible switching is stochastic but self-organized so as to maintain two forms of stable cell populations (i.e., small colony variant, normal colony variant) as a bet-hedging strategy. Thus, this heritable and reversible genome fluctuation seems to govern the bacterial life cycle; it has a profound impact on the course and outcomes of bacterial infections.

Strains and stressors: an analysis of touchscreen learning in genetically diverse mouse strains.

PubMed

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M; Bussey, Timothy J; Sagalyn, Erica; Williams, Robert W; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of "reversal learning," "motivation-related late reversal learning," "discrimination learning," "speed to respond," and "motivation during discrimination." Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks.

EINVis: a visualization tool for analyzing and exploring genetic interactions in large-scale association studies.

PubMed

Wu, Yubao; Zhu, Xiaofeng; Chen, Jian; Zhang, Xiang

2013-11-01

Epistasis (gene-gene interaction) detection in large-scale genetic association studies has recently drawn extensive research interests as many complex traits are likely caused by the joint effect of multiple genetic factors. The large number of possible interactions poses both statistical and computational challenges. A variety of approaches have been developed to address the analytical challenges in epistatic interaction detection. These methods usually output the identified genetic interactions and store them in flat file formats. It is highly desirable to develop an effective visualization tool to further investigate the detected interactions and unravel hidden interaction patterns. We have developed EINVis, a novel visualization tool that is specifically designed to analyze and explore genetic interactions. EINVis displays interactions among genetic markers as a network. It utilizes a circular layout (specially, a tree ring view) to simultaneously visualize the hierarchical interactions between single nucleotide polymorphisms (SNPs), genes, and chromosomes, and the network structure formed by these interactions. Using EINVis, the user can distinguish marginal effects from interactions, track interactions involving more than two markers, visualize interactions at different levels, and detect proxy SNPs based on linkage disequilibrium. EINVis is an effective and user-friendly free visualization tool for analyzing and exploring genetic interactions. It is publicly available with detailed documentation and online tutorial on the web at http://filer.case.edu/yxw407/einvis/. © 2013 WILEY PERIODICALS, INC.

Genetic Mechanisms of Immune Evasion in Colorectal Cancer.

PubMed

Grasso, Catherine S; Giannakis, Marios; Wells, Daniel K; Hamada, Tsuyoshi; Mu, Xinmeng Jasmine; Quist, Michael; Nowak, Jonathan A; Nishihara, Reiko; Qian, Zhi Rong; Inamura, Kentaro; Morikawa, Teppei; Nosho, Katsuhiko; Abril-Rodriguez, Gabriel; Connolly, Charles; Escuin-Ordinas, Helena; Geybels, Milan S; Grady, William M; Hsu, Li; Hu-Lieskovan, Siwen; Huyghe, Jeroen R; Kim, Yeon Joo; Krystofinski, Paige; Leiserson, Mark D M; Montoya, Dennis J; Nadel, Brian B; Pellegrini, Matteo; Pritchard, Colin C; Puig-Saus, Cristina; Quist, Elleanor H; Raphael, Ben J; Salipante, Stephen J; Shin, Daniel Sanghoon; Shinbrot, Eve; Shirts, Brian; Shukla, Sachet; Stanford, Janet L; Sun, Wei; Tsoi, Jennifer; Upfill-Brown, Alexander; Wheeler, David A; Wu, Catherine J; Yu, Ming; Zaidi, Syed H; Zaretsky, Jesse M; Gabriel, Stacey B; Lander, Eric S; Garraway, Levi A; Hudson, Thomas J; Fuchs, Charles S; Ribas, Antoni; Ogino, Shuji; Peters, Ulrike

2018-06-01

To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This large-scale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion. Significance: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not. Cancer Discov; 8(6); 730-49. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663 . ©2018 American Association for Cancer Research.

Manipulations in Maternal Environment Reverse Periodontitis in Genetically Predisposed Rats

PubMed Central

Sluyter, Frans; Breivik, Torbjørn; Cools, Alexander

2002-01-01

The predisposition to develop periodontitis is partly genetically determined in humans as well as in animals. Here we demonstrate, however, that early manipulations in the maternal environment of an animal (rat) model of periodontitis can fully reverse the genetic predisposition to develop periodontitis at adult age. PMID:12093700

The behavioural consequences of sex reversal in dragons

PubMed Central

Li, Hong; Holleley, Clare E.; Elphick, Melanie; Georges, Arthur

2016-01-01

Sex differences in morphology, physiology, and behaviour are caused by sex-linked genes, as well as by circulating sex-steroid levels. Thus, a shift from genotypic to environmental sex determination may create an organism that exhibits a mixture of male-like and female-like traits. We studied a lizard species (Central Bearded Dragon, Pogona vitticeps), in which the high-temperature incubation of eggs transforms genetically male individuals into functional females. Although they are reproductively female, sex-reversed dragons (individuals with ZZ genotype reversed to female phenotype) resemble genetic males rather than females in morphology (relative tail length), general behaviour (boldness and activity level), and thermoregulatory tactics. Indeed, sex-reversed ‘females’ are more male-like in some behavioural traits than are genetic males. This novel phenotype may impose strong selection on the frequency of sex reversal within natural populations, facilitating rapid shifts in sex-determining systems. A single period of high incubation temperatures (generating thermally induced sex reversal) can produce functionally female individuals with male-like (or novel) traits that enhance individual fitness, allowing the new temperature-dependent sex-determining system to rapidly replace the previous genetically based one.

Rapid group-, serotype-, and vaccine strain-specific identification of poliovirus isolates by real-time reverse transcription-PCR using degenerate primers and probes containing deoxyinosine residues.

PubMed

Kilpatrick, David R; Yang, Chen-Fu; Ching, Karen; Vincent, Annelet; Iber, Jane; Campagnoli, Ray; Mandelbaum, Mark; De, Lina; Yang, Su-Ju; Nix, Allan; Kew, Olen M

2009-06-01

We have adapted our previously described poliovirus diagnostic reverse transcription-PCR (RT-PCR) assays to a real-time RT-PCR (rRT-PCR) format. Our highly specific assays and rRT-PCR reagents are designed for use in the WHO Global Polio Laboratory Network for rapid and large-scale identification of poliovirus field isolates.

Marburg Virus Reverse Genetics Systems

PubMed Central

Schmidt, Kristina Maria; Mühlberger, Elke

2016-01-01

The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems. PMID:27338448

Marburg Virus Reverse Genetics Systems.

PubMed

Schmidt, Kristina Maria; Mühlberger, Elke

2016-06-22

The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

Prediction of monthly rainfall on homogeneous monsoon regions of India based on large scale circulation patterns using Genetic Programming

NASA Astrophysics Data System (ADS)

Kashid, Satishkumar S.; Maity, Rajib

2012-08-01

SummaryPrediction of Indian Summer Monsoon Rainfall (ISMR) is of vital importance for Indian economy, and it has been remained a great challenge for hydro-meteorologists due to inherent complexities in the climatic systems. The Large-scale atmospheric circulation patterns from tropical Pacific Ocean (ENSO) and those from tropical Indian Ocean (EQUINOO) are established to influence the Indian Summer Monsoon Rainfall. The information of these two large scale atmospheric circulation patterns in terms of their indices is used to model the complex relationship between Indian Summer Monsoon Rainfall and the ENSO as well as EQUINOO indices. However, extracting the signal from such large-scale indices for modeling such complex systems is significantly difficult. Rainfall predictions have been done for 'All India' as one unit, as well as for five 'homogeneous monsoon regions of India', defined by Indian Institute of Tropical Meteorology. Recent 'Artificial Intelligence' tool 'Genetic Programming' (GP) has been employed for modeling such problem. The Genetic Programming approach is found to capture the complex relationship between the monthly Indian Summer Monsoon Rainfall and large scale atmospheric circulation pattern indices - ENSO and EQUINOO. Research findings of this study indicate that GP-derived monthly rainfall forecasting models, that use large-scale atmospheric circulation information are successful in prediction of All India Summer Monsoon Rainfall with correlation coefficient as good as 0.866, which may appears attractive for such a complex system. A separate analysis is carried out for All India Summer Monsoon rainfall for India as one unit, and five homogeneous monsoon regions, based on ENSO and EQUINOO indices of months of March, April and May only, performed at end of month of May. In this case, All India Summer Monsoon Rainfall could be predicted with 0.70 as correlation coefficient with somewhat lesser Correlation Coefficient (C.C.) values for different 'homogeneous monsoon regions'.

Patterns of genetic diversity in the polymorphic ground snake (Sonora semiannulata).

PubMed

Cox, Christian L; Chippindale, Paul T

2014-08-01

We evaluated the genetic diversity of a snake species with color polymorphism to understand the evolutionary processes that drive genetic structure across a large geographic region. Specifically, we analyzed genetic structure of the highly polymorphic ground snake, Sonora semiannulata, (1) among populations, (2) among color morphs (3) at regional and local spatial scales, using an amplified fragment length polymorphism dataset and multiple population genetic analyses, including FST-based and clustering analytical techniques. Based upon these methods, we found that there was moderate to low genetic structure among populations. However, this diversity was not associated with geographic locality at either spatial scale. Similarly, we found no evidence for genetic divergence among color morphs at either spatial scale. These results suggest that despite dramatic color polymorphism, this phenotypic diversity is not a major driver of genetic diversity within or among populations of ground snakes. We suggest that there are two mechanisms that could explain existing genetic diversity in ground snakes: recent range expansion from a genetically diverse founder population and current or recent gene flow among populations. Our findings have further implications for the types of color polymorphism that may generate genetic diversity in snakes.

Genetic diversity and genetic structure of Persian walnut (Juglans regia) accessions from 14 European, African, and Asian countries using SSR markers

Treesearch

Aziz Ebrahimi; Abdolkarim Zarei; Shaneka Lawson; Keith E. Woeste; M. J. M. Smulders

2016-01-01

Persian walnut (Juglans regia L.) is the world's most widely grown nut crop, but large-scale assessments and comparisons of the genetic diversity of the crop are notably lacking. To guide the conservation and utilization of Persian walnut genetic resources, genotypes (n = 189) from 25 different regions in 14 countries on...

A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics.

PubMed

Lu, Qiongshi; Li, Boyang; Ou, Derek; Erlendsdottir, Margret; Powles, Ryan L; Jiang, Tony; Hu, Yiming; Chang, David; Jin, Chentian; Dai, Wei; He, Qidu; Liu, Zefeng; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

2017-12-07

Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses, we demonstrate that our method provides accurate covariance estimates, thereby enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (N total ≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOAD's correlation with cognitive traits and hints at an autoimmune component for ALS. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

An overview of C. elegans biology.

PubMed

Strange, Kevin

2006-01-01

The establishment of Caenorhabditis elegans as a "model organism" began with the efforts of Sydney Brenner in the early 1960s. Brenner's focus was to find a suitable animal model in which the tools of genetic analysis could be used to define molecular mechanisms of development and nervous system function. C. elegans provides numerous experimental advantages for such studies. These advantages include a short life cycle, production of large numbers of offspring, easy and inexpensive laboratory culture, forward and reverse genetic tractability, and a relatively simple anatomy. This chapter will provide a brief overview of C. elegans biology.

Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses.

PubMed

Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nantawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

2012-02-14

Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby canine kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 2(9) HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Self-fertilization, long-distance flash invasion and biogeography shape the population structure of Pseudosuccinea columella at the worldwide scale.

PubMed

Lounnas, M; Correa, A C; Vázquez, A A; Dia, A; Escobar, J S; Nicot, A; Arenas, J; Ayaqui, R; Dubois, M P; Gimenez, T; Gutiérrez, A; González-Ramírez, C; Noya, O; Prepelitchi, L; Uribe, N; Wisnivesky-Colli, C; Yong, M; David, P; Loker, E S; Jarne, P; Pointier, J P; Hurtrez-Boussès, S

2017-02-01

Population genetic studies are efficient for inferring the invasion history based on a comparison of native and invasive populations, especially when conducted at species scale. An expected outcome in invasive populations is variability loss, and this is especially true in self-fertilizing species. We here focus on the self-fertilizing Pseudosuccinea columella, an invasive hermaphroditic freshwater snail that has greatly expanded its geographic distribution and that acts as intermediate host of Fasciola hepatica, the causative agent of human and veterinary fasciolosis. We evaluated the distribution of genetic diversity at the largest geographic scale analysed to date in this species by surveying 80 populations collected during 16 years from 14 countries, using eight nuclear microsatellites and two mitochondrial genes. As expected, populations from North America, the putative origin area, were strongly structured by selfing and history and harboured much more genetic variability than invasive populations. We found high selfing rates (when it was possible to infer it), none-to-low genetic variability and strong population structure in most invasive populations. Strikingly, we found a unique genotype/haplotype in populations from eight invaded regions sampled all over the world. Moreover, snail populations resistant to infection by the parasite are genetically distinct from susceptible populations. Our results are compatible with repeated introductions in South America and flash worldwide invasion by this unique genotype/haplotype. Our study illustrates the population genetic consequences of biological invasion in a highly selfing species at very large geographic scale. We discuss how such a large-scale flash invasion may affect the spread of fasciolosis. © 2016 John Wiley & Sons Ltd.

Aquatic Plant Control Research Program. Large-Scale Operations Management Test (LSOMT) of Insects and Pathogens for Control of Waterhyacinth in Louisiana. Volume 1. Results for 1979-1981.

DTIC Science & Technology

1985-01-01

RD-Ai56 759 AQUATIC PLANT CONTROL RESEARCH PROGRAM LARGE-SCALE 1/2 OPERATIONS MRNAGEMENT..(U) ARMY ENGINEER WATERAYS EXPERIMENT STATION VICKSBURG MS...PO Box 631, Vicksburg, Aquatic Plant Control Mississippi 39180-0631 and University of Research Program Tennessee-Chattanooga, Chattanooga, 12...19. KEY WORDS (Continue on reverse side if necesary nd identify by block number) - Aquatic plant control Louisiana Biological control Plant

The relative influence of habitat amount and configuration on genetic structure across multiple spatial scales

PubMed Central

Millette, Katie L; Keyghobadi, Nusha

2015-01-01

Despite strong interest in understanding how habitat spatial structure shapes the genetics of populations, the relative importance of habitat amount and configuration for patterns of genetic differentiation remains largely unexplored in empirical systems. In this study, we evaluate the relative influence of, and interactions among, the amount of habitat and aspects of its spatial configuration on genetic differentiation in the pitcher plant midge, Metriocnemus knabi. Larvae of this species are found exclusively within the water-filled leaves of pitcher plants (Sarracenia purpurea) in a system that is naturally patchy at multiple spatial scales (i.e., leaf, plant, cluster, peatland). Using generalized linear mixed models and multimodel inference, we estimated effects of the amount of habitat, patch size, interpatch distance, and patch isolation, measured at different spatial scales, on genetic differentiation (FST) among larval samples from leaves within plants, plants within clusters, and clusters within peatlands. Among leaves and plants, genetic differentiation appears to be driven by female oviposition behaviors and is influenced by habitat isolation at a broad (peatland) scale. Among clusters, gene flow is spatially restricted and aspects of both the amount of habitat and configuration at the focal scale are important, as is their interaction. Our results suggest that both habitat amount and configuration can be important determinants of genetic structure and that their relative influence is scale dependent. PMID:25628865

The relative influence of habitat amount and configuration on genetic structure across multiple spatial scales.

PubMed

Millette, Katie L; Keyghobadi, Nusha

2015-01-01

Despite strong interest in understanding how habitat spatial structure shapes the genetics of populations, the relative importance of habitat amount and configuration for patterns of genetic differentiation remains largely unexplored in empirical systems. In this study, we evaluate the relative influence of, and interactions among, the amount of habitat and aspects of its spatial configuration on genetic differentiation in the pitcher plant midge, Metriocnemus knabi. Larvae of this species are found exclusively within the water-filled leaves of pitcher plants (Sarracenia purpurea) in a system that is naturally patchy at multiple spatial scales (i.e., leaf, plant, cluster, peatland). Using generalized linear mixed models and multimodel inference, we estimated effects of the amount of habitat, patch size, interpatch distance, and patch isolation, measured at different spatial scales, on genetic differentiation (F ST) among larval samples from leaves within plants, plants within clusters, and clusters within peatlands. Among leaves and plants, genetic differentiation appears to be driven by female oviposition behaviors and is influenced by habitat isolation at a broad (peatland) scale. Among clusters, gene flow is spatially restricted and aspects of both the amount of habitat and configuration at the focal scale are important, as is their interaction. Our results suggest that both habitat amount and configuration can be important determinants of genetic structure and that their relative influence is scale dependent.

Population Genetics of the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis) across Multiple Spatial Scales

PubMed Central

Unger, Shem D.; Rhodes, Olin E.; Sutton, Trent M.; Williams, Rod N.

2013-01-01

Conservation genetics is a powerful tool to assess the population structure of species and provides a framework for informing management of freshwater ecosystems. As lotic habitats become fragmented, the need to assess gene flow for species of conservation management becomes a priority. The eastern hellbender (Cryptobranchus alleganiensis alleganiensis) is a large, fully aquatic paedamorphic salamander. Many populations are experiencing declines throughout their geographic range, yet the genetic ramifications of these declines are currently unknown. To this end, we examined levels of genetic variation and genetic structure at both range-wide and drainage (hierarchical) scales. We collected 1,203 individuals from 77 rivers throughout nine states from June 2007 to August 2011. Levels of genetic diversity were relatively high among all sampling locations. We detected significant genetic structure across populations (Fst values ranged from 0.001 between rivers within a single watershed to 0.218 between states). We identified two genetically differentiated groups at the range-wide scale: 1) the Ohio River drainage and 2) the Tennessee River drainage. An analysis of molecular variance (AMOVA) based on landscape-scale sampling of basins within the Tennessee River drainage revealed the majority of genetic variation (∼94–98%) occurs within rivers. Eastern hellbenders show a strong pattern of isolation by stream distance (IBSD) at the drainage level. Understanding levels of genetic variation and differentiation at multiple spatial and biological scales will enable natural resource managers to make more informed decisions and plan effective conservation strategies for cryptic, lotic species. PMID:24204565

Genetic dissection of behavioral flexibility: reversal learning in mice.

PubMed

Laughlin, Rick E; Grant, Tara L; Williams, Robert W; Jentsch, J David

2011-06-01

Behavioral inflexibility is a feature of schizophrenia, attention-deficit/hyperactivity disorder, and behavior addictions that likely results from heritable deficits in the inhibitory control over behavior. Here, we investigate the genetic basis of individual differences in flexibility, measured using an operant reversal learning task. We quantified discrimination acquisition and subsequent reversal learning in a cohort of 51 BXD strains of mice (2-5 mice/strain, n = 176) for which we have matched data on sequence, gene expression in key central nervous system regions, and neuroreceptor levels. Strain variation in trials to criterion on acquisition and reversal was high, with moderate heritability (∼.3). Acquisition and reversal learning phenotypes did not covary at the strain level, suggesting that these traits are effectively under independent genetic control. Reversal performance did covary with dopamine D2 receptor levels in the ventral midbrain, consistent with a similar observed relationship between impulsivity and D2 receptors in humans. Reversal, but not acquisition, is linked to a locus on mouse chromosome 10 with a peak likelihood ratio statistic at 86.2 megabase (p < .05 genome-wide). Variance in messenger RNA levels of select transcripts expressed in neocortex, hippocampus, and striatum correlated with the reversal learning phenotype, including Syn3, Nt5dc3, and Hcfc2. This work demonstrates the clear trait independence between, and genetic control of, discrimination acquisition and reversal and illustrates how globally coherent data sets for a single panel of highly related strains can be interrogated and integrated to uncover genetic sources and molecular and neuropharmacological candidates of complex behavioral traits relevant to human psychopathology. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Native fish conservation areas: a vision for large-scale conservation of native fish communities

Treesearch

Jack E. Williams; Richard N. Williams; Russell F. Thurow; Leah Elwell; David P. Philipp; Fred A. Harris; Jeffrey L. Kershner; Patrick J. Martinez; Dirk Miller; Gordon H. Reeves; Christopher A. Frissell; James R. Sedell

2011-01-01

The status of freshwater fishes continues to decline despite substantial conservation efforts to reverse this trend and recover threatened and endangered aquatic species. Lack of success is partially due to working at smaller spatial scales and focusing on habitats and species that are already degraded. Protecting entire watersheds and aquatic communities, which we...

Desalination: Status and Federal Issues

DTIC Science & Technology

2009-12-30

on one side and lets purified water through. Reverse osmosis plants have fewer problems with corrosion and usually have lower energy requirements...Texas) and cities are actively researching and investigating the feasibility of large-scale desalination plants for municipal water supplies...desalination research and development, and in construction and operational costs of desalination demonstration projects and full-scale plants

Grand Minima and Equatorward Propagation in a Cycling Stellar Convective Dynamo

NASA Astrophysics Data System (ADS)

Augustson, Kyle C.; Brun, Allan Sacha; Miesch, Mark; Toomre, Juri

2015-08-01

The 3-D magnetohydrodynamic (MHD) Anelastic Spherical Harmonic (ASH) code, using slope-limited diffusion, is employed to capture convective and dynamo processes achieved in a global-scale stellar convection simulation for a model solar-mass star rotating at three times the solar rate. The dynamo generated magnetic fields possesses many time scales, with a prominent polarity cycle occurring roughly every 6.2 years. The magnetic field forms large-scale toroidal wreaths, whose formation is tied to the low Rossby number of the convection in this simulation. The polarity reversals are linked to the weakened differential rotation and a resistive collapse of the large-scale magnetic field. An equatorial migration of the magnetic field is seen, which is due to the strong modulation of the differential rotation rather than a dynamo wave. A poleward migration of magnetic flux from the equator eventually leads to the reversal of the polarity of the high-latitude magnetic field. This simulation also enters an interval with reduced magnetic energy at low latitudes lasting roughly 16 years (about 2.5 polarity cycles), during which the polarity cycles are disrupted and after which the dynamo recovers its regular polarity cycles. An analysis of this grand minimum reveals that it likely arises through the interplay of symmetric and antisymmetric dynamo families. This intermittent dynamo state potentially results from the simulations relatively low magnetic Prandtl number. A mean-field-based analysis of this dynamo simulation demonstrates that it is of the α-Ω type. The time scales that appear to be relevant to the magnetic polarity reversal are also identified.

Long-term dynamics of hawaiian volcanoes inferred by large-scale relative relocations of earthquakes

NASA Astrophysics Data System (ADS)

Got, J.-L.; Okubo, P.

2003-04-01

We investigated the microseismicity recorded in an active volcano to infer information concerning the volcano structure and long-term dynamics, by using relative relocations and focal mechanisms of microearthquakes. 32000 earthquakes of Mauna Loa and Kilauea volcanoes were recorded by more than 8 stations of the Hawaiian Volcano Observatory seismic network between 1988 and 1999. We studied 17000 of these events and relocated more than 70% with an accuracy ranging from 10 to 500 meters. About 75% of these relocated events are located in the vicinity of subhorizontal decollement planes, at 8 to 11 km depth. However, the striking features revealed by these relocation results are steep south-east dipping fault planes working as reverse faults, clearly located below the decollement plane and which intersect it. If this decollement plane coincides with the pre-Mauna Loa seafloor, as hypothesized by numerous authors, such reverse faults rupture the pre-Mauna Loa oceanic crust. The weight of the volcano and pressure in the magma storage system are possible causes of these ruptures, fully compatible with the local stress tensor computed by Gillard et al. (1996). Reverse faults are suspected of producing scarps revealed by km-long horizontal slip-perpendicular lineations along the decollement surface, and therefore large-scale roughness, asperities and normal stress variations. These are capable of generating stick-slip, large magnitude earthquakes, the spatial microseismic pattern observed in the south flank of Kilauea volcano, and Hilina-type instabilities. Ruptures intersecting the decollement surface, causing its large-scale roughness, may be an important parameter controlling the growth of Hawaiian volcanoes. Are there more or less rough decollement planes existing near the base of other volcanoes, such as Piton de la Fournaise or Etna, and able to explain part of their deformation and seismicity ?

Exploring the feasibility of using copy number variants as genetic markers through large-scale whole genome sequencing experiments

USDA-ARS?s Scientific Manuscript database

Copy number variants (CNV) are large scale duplications or deletions of genomic sequence that are caused by a diverse set of molecular phenomena that are distinct from single nucleotide polymorphism (SNP) formation. Due to their different mechanisms of formation, CNVs are often difficult to track us...

Comparative Approaches to Genetic Discrimination: Chasing Shadows?

PubMed

Joly, Yann; Feze, Ida Ngueng; Song, Lingqiao; Knoppers, Bartha M

2017-05-01

Genetic discrimination (GD) is one of the most pervasive issues associated with genetic research and its large-scale implementation. An increasing number of countries have adopted public policies to address this issue. Our research presents a worldwide comparative review and typology of these approaches. We conclude with suggestions for public policy development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variables Affecting Secondary School Students' Willingness to Eat Genetically Modified Food Crops

ERIC Educational Resources Information Center

Maes, Jasmien; Bourgonjon, Jeroen; Gheysen, Godelieve; Valcke, Martin

2018-01-01

A large-scale cross-sectional study (N = 4002) was set up to determine Flemish secondary school students' willingness to eat genetically modified food (WTE) and to link students' WTE to previously identified key variables from research on the acceptance of genetic modification (GM). These variables include subjective and objective knowledge about…

Practical strategies of black walnut genetic improvement—an update

Treesearch

George Rink; J.W. Van Sambeek; Phil O' Connor; Mark Coggeshall

2017-01-01

The ultimate goal of any tree improvement program is the large-scale production and distribution of genetically improved seedlings. In black walnut, projections based on earlier research indicate that genetically improved seedlings could provide growth improvement of between 15 to 25 percent by using seed or seedlings of the proper geographic origin (Bey 1980; Clausen...

Ecological dispersal barrier across the equatorial Atlantic in a migratory planktonic copepod

NASA Astrophysics Data System (ADS)

Goetze, Erica; Hüdepohl, Patricia T.; Chang, Chantel; Van Woudenberg, Lauren; Iacchei, Matthew; Peijnenburg, Katja T. C. A.

2017-11-01

Resolving the large-scale genetic structure of plankton populations is important to understanding their responses to climate change. However, few studies have reported on the presence and geographic extent of genetically distinct populations of marine zooplankton at ocean-basin scales. Using mitochondrial sequence data (mtCOI, 718 animals) from 18 sites across a basin-scale Atlantic transect (39°N-40°S), we show that populations of the dominant migratory copepod, Pleuromamma xiphias, are genetically subdivided across subtropical and tropical waters (global FST = 0.15, global ΦST = 0.21, both P < 0.00001), with a major genetic break observed in the equatorial Atlantic (between gyre FCT and ΦCT = 0.23, P < 0.005). This equatorial region of strong genetic transition coincides with an area of low abundance for the species. Transitional regions between the subtropical gyres and the equatorial province also harbor a distinct mitochondrial clade (clade 2), have higher haplotype and nucleotide diversities relative to the northern and/or southern subtropical gyres (e.g., mean h = 0.831 EQ, 0.742 North, 0.594 South, F2,11 = 20.53, P < 0.001), and are genetically differentiated from the majority of sites in the central gyre and temperate zones of the same hemisphere (significant pairwise ΦST 0.038-0.267, 79% significant). Our observations support the hypothesis that regions of low abundance within species mark areas of suboptimal habitat that serve as dispersal barriers for marine plankton, and we suggest that this may be a dominant mechanism driving the large-scale genetic structure of zooplankton species. Our results also demonstrate the potential importance of the Atlantic equatorial province as a region of evolutionary novelty for the holoplankton.

Spatial and Temporal Dynamics of Pacific Oyster Hemolymph Microbiota across Multiple Scales

PubMed Central

Lokmer, Ana; Goedknegt, M. Anouk; Thieltges, David W.; Fiorentino, Dario; Kuenzel, Sven; Baines, John F.; Wegner, K. Mathias

2016-01-01

Unveiling the factors and processes that shape the dynamics of host associated microbial communities (microbiota) under natural conditions is an important part of understanding and predicting an organism's response to a changing environment. The microbiota is shaped by host (i.e., genetic) factors as well as by the biotic and abiotic environment. Studying natural variation of microbial community composition in multiple host genetic backgrounds across spatial as well as temporal scales represents a means to untangle this complex interplay. Here, we combined a spatially-stratified with a longitudinal sampling scheme within differentiated host genetic backgrounds by reciprocally transplanting Pacific oysters between two sites in the Wadden Sea (Sylt and Texel). To further differentiate contingent site from host genetic effects, we repeatedly sampled the same individuals over a summer season to examine structure, diversity and dynamics of individual hemolymph microbiota following experimental removal of resident microbiota by antibiotic treatment. While a large proportion of microbiome variation could be attributed to immediate environmental conditions, we observed persistent effects of antibiotic treatment and translocation suggesting that hemolymph microbial community dynamics is subject to within-microbiome interactions and host population specific factors. In addition, the analysis of spatial variation revealed that the within-site microenvironmental heterogeneity resulted in high small-scale variability, as opposed to large-scale (between-site) stability. Similarly, considerable within-individual temporal variability was in contrast with the overall temporal stability at the site level. Overall, our longitudinal, spatially-stratified sampling design revealed that variation in hemolymph microbiota is strongly influenced by site and immediate environmental conditions, whereas internal microbiome dynamics and oyster-related factors add to their long-term stability. The combination of small and large scale resolution of spatial and temporal observations therefore represents a crucial but underused tool to study host-associated microbiome dynamics. PMID:27630625

Structural Variation Shapes the Landscape of Recombination in Mouse.

PubMed

Morgan, Andrew P; Gatti, Daniel M; Najarian, Maya L; Keane, Thomas M; Galante, Raymond J; Pack, Allan I; Mott, Richard; Churchill, Gary A; de Villena, Fernando Pardo-Manuel

2017-06-01

Meiotic recombination is an essential feature of sexual reproduction that ensures faithful segregation of chromosomes and redistributes genetic variants in populations. Multiparent populations such as the Diversity Outbred (DO) mouse stock accumulate large numbers of crossover (CO) events between founder haplotypes, and thus present a unique opportunity to study the role of genetic variation in shaping the recombination landscape. We obtained high-density genotype data from [Formula: see text] DO mice, and localized 2.2 million CO events to intervals with a median size of 28 kb. The resulting sex-averaged genetic map of the DO population is highly concordant with large-scale (order 10 Mb) features of previously reported genetic maps for mouse. To examine fine-scale (order 10 kb) patterns of recombination in the DO, we overlaid putative recombination hotspots onto our CO intervals. We found that CO intervals are enriched in hotspots compared to the genomic background. However, as many as [Formula: see text] of CO intervals do not overlap any putative hotspots, suggesting that our understanding of hotspots is incomplete. We also identified coldspots encompassing 329 Mb, or [Formula: see text] of observable genome, in which there is little or no recombination. In contrast to hotspots, which are a few kilobases in size, and widely scattered throughout the genome, coldspots have a median size of 2.1 Mb and are spatially clustered. Coldspots are strongly associated with copy-number variant (CNV) regions, especially multi-allelic clusters, identified from whole-genome sequencing of 228 DO mice. Genes in these regions have reduced expression, and epigenetic features of closed chromatin in male germ cells, which suggests that CNVs may repress recombination by altering chromatin structure in meiosis. Our findings demonstrate how multiparent populations, by bridging the gap between large-scale and fine-scale genetic mapping, can reveal new features of the recombination landscape. Copyright © 2017 by the Genetics Society of America.

Reversed gender ratio of autism spectrum disorder in Smith-Magenis syndrome.

PubMed

Nag, Heidi Elisabeth; Nordgren, Ann; Anderlid, Britt-Marie; Nærland, Terje

2018-01-01

A substantial amount of research shows a higher rate of autistic type of problems in males compared to females. The 4:1 male to female ratio is one of the most consistent findings in autism spectrum disorder (ASD).Lately, the interest in studying ASD in genetic disorders has increased, and research has shown a higher prevalence of ASD in some genetic disorders than in the general population.Smith-Magenis syndrome (SMS) is a rare and complex genetic syndrome caused by an interstitial deletion of chromosome 17p11.2 or a mutation on the retinoic acid induced 1 gene. The disorder is characterised by intellectual disability, multiple congenital anomalies, obesity, neurobehavioural abnormalities and a disrupted circadian sleep-wake pattern. Parents of 28 persons with SMS between 5 and 50 years old participated in this study. A total of 12 of the persons with SMS were above the age of 18 at the time of the study. A total of 11 came from Sweden and 17 were from Norway.We collected information regarding the number of autism spectrum symptoms using the Social Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS). Adaptive behaviour was also measured using the Vineland Adaptive Behavior Scale II. The level of intellectual disability was derived from a review of the medical chart. We found significant gender differences in ASD symptomatology using the SCQ and SRS questionnaires. We found approximately three females per male above the SCQ cutoff. The same differences were not found in the intellectual level and adaptive behaviour or for behavioural and emotional problems.Gender had an independent contribution in a regression model predicting the total SCQ score, and neither the Vineland Adaptive Behavior Scale II nor the Developmental Behaviour Checklist had an independent contribution to the SCQ scores. We found a clear reversed gender difference in ASD symptomatology in persons with SMS. This may be relevant in the search for female protective factors assumed to explain the male bias in ASD.

Rapid Two-Step Procedure for Large-Scale Purification of Pediocin-Like Bacteriocins and Other Cationic Antimicrobial Peptides from Complex Culture Medium

PubMed Central

Uteng, Marianne; Hauge, Håvard Hildeng; Brondz, Ilia; Nissen-Meyer, Jon; Fimland, Gunnar

2002-01-01

A rapid and simple two-step procedure suitable for both small- and large-scale purification of pediocin-like bacteriocins and other cationic peptides has been developed. In the first step, the bacterial culture was applied directly on a cation-exchange column (1-ml cation exchanger per 100-ml cell culture). Bacteria and anionic compounds passed through the column, and cationic bacteriocins were subsequently eluted with 1 M NaCl. In the second step, the bacteriocin fraction was applied on a low-pressure, reverse-phase column and the bacteriocins were detected as major optical density peaks upon elution with propanol. More than 80% of the activity that was initially in the culture supernatant was recovered in both purification steps, and the final bacteriocin preparation was more than 90% pure as judged by analytical reverse-phase chromatography and capillary electrophoresis. PMID:11823243

Allele Age Under Non-Classical Assumptions is Clarified by an Exact Computational Markov Chain Approach.

PubMed

De Sanctis, Bianca; Krukov, Ivan; de Koning, A P Jason

2017-09-19

Determination of the age of an allele based on its population frequency is a well-studied problem in population genetics, for which a variety of approximations have been proposed. We present a new result that, surprisingly, allows the expectation and variance of allele age to be computed exactly (within machine precision) for any finite absorbing Markov chain model in a matter of seconds. This approach makes none of the classical assumptions (e.g., weak selection, reversibility, infinite sites), exploits modern sparse linear algebra techniques, integrates over all sample paths, and is rapidly computable for Wright-Fisher populations up to N e  = 100,000. With this approach, we study the joint effect of recurrent mutation, dominance, and selection, and demonstrate new examples of "selective strolls" where the classical symmetry of allele age with respect to selection is violated by weakly selected alleles that are older than neutral alleles at the same frequency. We also show evidence for a strong age imbalance, where rare deleterious alleles are expected to be substantially older than advantageous alleles observed at the same frequency when population-scaled mutation rates are large. These results highlight the under-appreciated utility of computational methods for the direct analysis of Markov chain models in population genetics.

Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

PubMed Central

Nunes, José de Ribamar da Silva; Liu, Shikai; Pértille, Fábio; Perazza, Caio Augusto; Villela, Priscilla Marqui Schmidt; de Almeida-Val, Vera Maria Fonseca; Hilsdorf, Alexandre Wagner Silva; Liu, Zhanjiang; Coutinho, Luiz Lehmann

2017-01-01

Colossoma macropomum, or tambaqui, is the largest native Characiform species found in the Amazon and Orinoco river basins, yet few resources for genetic studies and the genetic improvement of tambaqui exist. In this study, we identified a large number of single-nucleotide polymorphisms (SNPs) for tambaqui and constructed a high-resolution genetic linkage map from a full-sib family of 124 individuals and their parents using the genotyping by sequencing method. In all, 68,584 SNPs were initially identified using minimum minor allele frequency (MAF) of 5%. Filtering parameters were used to select high-quality markers for linkage analysis. We selected 7,734 SNPs for linkage mapping, resulting in 27 linkage groups with a minimum logarithm of odds (LOD) of 8 and maximum recombination fraction of 0.35. The final genetic map contains 7,192 successfully mapped markers that span a total of 2,811 cM, with an average marker interval of 0.39 cM. Comparative genomic analysis between tambaqui and zebrafish revealed variable levels of genomic conservation across the 27 linkage groups which allowed for functional SNP annotations. The large-scale SNP discovery obtained here, allowed us to build a high-density linkage map in tambaqui, which will be useful to enhance genetic studies that can be applied in breeding programs. PMID:28387238

A network of epigenetic regulators guides developmental haematopoiesis in vivo.

PubMed

Huang, Hsuan-Ting; Kathrein, Katie L; Barton, Abby; Gitlin, Zachary; Huang, Yue-Hua; Ward, Thomas P; Hofmann, Oliver; Dibiase, Anthony; Song, Anhua; Tyekucheva, Svitlana; Hide, Winston; Zhou, Yi; Zon, Leonard I

2013-12-01

The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental haematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologues of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in haematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive haematopoietic stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodelling, SET1 methyltransferase, CBP-p300-HBO1-NuA4 acetyltransferase, HDAC-NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of haematopoietic cells in vivo.

Review of renal carcinoma with t(6;11)(p21;q12) with focus on clinical and pathobiological aspects.

PubMed

Kuroda, Naoto; Tanaka, Azusa; Sasaki, Naomi; Ishihara, Akira; Matsuura, Keiko; Moriyama, Masatsugu; Nagashima, Yoji; Inoue, Keiji; Petersson, Fredrik; Martignoni, Guido; Michal, Michal; Hes, Ondrej

2013-06-01

Recently, a new category of MiTF/TFE family translocation carcinomas of the kidney has been proposed. This category includes Xp11.2 renal cell carcinoma (RCC) and the t(6;11) RCC. These tumors share clinical, morphological, immunohistochemical and molecular genetic features. In this article, we review t(6;11) RCC. This tumor predominantly affects children and young adults. Macroscopically, the tumor generally forms a well circumscribed mass. Satellite nodules may be observed. Histologically, the tumor comprises large cells and small cells surrounded by basement membrane material. Immunohistochemically, tumor cells show nuclear immunolabeling for TFEB and usually express Cathepsin-K in the cytoplasm. Karyotyping detects the rearrangement between chromosome 6p21 and chromosome 11q12. Alpha-TFEB fusion can be detected by reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Most cases affecting children and young adults seem to be indolent, but some adult cases have presented with metastasis or caused death. As previously reported cases remain limited to date, further examination in a large scale study will be needed in order to elucidate clinical behavior and molecular characteristics.

[Methods of high-throughput plant phenotyping for large-scale breeding and genetic experiments].

PubMed

Afonnikov, D A; Genaev, M A; Doroshkov, A V; Komyshev, E G; Pshenichnikova, T A

2016-07-01

Phenomics is a field of science at the junction of biology and informatics which solves the problems of rapid, accurate estimation of the plant phenotype; it was rapidly developed because of the need to analyze phenotypic characteristics in large scale genetic and breeding experiments in plants. It is based on using the methods of computer image analysis and integration of biological data. Owing to automation, new approaches make it possible to considerably accelerate the process of estimating the characteristics of a phenotype, to increase its accuracy, and to remove a subjectivism (inherent to humans). The main technologies of high-throughput plant phenotyping in both controlled and field conditions, their advantages and disadvantages, and also the prospects of their use for the efficient solution of problems of plant genetics and breeding are presented in the review.

Fabrication of flexible oriented magnetic thin films with large in-plane uniaxial anisotropy by roll-to-roll nanoimprint lithography

NASA Astrophysics Data System (ADS)

Thantirige, Rukshan M.; John, Jacob; Pradhan, Nihar R.; Carter, Kenneth R.; Tuominen, Mark T.

2016-06-01

Here, we report wafer scale fabrication of densely packed Fe nanostripe-based magnetic thin films on a flexible substrate and their magnetic anisotropy properties. We find that Fe nanostripes exhibit large in-plane uniaxial anisotropy and nearly square hysteresis loops with energy products (BHmax) exceeding 3 MGOe at room temperature. High density Fe nanostripes were fabricated on 70 nm flexible polyethylene terephthalate (PET) gratings, which were made by a roll-to-roll (R2R) UV nanoimprint lithography technique. We observed large in-plane uniaxial anisotropies along the long dimension of nanostripes that can be attributed to the shape. Temperature dependent hysteresis measurements confirm that the magnetization reversal is driven by non-coherent rotation reversal processes.

Large-scale solar magnetic fields and H-alpha patterns

NASA Technical Reports Server (NTRS)

Mcintosh, P. S.

1972-01-01

Coronal and interplanetary magnetic fields computed from measurements of large-scale photospheric magnetic fields suffer from interruptions in day-to-day observations and the limitation of using only measurements made near the solar central meridian. Procedures were devised for inferring the lines of polarity reversal from H-alpha solar patrol photographs that map the same large-scale features found on Mt. Wilson magnetograms. These features may be monitored without interruption by combining observations from the global network of observatories associated with NOAA's Space Environment Services Center. The patterns of inferred magnetic fields may be followed accurately as far as 60 deg from central meridian. Such patterns will be used to improve predictions of coronal features during the next solar eclipse.

Strains and Stressors: An Analysis of Touchscreen Learning in Genetically Diverse Mouse Strains

PubMed Central

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M.; Bussey, Timothy J.; Sagalyn, Erica; Williams, Robert W.; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of “reversal learning,” “motivation-related late reversal learning,” “discrimination learning,” “speed to respond,” and “motivation during discrimination.” Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks. PMID:24586288

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

PubMed Central

Christophersen, Ingrid E.; Rienstra, Michiel; Roselli, Carolina; Yin, Xiaoyan; Geelhoed, Bastiaan; Barnard, John; Lin, Honghuang; Arking, Dan E.; Smith, Albert V.; Albert, Christine M.; Chaffin, Mark; Tucker, Nathan R.; Li, Molong; Klarin, Derek; Bihlmeyer, Nathan A; Low, Siew-Kee; Weeke, Peter E.; Müller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Dörr, Marcus; Trompet, Stella; Huffman, Jennifer; Gustafsson, Stefan; Schurman, Claudia; Kleber, Marcus E.; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Malik, Rainer; Horimoto, Andrea R. V. R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Thériault, Sébastien; Yao, Jie; Radmanesh, Farid; Weiss, Stefan; Teumer, Alexander; Choi, Seung Hoan; Weng, Lu-Chen; Clauss, Sebastian; Deo, Rajat; Rader, Daniel J.; Shah, Svati; Sun, Albert; Hopewell, Jemma C.; Debette, Stephanie; Chauhan, Ganesh; Yang, Qiong; Worrall, Bradford B.; Paré, Guillaume; Kamatani, Yoichiro; Hagemeijer, Yanick P.; Verweij, Niek; Siland, Joylene E.; Kubo, Michiaki; Smith, Jonathan D.; Van Wagoner, David R.; Bis, Joshua C.; Perz, Siegfried; Psaty, Bruce M.; Ridker, Paul M.; Magnani, Jared W.; Harris, Tamara B.; Launer, Lenore J.; Shoemaker, M. Benjamin; Padmanabhan, Sandosh; Haessler, Jeffrey; Bartz, Traci M.; Waldenberger, Melanie; Lichtner, Peter; Arendt, Marina; Krieger, Jose E.; Kähönen, Mika; Risch, Lorenz; Mansur, Alfredo J.; Peters, Annette; Smith, Blair H.; Lind, Lars; Scott, Stuart A.; Lu, Yingchang; Bottinger, Erwin B.; Hernesniemi, Jussi; Lindgren, Cecilia M.; Wong, Jorge; Huang, Jie; Eskola, Markku; Morris, Andrew P.; Ford, Ian; Reiner, Alex P.; Delgado, Graciela; Chen, Lin Y.; Chen, Yii-Der Ida; Sandhu, Roopinder K.; Li, Man; Boerwinkle, Eric; Eisele, Lewin; Lannfelt, Lars; Rost, Natalia; Anderson, Christopher D.; Taylor, Kent D.; Campbell, Archie; Magnusson, Patrik K.; Porteous, David; Hocking, Lynne J.; Vlachopoulou, Efthymia; Pedersen, Nancy L.; Nikus, Kjell; Orho-Melander, Marju; Hamsten, Anders; Heeringa, Jan; Denny, Joshua C.; Kriebel, Jennifer; Darbar, Dawood; Newton-Cheh, Christopher; Shaffer, Christian; Macfarlane, Peter W.; Heilmann, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Völker, Uwe; Jöckel, Karl-Heinz; Sinner, Moritz F.; Lin, Henry J.; Guo, Xiuqing; Dichgans, Martin; Ingelsson, Erik; Kooperberg, Charles; Melander, Olle; Loos, Ruth J. F.; Laurikka, Jari; Conen, David; Rosand, Jonathan; van der Harst, Pim; Lokki, Marja-Liisa; Kathiresan, Sekar; Pereira, Alexandre; Jukema, J. Wouter; Hayward, Caroline; Rotter, Jerome I.; März, Winfried; Lehtimäki, Terho; Stricker, Bruno H.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kääb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T.

2017-01-01

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups.3–7 To further define the genetic basis of atrial fibrillation, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with atrial fibrillation and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate new potential targets for drug discovery.8 PMID:28416818

Complex Genetics of Behavior: BXDs in the Automated Home-Cage.

PubMed

Loos, Maarten; Verhage, Matthijs; Spijker, Sabine; Smit, August B

2017-01-01

This chapter describes a use case for the genetic dissection and automated analysis of complex behavioral traits using the genetically diverse panel of BXD mouse recombinant inbred strains. Strains of the BXD resource differ widely in terms of gene and protein expression in the brain, as well as in their behavioral repertoire. A large mouse resource opens the possibility for gene finding studies underlying distinct behavioral phenotypes, however, such a resource poses a challenge in behavioral phenotyping. To address the specifics of large-scale screening we describe how to investigate: (1) how to assess mouse behavior systematically in addressing a large genetic cohort, (2) how to dissect automation-derived longitudinal mouse behavior into quantitative parameters, and (3) how to map these quantitative traits to the genome, deriving loci underlying aspects of behavior.

New Genes and New Insights from Old Genes: Update on Alzheimer Disease

PubMed Central

Ringman, John M.; Coppola, Giovanni

2013-01-01

Purpose of Review: This article discusses the current status of knowledge regarding the genetic basis of Alzheimer disease (AD) with a focus on clinically relevant aspects. Recent Findings: The genetic architecture of AD is complex, as it includes multiple susceptibility genes and likely nongenetic factors. Rare but highly penetrant autosomal dominant mutations explain a small minority of the cases but have allowed tremendous advances in understanding disease pathogenesis. The identification of a strong genetic risk factor, APOE, reshaped the field and introduced the notion of genetic risk for AD. More recently, large-scale genome-wide association studies are adding to the picture a number of common variants with very small effect sizes. Large-scale resequencing studies are expected to identify additional risk factors, including rare susceptibility variants and structural variation. Summary: Genetic assessment is currently of limited utility in clinical practice because of the low frequency (Mendelian mutations) or small effect size (common risk factors) of the currently known susceptibility genes. However, genetic studies are identifying with confidence a number of novel risk genes, and this will further our understanding of disease biology and possibly the identification of therapeutic targets. PMID:23558482

Spatial and temporal variation in population genetic structure of wild Nile tilapia (Oreochromis niloticus) across Africa

PubMed Central

2011-01-01

Background Reconstructing the evolutionary history of a species is challenging. It often depends not only on the past biogeographic and climatic events but also the contemporary and ecological factors, such as current connectivity and habitat heterogeneity. In fact, these factors might interact with each other and shape the current species distribution. However, to what extent the current population genetic structure reflects the past and the contemporary factors is largely unknown. Here we investigated spatio-temporal genetic structures of Nile tilapia (Oreochromis niloticus) populations, across their natural distribution in Africa. While its large biogeographic distribution can cause genetic differentiation at the paleo-biogeographic scales, its restricted dispersal capacity might induce a strong genetic structure at micro-geographic scales. Results Using nine microsatellite loci and 350 samples from ten natural populations, we found the highest genetic differentiation among the three ichthyofaunal provinces and regions (Ethiopian, Nilotic and Sudano-Sahelian) (RST = 0.38 - 0.69). This result suggests the predominant effect of paleo-geographic events at macro-geographic scale. In addition, intermediate divergences were found between rivers and lakes within the regions, presumably reflecting relatively recent interruptions of gene flow between hydrographic basins (RST = 0.24 - 0.32). The lowest differentiations were observed among connected populations within a basin (RST = 0.015 in the Volta basin). Comparison of temporal sample series revealed subtle changes in the gene pools in a few generations (F = 0 - 0.053). The estimated effective population sizes were 23 - 143 and the estimated migration rate was moderate (m ~ 0.094 - 0.097) in the Volta populations. Conclusions This study revealed clear hierarchical patterns of the population genetic structuring of O. niloticus in Africa. The effects of paleo-geographic and climatic events were predominant at macro-geographic scale, and the significant effect of geographic connectivity was detected at micro-geographic scale. The estimated effective population size, the moderate level of dispersal and the rapid temporal change in genetic composition might reflect a potential effect of life history strategy on population dynamics. This hypothesis deserves further investigation. The dynamic pattern revealed at micro-geographic and temporal scales appears important from a genetic resource management as well as from a biodiversity conservation point of view. PMID:22151746

Gone with the currents: lack of genetic differentiation at the circum-continental scale in the Antarctic krill Euphausia superba

PubMed Central

2011-01-01

Background Southern Ocean fauna represent a significant amount of global biodiversity, whose origin may be linked to glacial cycles determining local extinction/eradication with ice advance, survival of refugee populations and post-glacial re-colonization. This pattern implies high potential for differentiation in benthic shelf species with limited dispersal, yet consequences for pelagic organisms are less clear. The present study investigates levels of genetic variation and population structure of the Antarctic krill Euphausia superba using mitochondrial DNA and EST-linked microsatellite markers for an unprecedentedly comprehensive sampling of its populations over a circum-Antarctic range. Results MtDNA (ND1) sequences and EST-linked microsatellite markers indicated no clear sign of genetic structure among populations over large geographic scales, despite considerable power to detect differences inferred from forward-time simulations. Based on ND1, few instances of genetic heterogeneity, not significant after correction for multiple tests, were detected between geographic or temporal samples. Neutrality tests and mismatch distribution based on mtDNA sequences revealed strong evidence of past population expansion. Significant positive values of the parameter g (a measure of population growth) were obtained from microsatellite markers using a coalescent-based genealogical method and suggested a recent start (60 000 - 40 000 years ago) for the expansion. Conclusions The results provide evidence of lack of genetic heterogeneity of Antarctic krill at large geographic scales and unequivocal support for recent population expansion. Lack of genetic structuring likely reflects the tight link between krill and circum-Antarctic ocean currents and is consistent with the hypothesis that differentiation processes in Antarctic species are largely influenced by dispersal potential, whereas small-scale spatial and temporal differentiation might be due to local conditions leading to genetic patchiness. The signal of recent population growth suggests differential impact of glacial cycles on pelagic Antarctic species, which experienced population expansion during glaciations with increased available habitat, versus sedentary benthic shelf species. EST-linked microsatellites provide new perspectives to complement the results based on mtDNA and suggest that data-mining of EST libraries will be a useful approach to facilitate use of microsatellites for additional species. PMID:21486439

Factors affecting commercial application of embryo technologies in dairy cattle in Europe--a modelling approach.

PubMed

van Arendonk, Johan A M; Bijma, Piter

2003-01-15

Reproductive techniques have a major impact on the structure of breeding programmes, the rate of genetic gain and dissemination of genetic gain in populations. This manuscript reviews the impact of reproductive technologies on the underlying components of genetic gain and inbreeding with special reference to the role of female reproductive technology. Evaluation of alternative breeding schemes should be based on genetic gain while constraining inbreeding. Optimum breeding schemes can be characterised by: decreased importance of sib information; increased accuracy at the expense of intensity; and a factorial mating strategy. If large-scale embryo cloning becomes feasible, this will have a small impact on the rate of genetic gain but will have a large impact on the structure of breeding programmes.

Psychopathology in 7-year-old children: Differences in maternal and paternal ratings and the genetic epidemiology.

PubMed

Wesseldijk, Laura W; Fedko, Iryna O; Bartels, Meike; Nivard, Michel G; van Beijsterveldt, Catharina E M; Boomsma, Dorret I; Middeldorp, Christel M

2017-04-01

The assessment of children's psychopathology is often based on parental report. Earlier studies have suggested that rater bias can affect the estimates of genetic, shared environmental and unique environmental influences on differences between children. The availability of a large dataset of maternal as well as paternal ratings of psychopathology in 7-year old children enabled (i) the analysis of informant effects on these assessments, and (ii) to obtain more reliable estimates of the genetic and non-genetic effects. DSM-oriented measures of affective, anxiety, somatic, attention-deficit/hyperactivity, oppositional-defiant, conduct, and obsessive-compulsive problems were rated for 12,310 twin pairs from the Netherlands Twin Register by mothers (N = 12,085) and fathers (N = 8,516). The effects of genetic and non-genetic effects were estimated on the common and rater-specific variance. For all scales, mean scores on maternal ratings exceeded paternal ratings. Parents largely agreed on the ranking of their child's problems (r 0.60-0.75). The heritability was estimated over 55% for maternal and paternal ratings for all scales, except for conduct problems (44-46%). Unbiased shared environmental influences, i.e., on the common variance, were significant for affective (13%), oppositional (13%), and conduct problems (37%). In clinical settings, different cutoffs for (sub)clinical scores could be applied to paternal and maternal ratings of their child's psychopathology. Only for conduct problems, shared environmental and genetic influences explain an equal amount in differences between children. For the other scales, genetic factors explain the majority of the variance, especially for the common part that is free of rater bias. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Conflicts in maintaining biodiversity at multiple scales.

PubMed

Lankau, Richard A

2011-05-01

Biodiversity consists of multiple scales, including functional diversity in ecological traits, species diversity and genetic diversity within species, and is declining across the globe, largely in response to human activities. While species extinctions are the most obvious aspect of this, there has also been a more insidious loss of genetic diversity within species. While a vast literature concerns each of these scales of biodiversity, less is known about how different scales affect one another. In particular, genetic and species diversity may influence each other in numerous ways, both positively and negatively. However, we know little about the mechanism behind these patterns. In this issue of Molecular Ecology, Nestmann et al. (2011) experimentally explore the effect of species and functional diversity and composition of grassland plant communities on the genetic structure of one of the component species. Increasing species richness led to greater changes in the genetic composition of the focal populations over 4 years, primarily because of genetic drift in smaller population sizes. However, there were also genetic changes in response to particular plant functional groups, indicating selective differences driven by plant community composition. These results suggest that different levels of biodiversity can trade-off in communities, which may prove a challenge for conservation biologists seeking to preserve all aspects of biodiversity.

Liquid chromatographic determination of sennosides in Cassia angustifolia leaves.

PubMed

Srivastava, Alpuna; Pandey, Richa; Verma, Ram K; Gupta, Madan M

2006-01-01

A simple liquid chromatographic method was developed for the determination of sennosides B and A in leaves of Cassia angustifolia. These compounds were extracted from leaves with a mixture of methanol-water (70 + 30, v/v) after defatting with hexane. Analyte separation and quantitation were achieved by gradient reversed-phase liquid chromatography and UV absorbance at 270 nm using a photodiode array detector. The method involves the use of an RP-18 Lichrocart reversed-phase column (5 microm, 125 x 4.0 mm id) and a binary gradient mobile-phase profile. The various other aspects of analysis, namely, peak purity, similarity, recovery, repeatability, and robustness, were validated. Average recoveries of 98.5 and 98.6%, with a coefficient of variation of 0.8 and 0.3%, were obtained by spiking sample solution with 3 different concentration solutions of standards (60, 100, and 200 microg/mL). Detection limits were 10 microg/mL for sennoside B and 35 microg/mL for sennoside A, present in the sample solution. The quantitation limits were 28 and 100 microg/mL. The analytical method was applied to a large number of senna leaf samples. The new method provides a reliable tool for rapid screening of C. angustifolia samples in large numbers, which is needed in breeding/genetic engineering and genetic mapping experiments.

Learning, climate and the evolution of cultural capacity.

PubMed

Whitehead, Hal

2007-03-21

Patterns of environmental variation influence the utility, and thus evolution, of different learning strategies. I use stochastic, individual-based evolutionary models to assess the relative advantages of 15 different learning strategies (genetic determination, individual learning, vertical social learning, horizontal/oblique social learning, and contingent combinations of these) when competing in variable environments described by 1/f noise. When environmental variation has little effect on fitness, then genetic determinism persists. When environmental variation is large and equal over all time-scales ("white noise") then individual learning is adaptive. Social learning is advantageous in "red noise" environments when variation over long time-scales is large. Climatic variability increases with time-scale, so that short-lived organisms should be able to rely largely on genetic determination. Thermal climates usually are insufficiently red for social learning to be advantageous for species whose fitness is very determined by temperature. In contrast, population trajectories of many species, especially large mammals and aquatic carnivores, are sufficiently red to promote social learning in their predators. The ocean environment is generally redder than that on land. Thus, while individual learning should be adaptive for many longer-lived organisms, social learning will often be found in those dependent on the populations of other species, especially if they are marine. This provides a potential explanation for the evolution of a prevalence of social learning, and culture, in humans and cetaceans.

NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice.

PubMed

Bardgett, Mark E; Boeckman, Ryan; Krochmal, Daniel; Fernando, Hiran; Ahrens, Rebecca; Csernansky, John G

2003-04-15

The interpretation of learning and memory deficits in transgenic mice has largely involved theories of NMDA receptor and/or hippocampal function. However, there is little empirical data that describes what NMDA receptors or the hippocampus do in mice. This research assessed the effects of different doses of the NMDA receptor antagonist, MK-801, or different-sized hippocampal lesions on several behavioral parameters in adult male C57Bl/6 mice. In the first set of experiments, different doses of MK-801 (0.05-0.3mg/kg, s.c.) were assayed in fear conditioning, shock sensitivity, locomotion, anxiety, and position habit reversal tests. Contextual and cued fear conditioning, and position habit reversal were impaired in a dose-dependent manner. Locomotor activity was increased immediately after injection of the highest dose of MK-801. A second set of experiments determined the behavioral effects of a moderate and large excitotoxic hippocampal lesion. Both lesions impaired contextual conditioning, while the larger lesion interfered with cued conditioning. Reversal learning was significantly diminished by the large lesion, while the moderate lesion had a detrimental effect at a trend level (P<0.10). These results provide important reference data for studies involving genetic manipulations of NMDA receptor or hippocampal function in mice. Furthermore, they serve as a basis for a non-transgenic mouse model of the NMDA receptor or hippocampal dysfunction hypothesized to occur in human cognitive disorders.

New Algorithm and Software (BNOmics) for Inferring and Visualizing Bayesian Networks from Heterogeneous Big Biological and Genetic Data

PubMed Central

Gogoshin, Grigoriy; Boerwinkle, Eric

2017-01-01

Abstract Bayesian network (BN) reconstruction is a prototypical systems biology data analysis approach that has been successfully used to reverse engineer and model networks reflecting different layers of biological organization (ranging from genetic to epigenetic to cellular pathway to metabolomic). It is especially relevant in the context of modern (ongoing and prospective) studies that generate heterogeneous high-throughput omics datasets. However, there are both theoretical and practical obstacles to the seamless application of BN modeling to such big data, including computational inefficiency of optimal BN structure search algorithms, ambiguity in data discretization, mixing data types, imputation and validation, and, in general, limited scalability in both reconstruction and visualization of BNs. To overcome these and other obstacles, we present BNOmics, an improved algorithm and software toolkit for inferring and analyzing BNs from omics datasets. BNOmics aims at comprehensive systems biology—type data exploration, including both generating new biological hypothesis and testing and validating the existing ones. Novel aspects of the algorithm center around increasing scalability and applicability to varying data types (with different explicit and implicit distributional assumptions) within the same analysis framework. An output and visualization interface to widely available graph-rendering software is also included. Three diverse applications are detailed. BNOmics was originally developed in the context of genetic epidemiology data and is being continuously optimized to keep pace with the ever-increasing inflow of available large-scale omics datasets. As such, the software scalability and usability on the less than exotic computer hardware are a priority, as well as the applicability of the algorithm and software to the heterogeneous datasets containing many data types—single-nucleotide polymorphisms and other genetic/epigenetic/transcriptome variables, metabolite levels, epidemiological variables, endpoints, and phenotypes, etc. PMID:27681505

New Algorithm and Software (BNOmics) for Inferring and Visualizing Bayesian Networks from Heterogeneous Big Biological and Genetic Data.

PubMed

Gogoshin, Grigoriy; Boerwinkle, Eric; Rodin, Andrei S

2017-04-01

Bayesian network (BN) reconstruction is a prototypical systems biology data analysis approach that has been successfully used to reverse engineer and model networks reflecting different layers of biological organization (ranging from genetic to epigenetic to cellular pathway to metabolomic). It is especially relevant in the context of modern (ongoing and prospective) studies that generate heterogeneous high-throughput omics datasets. However, there are both theoretical and practical obstacles to the seamless application of BN modeling to such big data, including computational inefficiency of optimal BN structure search algorithms, ambiguity in data discretization, mixing data types, imputation and validation, and, in general, limited scalability in both reconstruction and visualization of BNs. To overcome these and other obstacles, we present BNOmics, an improved algorithm and software toolkit for inferring and analyzing BNs from omics datasets. BNOmics aims at comprehensive systems biology-type data exploration, including both generating new biological hypothesis and testing and validating the existing ones. Novel aspects of the algorithm center around increasing scalability and applicability to varying data types (with different explicit and implicit distributional assumptions) within the same analysis framework. An output and visualization interface to widely available graph-rendering software is also included. Three diverse applications are detailed. BNOmics was originally developed in the context of genetic epidemiology data and is being continuously optimized to keep pace with the ever-increasing inflow of available large-scale omics datasets. As such, the software scalability and usability on the less than exotic computer hardware are a priority, as well as the applicability of the algorithm and software to the heterogeneous datasets containing many data types-single-nucleotide polymorphisms and other genetic/epigenetic/transcriptome variables, metabolite levels, epidemiological variables, endpoints, and phenotypes, etc.

Novel Membranes and Systems for Industrial and Municipal Water Purification and Reuse

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

None

This factsheet describes a project that developed nano-engineered, high-permeance membrane materials with more than double the permeance of current reverse osmosis membranes as well as manufacturing technologies for large-scale production of the novel materials.

The fine-scale genetic structure of the two-spotted spider mite in a commercial greenhouse.

PubMed

Uesugi, R; Kunimoto, Y; Osakabe, Mh

2009-02-01

The fine-scale genetic structure of Tetranychus urticae Koch was studied to estimate local gene flow within a rose tree habitat in a commercial greenhouse using seven microsatellite markers. Two beds of rose trees with different population densities were selected and 18 consecutive quadrats of 1.2 m length were sequentially established in each bed. Heterozygote deficiency was positive within quadrats, which was most likely a result of the Wahlund effect because the mites usually form small breeding colonies. Low population density and frequent inbreeding could also accelerate genetic differentiation among the breeding colonies. A short-range (2.4-3.6 m) positive autocorrelation and clear genetic cline among quadrat populations was detected within a bed. This suggests that gene flow was limited to a short range even if population density was substantially increased. Therefore, large-scale dispersal such as aerial dispersal contributed very little to gene flow in the greenhouse.

Empty Promises: A Case Study of Restructuring and the Exclusion of English Language Learners in Two Brooklyn High Schools

ERIC Educational Resources Information Center

Asian American Legal Defense and Education Fund, 2009

2009-01-01

Since 2002, the New York City Department of Education (DOE) has attempted to reverse the city's severe drop-out crisis through a large scale restructuring of high schools, focused mainly on closing large, comprehensive high schools and replacing them with small high schools that offer a more personalized learning environment. Unfortunately, this…

Analysis of Ten Reverse Engineering Tools

NASA Astrophysics Data System (ADS)

Koskinen, Jussi; Lehmonen, Tero

Reverse engineering tools can be used in satisfying the information needs of software maintainers. Especially in case of maintaining large-scale legacy systems tool support is essential. Reverse engineering tools provide various kinds of capabilities to provide the needed information to the tool user. In this paper we analyze the provided capabilities in terms of four aspects: provided data structures, visualization mechanisms, information request specification mechanisms, and navigation features. We provide a compact analysis of ten representative reverse engineering tools for supporting C, C++ or Java: Eclipse Java Development Tools, Wind River Workbench (for C and C++), Understand (for C++), Imagix 4D, Creole, Javadoc, Javasrc, Source Navigator, Doxygen, and HyperSoft. The results of the study supplement the earlier findings in this important area.

Phenotypic Plasticity Influences the Size, Shape and Dynamics of the Geographic Distribution of an Invasive Plant

PubMed Central

Pichancourt, Jean-Baptiste; van Klinken, Rieks D.

2012-01-01

Phenotypic plasticity has long been suspected to allow invasive species to expand their geographic range across large-scale environmental gradients. We tested this possibility in Australia using a continental scale survey of the invasive tree Parkinsonia aculeata (Fabaceae) in twenty-three sites distributed across four climate regions and three habitat types. Using tree-level responses, we detected a trade-off between seed mass and seed number across the moisture gradient. Individual trees plastically and reversibly produced many small seeds at dry sites or years, and few big seeds at wet sites and years. Bigger seeds were positively correlated with higher seed and seedling survival rates. The trade-off, the relation between seed mass, seed and seedling survival, and other fitness components of the plant life-cycle were integrated within a matrix population model. The model confirms that the plastic response resulted in average fitness benefits across the life-cycle. Plasticity resulted in average fitness being positively maintained at the wet and dry range margins where extinction risks would otherwise have been high (“Jack-of-all-Trades” strategy JT), and fitness being maximized at the species range centre where extinction risks were already low (“Master-of-Some” strategy MS). The resulting hybrid “Jack-and-Master” strategy (JM) broadened the geographic range and amplified average fitness in the range centre. Our study provides the first empirical evidence for a JM species. It also confirms mechanistically the importance of phenotypic plasticity in determining the size, the shape and the dynamic of a species distribution. The JM allows rapid and reversible phenotypic responses to new or changing moisture conditions at different scales, providing the species with definite advantages over genetic adaptation when invading diverse and variable environments. Furthermore, natural selection pressure acting on phenotypic plasticity is predicted to result in maintenance of the JT and strengthening of the MS, further enhancing the species invasiveness in its range centre. PMID:22384216

PRELIMINARY ANALYSIS OF COMMON LOON GENETIC STRUCTURE IN NORTH AMERICA BASED ON FIVE MICROSATELLITE LOCI

EPA Science Inventory

This study seeks to determine fine-scale genetic structure of Common Loon breeding populations in order to link wintering birds with their breeding regions. Common Loons are large piscivorous birds that breed in lakes of northern North America and Iceland. Loons are highly phil...

Anomalous transport theory for the reversed field pinch

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

Terry, P.W.; Hegna, C.C; Sovinec, C.R.

1996-09-01

Physically motivated transport models with predictive capabilities and significance beyond the reversed field pinch (RFP) are presented. It is shown that the ambipolar constrained electron heat loss observed in MST can be quantitatively modeled by taking account of the clumping in parallel streaming electrons and the resultant self-consistent interaction with collective modes; that the discrete dynamo process is a relaxation oscillation whose dependence on the tearing instability and profile relaxation physics leads to amplitude and period scaling predictions consistent with experiment; that the Lundquist number scaling in relaxed plasmas driven by magnetic turbulence has a weak S{sup {minus}1/4} scaling; andmore » that radial E{times}B shear flow can lead to large reductions in the edge particle flux with little change in the heat flux, as observed in the RFP and tokamak. 24 refs.« less

Population signatures of large-scale, long-term disjunction and small-scale, short-term habitat fragmentation in an Afromontane forest bird

PubMed Central

Habel, J C; Mulwa, R K; Gassert, F; Rödder, D; Ulrich, W; Borghesio, L; Husemann, M; Lens, L

2014-01-01

The Eastern Afromontane cloud forests occur as geographically distinct mountain exclaves. The conditions of these forests range from large to small and from fairly intact to strongly degraded. For this study, we sampled individuals of the forest bird species, the Montane White-eye Zosterops poliogaster from 16 sites and four mountain archipelagos. We analysed 12 polymorphic microsatellites and three phenotypic traits, and calculated Species Distribution Models (SDMs) to project past distributions and predict potential future range shifts under a scenario of climate warming. We found well-supported genetic and morphologic clusters corresponding to the mountain ranges where populations were sampled, with 43% of all alleles being restricted to single mountains. Our data suggest that large-scale and long-term geographic isolation on mountain islands caused genetically and morphologically distinct population clusters in Z. poliogaster. However, major genetic and biometric splits were not correlated to the geographic distances among populations. This heterogeneous pattern can be explained by past climatic shifts, as highlighted by our SDM projections. Anthropogenically fragmented populations showed lower genetic diversity and a lower mean body mass, possibly in response to suboptimal habitat conditions. On the basis of these findings and the results from our SDM analysis we predict further loss of genotypic and phenotypic uniqueness in the wake of climate change, due to the contraction of the species' climatic niche and subsequent decline in population size. PMID:24713824

Population signatures of large-scale, long-term disjunction and small-scale, short-term habitat fragmentation in an Afromontane forest bird.

PubMed

Habel, J C; Mulwa, R K; Gassert, F; Rödder, D; Ulrich, W; Borghesio, L; Husemann, M; Lens, L

2014-09-01

The Eastern Afromontane cloud forests occur as geographically distinct mountain exclaves. The conditions of these forests range from large to small and from fairly intact to strongly degraded. For this study, we sampled individuals of the forest bird species, the Montane White-eye Zosterops poliogaster from 16 sites and four mountain archipelagos. We analysed 12 polymorphic microsatellites and three phenotypic traits, and calculated Species Distribution Models (SDMs) to project past distributions and predict potential future range shifts under a scenario of climate warming. We found well-supported genetic and morphologic clusters corresponding to the mountain ranges where populations were sampled, with 43% of all alleles being restricted to single mountains. Our data suggest that large-scale and long-term geographic isolation on mountain islands caused genetically and morphologically distinct population clusters in Z. poliogaster. However, major genetic and biometric splits were not correlated to the geographic distances among populations. This heterogeneous pattern can be explained by past climatic shifts, as highlighted by our SDM projections. Anthropogenically fragmented populations showed lower genetic diversity and a lower mean body mass, possibly in response to suboptimal habitat conditions. On the basis of these findings and the results from our SDM analysis we predict further loss of genotypic and phenotypic uniqueness in the wake of climate change, due to the contraction of the species' climatic niche and subsequent decline in population size.

Gene silencing in non-model insects: Overcoming hurdles using symbiotic bacteria for trauma-free sustainable delivery of RNA interference: Sustained RNA interference in insects mediated by symbiotic bacteria: Applications as a genetic tool and as a biocide.

PubMed

Whitten, Miranda; Dyson, Paul

2017-03-01

Insight into animal biology and development provided by classical genetic analysis of the model organism Drosophila melanogaster was an incentive to develop advanced genetic tools for this insect. But genetic systems for the over one million other known insect species are largely undeveloped. With increasing information about insect genomes resulting from next generation sequencing, RNA interference is now the method of choice for reverse genetics, although it is constrained by the means of delivery of interfering RNA. A recent advance to ensure sustained delivery with minimal experimental intervention or trauma to the insect is to exploit commensal bacteria for symbiont-mediated RNA interference. This technology not only offers an efficient means for RNA interference in insects in laboratory conditions, but also has potential for use in the control of human disease vectors, agricultural pests and pathogens of beneficial insects. © 2017 WILEY Periodicals, Inc.

MEAN-FIELD MODELING OF AN α{sup 2} DYNAMO COUPLED WITH DIRECT NUMERICAL SIMULATIONS OF RIGIDLY ROTATING CONVECTION

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

Masada, Youhei; Sano, Takayoshi, E-mail: ymasada@harbor.kobe-u.ac.jp, E-mail: sano@ile.osaka-u.ac.jp

2014-10-10

The mechanism of large-scale dynamos in rigidly rotating stratified convection is explored by direct numerical simulations (DNS) in Cartesian geometry. A mean-field dynamo model is also constructed using turbulent velocity profiles consistently extracted from the corresponding DNS results. By quantitative comparison between the DNS and our mean-field model, it is demonstrated that the oscillatory α{sup 2} dynamo wave, excited and sustained in the convection zone, is responsible for large-scale magnetic activities such as cyclic polarity reversal and spatiotemporal migration. The results provide strong evidence that a nonuniformity of the α-effect, which is a natural outcome of rotating stratified convection, canmore » be an important prerequisite for large-scale stellar dynamos, even without the Ω-effect.« less

Convergence between biological, behavioural and genetic determinants of obesity.

PubMed

Ghosh, Sujoy; Bouchard, Claude

2017-12-01

Multiple biological, behavioural and genetic determinants or correlates of obesity have been identified to date. Genome-wide association studies (GWAS) have contributed to the identification of more than 100 obesity-associated genetic variants, but their roles in causal processes leading to obesity remain largely unknown. Most variants are likely to have tissue-specific regulatory roles through joint contributions to biological pathways and networks, through changes in gene expression that influence quantitative traits, or through the regulation of the epigenome. The recent availability of large-scale functional genomics resources provides an opportunity to re-examine obesity GWAS data to begin elucidating the function of genetic variants. Interrogation of knockout mouse phenotype resources provides a further avenue to test for evidence of convergence between genetic variation and biological or behavioural determinants of obesity.

Structural Variation Shapes the Landscape of Recombination in Mouse

PubMed Central

Morgan, Andrew P.; Gatti, Daniel M.; Najarian, Maya L.; Keane, Thomas M.; Galante, Raymond J.; Pack, Allan I.; Mott, Richard; Churchill, Gary A.; de Villena, Fernando Pardo-Manuel

2017-01-01

Meiotic recombination is an essential feature of sexual reproduction that ensures faithful segregation of chromosomes and redistributes genetic variants in populations. Multiparent populations such as the Diversity Outbred (DO) mouse stock accumulate large numbers of crossover (CO) events between founder haplotypes, and thus present a unique opportunity to study the role of genetic variation in shaping the recombination landscape. We obtained high-density genotype data from 6886 DO mice, and localized 2.2 million CO events to intervals with a median size of 28 kb. The resulting sex-averaged genetic map of the DO population is highly concordant with large-scale (order 10 Mb) features of previously reported genetic maps for mouse. To examine fine-scale (order 10 kb) patterns of recombination in the DO, we overlaid putative recombination hotspots onto our CO intervals. We found that CO intervals are enriched in hotspots compared to the genomic background. However, as many as 26% of CO intervals do not overlap any putative hotspots, suggesting that our understanding of hotspots is incomplete. We also identified coldspots encompassing 329 Mb, or 12% of observable genome, in which there is little or no recombination. In contrast to hotspots, which are a few kilobases in size, and widely scattered throughout the genome, coldspots have a median size of 2.1 Mb and are spatially clustered. Coldspots are strongly associated with copy-number variant (CNV) regions, especially multi-allelic clusters, identified from whole-genome sequencing of 228 DO mice. Genes in these regions have reduced expression, and epigenetic features of closed chromatin in male germ cells, which suggests that CNVs may repress recombination by altering chromatin structure in meiosis. Our findings demonstrate how multiparent populations, by bridging the gap between large-scale and fine-scale genetic mapping, can reveal new features of the recombination landscape. PMID:28592499

Large-Scale Genetic Structuring of a Widely Distributed Carnivore - The Eurasian Lynx (Lynx lynx)

PubMed Central

Rueness, Eli K.; Naidenko, Sergei; Trosvik, Pål; Stenseth, Nils Chr.

2014-01-01

Over the last decades the phylogeography and genetic structure of a multitude of species inhabiting Europe and North America have been described. The flora and fauna of the vast landmasses of north-eastern Eurasia are still largely unexplored in this respect. The Eurasian lynx is a large felid that is relatively abundant over much of the Russian sub-continent and the adjoining countries. Analyzing 148 museum specimens collected throughout its range over the last 150 years we have described the large-scale genetic structuring in this highly mobile species. We have investigated the spatial genetic patterns using mitochondrial DNA sequences (D-loop and cytochrome b) and 11 microsatellite loci, and describe three phylogenetic clades and a clear structuring along an east-west gradient. The most likely scenario is that the contemporary Eurasian lynx populations originated in central Asia and that parts of Europe were inhabited by lynx during the Pleistocene. After the Last Glacial Maximum (LGM) range expansions lead to colonization of north-western Siberia and Scandinavia from the Caucasus and north-eastern Siberia from a refugium further east. No evidence of a Berinigan refugium could be detected in our data. We observed restricted gene flow and suggest that future studies of the Eurasian lynx explore to what extent the contemporary population structure may be explained by ecological variables. PMID:24695745

Multi-scale genetic dynamic modelling I : an algorithm to compute generators.

PubMed

Kirkilionis, Markus; Janus, Ulrich; Sbano, Luca

2011-09-01

We present a new approach or framework to model dynamic regulatory genetic activity. The framework is using a multi-scale analysis based upon generic assumptions on the relative time scales attached to the different transitions of molecular states defining the genetic system. At micro-level such systems are regulated by the interaction of two kinds of molecular players: macro-molecules like DNA or polymerases, and smaller molecules acting as transcription factors. The proposed genetic model then represents the larger less abundant molecules with a finite discrete state space, for example describing different conformations of these molecules. This is in contrast to the representations of the transcription factors which are-like in classical reaction kinetics-represented by their particle number only. We illustrate the method by considering the genetic activity associated to certain configurations of interacting genes that are fundamental to modelling (synthetic) genetic clocks. A largely unknown question is how different molecular details incorporated via this more realistic modelling approach lead to different macroscopic regulatory genetic models which dynamical behaviour might-in general-be different for different model choices. The theory will be applied to a real synthetic clock in a second accompanying article (Kirkilioniset al., Theory Biosci, 2011).

New generation pharmacogenomic tools: a SNP linkage disequilibrium Map, validated SNP assay resource, and high-throughput instrumentation system for large-scale genetic studies.

PubMed

De La Vega, Francisco M; Dailey, David; Ziegle, Janet; Williams, Julie; Madden, Dawn; Gilbert, Dennis A

2002-06-01

Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.

Diversity analysis in Cannabis sativa based on large-scale development of expressed sequence tag-derived simple sequence repeat markers.

PubMed

Gao, Chunsheng; Xin, Pengfei; Cheng, Chaohua; Tang, Qing; Chen, Ping; Wang, Changbiao; Zang, Gonggu; Zhao, Lining

2014-01-01

Cannabis sativa L. is an important economic plant for the production of food, fiber, oils, and intoxicants. However, lack of sufficient simple sequence repeat (SSR) markers has limited the development of cannabis genetic research. Here, large-scale development of expressed sequence tag simple sequence repeat (EST-SSR) markers was performed to obtain more informative genetic markers, and to assess genetic diversity in cannabis (Cannabis sativa L.). Based on the cannabis transcriptome, 4,577 SSRs were identified from 3,624 ESTs. From there, a total of 3,442 complementary primer pairs were designed as SSR markers. Among these markers, trinucleotide repeat motifs (50.99%) were the most abundant, followed by hexanucleotide (25.13%), dinucleotide (16.34%), tetranucloetide (3.8%), and pentanucleotide (3.74%) repeat motifs, respectively. The AAG/CTT trinucleotide repeat (17.96%) was the most abundant motif detected in the SSRs. One hundred and seventeen EST-SSR markers were randomly selected to evaluate primer quality in 24 cannabis varieties. Among these 117 markers, 108 (92.31%) were successfully amplified and 87 (74.36%) were polymorphic. Forty-five polymorphic primer pairs were selected to evaluate genetic diversity and relatedness among the 115 cannabis genotypes. The results showed that 115 varieties could be divided into 4 groups primarily based on geography: Northern China, Europe, Central China, and Southern China. Moreover, the coefficient of similarity when comparing cannabis from Northern China with the European group cannabis was higher than that when comparing with cannabis from the other two groups, owing to a similar climate. This study outlines the first large-scale development of SSR markers for cannabis. These data may serve as a foundation for the development of genetic linkage, quantitative trait loci mapping, and marker-assisted breeding of cannabis.

Diversity Analysis in Cannabis sativa Based on Large-Scale Development of Expressed Sequence Tag-Derived Simple Sequence Repeat Markers

PubMed Central

Cheng, Chaohua; Tang, Qing; Chen, Ping; Wang, Changbiao; Zang, Gonggu; Zhao, Lining

2014-01-01

Cannabis sativa L. is an important economic plant for the production of food, fiber, oils, and intoxicants. However, lack of sufficient simple sequence repeat (SSR) markers has limited the development of cannabis genetic research. Here, large-scale development of expressed sequence tag simple sequence repeat (EST-SSR) markers was performed to obtain more informative genetic markers, and to assess genetic diversity in cannabis (Cannabis sativa L.). Based on the cannabis transcriptome, 4,577 SSRs were identified from 3,624 ESTs. From there, a total of 3,442 complementary primer pairs were designed as SSR markers. Among these markers, trinucleotide repeat motifs (50.99%) were the most abundant, followed by hexanucleotide (25.13%), dinucleotide (16.34%), tetranucloetide (3.8%), and pentanucleotide (3.74%) repeat motifs, respectively. The AAG/CTT trinucleotide repeat (17.96%) was the most abundant motif detected in the SSRs. One hundred and seventeen EST-SSR markers were randomly selected to evaluate primer quality in 24 cannabis varieties. Among these 117 markers, 108 (92.31%) were successfully amplified and 87 (74.36%) were polymorphic. Forty-five polymorphic primer pairs were selected to evaluate genetic diversity and relatedness among the 115 cannabis genotypes. The results showed that 115 varieties could be divided into 4 groups primarily based on geography: Northern China, Europe, Central China, and Southern China. Moreover, the coefficient of similarity when comparing cannabis from Northern China with the European group cannabis was higher than that when comparing with cannabis from the other two groups, owing to a similar climate. This study outlines the first large-scale development of SSR markers for cannabis. These data may serve as a foundation for the development of genetic linkage, quantitative trait loci mapping, and marker-assisted breeding of cannabis. PMID:25329551

The genetic architecture of novel trophic specialists: larger effect sizes are associated with exceptional oral jaw diversification in a pupfish adaptive radiation.

PubMed

Martin, Christopher H; Erickson, Priscilla A; Miller, Craig T

2017-01-01

The genetic architecture of adaptation is fundamental to understanding the mechanisms and constraints governing diversification. However, most case studies focus on loss of complex traits or parallel speciation in similar environments. It is still unclear how the genetic architecture of these local adaptive processes compares to the architecture of evolutionary transitions contributing to morphological and ecological novelty. Here, we identify quantitative trait loci (QTL) between two trophic specialists in an excellent case study for examining the origins of ecological novelty: a sympatric radiation of pupfishes endemic to San Salvador Island, Bahamas, containing a large-jawed scale-eater and a short-jawed molluscivore with a skeletal nasal protrusion. These specialized niches and trophic traits are unique among over 2000 related species. Measurements of the fitness landscape on San Salvador demonstrate multiple fitness peaks and a larger fitness valley isolating the scale-eater from the putative ancestral intermediate phenotype of the generalist, suggesting that more large-effect QTL should contribute to its unique phenotype. We evaluated this prediction using an F2 intercross between these specialists. We present the first linkage map for pupfishes and detect significant QTL for sex and eight skeletal traits. Large-effect QTL contributed more to enlarged scale-eater jaws than the molluscivore nasal protrusion, consistent with predictions from the adaptive landscape. The microevolutionary genetic architecture of large-effect QTL for oral jaws parallels the exceptional diversification rates of oral jaws within the San Salvador radiation observed over macroevolutionary timescales and may have facilitated exceptional trophic novelty in this system. © 2016 John Wiley & Sons Ltd.

Large-Scale SNP Discovery and Genotyping for Constructing a High-Density Genetic Map of Tea Plant Using Specific-Locus Amplified Fragment Sequencing (SLAF-seq)

PubMed Central

Ma, Chun-Lei; Jin, Ji-Qiang; Li, Chun-Fang; Wang, Rong-Kai; Zheng, Hong-Kun; Yao, Ming-Zhe; Chen, Liang

2015-01-01

Genetic maps are important tools in plant genomics and breeding. The present study reports the large-scale discovery of single nucleotide polymorphisms (SNPs) for genetic map construction in tea plant. We developed a total of 6,042 valid SNP markers using specific-locus amplified fragment sequencing (SLAF-seq), and subsequently mapped them into the previous framework map. The final map contained 6,448 molecular markers, distributing on fifteen linkage groups corresponding to the number of tea plant chromosomes. The total map length was 3,965 cM, with an average inter-locus distance of 1.0 cM. This map is the first SNP-based reference map of tea plant, as well as the most saturated one developed to date. The SNP markers and map resources generated in this study provide a wealth of genetic information that can serve as a foundation for downstream genetic analyses, such as the fine mapping of quantitative trait loci (QTL), map-based cloning, marker-assisted selection, and anchoring of scaffolds to facilitate the process of whole genome sequencing projects for tea plant. PMID:26035838

Genetic Diversity and Ecological Niche Modelling of Wild Barley: Refugia, Large-Scale Post-LGM Range Expansion and Limited Mid-Future Climate Threats?

PubMed Central

Russell, Joanne; van Zonneveld, Maarten; Dawson, Ian K.; Booth, Allan; Waugh, Robbie; Steffenson, Brian

2014-01-01

Describing genetic diversity in wild barley (Hordeum vulgare ssp. spontaneum) in geographic and environmental space in the context of current, past and potential future climates is important for conservation and for breeding the domesticated crop (Hordeum vulgare ssp. vulgare). Spatial genetic diversity in wild barley was revealed by both nuclear- (2,505 SNP, 24 nSSR) and chloroplast-derived (5 cpSSR) markers in 256 widely-sampled geo-referenced accessions. Results were compared with MaxEnt-modelled geographic distributions under current, past (Last Glacial Maximum, LGM) and mid-term future (anthropogenic scenario A2, the 2080s) climates. Comparisons suggest large-scale post-LGM range expansion in Central Asia and relatively small, but statistically significant, reductions in range-wide genetic diversity under future climate. Our analyses support the utility of ecological niche modelling for locating genetic diversity hotspots and determine priority geographic areas for wild barley conservation under anthropogenic climate change. Similar research on other cereal crop progenitors could play an important role in tailoring conservation and crop improvement strategies to support future human food security. PMID:24505252

Disease Modeling via Large-Scale Network Analysis

DTIC Science & Technology

2015-05-20

SECURITY CLASSIFICATION OF: A central goal of genetics is to learn how the genotype of an organism determines its phenotype. We address the implicit...guarantees for the methods. In the past, we have developed predictive methods general enough to apply to potentially any genetic trait, varying from... genetics is to learn how the genotype of an organism determines its phenotype. We address the implicit problem of predicting the association of genes with

How Large Scales Flows May Influence Solar Activity

NASA Technical Reports Server (NTRS)

Hathaway, D. H.

2004-01-01

Large scale flows within the solar convection zone are the primary drivers of the Sun's magnetic activity cycle and play important roles in shaping the Sun's magnetic field. Differential rotation amplifies the magnetic field through its shearing action and converts poloidal field into toroidal field. Poleward meridional flow near the surface carries magnetic flux that reverses the magnetic poles at about the time of solar maximum. The deeper, equatorward meridional flow can carry magnetic flux back toward the lower latitudes where it erupts through the surface to form tilted active regions that convert toroidal fields into oppositely directed poloidal fields. These axisymmetric flows are themselves driven by large scale convective motions. The effects of the Sun's rotation on convection produce velocity correlations that can maintain both the differential rotation and the meridional circulation. These convective motions can also influence solar activity directly by shaping the magnetic field pattern. While considerable theoretical advances have been made toward understanding these large scale flows, outstanding problems in matching theory to observations still remain.

Early genetic consequences of defaunation in a large-seeded vertebrate-dispersed palm (Syagrus romanzoffiana)

PubMed Central

Giombini, M I; Bravo, S P; Sica, Y V; Tosto, D S

2017-01-01

Plant populations are seriously threatened by anthropogenic habitat disturbance. In particular, defaunation may disrupt plant-disperser mutualisms, thus reducing levels of seed-mediated gene flow and genetic variation in animal-dispersed plants. This may ultimately limit their adaptive potential and ability to cope with environmental change. Tropical forest remnants are typically deprived of medium to large vertebrates upon which many large-seeded plants rely for accomplishing effective seed dispersal. Our main goal was to examine the potential early genetic consequences of the loss of large vertebrates for large-seeded vertebrate-dispersed plants. We compared the genetic variation in early-stage individuals of the large-seeded palm Syagrus romanzoffiana between continuous protected forest and nearby partially defaunated fragments in the Atlantic Forest of South America. Using nine microsatellites, we found lower allelic richness and stronger fine-scale spatial genetic structure in the disturbed area. In addition, the percentage of dispersed recruits around conspecific adults was lower, although not significantly, in the disturbed area (median values: 0.0 vs 14.4%). On the other hand, no evidence of increased inbreeding or reduced pollen-mediated gene flow (selfing rate and diversity of pollen donors) was found in the disturbed area. Our findings are strongly suggestive of some early genetic consequences resulting from the limitation in contemporary gene flow via seeds, but not pollen, in defaunated areas. Plant-disperser mutualisms involving medium–large frugivores, which are seriously threatened in tropical systems, should therefore be protected to warrant the maintenance of seed-mediated gene flow and genetic diversity in large-seeded plants. PMID:28121308

Osborne Reynolds pipe flow: Direct simulation from laminar through gradual transition to fully developed turbulence.

PubMed

Wu, Xiaohua; Moin, Parviz; Adrian, Ronald J; Baltzer, Jon R

2015-06-30

The precise dynamics of breakdown in pipe transition is a century-old unresolved problem in fluid mechanics. We demonstrate that the abruptness and mysteriousness attributed to the Osborne Reynolds pipe transition can be partially resolved with a spatially developing direct simulation that carries weakly but finitely perturbed laminar inflow through gradual rather than abrupt transition arriving at the fully developed turbulent state. Our results with this approach show during transition the energy norms of such inlet perturbations grow exponentially rather than algebraically with axial distance. When inlet disturbance is located in the core region, helical vortex filaments evolve into large-scale reverse hairpin vortices. The interaction of these reverse hairpins among themselves or with the near-wall flow when they descend to the surface from the core produces small-scale hairpin packets, which leads to breakdown. When inlet disturbance is near the wall, certain quasi-spanwise structure is stretched into a Lambda vortex, and develops into a large-scale hairpin vortex. Small-scale hairpin packets emerge near the tip region of the large-scale hairpin vortex, and subsequently grow into a turbulent spot, which is itself a local concentration of small-scale hairpin vortices. This vortex dynamics is broadly analogous to that in the boundary layer bypass transition and in the secondary instability and breakdown stage of natural transition, suggesting the possibility of a partial unification. Under parabolic base flow the friction factor overshoots Moody's correlation. Plug base flow requires stronger inlet disturbance for transition. Accuracy of the results is demonstrated by comparing with analytical solutions before breakdown, and with fully developed turbulence measurements after the completion of transition.

Osborne Reynolds pipe flow: Direct simulation from laminar through gradual transition to fully developed turbulence

PubMed Central

Wu, Xiaohua; Moin, Parviz; Adrian, Ronald J.; Baltzer, Jon R.

2015-01-01

The precise dynamics of breakdown in pipe transition is a century-old unresolved problem in fluid mechanics. We demonstrate that the abruptness and mysteriousness attributed to the Osborne Reynolds pipe transition can be partially resolved with a spatially developing direct simulation that carries weakly but finitely perturbed laminar inflow through gradual rather than abrupt transition arriving at the fully developed turbulent state. Our results with this approach show during transition the energy norms of such inlet perturbations grow exponentially rather than algebraically with axial distance. When inlet disturbance is located in the core region, helical vortex filaments evolve into large-scale reverse hairpin vortices. The interaction of these reverse hairpins among themselves or with the near-wall flow when they descend to the surface from the core produces small-scale hairpin packets, which leads to breakdown. When inlet disturbance is near the wall, certain quasi-spanwise structure is stretched into a Lambda vortex, and develops into a large-scale hairpin vortex. Small-scale hairpin packets emerge near the tip region of the large-scale hairpin vortex, and subsequently grow into a turbulent spot, which is itself a local concentration of small-scale hairpin vortices. This vortex dynamics is broadly analogous to that in the boundary layer bypass transition and in the secondary instability and breakdown stage of natural transition, suggesting the possibility of a partial unification. Under parabolic base flow the friction factor overshoots Moody’s correlation. Plug base flow requires stronger inlet disturbance for transition. Accuracy of the results is demonstrated by comparing with analytical solutions before breakdown, and with fully developed turbulence measurements after the completion of transition. PMID:26080447

Osborne Reynolds pipe flow: Direct simulation from laminar through gradual transition to fully developed turbulence

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

Wu, Xiaohua; Moin, Parviz; Adrian, Ronald J.

We report that the precise dynamics of breakdown in pipe transition is a century-old unresolved problem in fluid mechanics. We demonstrate that the abruptness and mysteriousness attributed to the Osborne Reynolds pipe transition can be partially resolved with a spatially developing direct simulation that carries weakly but finitely perturbed laminar inflow through gradual rather than abrupt transition arriving at the fully developed turbulent state. Our results with this approach show during transition the energy norms of such inlet perturbations grow exponentially rather than algebraically with axial distance. When inlet disturbance is located in the core region, helical vortex filaments evolvemore » into large-scale reverse hairpin vortices. The interaction of these reverse hairpins among themselves or with the near-wall flow when they descend to the surface from the core produces small-scale hairpin packets, which leads to breakdown. When inlet disturbance is near the wall, certain quasi-spanwise structure is stretched into a Lambda vortex, and develops into a large-scale hairpin vortex. Small-scale hairpin packets emerge near the tip region of the large-scale hairpin vortex, and subsequently grow into a turbulent spot, which is itself a local concentration of small-scale hairpin vortices. This vortex dynamics is broadly analogous to that in the boundary layer bypass transition and in the secondary instability and breakdown stage of natural transition, suggesting the possibility of a partial unification. Under parabolic base flow the friction factor overshoots Moody’s correlation. Plug base flow requires stronger inlet disturbance for transition. Finally, accuracy of the results is demonstrated by comparing with analytical solutions before breakdown, and with fully developed turbulence measurements after the completion of transition.« less

Osborne Reynolds pipe flow: Direct simulation from laminar through gradual transition to fully developed turbulence

DOE PAGES

Wu, Xiaohua; Moin, Parviz; Adrian, Ronald J.; ...

2015-06-15

We report that the precise dynamics of breakdown in pipe transition is a century-old unresolved problem in fluid mechanics. We demonstrate that the abruptness and mysteriousness attributed to the Osborne Reynolds pipe transition can be partially resolved with a spatially developing direct simulation that carries weakly but finitely perturbed laminar inflow through gradual rather than abrupt transition arriving at the fully developed turbulent state. Our results with this approach show during transition the energy norms of such inlet perturbations grow exponentially rather than algebraically with axial distance. When inlet disturbance is located in the core region, helical vortex filaments evolvemore » into large-scale reverse hairpin vortices. The interaction of these reverse hairpins among themselves or with the near-wall flow when they descend to the surface from the core produces small-scale hairpin packets, which leads to breakdown. When inlet disturbance is near the wall, certain quasi-spanwise structure is stretched into a Lambda vortex, and develops into a large-scale hairpin vortex. Small-scale hairpin packets emerge near the tip region of the large-scale hairpin vortex, and subsequently grow into a turbulent spot, which is itself a local concentration of small-scale hairpin vortices. This vortex dynamics is broadly analogous to that in the boundary layer bypass transition and in the secondary instability and breakdown stage of natural transition, suggesting the possibility of a partial unification. Under parabolic base flow the friction factor overshoots Moody’s correlation. Plug base flow requires stronger inlet disturbance for transition. Finally, accuracy of the results is demonstrated by comparing with analytical solutions before breakdown, and with fully developed turbulence measurements after the completion of transition.« less

Energy Systems Integration Partnerships: NREL + Giner

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

2017-03-22

This fact sheet highlights work done at the ESIF in partnership with Giner. Giner, a developer of proton-exchange membrane (PEM) technologies, has contracted with NREL to validate the performance of its large-scale PEM electrolyzer stacks. PEM electrolyzers work much like fuel cells run in reverse.

Annual Research Review: Developmental Considerations of Gene by Environment Interactions

ERIC Educational Resources Information Center

Lenroot, Rhoshel K.; Giedd, Jay N.

2011-01-01

Biological development is driven by a complex dance between nurture and nature, determined not only by the specific features of the interacting genetic and environmental influences but also by the timing of their rendezvous. The initiation of large-scale longitudinal studies, ever-expanding knowledge of genetics, and increasing availability of…

Evidence of evolutionary history and selective sweeps in the genome of Meishan pig reveals its genetic and phenotypic characterization

USDA-ARS?s Scientific Manuscript database

Meishan is a famous Chinese indigenous pig breed known for its extremely high fecundity. To explore if Meishan has unique evolutionary process and genome characteristics differing from other pig breeds, we systematically analyzed its genetic divergence, and demographic history by large-scale reseque...

Possible roles for fronto-striatal circuits in reading disorder

PubMed Central

Hancock, Roeland; Richlan, Fabio; Hoeft, Fumiko

2016-01-01

Several studies have reported hyperactivation in frontal and striatal regions in individuals with reading disorder (RD) during reading-related tasks. Hyperactivation in these regions is typically interpreted as a form of neural compensation and related to articulatory processing. Fronto-striatal hyperactivation in RD can however, also arise from fundamental impairment in reading related processes, such as phonological processing and implicit sequence learning relevant to early language acquisition. We review current evidence for the compensation hypothesis in RD and apply large-scale reverse inference to investigate anatomical overlap between hyperactivation regions and neural systems for articulation, phonological processing, implicit sequence learning. We found anatomical convergence between hyperactivation regions and regions supporting articulation, consistent with the proposed compensatory role of these regions, and low convergence with phonological and implicit sequence learning regions. Although the application of large-scale reverse inference to decode function in a clinical population should be interpreted cautiously, our findings suggest future lines of research that may clarify the functional significance of hyperactivation in RD. PMID:27826071

Chaotic gas turbine subject to augmented Lorenz equations.

PubMed

Cho, Kenichiro; Miyano, Takaya; Toriyama, Toshiyuki

2012-09-01

Inspired by the chaotic waterwheel invented by Malkus and Howard about 40 years ago, we have developed a gas turbine that randomly switches the sense of rotation between clockwise and counterclockwise. The nondimensionalized expressions for the equations of motion of our turbine are represented as a starlike network of many Lorenz subsystems sharing the angular velocity of the turbine rotor as the central node, referred to as augmented Lorenz equations. We show qualitative similarities between the statistical properties of the angular velocity of the turbine rotor and the velocity field of large-scale wind in turbulent Rayleigh-Bénard convection reported by Sreenivasan et al. [Phys. Rev. E 65, 056306 (2002)]. Our equations of motion achieve the random reversal of the turbine rotor through the stochastic resonance of the angular velocity in a double-well potential and the force applied by rapidly oscillating fields. These results suggest that the augmented Lorenz model is applicable as a dynamical model for the random reversal of turbulent large-scale wind through cessation.

Ecological transition predictably associated with gene degeneration.

PubMed

Wessinger, Carolyn A; Rausher, Mark D

2015-02-01

Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Serum total bilirubin levels and coronary heart disease--Causal association or epiphenomenon?

PubMed

Kunutsor, Setor K

2015-12-01

Observational epidemiological evidence supports a linear inverse and independent association between serum total bilirubin levels and coronary heart disease (CHD) risk, but whether this association is causal remains to be ascertained. A Mendelian randomization approach was employed to test whether serum total bilirubin is causally linked to CHD. The genetic variant rs6742078--well known to specifically modify levels of serum total bilirubin and accounting for up to 20% of the variance in circulating serum total bilirubin levels--was used as an instrumental variable. In pooled analysis of estimates reported from published genome-wide association studies, every copy of the T allele of rs6742078 was associated with 0.42 standard deviation (SD) higher levels of serum total bilirubin (95% confidence interval, 0.40 to 0.43). Based on combined data from the Coronary Artery Disease Genome wide Replication and Meta-analyses and the Coronary Artery Disease (C4D) Genetics Consortium involving a total of 36,763 CHD cases and 76,997 controls, the odds ratio for CHD per copy of the T allele was 1.01 (95% confidence interval, 0.99 to 1.04). The odds ratio of CHD for a 1 SD genetically elevated serum total bilirubin level was 1.03 (95% confidence interval, 0.98 to 1.09). The current findings casts doubt on a strong causal association of serum total bilirubin levels with CHD. The inverse associations demonstrated in observational studies may be driven by biases such as unmeasured confounding and/or reverse causation. However, further research in large-scale consortia is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Gyrokinetic particle simulation of a field reversed configuration

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

Fulton, D. P., E-mail: dfulton@uci.edu; Lau, C. K.; Holod, I.

2016-01-15

Gyrokinetic particle simulation of the field-reversed configuration (FRC) has been developed using the gyrokinetic toroidal code (GTC). The magnetohydrodynamic equilibrium is mapped from cylindrical coordinates to Boozer coordinates for the FRC core and scrape-off layer (SOL), respectively. A field-aligned mesh is constructed for solving self-consistent electric fields using a semi-spectral solver in a partial torus FRC geometry. This new simulation capability has been successfully verified and driftwave instability in the FRC has been studied using the gyrokinetic simulation for the first time. Initial GTC simulations find that in the FRC core, the ion-scale driftwave is stabilized by the large ionmore » gyroradius. In the SOL, the driftwave is unstable on both ion and electron scales.« less

Combined heat and power supply using Carnot engines

NASA Astrophysics Data System (ADS)

Horlock, J. H.

The Marshall Report on the thermodynamic and economic feasibility of introducing large scale combined heat and electrical power generation (CHP) into the United Kingdom is summarized. Combinations of reversible power plant (Carnot engines) to meet a given demand of power and heat production are analyzed. The Marshall Report states that fairly large scale CHP plants are an attractive energy saving option for areas of high heat load densities. Analysis shows that for given requirements, the total heat supply and utilization factor are functions of heat output, reservoir supply temperature, temperature of heat rejected to the reservoir, and an intermediate temperature for district heating.

Development of an innovative immunoassay for CP4EPSPS and Cry1AB genetically modified protein detection and quantification.

PubMed

Ermolli, M; Prospero, A; Balla, B; Querci, M; Mazzeo, A; Van Den Eede, G

2006-09-01

An innovative immunoassay, called enzyme-linked immunoabsorbant assay (ELISA) Reverse, based on a new conformation of the solid phase, was developed. The solid support was expressly designed to be immersed directly in liquid samples to detect the presence of protein targets. Its application is proposed in those cases where a large number of samples have to be screened simultaneously or when the simultaneous detection of different proteins is required. As a first application, a quantitative immunoassay for Cry1AB protein in genetically modified maize was optimized. The method was tested using genetically modified organism concentrations from 0.1 to 2.0%. The limit of detection and limit of quantitation of the method were determined as 0.0056 and 0.0168 (expressed as the percentage of genetically modified organisms content), respectively. A qualitative multiplex assay to assess the presence of two genetically modified proteins simultaneously was also established for the case of the Cry1AB and the CP4EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) present in genetically modified maize and soy, respectively.

Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed?

PubMed Central

Macias, Vanessa M.; Ohm, Johanna R.; Rasgon, Jason L.

2017-01-01

Mosquito-borne pathogens place an enormous burden on human health. The existing toolkit is insufficient to support ongoing vector-control efforts towards meeting disease elimination and eradication goals. The perspective that genetic approaches can potentially add a significant set of tools toward mosquito control is not new, but the recent improvements in site-specific gene editing with CRISPR/Cas9 systems have enhanced our ability to both study mosquito biology using reverse genetics and produce genetics-based tools. Cas9-mediated gene-editing is an efficient and adaptable platform for gene drive strategies, which have advantages over innundative release strategies for introgressing desirable suppression and pathogen-blocking genotypes into wild mosquito populations; until recently, an effective gene drive has been largely out of reach. Many considerations will inform the effective use of new genetic tools, including gene drives. Here we review the lengthy history of genetic advances in mosquito biology and discuss both the impact of efficient site-specific gene editing on vector biology and the resulting potential to deploy new genetic tools for the abatement of mosquito-borne disease. PMID:28869513

A High-Resolution InDel (Insertion–Deletion) Markers-Anchored Consensus Genetic Map Identifies Major QTLs Governing Pod Number and Seed Yield in Chickpea

PubMed Central

Srivastava, Rishi; Singh, Mohar; Bajaj, Deepak; Parida, Swarup K.

2016-01-01

Development and large-scale genotyping of user-friendly informative genome/gene-derived InDel markers in natural and mapping populations is vital for accelerating genomics-assisted breeding applications of chickpea with minimal resource expenses. The present investigation employed a high-throughput whole genome next-generation resequencing strategy in low and high pod number parental accessions and homozygous individuals constituting the bulks from each of two inter-specific mapping populations [(Pusa 1103 × ILWC 46) and (Pusa 256 × ILWC 46)] to develop non-erroneous InDel markers at a genome-wide scale. Comparing these high-quality genomic sequences, 82,360 InDel markers with reference to kabuli genome and 13,891 InDel markers exhibiting differentiation between low and high pod number parental accessions and bulks of aforementioned mapping populations were developed. These informative markers were structurally and functionally annotated in diverse coding and non-coding sequence components of genome/genes of kabuli chickpea. The functional significance of regulatory and coding (frameshift and large-effect mutations) InDel markers for establishing marker-trait linkages through association/genetic mapping was apparent. The markers detected a greater amplification (97%) and intra-specific polymorphic potential (58–87%) among a diverse panel of cultivated desi, kabuli, and wild accessions even by using a simpler cost-efficient agarose gel-based assay implicating their utility in large-scale genetic analysis especially in domesticated chickpea with narrow genetic base. Two high-density inter-specific genetic linkage maps generated using aforesaid mapping populations were integrated to construct a consensus 1479 InDel markers-anchored high-resolution (inter-marker distance: 0.66 cM) genetic map for efficient molecular mapping of major QTLs governing pod number and seed yield per plant in chickpea. Utilizing these high-density genetic maps as anchors, three major genomic regions harboring each of pod number and seed yield robust QTLs (15–28% phenotypic variation explained) were identified on chromosomes 2, 4, and 6. The integration of genetic and physical maps at these QTLs mapped on chromosomes scaled-down the long major QTL intervals into high-resolution short pod number and seed yield robust QTL physical intervals (0.89–2.94 Mb) which were essentially got validated in multiple genetic backgrounds of two chickpea mapping populations. The genome-wide InDel markers including natural allelic variants and genomic loci/genes delineated at major six especially in one colocalized novel congruent robust pod number and seed yield robust QTLs mapped on a high-density consensus genetic map were found most promising in chickpea. These functionally relevant molecular tags can drive marker-assisted genetic enhancement to develop high-yielding cultivars with increased seed/pod number and yield in chickpea. PMID:27695461

Reverse Ecology: from systems to environments and back.

PubMed

Levy, Roie; Borenstein, Elhanan

2012-01-01

The structure of complex biological systems reflects not only their function but also the environments in which they evolved and are adapted to. Reverse Ecology-an emerging new frontier in Evolutionary Systems Biology-aims to extract this information and to obtain novel insights into an organism's ecology. The Reverse Ecology framework facilitates the translation of high-throughput genomic data into large-scale ecological data, and has the potential to transform ecology into a high-throughput field. In this chapter, we describe some of the pioneering work in Reverse Ecology, demonstrating how system-level analysis of complex biological networks can be used to predict the natural habitats of poorly characterized microbial species, their interactions with other species, and universal patterns governing the adaptation of organisms to their environments. We further present several studies that applied Reverse Ecology to elucidate various aspects of microbial ecology, and lay out exciting future directions and potential future applications in biotechnology, biomedicine, and ecological engineering.

Cryptic biodiversity loss linked to global climate change

NASA Astrophysics Data System (ADS)

Bálint, M.; Domisch, S.; Engelhardt, C. H. M.; Haase, P.; Lehrian, S.; Sauer, J.; Theissinger, K.; Pauls, S. U.; Nowak, C.

2011-09-01

Global climate change (GCC) significantly affects distributional patterns of organisms, and considerable impacts on biodiversity are predicted for the next decades. Inferred effects include large-scale range shifts towards higher altitudes and latitudes, facilitation of biological invasions and species extinctions. Alterations of biotic patterns caused by GCC have usually been predicted on the scale of taxonomically recognized morphospecies. However, the effects of climate change at the most fundamental level of biodiversity--intraspecific genetic diversity--remain elusive. Here we show that the use of morphospecies-based assessments of GCC effects will result in underestimations of the true scale of biodiversity loss. Species distribution modelling and assessments of mitochondrial DNA variability in nine montane aquatic insect species in Europe indicate that future range contractions will be accompanied by severe losses of cryptic evolutionary lineages and genetic diversity within these lineages. These losses greatly exceed those at the scale of morphospecies. We also document that the extent of range reduction may be a useful proxy when predicting losses of genetic diversity. Our results demonstrate that intraspecific patterns of genetic diversity should be considered when estimating the effects of climate change on biodiversity.

Molecular subtyping of European swine influenza viruses and scaling to high-throughput analysis.

PubMed

Bonin, Emilie; Quéguiner, Stéphane; Woudstra, Cédric; Gorin, Stéphane; Barbier, Nicolas; Harder, Timm C; Fach, Patrick; Hervé, Séverine; Simon, Gaëlle

2018-01-10

Swine influenza is a respiratory infection of pigs that may have a significant economic impact in affected herds and pose a threat to the human population since swine influenza A viruses (swIAVs) are zoonotic pathogens. Due to the increasing genetic diversity of swIAVs and because novel reassortants or variants may become enzootic or have zoonotic implications, surveillance is strongly encouraged. Therefore, diagnostic tests and advanced technologies able to identify the circulating strains rapidly are critically important. Several reverse transcription real-time PCR assays (RT-qPCRs) were developed to subtype European swIAVs in clinical samples previously identified as containing IAV genome. The RT-qPCRs aimed to discriminate HA genes of four H1 genetic lineages (H1 av , H1 hu , H1 huΔ146-147 , H1pdm) and one H3 lineage, and NA genes of two N1 lineages (N1, N1pdm) and one N2 lineage. After individual validation, each RT-qPCR was adapted to high-throughput analyses in parallel to the amplification of the IAV M gene (target for IAV detection) and the β-actin gene (as an internal control), in order to test the ten target genes simultaneously on a large number of clinical samples, using low volumes of reagents and RNA extracts. The RT-qPCRs dedicated to IAV molecular subtyping enabled the identification of swIAVs from the four viral subtypes that are known to be enzootic in European pigs, i.e. H1 av N1, H1 hu N2, H3N2 and H1N1pdm. They also made it possible to discriminate a new antigenic variant (H1 hu N2 Δ146-147 ) among H1 hu N2 viruses, as well as reassortant viruses, such as H1 hu N1 or H1 av N2 for example, and virus mixtures. These PCR techniques exhibited a gain in sensitivity as compared to end-point RT-PCRs, enabling the characterization of biological samples with low genetic loads, with considerable time saving. Adaptation to high-throughput analyses appeared effective, both in terms of specificity and sensitivity. This new development opens novel perspectives in diagnostic capacities that could be very useful for swIAV surveillance and large-scale epidemiological studies.

Representation matters: quantitative behavioral variation in wild worm strains

NASA Astrophysics Data System (ADS)

Brown, Andre

Natural genetic variation in populations is the basis of genome-wide association studies, an approach that has been applied in large studies of humans to study the genetic architecture of complex traits including disease risk. Of course, the traits you choose to measure determine which associated genes you discover (or miss). In large-scale human studies, the measured traits are usually taken as a given during the association step because they are expensive to collect and standardize. Working with the nematode worm C. elegans, we do not have the same constraints. In this talk I will describe how large-scale imaging of worm behavior allows us to develop alternative representations of behavior that vary differently across wild populations. The alternative representations yield novel traits that can be used for genome-wide association studies and may reveal basic properties of the genotype-phenotype map that are obscured if only a small set of fixed traits are used.

Partition of genetic trends by origin in Landrace and Large-White pigs.

PubMed

Škorput, D; Gorjanc, G; Kasap, A; Luković, Z

2015-10-01

The objective of this study was to analyse the effectiveness of genetic improvement via domestic selection and import for backfat thickness and time on test in a conventional pig breeding programme for Landrace (L) and Large-White (LW) breeds. Phenotype data was available for 25 553 L and 10 432 LW pigs born between 2002 and 2012 from four large-scale farms and 72 family farms. Pedigree information indicated whether each animal was born and registered within the domestic breeding programme or has been imported. This information was used for defining the genetic groups of unknown parents in a pedigree and the partitioning analysis. Breeding values were estimated using a Bayesian analysis of an animal model with and without genetic groups. Such analysis enabled full Bayesian inference of the genetic trends and their partitioning by the origin of germplasm. Estimates of genetic group indicated that imported germplasm was overall better than domestic and substantial changes in estimates of breeding values was observed when genetic group were fitted. The estimated genetic trends in L were favourable and significantly different from zero by the end of the analysed period. Overall, the genetic trends in LW were not different from zero. The relative contribution of imported germplasm to genetic trends was large, especially towards the end of analysed period with 78% and 67% in L and from 50% to 67% in LW. The analyses suggest that domestic breeding activities and sources of imported animals need to be re-evaluated, in particular in LW breed.

Molecular Identification of XY Sex-Reversed Female and YY Male Channel Catfish

USDA-ARS?s Scientific Manuscript database

Production of channel catfish leads U.S. aquaculture, and monosex culture may provide higher production efficiencies. Determination of phenotypic sex is labor intensive and not practical for large scale culture. Catfish have an X-Y sex determination system with monomorphic sex chromosomes. Hormonal...

Large-Scale Mitochondrial DNA Analysis of the Domestic Goat Reveals Six Haplogroups with High Diversity

PubMed Central

Naderi, Saeid; Rezaei, Hamid-Reza; Taberlet, Pierre; Zundel, Stéphanie; Rafat, Seyed-Abbas; Naghash, Hamid-Reza; El-Barody, Mohamed A. A.; Ertugrul, Okan; Pompanon, François

2007-01-01

Background From the beginning of domestication, the transportation of domestic animals resulted in genetic and demographic processes that explain their present distribution and genetic structure. Thus studying the present genetic diversity helps to better understand the history of domestic species. Methodology/Principal Findings The genetic diversity of domestic goats has been characterized with 2430 individuals from all over the old world, including 946 new individuals from regions poorly studied until now (mainly the Fertile Crescent). These individuals represented 1540 haplotypes for the HVI segment of the mitochondrial DNA (mtDNA) control region. This large-scale study allowed the establishment of a clear nomenclature of the goat maternal haplogroups. Only five of the six previously defined groups of haplotypes were divergent enough to be considered as different haplogroups. Moreover a new mitochondrial group has been localized around the Fertile Crescent. All groups showed very high haplotype diversity. Most of this diversity was distributed among groups and within geographic regions. The weak geographic structure may result from the worldwide distribution of the dominant A haplogroup (more than 90% of the individuals). The large-scale distribution of other haplogroups (except one), may be related to human migration. The recent fragmentation of local goat populations into discrete breeds is not detectable with mitochondrial markers. The estimation of demographic parameters from mismatch analyses showed that all groups had a recent demographic expansion corresponding roughly to the period when domestication took place. But even with a large data set it remains difficult to give relative dates of expansion for different haplogroups because of large confidence intervals. Conclusions/Significance We propose standard criteria for the definition of the different haplogroups based on the result of mismatch analysis and on the use of sequences of reference. Such a method could be also applied for clarifying the nomenclature of mitochondrial haplogroups in other domestic species. PMID:17925860

Understanding the Spatial Scale of Genetic Connectivity at Sea: Unique Insights from a Land Fish and a Meta-Analysis.

PubMed

Cooke, Georgina M; Schlub, Timothy E; Sherwin, William B; Ord, Terry J

2016-01-01

Quantifying the spatial scale of population connectivity is important for understanding the evolutionary potential of ecologically divergent populations and for designing conservation strategies to preserve those populations. For marine organisms like fish, the spatial scale of connectivity is generally set by a pelagic larval phase. This has complicated past estimates of connectivity because detailed information on larval movements are difficult to obtain. Genetic approaches provide a tractable alternative and have the added benefit of estimating directly the reproductive isolation of populations. In this study, we leveraged empirical estimates of genetic differentiation among populations with simulations and a meta-analysis to provide a general estimate of the spatial scale of genetic connectivity in marine environments. We used neutral genetic markers to first quantify the genetic differentiation of ecologically-isolated adult populations of a land dwelling fish, the Pacific leaping blenny (Alticus arnoldorum), where marine larval dispersal is the only probable means of connectivity among populations. We then compared these estimates to simulations of a range of marine dispersal scenarios and to collated FST and distance data from the literature for marine fish across diverse spatial scales. We found genetic connectivity at sea was extensive among marine populations and in the case of A. arnoldorum, apparently little affected by the presence of ecological barriers. We estimated that ~5000 km (with broad confidence intervals ranging from 810-11,692 km) was the spatial scale at which evolutionarily meaningful barriers to gene flow start to occur at sea, although substantially shorter distances are also possible for some taxa. In general, however, such a large estimate of connectivity has important implications for the evolutionary and conservation potential of many marine fish communities.

The fine-scale genetic structure and evolution of the Japanese population.

PubMed

Takeuchi, Fumihiko; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Isomura, Minoru; Ohkubo, Takayoshi; Tabara, Yasuharu; Yamamoto, Ken; Yokota, Mitsuhiro; Liu, Xuanyao; Saw, Woei-Yuh; Mamatyusupu, Dolikun; Yang, Wenjun; Xu, Shuhua; Teo, Yik-Ying; Kato, Norihiro

2017-01-01

The contemporary Japanese populations largely consist of three genetically distinct groups-Hondo, Ryukyu and Ainu. By principal-component analysis, while the three groups can be clearly separated, the Hondo people, comprising 99% of the Japanese, form one almost indistinguishable cluster. To understand fine-scale genetic structure, we applied powerful haplotype-based statistical methods to genome-wide single nucleotide polymorphism data from 1600 Japanese individuals, sampled from eight distinct regions in Japan. We then combined the Japanese data with 26 other Asian populations data to analyze the shared ancestry and genetic differentiation. We found that the Japanese could be separated into nine genetic clusters in our dataset, showing a marked concordance with geography; and that major components of ancestry profile of Japanese were from the Korean and Han Chinese clusters. We also detected and dated admixture in the Japanese. While genetic differentiation between Ryukyu and Hondo was suggested to be caused in part by positive selection, genetic differentiation among the Hondo clusters appeared to result principally from genetic drift. Notably, in Asians, we found the possibility that positive selection accentuated genetic differentiation among distant populations but attenuated genetic differentiation among close populations. These findings are significant for studies of human evolution and medical genetics.

Neural network classifications and correlation analysis of EEG and MEG activity accompanying spontaneous reversals of the Necker cube.

PubMed

Gaetz, M; Weinberg, H; Rzempoluck, E; Jantzen, K J

1998-04-01

It has recently been suggested that reentrant connections are essential in systems that process complex information [A. Damasio, H. Damasio, Cortical systems for the retrieval of concrete knowledge: the convergence zone framework, in: C. Koch, J.L. Davis (Eds.), Large Scale Neuronal Theories of the Brain, The MIT Press, Cambridge, 1995, pp. 61-74; G. Edelman, The Remembered Present, Basic Books, New York, 1989; M.I. Posner, M. Rothbart, Constructing neuronal theories of mind, in: C. Koch, J.L. Davis (Eds.), Large Scale Neuronal Theories of the Brain, The MIT Press, Cambridge, 1995, pp. 183-199; C. von der Malsburg, W. Schneider, A neuronal cocktail party processor, Biol. Cybem., 54 (1986) 29-40]. Reentry is not feedback, but parallel signalling in the time domain between spatially distributed maps, similar to a process of correlation between distributed systems. Accordingly, it was expected that during spontaneous reversals of the Necker cube, complex patterns of correlations between distributed systems would be present in the cortex. The present study included EEG (n=4) and MEG recordings (n=5). Two experimental questions were posed: (1) Can distributed cortical patterns present during perceptual reversals be classified differently using a generalised regression neural network (GRNN) compared to processing of a two-dimensional figure? (2) Does correlated cortical activity increase significantly during perception of a Necker cube reversal? One-second duration single trials of EEG and MEG data were analysed using the GRNN. Electrode/sensor pairings based on cortico-cortical connections were selected to assess correlated activity in each condition. The GRNN significantly classified single trials recorded during Necker cube reversals as different from single trials recorded during perception of a two-dimensional figure for both EEG and MEG. In addition, correlated cortical activity increased significantly in the Necker cube reversal condition for EEG and MEG compared to the perception of a non-reversing stimulus. Coherent MEG activity observed over occipital, parietal and temporal regions is believed to represent neural systems related to the perception of Necker cube reversals. Copyright 1998 Elsevier Science B.V.

FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans

PubMed Central

Dahiya, Yogesh; Babu, Kavita

2018-01-01

Animal behavior is critically dependent on the activity of neuropeptides. Reversals, one of the most conspicuous behaviors in Caenorhabditis elegans, plays an important role in determining the navigation strategy of the animal. Our experiments on hermaphrodite C. elegans show the involvement of a neuropeptide FLP-18 in modulating reversal length in these hermaphrodites. We show that FLP-18 controls the reversal length by regulating the activity of AVA interneurons through the G-protein-coupled neuropeptide receptors, NPR-4 and NPR-1. We go on to show that the site of action of these receptors is the AVA interneuron for NPR-4 and the ASE sensory neurons for NPR-1. We further show that mutants in the neuropeptide, flp-18, and its receptors show increased reversal lengths. Consistent with the behavioral data, calcium levels in the AVA neuron of freely reversing C. elegans were significantly higher and persisted for longer durations in flp-18, npr-1, npr-4, and npr-1 npr-4 genetic backgrounds compared with wild-type control animals. Finally, we show that increasing FLP-18 levels through genetic and physiological manipulations causes shorter reversal lengths. Together, our analysis suggests that the FLP-18/NPR-1/NPR-4 signaling is a pivotal point in the regulation of reversal length under varied genetic and environmental conditions. PMID:29712787

Genetic drift at expanding frontiers promotes gene segregation

PubMed Central

Hallatschek, Oskar; Hersen, Pascal; Ramanathan, Sharad; Nelson, David R.

2007-01-01

Competition between random genetic drift and natural selection play a central role in evolution: Whereas nonbeneficial mutations often prevail in small populations by chance, mutations that sweep through large populations typically confer a selective advantage. Here, however, we observe chance effects during range expansions that dramatically alter the gene pool even in large microbial populations. Initially well mixed populations of two fluorescently labeled strains of Escherichia coli develop well defined, sector-like regions with fractal boundaries in expanding colonies. The formation of these regions is driven by random fluctuations that originate in a thin band of pioneers at the expanding frontier. A comparison of bacterial and yeast colonies (Saccharomyces cerevisiae) suggests that this large-scale genetic sectoring is a generic phenomenon that may provide a detectable footprint of past range expansions. PMID:18056799

Rapid divergence of mussel populations despite incomplete barriers to dispersal.

PubMed

Maas, Diede L; Prost, Stefan; Bi, Ke; Smith, Lydia L; Armstrong, Ellie E; Aji, Ludi P; Toha, Abdul Hamid A; Gillespie, Rosemary G; Becking, Leontine E

2018-04-01

Striking genetic structure among marine populations at small spatial scales is becoming evident with extensive molecular studies. Such observations suggest isolation at small scales may play an important role in forming patterns of genetic diversity within species. Isolation-by-distance, isolation-by-environment and historical priority effects are umbrella terms for a suite of processes that underlie genetic structure, but their relative importance at different spatial and temporal scales remains elusive. Here, we use marine lakes in Indonesia to assess genetic structure and assess the relative roles of the processes in shaping genetic differentiation in populations of a bivalve mussel (Brachidontes sp.). Marine lakes are landlocked waterbodies of similar age (6,000-10,000 years), but with heterogeneous environments and varying degrees of connection to the sea. Using a population genomic approach (double-digest restriction-site-associated DNA sequencing), we show strong genetic structuring across populations (range F ST : 0.07-0.24) and find limited gene flow through admixture plots. At large spatial scales (>1,400 km), a clear isolation-by-distance pattern was detected. At smaller spatial scales (<200 km), this pattern is maintained, but accompanied by an association of genetic divergence with degree of connection. We hypothesize that (incomplete) dispersal barriers can cause initial isolation, allowing priority effects to give the numerical advantage necessary to initiate strong genetic structure. Priority effects may be strengthened by local adaptation, which the data may corroborate by showing a high correlation between mussel genotypes and temperature. Our study indicates an often-neglected role of (evolution-mediated) priority effects in shaping population divergence. © 2018 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.

Can Man Control His Biological Evolution? A Symposium on Genetic Engineering. Probabilities and Practicalities

ERIC Educational Resources Information Center

Djerassi, Carl

1972-01-01

Manipulation of genes in human beings on a large scale is not possible under present conditions because it lacks economic potential and other attractions for industry. However, preventive'' genetic engineering may be a field for vast research in the future and will perhaps be approved by governments, parishes, people and industry. (PS)

Transposable element genomic fissuring in Pyrenophora teres is associated with genome expansion and dynamics of host-pathogen genetic interactions

USDA-ARS?s Scientific Manuscript database

Pyrenophora teres, P. teres f. teres (PTT) and P. teres f. maculata (PTM) cause significant diseases in barley, but little is known about the large-scale genomic differences that may distinguish the two forms. Comprehensive genome assemblies were constructed from long DNA reads, optical and genetic ...

Reverse Genetics Approaches for the Development of Influenza Vaccines

PubMed Central

Nogales, Aitor; Martínez-Sobrido, Luis

2016-01-01

Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

Nonreciprocity in the dynamics of coupled oscillators with nonlinearity, asymmetry, and scale hierarchy

NASA Astrophysics Data System (ADS)

Moore, Keegan J.; Bunyan, Jonathan; Tawfick, Sameh; Gendelman, Oleg V.; Li, Shuangbao; Leamy, Michael; Vakakis, Alexander F.

2018-01-01

In linear time-invariant dynamical and acoustical systems, reciprocity holds by the Onsager-Casimir principle of microscopic reversibility, and this can be broken only by odd external biases, nonlinearities, or time-dependent properties. A concept is proposed in this work for breaking dynamic reciprocity based on irreversible nonlinear energy transfers from large to small scales in a system with nonlinear hierarchical internal structure, asymmetry, and intentional strong stiffness nonlinearity. The resulting nonreciprocal large-to-small scale energy transfers mimic analogous nonlinear energy transfer cascades that occur in nature (e.g., in turbulent flows), and are caused by the strong frequency-energy dependence of the essentially nonlinear small-scale components of the system considered. The theoretical part of this work is mainly based on action-angle transformations, followed by direct numerical simulations of the resulting system of nonlinear coupled oscillators. The experimental part considers a system with two scales—a linear large-scale oscillator coupled to a small scale by a nonlinear spring—and validates the theoretical findings demonstrating nonreciprocal large-to-small scale energy transfer. The proposed study promotes a paradigm for designing nonreciprocal acoustic materials harnessing strong nonlinearity, which in a future application will be implemented in designing lattices incorporating nonlinear hierarchical internal structures, asymmetry, and scale mixing.

Assessing the weighted multi-objective adaptive surrogate model optimization to derive large-scale reservoir operating rules with sensitivity analysis

NASA Astrophysics Data System (ADS)

Zhang, Jingwen; Wang, Xu; Liu, Pan; Lei, Xiaohui; Li, Zejun; Gong, Wei; Duan, Qingyun; Wang, Hao

2017-01-01

The optimization of large-scale reservoir system is time-consuming due to its intrinsic characteristics of non-commensurable objectives and high dimensionality. One way to solve the problem is to employ an efficient multi-objective optimization algorithm in the derivation of large-scale reservoir operating rules. In this study, the Weighted Multi-Objective Adaptive Surrogate Model Optimization (WMO-ASMO) algorithm is used. It consists of three steps: (1) simplifying the large-scale reservoir operating rules by the aggregation-decomposition model, (2) identifying the most sensitive parameters through multivariate adaptive regression splines (MARS) for dimensional reduction, and (3) reducing computational cost and speeding the searching process by WMO-ASMO, embedded with weighted non-dominated sorting genetic algorithm II (WNSGAII). The intercomparison of non-dominated sorting genetic algorithm (NSGAII), WNSGAII and WMO-ASMO are conducted in the large-scale reservoir system of Xijiang river basin in China. Results indicate that: (1) WNSGAII surpasses NSGAII in the median of annual power generation, increased by 1.03% (from 523.29 to 528.67 billion kW h), and the median of ecological index, optimized by 3.87% (from 1.879 to 1.809) with 500 simulations, because of the weighted crowding distance and (2) WMO-ASMO outperforms NSGAII and WNSGAII in terms of better solutions (annual power generation (530.032 billion kW h) and ecological index (1.675)) with 1000 simulations and computational time reduced by 25% (from 10 h to 8 h) with 500 simulations. Therefore, the proposed method is proved to be more efficient and could provide better Pareto frontier.

Extreme inbreeding in Leishmania braziliensis

PubMed Central

Rougeron, Virginie; De Meeûs, Thierry; Hide, Mallorie; Waleckx, Etienne; Bermudez, Herman; Arevalo, Jorge; Llanos-Cuentas, Alejandro; Dujardin, Jean-Claude; De Doncker, Simone; Le Ray, Dominique; Ayala, Francisco J.; Bañuls, Anne-Laure

2009-01-01

Leishmania species of the subgenus Viannia and especially Leishmania braziliensis are responsible for a large proportion of New World leishmaniasis cases. The reproductive mode of Leishmania species has often been assumed to be predominantly clonal, but remains unsettled. We have investigated the genetic polymorphism at 12 microsatellite loci on 124 human strains of Leishmania braziliensis from 2 countries, Peru and Bolivia. There is substantial genetic diversity, with an average of 12.4 ± 4.4 alleles per locus. There is linkage disequilibrium at a genome-wide scale, as well as a substantial heterozygote deficit (more than 50% the expected value from Hardy−Weinberg equilibrium), which indicates high levels of inbreeding. These observations are inconsistent with a strictly clonal model of reproduction, which implies excess heterozygosity. Moreover, there is large genetic heterogeneity between populations within countries (Wahlund effect), which evinces a strong population structure at a microgeographic scale. Our findings are compatible with the existence of population foci at a microgeographic scale, where clonality alternates with sexuality of an endogamic nature, with possible occasional recombination events between individuals of different genotypes. These findings provide key clues on the ecology and transmission patterns of Leishmania parasites. PMID:19497885

Comparative performance of a genetically-encoded voltage indicator and a blue voltage sensitive dye for large scale cortical voltage imaging

PubMed Central

Mutoh, Hiroki; Mishina, Yukiko; Gallero-Salas, Yasir; Knöpfel, Thomas

2015-01-01

Traditional small molecule voltage sensitive dye indicators have been a powerful tool for monitoring large scale dynamics of neuronal activities but have several limitations including the lack of cell class specific targeting, invasiveness and difficulties in conducting longitudinal studies. Recent advances in the development of genetically-encoded voltage indicators have successfully overcome these limitations. Genetically-encoded voltage indicators (GEVIs) provide sufficient sensitivity to map cortical representations of sensory information and spontaneous network activities across cortical areas and different brain states. In this study, we directly compared the performance of a prototypic GEVI, VSFP2.3, with that of a widely used small molecule voltage sensitive dye (VSD), RH1691, in terms of their ability to resolve mesoscopic scale cortical population responses. We used three synchronized CCD cameras to simultaneously record the dual emission ratiometric fluorescence signal from VSFP2.3 and RH1691 fluorescence. The results show that VSFP2.3 offers more stable and less invasive recording conditions, while the signal-to-noise level and the response dynamics to sensory inputs are comparable to RH1691 recordings. PMID:25964738

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.

PubMed

Willems, Sara M; Wright, Daniel J; Day, Felix R; Trajanoska, Katerina; Joshi, Peter K; Morris, John A; Matteini, Amy M; Garton, Fleur C; Grarup, Niels; Oskolkov, Nikolay; Thalamuthu, Anbupalam; Mangino, Massimo; Liu, Jun; Demirkan, Ayse; Lek, Monkol; Xu, Liwen; Wang, Guan; Oldmeadow, Christopher; Gaulton, Kyle J; Lotta, Luca A; Miyamoto-Mikami, Eri; Rivas, Manuel A; White, Tom; Loh, Po-Ru; Aadahl, Mette; Amin, Najaf; Attia, John R; Austin, Krista; Benyamin, Beben; Brage, Søren; Cheng, Yu-Ching; Cięszczyk, Paweł; Derave, Wim; Eriksson, Karl-Fredrik; Eynon, Nir; Linneberg, Allan; Lucia, Alejandro; Massidda, Myosotis; Mitchell, Braxton D; Miyachi, Motohiko; Murakami, Haruka; Padmanabhan, Sandosh; Pandey, Ashutosh; Papadimitriou, Ioannis; Rajpal, Deepak K; Sale, Craig; Schnurr, Theresia M; Sessa, Francesco; Shrine, Nick; Tobin, Martin D; Varley, Ian; Wain, Louise V; Wray, Naomi R; Lindgren, Cecilia M; MacArthur, Daniel G; Waterworth, Dawn M; McCarthy, Mark I; Pedersen, Oluf; Khaw, Kay-Tee; Kiel, Douglas P; Pitsiladis, Yannis; Fuku, Noriyuki; Franks, Paul W; North, Kathryn N; van Duijn, Cornelia M; Mather, Karen A; Hansen, Torben; Hansson, Ola; Spector, Tim; Murabito, Joanne M; Richards, J Brent; Rivadeneira, Fernando; Langenberg, Claudia; Perry, John R B; Wareham, Nick J; Scott, Robert A

2017-07-12

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10 -8 ) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

Scaling up digital circuit computation with DNA strand displacement cascades.

PubMed

Qian, Lulu; Winfree, Erik

2011-06-03

To construct sophisticated biochemical circuits from scratch, one needs to understand how simple the building blocks can be and how robustly such circuits can scale up. Using a simple DNA reaction mechanism based on a reversible strand displacement process, we experimentally demonstrated several digital logic circuits, culminating in a four-bit square-root circuit that comprises 130 DNA strands. These multilayer circuits include thresholding and catalysis within every logical operation to perform digital signal restoration, which enables fast and reliable function in large circuits with roughly constant switching time and linear signal propagation delays. The design naturally incorporates other crucial elements for large-scale circuitry, such as general debugging tools, parallel circuit preparation, and an abstraction hierarchy supported by an automated circuit compiler.

The stability properties of cylindrical force-free fields - Effect of an external potential field

NASA Technical Reports Server (NTRS)

Chiuderi, C.; Einaudi, G.; Ma, S. S.; Van Hoven, G.

1980-01-01

A large-scale potential field with an embedded smaller-scale force-free structure gradient x B equals alpha B is studied in cylindrical geometry. Cases in which alpha goes continuously from a constant value alpha 0 on the axis to zero at large r are considered. Such a choice of alpha (r) produces fields which are realistic (few field reversals) but not completely stable. The MHD-unstable wavenumber regime is found. Since the considered equilibrium field exhibits a certain amount of magnetic shear, resistive instabilities can arise. The growth rates of the tearing mode in the limited MHD-stable region of k space are calculated, showing time-scales much shorter than the resistive decay time.

Bioinformatics and genomic analysis of transposable elements in eukaryotic genomes.

PubMed

Janicki, Mateusz; Rooke, Rebecca; Yang, Guojun

2011-08-01

A major portion of most eukaryotic genomes are transposable elements (TEs). During evolution, TEs have introduced profound changes to genome size, structure, and function. As integral parts of genomes, the dynamic presence of TEs will continue to be a major force in reshaping genomes. Early computational analyses of TEs in genome sequences focused on filtering out "junk" sequences to facilitate gene annotation. When the high abundance and diversity of TEs in eukaryotic genomes were recognized, these early efforts transformed into the systematic genome-wide categorization and classification of TEs. The availability of genomic sequence data reversed the classical genetic approaches to discovering new TE families and superfamilies. Curated TE databases and their accurate annotation of genome sequences in turn facilitated the studies on TEs in a number of frontiers including: (1) TE-mediated changes of genome size and structure, (2) the influence of TEs on genome and gene functions, (3) TE regulation by host, (4) the evolution of TEs and their population dynamics, and (5) genomic scale studies of TE activity. Bioinformatics and genomic approaches have become an integral part of large-scale studies on TEs to extract information with pure in silico analyses or to assist wet lab experimental studies. The current revolution in genome sequencing technology facilitates further progress in the existing frontiers of research and emergence of new initiatives. The rapid generation of large-sequence datasets at record low costs on a routine basis is challenging the computing industry on storage capacity and manipulation speed and the bioinformatics community for improvement in algorithms and their implementations.

Genetic Approaches to Study Meiosis and Meiosis-Specific Gene Expression in Saccharomyces cerevisiae.

PubMed

Kassir, Yona; Stuart, David T

2017-01-01

The budding yeast Saccharomyces cerevisiae has a long history as a model organism for studies of meiosis and the cell cycle. The popularity of this yeast as a model is in large part due to the variety of genetic and cytological approaches that can be effectively performed with the cells. Cultures of the cells can be induced to synchronously progress through meiosis and sporulation allowing large-scale gene expression and biochemical studies to be performed. Additionally, the spore tetrads resulting from meiosis make it possible to characterize the haploid products of meiosis allowing investigation of meiotic recombination and chromosome segregation. Here we describe genetic methods for analysis progression of S. cerevisiae through meiosis and sporulation with an emphasis on strategies for the genetic analysis of regulators of meiosis-specific genes.

Reinventing the ames test as a quantitative lab that connects classical and molecular genetics.

PubMed

Goodson-Gregg, Nathan; De Stasio, Elizabeth A

2009-01-01

While many institutions use a version of the Ames test in the undergraduate genetics laboratory, students typically are not exposed to techniques or procedures beyond qualitative analysis of phenotypic reversion, thereby seriously limiting the scope of learning. We have extended the Ames test to include both quantitative analysis of reversion frequency and molecular analysis of revertant gene sequences. By giving students a role in designing their quantitative methods and analyses, students practice and apply quantitative skills. To help students connect classical and molecular genetic concepts and techniques, we report here procedures for characterizing the molecular lesions that confer a revertant phenotype. We suggest undertaking reversion of both missense and frameshift mutants to allow a more sophisticated molecular genetic analysis. These modifications and additions broaden the educational content of the traditional Ames test teaching laboratory, while simultaneously enhancing students' skills in experimental design, quantitative analysis, and data interpretation.

Phylogenetic congruence of lichenised fungi and algae is affected by spatial scale and taxonomic diversity.

PubMed

Buckley, Hannah L; Rafat, Arash; Ridden, Johnathon D; Cruickshank, Robert H; Ridgway, Hayley J; Paterson, Adrian M

2014-01-01

The role of species' interactions in structuring biological communities remains unclear. Mutualistic symbioses, involving close positive interactions between two distinct organismal lineages, provide an excellent means to explore the roles of both evolutionary and ecological processes in determining how positive interactions affect community structure. In this study, we investigate patterns of co-diversification between fungi and algae for a range of New Zealand lichens at the community, genus, and species levels and explore explanations for possible patterns related to spatial scale and pattern, taxonomic diversity of the lichens considered, and the level sampling replication. We assembled six independent datasets to compare patterns in phylogenetic congruence with varied spatial extent of sampling, taxonomic diversity and level of specimen replication. For each dataset, we used the DNA sequences from the ITS regions of both the fungal and algal genomes from lichen specimens to produce genetic distance matrices. Phylogenetic congruence between fungi and algae was quantified using distance-based redundancy analysis and we used geographic distance matrices in Moran's eigenvector mapping and variance partitioning to evaluate the effects of spatial variation on the quantification of phylogenetic congruence. Phylogenetic congruence was highly significant for all datasets and a large proportion of variance in both algal and fungal genetic distances was explained by partner genetic variation. Spatial variables, primarily at large and intermediate scales, were also important for explaining genetic diversity patterns in all datasets. Interestingly, spatial structuring was stronger for fungal than algal genetic variation. As the spatial extent of the samples increased, so too did the proportion of explained variation that was shared between the spatial variables and the partners' genetic variation. Different lichen taxa showed some variation in their phylogenetic congruence and spatial genetic patterns and where greater sample replication was used, the amount of variation explained by partner genetic variation increased. Our results suggest that the phylogenetic congruence pattern, at least at small spatial scales, is likely due to reciprocal co-adaptation or co-dispersal. However, the detection of these patterns varies among different lichen taxa, across spatial scales and with different levels of sample replication. This work provides insight into the complexities faced in determining how evolutionary and ecological processes may interact to generate diversity in symbiotic association patterns at the population and community levels. Further, it highlights the critical importance of considering sample replication, taxonomic diversity and spatial scale in designing studies of co-diversification.

Stochastic models for regulatory networks of the genetic toggle switch.

PubMed

Tian, Tianhai; Burrage, Kevin

2006-05-30

Bistability arises within a wide range of biological systems from the lambda phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

Stochastic models for regulatory networks of the genetic toggle switch

PubMed Central

Tian, Tianhai; Burrage, Kevin

2006-01-01

Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks. PMID:16714385

Natural Allelic Diversity, Genetic Structure and Linkage Disequilibrium Pattern in Wild Chickpea

PubMed Central

Kujur, Alice; Das, Shouvik; Badoni, Saurabh; Kumar, Vinod; Singh, Mohar; Bansal, Kailash C.; Tyagi, Akhilesh K.; Parida, Swarup K.

2014-01-01

Characterization of natural allelic diversity and understanding the genetic structure and linkage disequilibrium (LD) pattern in wild germplasm accessions by large-scale genotyping of informative microsatellite and single nucleotide polymorphism (SNP) markers is requisite to facilitate chickpea genetic improvement. Large-scale validation and high-throughput genotyping of genome-wide physically mapped 478 genic and genomic microsatellite markers and 380 transcription factor gene-derived SNP markers using gel-based assay, fluorescent dye-labelled automated fragment analyser and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass array have been performed. Outcome revealed their high genotyping success rate (97.5%) and existence of a high level of natural allelic diversity among 94 wild and cultivated Cicer accessions. High intra- and inter-specific polymorphic potential and wider molecular diversity (11–94%) along with a broader genetic base (13–78%) specifically in the functional genic regions of wild accessions was assayed by mapped markers. It suggested their utility in monitoring introgression and transferring target trait-specific genomic (gene) regions from wild to cultivated gene pool for the genetic enhancement. Distinct species/gene pool-wise differentiation, admixed domestication pattern, and differential genome-wide recombination and LD estimates/decay observed in a six structured population of wild and cultivated accessions using mapped markers further signifies their usefulness in chickpea genetics, genomics and breeding. PMID:25222488

International Childhood Cancer Cohort Consortium

Cancer.gov

An alliance of several large-scale prospective cohort studies of children to pool data and biospecimens from individual cohorts to study various modifiable and genetic factors in relation to cancer risk

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

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

PubMed

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

2017-09-12

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

Genetic analysis reveals efficient sexual spore dispersal at a fine spatial scale in Armillaria ostoyae, the causal agent of root-rot disease in conifers.

PubMed

Dutech, Cyril; Labbé, Frédéric; Capdevielle, Xavier; Lung-Escarmant, Brigitte

Armillaria ostoyae (sometimes named Armillaria solidipes) is a fungal species causing root diseases in numerous coniferous forests of the northern hemisphere. The importance of sexual spores for the establishment of new disease centres remains unclear, particularly in the large maritime pine plantations of southwestern France. An analysis of the genetic diversity of a local fungal population distributed over 500 ha in this French forest showed genetic recombination between genotypes to be frequent, consistent with regular sexual reproduction within the population. The estimated spatial genetic structure displayed a significant pattern of isolation by distance, consistent with the dispersal of sexual spores mostly at the spatial scale studied. Using these genetic data, we inferred an effective density of reproductive individuals of 0.1-0.3 individuals/ha, and a second moment of parent-progeny dispersal distance of 130-800 m, compatible with the main models of fungal spore dispersal. These results contrast with those obtained for studies of A. ostoyae over larger spatial scales, suggesting that inferences about mean spore dispersal may be best performed at fine spatial scales (i.e. a few kilometres) for most fungal species. Copyright © 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

The Genetics of Mexico Recapitulates Native American Substructure and Affects Biomedical Traits

PubMed Central

Moreno-Estrada, Andrés; Gignoux, Christopher R.; Fernández-López, Juan Carlos; Zakharia, Fouad; Sikora, Martin; Contreras, Alejandra V.; Acuña-Alonzo, Victor; Sandoval, Karla; Eng, Celeste; Romero-Hidalgo, Sandra; Ortiz-Tello, Patricia; Robles, Victoria; Kenny, Eimear E.; Nuño-Arana, Ismael; Barquera-Lozano, Rodrigo; Macín-Pérez, Gastón; Granados-Arriola, Julio; Huntsman, Scott; Galanter, Joshua M.; Via, Marc; Ford, Jean G.; Chapela, Rocío; Rodriguez-Cintron, William; Rodríguez-Santana, Jose R.; Romieu, Isabelle; Sienra-Monge, Juan José; Navarro, Blanca del Rio; London, Stephanie J.; Ruiz-Linares, Andrés; Garcia-Herrera, Rodrigo; Estrada, Karol; Hidalgo-Miranda, Alfredo; Jimenez-Sanchez, Gerardo; Carnevale, Alessandra; Soberón, Xavier; Canizales-Quinteros, Samuel; Rangel-Villalobos, Héctor; Silva-Zolezzi, Irma; Burchard, Esteban Gonzalez; Bustamante, Carlos D.

2014-01-01

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1,000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between sub-continental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide. PMID:24926019

Visualization, documentation, analysis, and communication of large scale gene regulatory networks

PubMed Central

Longabaugh, William J.R.; Davidson, Eric H.; Bolouri, Hamid

2009-01-01

Summary Genetic regulatory networks (GRNs) are complex, large-scale, and spatially and temporally distributed. These characteristics impose challenging demands on computational GRN modeling tools, and there is a need for custom modeling tools. In this paper, we report on our ongoing development of BioTapestry, an open source, freely available computational tool designed specifically for GRN modeling. We also outline our future development plans, and give some examples of current applications of BioTapestry. PMID:18757046

Co-Utilization of Glucose and Xylose for Enhanced Lignocellulosic Ethanol Production with Reverse Membrane Bioreactors

PubMed Central

Ishola, Mofoluwake M.; Ylitervo, Päivi; Taherzadeh, Mohammad J.

2015-01-01

Integrated permeate channel (IPC) flat sheet membranes were examined for use as a reverse membrane bioreactor (rMBR) for lignocellulosic ethanol production. The fermenting organism, Saccharomyces cerevisiae (T0936), a genetically-modified strain with the ability to ferment xylose, was used inside the rMBR. The rMBR was evaluated for simultaneous glucose and xylose utilization as well as in situ detoxification of furfural and hydroxylmethyl furfural (HMF). The synthetic medium was investigated, after which the pretreated wheat straw was used as a xylose-rich lignocellulosic substrate. The IPC membrane panels were successfully used as the rMBR during the batch fermentations, which lasted for up to eight days without fouling. With the rMBR, complete glucose and xylose utilization, resulting in 86% of the theoretical ethanol yield, was observed with the synthetic medium. Its application with the pretreated wheat straw resulted in complete glucose consumption and 87% xylose utilization; a final ethanol concentration of 30.3 g/L was obtained, which corresponds to 83% of the theoretical yield. Moreover, complete in situ detoxification of furfural and HMF was obtained within 36 h and 60 h, respectively, with the rMBR. The use of the rMBR is a promising technology for large-scale lignocellulosic ethanol production, since it facilitates the co-utilization of glucose and xylose; moreover, the technology would also allow the reuse of the yeast for several batches. PMID:26633530

Reduced fine-scale spatial genetic structure in grazed populations of Dianthus carthusianorum

PubMed Central

Rico, Y; Wagner, H H

2016-01-01

Strong spatial genetic structure in plant populations can increase homozygosity, reducing genetic diversity and adaptive potential. The strength of spatial genetic structure largely depends on rates of seed dispersal and pollen flow. Seeds without dispersal adaptations are likely to be dispersed over short distances within the vicinity of the mother plant, resulting in spatial clustering of related genotypes (fine-scale spatial genetic structure, hereafter spatial genetic structure (SGS)). However, primary seed dispersal by zoochory can promote effective dispersal, increasing the mixing of seeds and influencing SGS within plant populations. In this study, we investigated the effects of seed dispersal by rotational sheep grazing on the strength of SGS and genetic diversity using 11 nuclear microsatellites for 49 populations of the calcareous grassland forb Dianthus carthusianorum. Populations connected by rotational sheep grazing showed significantly weaker SGS and higher genetic diversity than populations in ungrazed grasslands. Independent of grazing treatment, small populations showed significantly stronger SGS and lower genetic diversity than larger populations, likely due to genetic drift. A lack of significant differences in the strength of SGS and genetic diversity between populations that were recently colonized and pre-existing populations suggested that populations colonized after the reintroduction of rotational sheep grazing were likely founded by colonists from diverse source populations. We conclude that dispersal by rotational sheep grazing has the potential to considerably reduce SGS within D. carthusianorum populations. Our study highlights the effectiveness of landscape management by rotational sheep grazing to importantly reduce genetic structure at local scales within restored plant populations. PMID:27381322

Reduced fine-scale spatial genetic structure in grazed populations of Dianthus carthusianorum.

PubMed

Rico, Y; Wagner, H H

2016-11-01

Strong spatial genetic structure in plant populations can increase homozygosity, reducing genetic diversity and adaptive potential. The strength of spatial genetic structure largely depends on rates of seed dispersal and pollen flow. Seeds without dispersal adaptations are likely to be dispersed over short distances within the vicinity of the mother plant, resulting in spatial clustering of related genotypes (fine-scale spatial genetic structure, hereafter spatial genetic structure (SGS)). However, primary seed dispersal by zoochory can promote effective dispersal, increasing the mixing of seeds and influencing SGS within plant populations. In this study, we investigated the effects of seed dispersal by rotational sheep grazing on the strength of SGS and genetic diversity using 11 nuclear microsatellites for 49 populations of the calcareous grassland forb Dianthus carthusianorum. Populations connected by rotational sheep grazing showed significantly weaker SGS and higher genetic diversity than populations in ungrazed grasslands. Independent of grazing treatment, small populations showed significantly stronger SGS and lower genetic diversity than larger populations, likely due to genetic drift. A lack of significant differences in the strength of SGS and genetic diversity between populations that were recently colonized and pre-existing populations suggested that populations colonized after the reintroduction of rotational sheep grazing were likely founded by colonists from diverse source populations. We conclude that dispersal by rotational sheep grazing has the potential to considerably reduce SGS within D. carthusianorum populations. Our study highlights the effectiveness of landscape management by rotational sheep grazing to importantly reduce genetic structure at local scales within restored plant populations.

Combining semi-automated image analysis techniques with machine learning algorithms to accelerate large-scale genetic studies.

PubMed

Atkinson, Jonathan A; Lobet, Guillaume; Noll, Manuel; Meyer, Patrick E; Griffiths, Marcus; Wells, Darren M

2017-10-01

Genetic analyses of plant root systems require large datasets of extracted architectural traits. To quantify such traits from images of root systems, researchers often have to choose between automated tools (that are prone to error and extract only a limited number of architectural traits) or semi-automated ones (that are highly time consuming). We trained a Random Forest algorithm to infer architectural traits from automatically extracted image descriptors. The training was performed on a subset of the dataset, then applied to its entirety. This strategy allowed us to (i) decrease the image analysis time by 73% and (ii) extract meaningful architectural traits based on image descriptors. We also show that these traits are sufficient to identify the quantitative trait loci that had previously been discovered using a semi-automated method. We have shown that combining semi-automated image analysis with machine learning algorithms has the power to increase the throughput of large-scale root studies. We expect that such an approach will enable the quantification of more complex root systems for genetic studies. We also believe that our approach could be extended to other areas of plant phenotyping. © The Authors 2017. Published by Oxford University Press.

Combining semi-automated image analysis techniques with machine learning algorithms to accelerate large-scale genetic studies

PubMed Central

Atkinson, Jonathan A.; Lobet, Guillaume; Noll, Manuel; Meyer, Patrick E.; Griffiths, Marcus

2017-01-01

Abstract Genetic analyses of plant root systems require large datasets of extracted architectural traits. To quantify such traits from images of root systems, researchers often have to choose between automated tools (that are prone to error and extract only a limited number of architectural traits) or semi-automated ones (that are highly time consuming). We trained a Random Forest algorithm to infer architectural traits from automatically extracted image descriptors. The training was performed on a subset of the dataset, then applied to its entirety. This strategy allowed us to (i) decrease the image analysis time by 73% and (ii) extract meaningful architectural traits based on image descriptors. We also show that these traits are sufficient to identify the quantitative trait loci that had previously been discovered using a semi-automated method. We have shown that combining semi-automated image analysis with machine learning algorithms has the power to increase the throughput of large-scale root studies. We expect that such an approach will enable the quantification of more complex root systems for genetic studies. We also believe that our approach could be extended to other areas of plant phenotyping. PMID:29020748

Oral delivery of dsRNA by microbes: Beyond pest control.

PubMed

Abrieux, Antoine; Chiu, Joanna C

2016-01-01

RNA interference (RNAi) by oral delivery of dsRNA in insects has great potential as a tool for integrated pest management (IPM), especially with respect to addressing the need to reduce off-target effect and slow down resistance development to chemical insecticides. Employing the natural association existing between insect and yeast, we developed a novel method to enable the knock down of vital genes in the pest insect Drosophila suzukii through oral delivery of species-specific dsRNA using genetically modified Saccharomyces cerevisae. D. suzukii that were fed with our "yeast biopesticide" showed a significant decrease in fitness. In this perspective article, we postulate that this approach could be adapted to a large number of species, given the great diversity of symbiotic interactions involving microorganisms and host species. Furthermore, we speculate that beyond its application as biopesticide, dsRNA delivery by genetically modified microbes can also serve to facilitate reverse genetic applications, specifically in non-model organisms.

Engineering and Functional Analysis of Mitotic Kinases Through Chemical Genetics.

PubMed

Jones, Mathew J K; Jallepalli, Prasad V

2016-01-01

During mitosis, multiple protein kinases transform the cytoskeleton and chromosomes into new and highly dynamic structures that mediate the faithful transmission of genetic information and cell division. However, the large number and strong conservation of mammalian kinases in general pose significant obstacles to interrogating them with small molecules, due to the difficulty in identifying and validating those which are truly selective. To overcome this problem, a steric complementation strategy has been developed, in which a bulky "gatekeeper" residue within the active site of the kinase of interest is replaced with a smaller amino acid, such as glycine or alanine. The enlarged catalytic pocket can then be targeted in an allele-specific manner with bulky purine analogs. This strategy provides a general framework for dissecting kinase function with high selectivity, rapid kinetics, and reversibility. In this chapter we discuss the principles and techniques needed to implement this chemical genetic approach in mammalian cells.

Identification of tissue-specific, abiotic stress-responsive gene expression patterns in wine grape (Vitis vinifera L.) based on curation and mining of large-scale EST data sets

PubMed Central

2011-01-01

Background Abiotic stresses, such as water deficit and soil salinity, result in changes in physiology, nutrient use, and vegetative growth in vines, and ultimately, yield and flavor in berries of wine grape, Vitis vinifera L. Large-scale expressed sequence tags (ESTs) were generated, curated, and analyzed to identify major genetic determinants responsible for stress-adaptive responses. Although roots serve as the first site of perception and/or injury for many types of abiotic stress, EST sequencing in root tissues of wine grape exposed to abiotic stresses has been extremely limited to date. To overcome this limitation, large-scale EST sequencing was conducted from root tissues exposed to multiple abiotic stresses. Results A total of 62,236 expressed sequence tags (ESTs) were generated from leaf, berry, and root tissues from vines subjected to abiotic stresses and compared with 32,286 ESTs sequenced from 20 public cDNA libraries. Curation to correct annotation errors, clustering and assembly of the berry and leaf ESTs with currently available V. vinifera full-length transcripts and ESTs yielded a total of 13,278 unique sequences, with 2302 singletons and 10,976 mapped to V. vinifera gene models. Of these, 739 transcripts were found to have significant differential expression in stressed leaves and berries including 250 genes not described previously as being abiotic stress responsive. In a second analysis of 16,452 ESTs from a normalized root cDNA library derived from roots exposed to multiple, short-term, abiotic stresses, 135 genes with root-enriched expression patterns were identified on the basis of their relative EST abundance in roots relative to other tissues. Conclusions The large-scale analysis of relative EST frequency counts among a diverse collection of 23 different cDNA libraries from leaf, berry, and root tissues of wine grape exposed to a variety of abiotic stress conditions revealed distinct, tissue-specific expression patterns, previously unrecognized stress-induced genes, and many novel genes with root-enriched mRNA expression for improving our understanding of root biology and manipulation of rootstock traits in wine grape. mRNA abundance estimates based on EST library-enriched expression patterns showed only modest correlations between microarray and quantitative, real-time reverse transcription-polymerase chain reaction (qRT-PCR) methods highlighting the need for deep-sequencing expression profiling methods. PMID:21592389

Grand Minima and Equatorward Propagation in a Cycling Stellar Convective Dynamo

NASA Astrophysics Data System (ADS)

Augustson, Kyle; Brun, Allan Sacha; Miesch, Mark; Toomre, Juri

2015-08-01

The 3D MHD Anelastic Spherical Harmonic code, using slope-limited diffusion, is employed to capture convective and dynamo processes achieved in a global-scale stellar convection simulation for a model solar-mass star rotating at three times the solar rate. The dynamo-generated magnetic fields possesses many timescales, with a prominent polarity cycle occurring roughly every 6.2 years. The magnetic field forms large-scale toroidal wreaths, whose formation is tied to the low Rossby number of the convection in this simulation. The polarity reversals are linked to the weakened differential rotation and a resistive collapse of the large-scale magnetic field. An equatorial migration of the magnetic field is seen, which is due to the strong modulation of the differential rotation rather than a dynamo wave. A poleward migration of magnetic flux from the equator eventually leads to the reversal of the polarity of the high-latitude magnetic field. This simulation also enters an interval with reduced magnetic energy at low latitudes lasting roughly 16 years (about 2.5 polarity cycles), during which the polarity cycles are disrupted and after which the dynamo recovers its regular polarity cycles. An analysis of this grand minimum reveals that it likely arises through the interplay of symmetric and antisymmetric dynamo families. This intermittent dynamo state potentially results from the simulation’s relatively low magnetic Prandtl number. A mean-field-based analysis of this dynamo simulation demonstrates that it is of the α-Ω type. The timescales that appear to be relevant to the magnetic polarity reversal are also identified.

GRAND MINIMA AND EQUATORWARD PROPAGATION IN A CYCLING STELLAR CONVECTIVE DYNAMO

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

Augustson, Kyle; Miesch, Mark; Brun, Allan Sacha

2015-08-20

The 3D MHD Anelastic Spherical Harmonic code, using slope-limited diffusion, is employed to capture convective and dynamo processes achieved in a global-scale stellar convection simulation for a model solar-mass star rotating at three times the solar rate. The dynamo-generated magnetic fields possesses many timescales, with a prominent polarity cycle occurring roughly every 6.2 years. The magnetic field forms large-scale toroidal wreaths, whose formation is tied to the low Rossby number of the convection in this simulation. The polarity reversals are linked to the weakened differential rotation and a resistive collapse of the large-scale magnetic field. An equatorial migration of themore » magnetic field is seen, which is due to the strong modulation of the differential rotation rather than a dynamo wave. A poleward migration of magnetic flux from the equator eventually leads to the reversal of the polarity of the high-latitude magnetic field. This simulation also enters an interval with reduced magnetic energy at low latitudes lasting roughly 16 years (about 2.5 polarity cycles), during which the polarity cycles are disrupted and after which the dynamo recovers its regular polarity cycles. An analysis of this grand minimum reveals that it likely arises through the interplay of symmetric and antisymmetric dynamo families. This intermittent dynamo state potentially results from the simulation’s relatively low magnetic Prandtl number. A mean-field-based analysis of this dynamo simulation demonstrates that it is of the α-Ω type. The timescales that appear to be relevant to the magnetic polarity reversal are also identified.« less

Accounting for Sampling Error in Genetic Eigenvalues Using Random Matrix Theory.

PubMed

Sztepanacz, Jacqueline L; Blows, Mark W

2017-07-01

The distribution of genetic variance in multivariate phenotypes is characterized by the empirical spectral distribution of the eigenvalues of the genetic covariance matrix. Empirical estimates of genetic eigenvalues from random effects linear models are known to be overdispersed by sampling error, where large eigenvalues are biased upward, and small eigenvalues are biased downward. The overdispersion of the leading eigenvalues of sample covariance matrices have been demonstrated to conform to the Tracy-Widom (TW) distribution. Here we show that genetic eigenvalues estimated using restricted maximum likelihood (REML) in a multivariate random effects model with an unconstrained genetic covariance structure will also conform to the TW distribution after empirical scaling and centering. However, where estimation procedures using either REML or MCMC impose boundary constraints, the resulting genetic eigenvalues tend not be TW distributed. We show how using confidence intervals from sampling distributions of genetic eigenvalues without reference to the TW distribution is insufficient protection against mistaking sampling error as genetic variance, particularly when eigenvalues are small. By scaling such sampling distributions to the appropriate TW distribution, the critical value of the TW statistic can be used to determine if the magnitude of a genetic eigenvalue exceeds the sampling error for each eigenvalue in the spectral distribution of a given genetic covariance matrix. Copyright © 2017 by the Genetics Society of America.

Genetic diversity is largely unpredictable but scales with museum occurrences in a species-rich clade of Australian lizards

PubMed Central

Huang, Huateng; Title, Pascal O.; Donnellan, Stephen C.; Holmes, Iris; Rabosky, Daniel L.

2017-01-01

Genetic diversity is a fundamental characteristic of species and is affected by many factors, including mutation rate, population size, life history and demography. To better understand the processes that influence levels of genetic diversity across taxa, we collected genome-wide restriction-associated DNA data from more than 500 individuals spanning 76 nominal species of Australian scincid lizards in the genus Ctenotus. To avoid potential biases associated with variation in taxonomic practice across the group, we used coalescent-based species delimitation to delineate 83 species-level lineages within the genus for downstream analyses. We then used these genetic data to infer levels of within-population genetic diversity. Using a phylogenetically informed approach, we tested whether variation in genetic diversity could be explained by population size, environmental heterogeneity or historical demography. We find that the strongest predictor of genetic diversity is a novel proxy for census population size: the number of vouchered occurrences in museum databases. However, museum occurrences only explain a limited proportion of the variance in genetic diversity, suggesting that genetic diversity might be difficult to predict at shallower phylogenetic scales. PMID:28469025

Genetic diversity is largely unpredictable but scales with museum occurrences in a species-rich clade of Australian lizards.

PubMed

Singhal, Sonal; Huang, Huateng; Title, Pascal O; Donnellan, Stephen C; Holmes, Iris; Rabosky, Daniel L

2017-05-17

Genetic diversity is a fundamental characteristic of species and is affected by many factors, including mutation rate, population size, life history and demography. To better understand the processes that influence levels of genetic diversity across taxa, we collected genome-wide restriction-associated DNA data from more than 500 individuals spanning 76 nominal species of Australian scincid lizards in the genus Ctenotus To avoid potential biases associated with variation in taxonomic practice across the group, we used coalescent-based species delimitation to delineate 83 species-level lineages within the genus for downstream analyses. We then used these genetic data to infer levels of within-population genetic diversity. Using a phylogenetically informed approach, we tested whether variation in genetic diversity could be explained by population size, environmental heterogeneity or historical demography. We find that the strongest predictor of genetic diversity is a novel proxy for census population size: the number of vouchered occurrences in museum databases. However, museum occurrences only explain a limited proportion of the variance in genetic diversity, suggesting that genetic diversity might be difficult to predict at shallower phylogenetic scales. © 2017 The Author(s).

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

PubMed

Thompson, Paul M; Stein, Jason L; Medland, Sarah E; Hibar, Derrek P; Vasquez, Alejandro Arias; Renteria, Miguel E; Toro, Roberto; Jahanshad, Neda; Schumann, Gunter; Franke, Barbara; Wright, Margaret J; Martin, Nicholas G; Agartz, Ingrid; Alda, Martin; Alhusaini, Saud; Almasy, Laura; Almeida, Jorge; Alpert, Kathryn; Andreasen, Nancy C; Andreassen, Ole A; Apostolova, Liana G; Appel, Katja; Armstrong, Nicola J; Aribisala, Benjamin; Bastin, Mark E; Bauer, Michael; Bearden, Carrie E; Bergmann, Orjan; Binder, Elisabeth B; Blangero, John; Bockholt, Henry J; Bøen, Erlend; Bois, Catherine; Boomsma, Dorret I; Booth, Tom; Bowman, Ian J; Bralten, Janita; Brouwer, Rachel M; Brunner, Han G; Brohawn, David G; Buckner, Randy L; Buitelaar, Jan; Bulayeva, Kazima; Bustillo, Juan R; Calhoun, Vince D; Cannon, Dara M; Cantor, Rita M; Carless, Melanie A; Caseras, Xavier; Cavalleri, Gianpiero L; Chakravarty, M Mallar; Chang, Kiki D; Ching, Christopher R K; Christoforou, Andrea; Cichon, Sven; Clark, Vincent P; Conrod, Patricia; Coppola, Giovanni; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Deary, Ian J; de Geus, Eco J C; den Braber, Anouk; Delvecchio, Giuseppe; Depondt, Chantal; de Haan, Lieuwe; de Zubicaray, Greig I; Dima, Danai; Dimitrova, Rali; Djurovic, Srdjan; Dong, Hongwei; Donohoe, Gary; Duggirala, Ravindranath; Dyer, Thomas D; Ehrlich, Stefan; Ekman, Carl Johan; Elvsåshagen, Torbjørn; Emsell, Louise; Erk, Susanne; Espeseth, Thomas; Fagerness, Jesen; Fears, Scott; Fedko, Iryna; Fernández, Guillén; Fisher, Simon E; Foroud, Tatiana; Fox, Peter T; Francks, Clyde; Frangou, Sophia; Frey, Eva Maria; Frodl, Thomas; Frouin, Vincent; Garavan, Hugh; Giddaluru, Sudheer; Glahn, David C; Godlewska, Beata; Goldstein, Rita Z; Gollub, Randy L; Grabe, Hans J; Grimm, Oliver; Gruber, Oliver; Guadalupe, Tulio; Gur, Raquel E; Gur, Ruben C; Göring, Harald H H; Hagenaars, Saskia; Hajek, Tomas; Hall, Geoffrey B; Hall, Jeremy; Hardy, John; Hartman, Catharina A; Hass, Johanna; Hatton, Sean N; Haukvik, Unn K; Hegenscheid, Katrin; Heinz, Andreas; Hickie, Ian B; Ho, Beng-Choon; Hoehn, David; Hoekstra, Pieter J; Hollinshead, Marisa; Holmes, Avram J; Homuth, Georg; Hoogman, Martine; Hong, L Elliot; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Hwang, Kristy S; Jack, Clifford R; Jenkinson, Mark; Johnston, Caroline; Jönsson, Erik G; Kahn, René S; Kasperaviciute, Dalia; Kelly, Sinead; Kim, Sungeun; Kochunov, Peter; Koenders, Laura; Krämer, Bernd; Kwok, John B J; Lagopoulos, Jim; Laje, Gonzalo; Landen, Mikael; Landman, Bennett A; Lauriello, John; Lawrie, Stephen M; Lee, Phil H; Le Hellard, Stephanie; Lemaître, Herve; Leonardo, Cassandra D; Li, Chiang-Shan; Liberg, Benny; Liewald, David C; Liu, Xinmin; Lopez, Lorna M; Loth, Eva; Lourdusamy, Anbarasu; Luciano, Michelle; Macciardi, Fabio; Machielsen, Marise W J; Macqueen, Glenda M; Malt, Ulrik F; Mandl, René; Manoach, Dara S; Martinot, Jean-Luc; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mattingsdal, Morten; Meyer-Lindenberg, Andreas; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Milaneschi, Yuri; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Moses, Eric K; Mueller, Bryon A; Muñoz Maniega, Susana; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Mwangi, Benson; Nauck, Matthias; Nho, Kwangsik; Nichols, Thomas E; Nilsson, Lars-Göran; Nugent, Allison C; Nyberg, Lars; Olvera, Rene L; Oosterlaan, Jaap; Ophoff, Roel A; Pandolfo, Massimo; Papalampropoulou-Tsiridou, Melina; Papmeyer, Martina; Paus, Tomas; Pausova, Zdenka; Pearlson, Godfrey D; Penninx, Brenda W; Peterson, Charles P; Pfennig, Andrea; Phillips, Mary; Pike, G Bruce; Poline, Jean-Baptiste; Potkin, Steven G; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rietschel, Marcella; Rijpkema, Mark; Risacher, Shannon L; Roffman, Joshua L; Roiz-Santiañez, Roberto; Romanczuk-Seiferth, Nina; Rose, Emma J; Royle, Natalie A; Rujescu, Dan; Ryten, Mina; Sachdev, Perminder S; Salami, Alireza; Satterthwaite, Theodore D; Savitz, Jonathan; Saykin, Andrew J; Scanlon, Cathy; Schmaal, Lianne; Schnack, Hugo G; Schork, Andrew J; Schulz, S Charles; Schür, Remmelt; Seidman, Larry; Shen, Li; Shoemaker, Jody M; Simmons, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soares, Jair C; Sponheim, Scott R; Sprooten, Emma; Starr, John M; Steen, Vidar M; Strakowski, Stephen; Strike, Lachlan; Sussmann, Jessika; Sämann, Philipp G; Teumer, Alexander; Toga, Arthur W; Tordesillas-Gutierrez, Diana; Trabzuni, Daniah; Trost, Sarah; Turner, Jessica; Van den Heuvel, Martijn; van der Wee, Nic J; van Eijk, Kristel; van Erp, Theo G M; van Haren, Neeltje E M; van 't Ent, Dennis; van Tol, Marie-Jose; Valdés Hernández, Maria C; Veltman, Dick J; Versace, Amelia; Völzke, Henry; Walker, Robert; Walter, Henrik; Wang, Lei; Wardlaw, Joanna M; Weale, Michael E; Weiner, Michael W; Wen, Wei; Westlye, Lars T; Whalley, Heather C; Whelan, Christopher D; White, Tonya; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Zilles, David; Zwiers, Marcel P; Thalamuthu, Anbupalam; Schofield, Peter R; Freimer, Nelson B; Lawrence, Natalia S; Drevets, Wayne

2014-06-01

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

An activity index for geomagnetic paleosecular variation, excursions, and reversals

NASA Astrophysics Data System (ADS)

Panovska, S.; Constable, C. G.

2017-04-01

Magnetic indices provide quantitative measures of space weather phenomena that are widely used by researchers in geomagnetism. We introduce an index focused on the internally generated field that can be used to evaluate long term variations or climatology of modern and paleomagnetic secular variation, including geomagnetic excursions, polarity reversals, and changes in reversal rate. The paleosecular variation index, Pi, represents instantaneous or average deviation from a geocentric axial dipole field using normalized ratios of virtual geomagnetic pole colatitude and virtual dipole moment. The activity level of the index, σPi, provides a measure of field stability through the temporal standard deviation of Pi. Pi can be calculated on a global grid from geomagnetic field models to reveal large scale geographic variations in field structure. It can be determined for individual time series, or averaged at local, regional, and global scales to detect long term changes in geomagnetic activity, identify excursions, and transitional field behavior. For recent field models, Pi ranges from less than 0.05 to 0.30. Conventional definitions for geomagnetic excursions are characterized by Pi exceeding 0.5. Strong field intensities are associated with low Pi unless they are accompanied by large deviations from axial dipole field directions. σPi provides a measure of geomagnetic stability that is modulated by the level of PSV or frequency of excursional activity and reversal rate. We demonstrate uses of Pi for paleomagnetic observations and field models and show how it could be used to assess whether numerical simulations of the geodynamo exhibit Earth-like properties.

The Genetic Interpretation of Area under the ROC Curve in Genomic Profiling

PubMed Central

Wray, Naomi R.; Yang, Jian; Goddard, Michael E.; Visscher, Peter M.

2010-01-01

Genome-wide association studies in human populations have facilitated the creation of genomic profiles which combine the effects of many associated genetic variants to predict risk of disease. The area under the receiver operator characteristic (ROC) curve is a well established measure for determining the efficacy of tests in correctly classifying diseased and non-diseased individuals. We use quantitative genetics theory to provide insight into the genetic interpretation of the area under the ROC curve (AUC) when the test classifier is a predictor of genetic risk. Even when the proportion of genetic variance explained by the test is 100%, there is a maximum value for AUC that depends on the genetic epidemiology of the disease, i.e. either the sibling recurrence risk or heritability and disease prevalence. We derive an equation relating maximum AUC to heritability and disease prevalence. The expression can be reversed to calculate the proportion of genetic variance explained given AUC, disease prevalence, and heritability. We use published estimates of disease prevalence and sibling recurrence risk for 17 complex genetic diseases to calculate the proportion of genetic variance that a test must explain to achieve AUC = 0.75; this varied from 0.10 to 0.74. We provide a genetic interpretation of AUC for use with predictors of genetic risk based on genomic profiles. We provide a strategy to estimate proportion of genetic variance explained on the liability scale from estimates of AUC, disease prevalence, and heritability (or sibling recurrence risk) available as an online calculator. PMID:20195508

Genome-environment association study suggests local adaptation to climate at the regional scale in Fagus sylvatica.

PubMed

Pluess, Andrea R; Frank, Aline; Heiri, Caroline; Lalagüe, Hadrien; Vendramin, Giovanni G; Oddou-Muratorio, Sylvie

2016-04-01

The evolutionary potential of long-lived species, such as forest trees, is fundamental for their local persistence under climate change (CC). Genome-environment association (GEA) analyses reveal if species in heterogeneous environments at the regional scale are under differential selection resulting in populations with potential preadaptation to CC within this area. In 79 natural Fagus sylvatica populations, neutral genetic patterns were characterized using 12 simple sequence repeat (SSR) markers, and genomic variation (144 single nucleotide polymorphisms (SNPs) out of 52 candidate genes) was related to 87 environmental predictors in the latent factor mixed model, logistic regressions and isolation by distance/environmental (IBD/IBE) tests. SSR diversity revealed relatedness at up to 150 m intertree distance but an absence of large-scale spatial genetic structure and IBE. In the GEA analyses, 16 SNPs in 10 genes responded to one or several environmental predictors and IBE, corrected for IBD, was confirmed. The GEA often reflected the proposed gene functions, including indications for adaptation to water availability and temperature. Genomic divergence and the lack of large-scale neutral genetic patterns suggest that gene flow allows the spread of advantageous alleles in adaptive genes. Thereby, adaptation processes are likely to take place in species occurring in heterogeneous environments, which might reduce their regional extinction risk under CC. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Genome and methylome of the oleaginous diatom Cyclotella cryptica reveal genetic flexibility toward a high lipid phenotype

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

Traller, Jesse C.; Cokus, Shawn J.; Lopez, David A.

Here, improvement in the performance of eukaryotic microalgae for biofuel and bioproduct production is largely dependent on characterization of metabolic mechanisms within the cell. The marine diatom Cyclotella cryptica, which was originally identified in the Aquatic Species Program, is a promising strain of microalgae for large-scale production of biofuel and bioproducts, such as omega-3 fatty acids. As a result, we sequenced the nuclear genome and methylome of this oleaginous diatom to identify the genetic traits that enable substantial accumulation of triacylglycerol. The genome is comprised of highly methylated repetitive sequence, which does not significantly change under silicon starved lipid induction,more » and data further suggests the primary role of DNA methylation is to suppress DNA transposition. Annotation of pivotal glycolytic, lipid metabolism, and carbohydrate degradation processes reveal an expanded enzyme repertoire in C. cryptica that would allow for an increased metabolic capacity toward triacylglycerol production. Identification of previously unidentified genes, including those involved in carbon transport and chitin metabolism, provide potential targets for genetic manipulation of carbon flux to further increase its lipid phenotype. New genetic tools were developed, bringing this organism on a par with other microalgae in terms of genetic manipulation and characterization approaches. Furthermore, functional annotation and detailed cross-species comparison of key carbon rich processes in C. cryptica highlights the importance of enzymatic subcellular compartmentation for regulation of carbon flux, which is often overlooked in photosynthetic microeukaryotes. The availability of the genome sequence, as well as advanced genetic manipulation tools enable further development of this organism for deployment in large-scale production systems.« less

Genome and methylome of the oleaginous diatom Cyclotella cryptica reveal genetic flexibility toward a high lipid phenotype

DOE PAGES

Traller, Jesse C.; Cokus, Shawn J.; Lopez, David A.; ...

2016-11-25

Here, improvement in the performance of eukaryotic microalgae for biofuel and bioproduct production is largely dependent on characterization of metabolic mechanisms within the cell. The marine diatom Cyclotella cryptica, which was originally identified in the Aquatic Species Program, is a promising strain of microalgae for large-scale production of biofuel and bioproducts, such as omega-3 fatty acids. As a result, we sequenced the nuclear genome and methylome of this oleaginous diatom to identify the genetic traits that enable substantial accumulation of triacylglycerol. The genome is comprised of highly methylated repetitive sequence, which does not significantly change under silicon starved lipid induction,more » and data further suggests the primary role of DNA methylation is to suppress DNA transposition. Annotation of pivotal glycolytic, lipid metabolism, and carbohydrate degradation processes reveal an expanded enzyme repertoire in C. cryptica that would allow for an increased metabolic capacity toward triacylglycerol production. Identification of previously unidentified genes, including those involved in carbon transport and chitin metabolism, provide potential targets for genetic manipulation of carbon flux to further increase its lipid phenotype. New genetic tools were developed, bringing this organism on a par with other microalgae in terms of genetic manipulation and characterization approaches. Furthermore, functional annotation and detailed cross-species comparison of key carbon rich processes in C. cryptica highlights the importance of enzymatic subcellular compartmentation for regulation of carbon flux, which is often overlooked in photosynthetic microeukaryotes. The availability of the genome sequence, as well as advanced genetic manipulation tools enable further development of this organism for deployment in large-scale production systems.« less

GAN: a platform of genomics and genetics analysis and application in Nicotiana

PubMed Central

Yang, Shuai; Zhang, Xingwei; Li, Huayang; Chen, Yudong

2018-01-01

Abstract Nicotiana is an important Solanaceae genus, and plays a significant role in modern biological research. Massive Nicotiana biological data have emerged from in-depth genomics and genetics studies. From big data to big discovery, large-scale analysis and application with new platforms is critical. Based on data accumulation, a comprehensive platform of Genomics and Genetics Analysis and Application in Nicotiana (GAN) has been developed, and is publicly available at http://biodb.sdau.edu.cn/gan/. GAN consists of four main sections: (i) Sources, a total of 5267 germplasm lines, along with detailed descriptions of associated characteristics, are all available on the Germplasm page, which can be queried using eight different inquiry modes. Seven fully sequenced species with accompanying sequences and detailed genomic annotation are available on the Genomics page. (ii) Genetics, detailed descriptions of 10 genetic linkage maps, constructed by different parents, 2239 KEGG metabolic pathway maps and 209 945 gene families across all catalogued genes, along with two co-linearity maps combining N. tabacum with available tomato and potato linkage maps are available here. Furthermore, 3 963 119 genome-SSRs, 10 621 016 SNPs, 12 388 PIPs and 102 895 reverse transcription-polymerase chain reaction primers, are all available to be used and searched on the Markers page. (iii) Tools, the genome browser JBrowse and five useful online bioinformatics softwares, Blast, Primer3, SSR-detect, Nucl-Protein and E-PCR, are provided on the JBrowse and Tools pages. (iv) Auxiliary, all the datasets are shown on a Statistics page, and are available for download on a Download page. In addition, the user’s manual is provided on a Manual page in English and Chinese languages. GAN provides a user-friendly Web interface for searching, browsing and downloading the genomics and genetics datasets in Nicotiana. As far as we can ascertain, GAN is the most comprehensive source of bio-data available, and the most applicable resource for breeding, gene mapping, gene cloning, the study of the origin and evolution of polyploidy, and related studies in Nicotiana. Database URL: http://biodb.sdau.edu.cn/gan/ PMID:29688356

Fast Crystallization of the Phase Change Compound GeTe by Large-Scale Molecular Dynamics Simulations.

PubMed

Sosso, Gabriele C; Miceli, Giacomo; Caravati, Sebastiano; Giberti, Federico; Behler, Jörg; Bernasconi, Marco

2013-12-19

Phase change materials are of great interest as active layers in rewritable optical disks and novel electronic nonvolatile memories. These applications rest on a fast and reversible transformation between the amorphous and crystalline phases upon heating, taking place on the nanosecond time scale. In this work, we investigate the microscopic origin of the fast crystallization process by means of large-scale molecular dynamics simulations of the phase change compound GeTe. To this end, we use an interatomic potential generated from a Neural Network fitting of a large database of ab initio energies. We demonstrate that in the temperature range of the programming protocols of the electronic memories (500-700 K), nucleation of the crystal in the supercooled liquid is not rate-limiting. In this temperature range, the growth of supercritical nuclei is very fast because of a large atomic mobility, which is, in turn, the consequence of the high fragility of the supercooled liquid and the associated breakdown of the Stokes-Einstein relation between viscosity and diffusivity.

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

Perumalla, Kalyan S.; Yoginath, Srikanth B.

Problems such as fault tolerance and scalable synchronization can be efficiently solved using reversibility of applications. Making applications reversible by relying on computation rather than on memory is ideal for large scale parallel computing, especially for the next generation of supercomputers in which memory is expensive in terms of latency, energy, and price. In this direction, a case study is presented here in reversing a computational core, namely, Basic Linear Algebra Subprograms, which is widely used in scientific applications. A new Reversible BLAS (RBLAS) library interface has been designed, and a prototype has been implemented with two modes: (1) amore » memory-mode in which reversibility is obtained by checkpointing to memory in forward and restoring from memory in reverse, and (2) a computational-mode in which nothing is saved in the forward, but restoration is done entirely via inverse computation in reverse. The article is focused on detailed performance benchmarking to evaluate the runtime dynamics and performance effects, comparing reversible computation with checkpointing on both traditional CPU platforms and recent GPU accelerator platforms. For BLAS Level-1 subprograms, data indicates over an order of magnitude better speed of reversible computation compared to checkpointing. For BLAS Level-2 and Level-3, a more complex tradeoff is observed between reversible computation and checkpointing, depending on computational and memory complexities of the subprograms.« less

Small Traditional Human Communities Sustain Genomic Diversity over Microgeographic Scales despite Linguistic Isolation

PubMed Central

Cox, Murray P.; Hudjashov, Georgi; Sim, Andre; Savina, Olga; Karafet, Tatiana M.; Sudoyo, Herawati; Lansing, J. Stephen

2016-01-01

At least since the Neolithic, humans have largely lived in networks of small, traditional communities. Often socially isolated, these groups evolved distinct languages and cultures over microgeographic scales of just tens of kilometers. Population genetic theory tells us that genetic drift should act quickly in such isolated groups, thus raising the question: do networks of small human communities maintain levels of genetic diversity over microgeographic scales? This question can no longer be asked in most parts of the world, which have been heavily impacted by historical events that make traditional society structures the exception. However, such studies remain possible in parts of Island Southeast Asia and Oceania, where traditional ways of life are still practiced. We captured genome-wide genetic data, together with linguistic records, for a case–study system—eight villages distributed across Sumba, a small, remote island in eastern Indonesia. More than 4,000 years after these communities were established during the Neolithic period, most speak different languages and can be distinguished genetically. Yet their nuclear diversity is not reduced, instead being comparable to other, even much larger, regional groups. Modeling reveals a separation of time scales: while languages and culture can evolve quickly, creating social barriers, sporadic migration averaged over many generations is sufficient to keep villages linked genetically. This loosely-connected network structure, once the global norm and still extant on Sumba today, provides a living proxy to explore fine-scale genome dynamics in the sort of small traditional communities within which the most recent episodes of human evolution occurred. PMID:27274003

The fine-scale genetic structure and evolution of the Japanese population

PubMed Central

Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Isomura, Minoru; Ohkubo, Takayoshi; Tabara, Yasuharu; Yamamoto, Ken; Yokota, Mitsuhiro; Liu, Xuanyao; Saw, Woei-Yuh; Mamatyusupu, Dolikun; Yang, Wenjun; Xu, Shuhua

2017-01-01

The contemporary Japanese populations largely consist of three genetically distinct groups—Hondo, Ryukyu and Ainu. By principal-component analysis, while the three groups can be clearly separated, the Hondo people, comprising 99% of the Japanese, form one almost indistinguishable cluster. To understand fine-scale genetic structure, we applied powerful haplotype-based statistical methods to genome-wide single nucleotide polymorphism data from 1600 Japanese individuals, sampled from eight distinct regions in Japan. We then combined the Japanese data with 26 other Asian populations data to analyze the shared ancestry and genetic differentiation. We found that the Japanese could be separated into nine genetic clusters in our dataset, showing a marked concordance with geography; and that major components of ancestry profile of Japanese were from the Korean and Han Chinese clusters. We also detected and dated admixture in the Japanese. While genetic differentiation between Ryukyu and Hondo was suggested to be caused in part by positive selection, genetic differentiation among the Hondo clusters appeared to result principally from genetic drift. Notably, in Asians, we found the possibility that positive selection accentuated genetic differentiation among distant populations but attenuated genetic differentiation among close populations. These findings are significant for studies of human evolution and medical genetics. PMID:29091727

Original BPC3 Research Plan

Cancer.gov

The Breast and Prostate Cancer and Hormone-Related Gene Variant Study allows large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism.

Biological science in conservation

Treesearch

David M. Johns

2000-01-01

Large-scale wildlands reserve systems offer one of the best hopes for slowing, if not reversing, the loss of biodiversity and wilderness. Establishing such reserves requires both sound biology and effective advocacy. Attempts by The Wildlands Project and its cooperators to meld science and advocacy in the service of conservation is working, but is not without some...

Oscillations and Synchrony in Large-scale Cortical Network Models

DTIC Science & Technology

2008-06-17

synaptic current is computed as In = −gn(xpostn − xrp ), (7) where gsyn is the strength of the synaptic coupling and the indices pre and post stand... xrp defines the reversal potential and, therefore, the type of synapse: excitatory ( xrp = 0) or inhibitory ( xrp = −1.1). To include the effects of short

Sex reversal triggers the rapid transition from genetic to temperature-dependent sex.

PubMed

Holleley, Clare E; O'Meally, Denis; Sarre, Stephen D; Marshall Graves, Jennifer A; Ezaz, Tariq; Matsubara, Kazumi; Azad, Bhumika; Zhang, Xiuwen; Georges, Arthur

2015-07-02

Sex determination in animals is amazingly plastic. Vertebrates display contrasting strategies ranging from complete genetic control of sex (genotypic sex determination) to environmentally determined sex (for example, temperature-dependent sex determination). Phylogenetic analyses suggest frequent evolutionary transitions between genotypic and temperature-dependent sex determination in environmentally sensitive lineages, including reptiles. These transitions are thought to involve a genotypic system becoming sensitive to temperature, with sex determined by gene-environment interactions. Most mechanistic models of transitions invoke a role for sex reversal. Sex reversal has not yet been demonstrated in nature for any amniote, although it occurs in fish and rarely in amphibians. Here we make the first report of reptile sex reversal in the wild, in the Australian bearded dragon (Pogona vitticeps), and use sex-reversed animals to experimentally induce a rapid transition from genotypic to temperature-dependent sex determination. Controlled mating of normal males to sex-reversed females produces viable and fertile offspring whose phenotypic sex is determined solely by temperature (temperature-dependent sex determination). The W sex chromosome is eliminated from this lineage in the first generation. The instantaneous creation of a lineage of ZZ temperature-sensitive animals reveals a novel, climate-induced pathway for the rapid transition between genetic and temperature-dependent sex determination, and adds to concern about adaptation to rapid global climate change.

Torsional Oscillations in a Global Solar Dynamo

NASA Astrophysics Data System (ADS)

Beaudoin, P.; Charbonneau, P.; Racine, E.; Smolarkiewicz, P. K.

2013-02-01

We characterize and analyze rotational torsional oscillations developing in a large-eddy magnetohydrodynamical simulation of solar convection (Ghizaru, Charbonneau, and Smolarkiewicz, Astrophys. J. Lett. 715, L133, 2010; Racine et al., Astrophys. J. 735, 46, 2011) producing an axisymmetric, large-scale, magnetic field undergoing periodic polarity reversals. Motivated by the many solar-like features exhibited by these oscillations, we carry out an analysis of the large-scale zonal dynamics. We demonstrate that simulated torsional oscillations are not driven primarily by the periodically varying large-scale magnetic torque, as one might have expected, but rather via the magnetic modulation of angular-momentum transport by the large-scale meridional flow. This result is confirmed by a straightforward energy analysis. We also detect a fairly sharp transition in rotational dynamics taking place as one moves from the base of the convecting layers to the base of the thin tachocline-like shear layer formed in the stably stratified fluid layers immediately below. We conclude by discussing the implications of our analyses with regard to the mechanism of amplitude saturation in the global dynamo operating in the simulation, and speculate on the possible precursor value of torsional oscillations for the forecast of solar-cycle characteristics.

Genetic structure of Zymoseptoria tritici in northern France at region, field, plant and leaf layer scales.

PubMed

Siah, Ali; Bomble, Myriam; Tisserant, Benoit; Cadalen, Thierry; Holvoet, Maxime; Hilbert, Jean-Louis; Halama, Patrice; Reignault, Philippe Lucien

2018-04-16

Population genetic structure of the worldwide-distributed wheat pathogen Zymoseptoria tritici has been extensively studied at large geographical scales, but to a much less extent at small or local spatial scales. A total of 627 single-conidial fungal isolates were sampled from several locations in northern France (Hauts-de-France Region) to assess fungal genetic structure at region, field, plant and leaf layer scales, using highly polymorphic microsatellite markers and mating type idiomorphs. Important and overall similar levels of both gene and genotype diversities (gene diversity values ≥ 0.44 and haplotype frequencies ≥ 94 %) were found at all the examined scales. Such rates of diversity are likely due to an active sexual recombination in the investigated areas, as revealed by equal proportions of the two mating types scored in all sampled populations. Interestingly, a rare occurrence of clones among lesions from a same leaf, as well as among leaves from different plant leaf layers (e.g. upper vs lower leaves), was highlighted, indicating that ascospores contribute much more than expected to Z. tritci epidemics, compared to pycnidiospores. Population structure and AMOVA analyses revealed significant genetic differentiation at the regional scale (GST = 0.23) and, as expected, not at the other more local scales (GST ≤ 0.01). Further analyses using Bayesian and unweighted neighbor-joining statistical methods detected six genetic clusters within the regional population, overall distributed according to the locations from which the isolates were sampled. Neither clear directional relative migration linked to the geographical distribution of the locations, nor isolation by distance, were observed. Separate evolutionary trajectories caused by selection and adaptations to habitat heterogeneity could be the main forces shaping such structuration. This study provides new insights into the epidemiology and the genetic structure of Z. tritici at small local and, for the first time, at single plant and leaf layer scales. Such findings would be helpful in implementing effective control strategies.

Reverse Fluorescence Enhancement and Colorimetric Bimodal Signal Readout Immunochromatography Test Strip for Ultrasensitive Large-Scale Screening and Postoperative Monitoring.

PubMed

Yao, Yingyi; Guo, Weisheng; Zhang, Jian; Wu, Yudong; Fu, Weihua; Liu, Tingting; Wu, Xiaoli; Wang, Hanjie; Gong, Xiaoqun; Liang, Xing-Jie; Chang, Jin

2016-09-07

Ultrasensitive and quantitative fast screening of cancer biomarkers by immunochromatography test strip (ICTS) is still challenging in clinic. The gold nanoparticles (NPs) based ICTS with colorimetric readout enables a quick spectrum screening but suffers from nonquantitative performance; although ICTS with fluorescence readout (FICTS) allows quantitative detection, its sensitivity still deserves more efforts and attentions. In this work, by taking advantages of colorimetric ICTS and FICTS, we described a reverse fluorescence enhancement ICTS (rFICTS) with bimodal signal readout for ultrasensitive and quantitative fast screening of carcinoembryonic antigen (CEA). In the presence of target, gold NPs aggregation in T line induced colorimetric readout, allowing on-the-spot spectrum screening in 10 min by naked eye. Meanwhile, the reverse fluorescence enhancement signal enabled more accurately quantitative detection with better sensitivity (5.89 pg/mL for CEA), which is more than 2 orders of magnitude lower than that of the conventional FICTS. The accuracy and stability of the rFICTS were investigated with more than 100 clinical serum samples for large-scale screening. Furthermore, this rFICTS also realized postoperative monitoring by detecting CEA in a patient with colon cancer and comparing with CT imaging diagnosis. These results indicated this rFICTS is particularly suitable for point-of-care (POC) diagnostics in both resource-rich and resource-limited settings.

Comparing centralised and decentralised anaerobic digestion of stillage from a large-scale bioethanol plant to animal feed production.

PubMed

Drosg, B; Wirthensohn, T; Konrad, G; Hornbachner, D; Resch, C; Wäger, F; Loderer, C; Waltenberger, R; Kirchmayr, R; Braun, R

2008-01-01

A comparison of stillage treatment options for large-scale bioethanol plants was based on the data of an existing plant producing approximately 200,000 t/yr of bioethanol and 1,400,000 t/yr of stillage. Animal feed production--the state-of-the-art technology at the plant--was compared to anaerobic digestion. The latter was simulated in two different scenarios: digestion in small-scale biogas plants in the surrounding area versus digestion in a large-scale biogas plant at the bioethanol production site. Emphasis was placed on a holistic simulation balancing chemical parameters and calculating logistic algorithms to compare the efficiency of the stillage treatment solutions. For central anaerobic digestion different digestate handling solutions were considered because of the large amount of digestate. For land application a minimum of 36,000 ha of available agricultural area would be needed and 600,000 m(3) of storage volume. Secondly membrane purification of the digestate was investigated consisting of decanter, microfiltration, and reverse osmosis. As a third option aerobic wastewater treatment of the digestate was discussed. The final outcome was an economic evaluation of the three mentioned stillage treatment options, as a guide to stillage management for operators of large-scale bioethanol plants. Copyright IWA Publishing 2008.

Osmosis process for leachate treatment in industrial platform: Economic and performances evaluations to zero liquid discharge.

PubMed

Cingolani, Diego; Eusebi, Anna Laura; Battistoni, Paolo

2017-12-01

The industrial processes require large quantities of water. The presence of discharges results not only in significant environmental impact but implies wastage of water resources. This problem could be solved treating and reusing the produced wastewaters and applying the new zero liquid discharge approach. This paper discusses the design and the performances of reverse osmosis membranes for the upgrading of full scale platform for industrial liquid wastes. The final effluent from the ultrafiltration unit of the full scale plant was monitored to design the reverse osmosis unit. Previous modelling phase was used to evaluate the specific ordinary and maintenance costs and the final effluent quality (2.7 €/m 3 ). The system was designed in triple stages at different operative pressures. The economic feasibility and the payback period of the technology at different percentages of produced permeate were determined. The recovery of 90% was identified as profitable for the reverse osmosis application. One experimental pilot plant applying the reverse osmosis was used to test the final effluent. Moreover, the same flow was treated with second pilot system based on the forward osmosis process. The final efficiencies were compared. Removals higher than 95% using the reverse system were obtained for the main macropollutants and ions. No sustainable applicability of the forward osmosis was determined. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reversible Redox Chemistry of Azo Compounds for Sodium-Ion Batteries

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

Luo, Chao; Xu, Gui-Liang; Ji, Xiao

Sustainable sodium-ion batteries (SSIBs) using renewable organic electrodes are promising alternatives to lithium-ion batteries for the large-scale renewable energy storage. However, the lack of high-performance anode material impedes the development of SSIBs. Herein, we report a new type of organic anode material based on azo group for SSIBs. Azobenzene-4,4'-dicarboxylic acid sodium salt is used as a model to investigate the electrochemical behaviors and reaction mechanism of azo compound. It exhibits a reversible capacity of 170 mAhg -1 at 0.2C. When current density is increased to 20C, the reversible capacities of 98 mAhg -1 can be retained for 2000 cycles, demonstratingmore » excellent cycling stability and high rate capability. The detailed characterizations reveal that azo group acts as an electrochemical active site to reversibly bond with Na +. The reversible redox chemistry between azo compound and Na ions offer opportunities for developing longcycle-life and high-rate SSIBs.« less

Reversible Redox Chemistry of Azo Compounds for Sodium-Ion Batteries

DOE PAGES

Luo, Chao; Xu, Gui-Liang; Ji, Xiao; ...

2018-01-29

Sustainable sodium-ion batteries (SSIBs) using renewable organic electrodes are promising alternatives to lithium-ion batteries for the large-scale renewable energy storage. However, the lack of high-performance anode material impedes the development of SSIBs. Herein, we report a new type of organic anode material based on azo group for SSIBs. Azobenzene-4,4'-dicarboxylic acid sodium salt is used as a model to investigate the electrochemical behaviors and reaction mechanism of azo compound. It exhibits a reversible capacity of 170 mAhg -1 at 0.2C. When current density is increased to 20C, the reversible capacities of 98 mAhg -1 can be retained for 2000 cycles, demonstratingmore » excellent cycling stability and high rate capability. The detailed characterizations reveal that azo group acts as an electrochemical active site to reversibly bond with Na +. The reversible redox chemistry between azo compound and Na ions offer opportunities for developing longcycle-life and high-rate SSIBs.« less

Coronal Polarization of Pseudostreamers and the Solar Polar Field Reversal

NASA Technical Reports Server (NTRS)

Rachmeler, L. A.; Guennou, C.; Seaton, D. B.; Gibson, S. E.; Auchere, F.

2016-01-01

The reversal of the solar polar magnetic field is notoriously hard to pin down due to the extreme viewing angle of the pole. In Cycle 24, the southern polar field reversal can be pinpointed with high accuracy due to a large-scale pseudostreamer that formed over the pole and persisted for approximately a year. We tracked the size and shape of this structure with multiple observations and analysis techniques including PROBA2/SWAP EUV images, AIA EUV images, CoMP polarization data, and 3D tomographic reconstructions. We find that the heliospheric field reversed polarity in February 2014, whereas in the photosphere, the last vestiges of the previous polar field polarity remained until March 2015. We present here the evolution of the structure and describe its identification in the Fe XII 1074nm coronal emission line, sensitive to the Hanle effect in the corona.

Genetic diversity of Brazilian natural populations of Anthonomus grandis Boheman (Coleoptera: Curculionidae), the major cotton pest in the New World.

PubMed

Martins, W F S; Ayres, C F J; Lucena, W A

2007-01-27

Twenty-five RAPD loci and 6 isozyme loci were studied to characterize the genetic variability of natural populations of Anthonomus grandis from two agroecosystems of Brazil. The random-amplified polymorphic DNA data disclosed a polymorphism that varied from 52 to 84% and a heterozygosity of 0.189 to 0.347. The index of genetic differentiation (GST) among the six populations was 0.258. The analysis of isozymes showed a polymorphism and a heterozygosity ranging from 25 to 100% and 0.174 to 0.277, respectively. The genetic differentiation (FST) among the populations obtained by isozyme data was 0.544. It was possible to observe rare alleles in the populations from the Northeast region. The markers examined allowed us to distinguish populations from large-scale, intensive farming region (cotton belts) versus populations from areas of small-scale farming

Efficacy or inefficacy, that's the question: burnout and work engagement, and their relationships with efficacy beliefs.

PubMed

Schaufeli, Wilmar B; Salanova, Marisa

2007-06-01

We challenge traditional view that lack of efficacy - measured with the corresponding reversed efficacy scale (Maslach Burnout Inventory, MBI) - is a burnout dimension. Instead, we claim that in addition to exhaustion and cynicism, inefficacy - measured with a newly developed scale - characterizes burnout. MBI-efficacy is apparently related to work engagement, considered as the positive antithesis of burnout. We performed Structural Equation Modeling in two samples of Spanish (n=239) and Dutch (n=235) university students, and two Spanish employee samples, working in various jobs (n=342) and working with information and communication technologies (n=283). Our expectations were largely confirmed: (1) compared with efficacy beliefs inefficacy beliefs relate more strongly to the other two burnout components; (2) the alternative three-factor burnout model including inefficacy fits better to the data than the traditional model including efficacy; (3) a model with inefficacy loading on burnout and efficacy loading on engagement fits the data. It is suggested that an inefficacy scale rather than a reversed efficacy scale should be used to assess burnout in future studies.

Temporal Organization of Sound Information in Auditory Memory.

PubMed

Song, Kun; Luo, Huan

2017-01-01

Memory is a constructive and organizational process. Instead of being stored with all the fine details, external information is reorganized and structured at certain spatiotemporal scales. It is well acknowledged that time plays a central role in audition by segmenting sound inputs into temporal chunks of appropriate length. However, it remains largely unknown whether critical temporal structures exist to mediate sound representation in auditory memory. To address the issue, here we designed an auditory memory transferring study, by combining a previously developed unsupervised white noise memory paradigm with a reversed sound manipulation method. Specifically, we systematically measured the memory transferring from a random white noise sound to its locally temporal reversed version on various temporal scales in seven experiments. We demonstrate a U-shape memory-transferring pattern with the minimum value around temporal scale of 200 ms. Furthermore, neither auditory perceptual similarity nor physical similarity as a function of the manipulating temporal scale can account for the memory-transferring results. Our results suggest that sounds are not stored with all the fine spectrotemporal details but are organized and structured at discrete temporal chunks in long-term auditory memory representation.

A behavioral genetic study of intrapersonal and interpersonal dimensions of narcissism.

PubMed

Luo, Yu L L; Cai, Huajian; Song, Hairong

2014-01-01

Narcissism, characterized by grandiose self-image and entitled feelings to others, has been increasingly prevalent in the past decades. This study examined genetic and environmental bases of two dimensions of narcissism: intrapersonal grandiosity and interpersonal entitlement. A total of 304 pairs of twins from Beijing, China completed the Narcissistic Grandiosity Scale and the Psychological Entitlement Scale. Both grandiosity (23%) and entitlement (35%) were found to be moderately heritable, while simultaneously showing considerable non-shared environmental influences. Moreover, the genetic and environmental influences on the two dimensions were mostly unique (92-93%), with few genetic and environmental effects in common (7-8%). The two dimensions of narcissism, intrapersonal grandiosity and interpersonal entitlement, are heritable and largely independent of each other in terms of their genetic and environmental sources. These findings extend our understanding of the heritability of narcissism on the one hand. On the other hand, the study demonstrates the rationale for distinguishing between intrapersonal and interpersonal dimensions of narcissism, and possibly personality in general as well.

A Behavioral Genetic Study of Intrapersonal and Interpersonal Dimensions of Narcissism

PubMed Central

Luo, Yu L. L.; Cai, Huajian; Song, Hairong

2014-01-01

Narcissism, characterized by grandiose self-image and entitled feelings to others, has been increasingly prevalent in the past decades. This study examined genetic and environmental bases of two dimensions of narcissism: intrapersonal grandiosity and interpersonal entitlement. A total of 304 pairs of twins from Beijing, China completed the Narcissistic Grandiosity Scale and the Psychological Entitlement Scale. Both grandiosity (23%) and entitlement (35%) were found to be moderately heritable, while simultaneously showing considerable non-shared environmental influences. Moreover, the genetic and environmental influences on the two dimensions were mostly unique (92–93%), with few genetic and environmental effects in common (7–8%). The two dimensions of narcissism, intrapersonal grandiosity and interpersonal entitlement, are heritable and largely independent of each other in terms of their genetic and environmental sources. These findings extend our understanding of the heritability of narcissism on the one hand. On the other hand, the study demonstrates the rationale for distinguishing between intrapersonal and interpersonal dimensions of narcissism, and possibly personality in general as well. PMID:24695616

A new large-scale process for taxol and related taxanes from Taxus brevifolia.

PubMed

Rao, K V; Hanuman, J B; Alvarez, C; Stoy, M; Juchum, J; Davies, R M; Baxley, R

1995-07-01

In view of the demonstrated antitumor activity of taxol, ready availability of the drug is important. The current isolation methods starting from the bark of Taxus brevifolia involve multiple manipulations, leading to only taxol and in a yield of 0.01%. A new process consisting of a single reverse phase column is introduced here, and the present purpose is to determine its large scale applicability. The chloroform extractable fraction of the bark of T. brevifolia is applied directly on to a C-18 bonded silica column in 25% acetonitrile/water, with elution using a step gradient: 30-50% acetonitrile/water. On standing, eight different taxanes, including taxol, crystallize out directly from different fractions. The crystals are filtered and purified further by recrystallization. Taxol and four other taxanes are purified this way. The other three require a short silica column. Taxol is freed from cephalomannine by selective ozonolysis. The large scale process gave taxol (0.04%), 10-deacetylbaccatin III (0.02%), 10-deacetyl taxol-7-xyloside (0.1%), 10-deacetyl taxol-C-7-xyloside (0.04%), 10-deacetyl cephalomannine-7-xyloside (0.006%), taxol-7-xyloside (0.008%), 10-deacetyl taxol (0.008%) and cephalomannine (0.004%). Processing of the needles of T. brevifolia gave brevifoliol (0.17%), and that of the wood, 10-deacetyl taxol-C-7-xyloside (0.01%) and 10-deacetyl taxol-C. The reverse phase column process is simpler (one column, direct crystallization), more efficient (eight taxanes obtained simultaneously) and also gives higher yields.

Reversible chemical delithiation/lithiation of LiFePO4: towards a redox flow lithium-ion battery.

PubMed

Huang, Qizhao; Li, Hong; Grätzel, Michael; Wang, Qing

2013-02-14

Reversible chemical delithiation/lithiation of LiFePO(4) was successfully demonstrated using ferrocene derivatives, based on which a novel energy storage system--the redox flow lithium-ion battery (RFLB), was devised by integrating the operation flexibility of a redox flow battery and high energy density of a lithium-ion battery. Distinct from the recent semi-solid lithium rechargeable flow battery, the energy storage materials of RFLB stored in separate energy tanks remain stationary upon operation, giving us a fresh perspective on building large-scale energy storage systems with higher energy density and improved safety.

ARACNe-AP: Gene Network Reverse Engineering through Adaptive Partitioning inference of Mutual Information. | Office of Cancer Genomics

Cancer.gov

The accurate reconstruction of gene regulatory networks from large scale molecular profile datasets represents one of the grand challenges of Systems Biology. The Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) represents one of the most effective tools to accomplish this goal. However, the initial Fixed Bandwidth (FB) implementation is both inefficient and unable to deal with sample sets providing largely uneven coverage of the probability density space.

A Chromosome-Scale Assembly of the Bactrocera cucurbitae Genome Provides Insight to the Genetic Basis of white pupae

PubMed Central

Sim, Sheina B.; Geib, Scott M.

2017-01-01

Genetic sexing strains (GSS) used in sterile insect technique (SIT) programs are textbook examples of how classical Mendelian genetics can be directly implemented in the management of agricultural insect pests. Although the foundation of traditionally developed GSS are single locus, autosomal recessive traits, their genetic basis are largely unknown. With the advent of modern genomic techniques, the genetic basis of sexing traits in GSS can now be further investigated. This study is the first of its kind to integrate traditional genetic techniques with emerging genomics to characterize a GSS using the tephritid fruit fly pest Bactrocera cucurbitae as a model. These techniques include whole-genome sequencing, the development of a mapping population and linkage map, and quantitative trait analysis. The experiment designed to map the genetic sexing trait in B. cucurbitae, white pupae (wp), also enabled the generation of a chromosome-scale genome assembly by integrating the linkage map with the assembly. Quantitative trait loci analysis revealed SNP loci near position 42 MB on chromosome 3 to be tightly linked to wp. Gene annotation and synteny analysis show a near perfect relationship between chromosomes in B. cucurbitae and Muller elements A–E in Drosophila melanogaster. This chromosome-scale genome assembly is complete, has high contiguity, was generated using a minimal input DNA, and will be used to further characterize the genetic mechanisms underlying wp. Knowledge of the genetic basis of genetic sexing traits can be used to improve SIT in this species and expand it to other economically important Diptera. PMID:28450369

Giant reversible anisotropy changes at room temperature in a (La,Sr)MnO3/Pb(Mg,Nb,Ti)O3 magneto-electric heterostructure.

PubMed

Chopdekar, Rajesh Vilas; Buzzi, Michele; Jenkins, Catherine; Arenholz, Elke; Nolting, Frithjof; Takamura, Yayoi

2016-06-08

In a model artificial multiferroic system consisting of a (011)-oriented ferroelectric Pb(Mg,Nb,Ti)O3 substrate intimately coupled to an epitaxial ferromagnetic (La,Sr)MnO3 film, electric field pulse sequences of less than 6 kV/cm induce large, reversible, and bistable remanent strains. The magnetic anisotropy symmetry reversibly switches from a highly anisotropic two-fold state to a more isotropic one, with concomitant changes in resistivity. Anisotropy changes at the scale of a single ferromagnetic domain were measured using X-ray microscopy, with electric-field dependent magnetic domain reversal showing that the energy barrier for magnetization reversal is drastically lowered. Free energy calculations confirm this barrier lowering by up to 70% due to the anisotropic strain changes generated by the substrate. Thus, we demonstrate that an electric field pulse can be used to 'set' and 'reset' the magnetic anisotropy orientation and resistive state in the film, as well as to lower the magnetization reversal barrier, showing a promising route towards electric-field manipulation of multifunctional nanostructures at room temperature.

Scaling of confinement and profiles in the EXTRAP T2 reversed-field pinch

NASA Astrophysics Data System (ADS)

Welander, A.

1999-01-01

In the EXTRAP T2 reversed-field pinch the diagnostic techniques for the measurement of electron density and temperature include; Thomson scattering which gives values at three radial positions in the core (r/a = 0, 0.28, 0.56), Langmuir probes which give values at the edge (r/a > 0.9) and interferometry which gives a line-averaged density. The empirical scaling of electron density and temperature including profile information with global plasma parameters has been studied. The density profile is subject to large variations, with an average parabolic shape when the density is low and flatter shapes when the density is increased. The change in the profile shape can be attributed to a shift in the penetration length of neutrals from the vicinity of the wall. The temperature scales roughly as I/n1/2 where I is the plasma current and n is the density. The temperature profile is always quite flat with lower variations and there is a tendency for a flatter profile at higher temperatures.

Analysis of the Genetic Basis of Disease in the Context of Worldwide Human Relationships and Migration

PubMed Central

Corona, Erik; Chen, Rong; Sikora, Martin; Morgan, Alexander A.; Patel, Chirag J.; Ramesh, Aditya; Bustamante, Carlos D.; Butte, Atul J.

2013-01-01

Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation. PMID:23717210

Macro-scale assessment of demographic and environmental variation within genetically derived evolutionary lineages of eastern hemlock (Tsuga canadensis), an imperiled conifer of the eastern United States

Treesearch

Anantha M. Prasad; Kevin M. Potter

2017-01-01

Eastern hemlock (Tsuga canadensis) occupies a large swath of eastern North America and has historically undergone range expansion and contraction resulting in several genetically separate lineages. This conifer is currently experiencing mortality across most of its range following infestation of a non-native insect. With the goal of better...

Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the Challenges

PubMed Central

2018-01-01

Schizophrenia (SZ) is a heritable brain disease originating from a complex interaction of genetic and environmental factors. The genes underpinning the neurobiology of SZ are largely unknown but recent data suggest strong evidence for genetic variations, such as single nucleotide polymorphisms, making the brain vulnerable to the risk of SZ. Structural and functional brain mapping of these genetic variations are essential for the development of agents and tools for better diagnosis, treatment and prevention of SZ. Addressing this, neuroimaging methods in combination with genetic analysis have been increasingly used for almost 20 years. So-called imaging genetics, the opportunities of this approach along with its limitations for SZ research will be outlined in this invited paper. While the problems such as reproducibility, genetic effect size, specificity and sensitivity exist, opportunities such as multivariate analysis, development of multisite consortia for large-scale data collection, emergence of non-candidate gene (hypothesis-free) approach of neuroimaging genetics are likely to contribute to a rapid progress for gene discovery besides to gene validation studies that are related to SZ. PMID:29324666

Preliminary Design of a Manned Nuclear Electric Propulsion Vehicle Using Genetic Algorithms

NASA Technical Reports Server (NTRS)

Irwin, Ryan W.; Tinker, Michael L.

2005-01-01

Nuclear electric propulsion (NEP) vehicles will be needed for future manned missions to Mars and beyond. Candidate designs must be identified for further detailed design from a large array of possibilities. Genetic algorithms have proven their utility in conceptual design studies by effectively searching a large design space to pinpoint unique optimal designs. This research combined analysis codes for NEP subsystems with a genetic algorithm. The use of penalty functions with scaling ratios was investigated to increase computational efficiency. Also, the selection of design variables for optimization was considered to reduce computation time without losing beneficial design search space. Finally, trend analysis of a reference mission to the asteroids yielded a group of candidate designs for further analysis.

Breaking the rules: sex roles and genetic mating system of the pheasant coucal.

PubMed

Maurer, G; Double, M C; Milenkaya, O; Süsser, M; Magrath, R D

2011-10-01

Generally in birds, the classic sex roles of male competition and female choice result in females providing most offspring care while males face uncertain parentage. In less than 5% of species, however, reversed courtship sex roles lead to predominantly male care and low extra-pair paternity. These role-reversed species usually have reversed sexual size dimorphism and polyandry, confirming that sexual selection acts most strongly on the sex with the smaller parental investment and accordingly higher potential reproductive rate. We used parentage analyses and observations from three field seasons to establish the social and genetic mating system of pheasant coucals, Centropus phasianinus, a tropical nesting cuckoo, where males are much smaller than females and provide most parental care. Pheasant coucals are socially monogamous and in this study males produced about 80% of calls in the dawn chorus, implying greater male sexual competition. Despite the substantial male investments, extra-pair paternity was unusually high for a socially monogamous, duetting species. Using two or more mismatches to determine extra-pair parentage, we found that 11 of 59 young (18.6%) in 10 of 21 broods (47.6%) were not sired by their putative father. Male incubation, starting early in the laying sequence, may give the female opportunity and reason to seek these extra-pair copulations. Monogamy, rather than the polyandry and sex-role reversal typical of its congener, C. grillii, may be the result of the large territory size, which could prevent females from monopolising multiple males. The pheasant coucal's exceptional combination of classic sex-roles and male-biased care for extra-pair young is hard to reconcile with current sexual selection theory, but may represent an intermediate stage in the evolution of polyandry or an evolutionary remnant of polyandry.

Sex Reversal in Birds.

PubMed

Major, Andrew T; Smith, Craig A

2016-01-01

Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

Efficient and Robust Paramyxoviridae Reverse Genetics Systems

PubMed Central

Beaty, Shannon M.; Won, Sohui T.; Hong, Patrick; Lyons, Michael; Vigant, Frederic; Freiberg, Alexander N.; tenOever, Benjamin R.; Duprex, W. Paul

2017-01-01

ABSTRACT The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i.e., the number of attempts that result in successful rescue) has been improved in some systems with the use of stable cell lines, the efficiency of rescue (i.e., the proportion of transfected cells that yield at least one successful rescue event) has remained low. We have substantially increased rescue efficiency for representative viruses from all five major Paramyxoviridae genera (from ~1 in 106-107 to ~1 in 102-103 transfected cells) by the addition of a self-cleaving hammerhead ribozyme (Hh-Rbz) sequence immediately preceding the start of the recombinant viral antigenome and the use of a codon-optimized T7 polymerase (T7opt) gene to drive paramyxovirus rescue. Here, we report a strategy for robust, reliable, and high-efficiency rescue of paramyxovirus reverse genetics systems, featuring several major improvements: (i) a vaccinia virus-free method, (ii) freedom to use any transfectable cell type for viral rescue, (iii) a single-step transfection protocol, and (iv) use of the optimal T7 promoter sequence for high transcription levels from the antigenomic plasmid without incorporation of nontemplated G residues. The robustness of our T7opt-HhRbz system also allows for greater latitude in the ratios of transfected accessory plasmids used that result in successful rescue. Thus, our system may facilitate the rescue and interrogation of the increasing number of emerging paramyxoviruses. IMPORTANCE The ability to manipulate the genome of paramyxoviruses and evaluate the effects of these changes at the phenotypic level is a powerful tool for the investigation of specific aspects of the viral life cycle and viral pathogenesis. However, reverse genetics systems for paramyxoviruses are notoriously inefficient, when successful. The ability to efficiently and robustly rescue paramyxovirus reverse genetics systems can be used to answer basic questions about the biology of paramyxoviruses, as well as to facilitate the considerable translational efforts being devoted to developing live attenuated paramyxovirus vaccine vectors. PMID:28405630

Caught you: threats to confidentiality due to the public release of large-scale genetic data sets

PubMed Central

2010-01-01

Background Large-scale genetic data sets are frequently shared with other research groups and even released on the Internet to allow for secondary analysis. Study participants are usually not informed about such data sharing because data sets are assumed to be anonymous after stripping off personal identifiers. Discussion The assumption of anonymity of genetic data sets, however, is tenuous because genetic data are intrinsically self-identifying. Two types of re-identification are possible: the "Netflix" type and the "profiling" type. The "Netflix" type needs another small genetic data set, usually with less than 100 SNPs but including a personal identifier. This second data set might originate from another clinical examination, a study of leftover samples or forensic testing. When merged to the primary, unidentified set it will re-identify all samples of that individual. Even with no second data set at hand, a "profiling" strategy can be developed to extract as much information as possible from a sample collection. Starting with the identification of ethnic subgroups along with predictions of body characteristics and diseases, the asthma kids case as a real-life example is used to illustrate that approach. Summary Depending on the degree of supplemental information, there is a good chance that at least a few individuals can be identified from an anonymized data set. Any re-identification, however, may potentially harm study participants because it will release individual genetic disease risks to the public. PMID:21190545

Caught you: threats to confidentiality due to the public release of large-scale genetic data sets.

PubMed

Wjst, Matthias

2010-12-29

Large-scale genetic data sets are frequently shared with other research groups and even released on the Internet to allow for secondary analysis. Study participants are usually not informed about such data sharing because data sets are assumed to be anonymous after stripping off personal identifiers. The assumption of anonymity of genetic data sets, however, is tenuous because genetic data are intrinsically self-identifying. Two types of re-identification are possible: the "Netflix" type and the "profiling" type. The "Netflix" type needs another small genetic data set, usually with less than 100 SNPs but including a personal identifier. This second data set might originate from another clinical examination, a study of leftover samples or forensic testing. When merged to the primary, unidentified set it will re-identify all samples of that individual. Even with no second data set at hand, a "profiling" strategy can be developed to extract as much information as possible from a sample collection. Starting with the identification of ethnic subgroups along with predictions of body characteristics and diseases, the asthma kids case as a real-life example is used to illustrate that approach. Depending on the degree of supplemental information, there is a good chance that at least a few individuals can be identified from an anonymized data set. Any re-identification, however, may potentially harm study participants because it will release individual genetic disease risks to the public.

Genome-wide analysis highlights genetic dilution in Algerian sheep.

PubMed

Gaouar, S B S; Lafri, M; Djaout, A; El-Bouyahiaoui, R; Bouri, A; Bouchatal, A; Maftah, A; Ciani, E; Da Silva, A B

2017-03-01

Algeria represents a reservoir of genetic diversity with local sheep breeds adapted to a large range of environments and showing specific features necessary to deal with harsh conditions. This remarkable diversity results from the traditional management of dryland by pastoralists over centuries. Most of these breeds are poorly productive, and the economic pressure leads farmers to realize anarchic cross-breeding (that is, not carried out in the framework of selection plans) with the hope to increase animal's conformation. In this study, eight of the nine local Algerian sheep breeds (D'men, Hamra, Ouled-Djellal, Rembi, Sidaoun, Tazegzawt, Berber and Barbarine) were investigated for the first time by genome-wide single-nucleotide polymorphism genotyping. At an international scale, Algerian sheep occupied an original position shaped by relations with African and European (particularly Italian) breeds. The strong genetic proximity with Caribbean and Brazilian breeds confirmed that the genetic make-up of these American breeds was largely influenced by the Atlantic slave trade. At a national scale, an alarming genetic dilution of the Berber (a primitive breed) and the Rembi was observed, as a consequence of uncontrolled mating practices with Ouled-Djellal. A similar, though less pronounced, phenomenon was also detected for the Barbarine, another ancestral breed. Genetic originality appeared to be better preserved in Tazegzawt, Hamra, D'men and Sidaoun. These breeds should be given high priority in the establishment of conservation plans to halt their progressive loss. For Berber and Barbarine that also occur in the bordering neighbor countries, urgent concerted transnational actions are needed.

Towards reversible basic linear algebra subprograms: A performance study

DOE PAGES

Perumalla, Kalyan S.; Yoginath, Srikanth B.

2014-12-06

Problems such as fault tolerance and scalable synchronization can be efficiently solved using reversibility of applications. Making applications reversible by relying on computation rather than on memory is ideal for large scale parallel computing, especially for the next generation of supercomputers in which memory is expensive in terms of latency, energy, and price. In this direction, a case study is presented here in reversing a computational core, namely, Basic Linear Algebra Subprograms, which is widely used in scientific applications. A new Reversible BLAS (RBLAS) library interface has been designed, and a prototype has been implemented with two modes: (1) amore » memory-mode in which reversibility is obtained by checkpointing to memory in forward and restoring from memory in reverse, and (2) a computational-mode in which nothing is saved in the forward, but restoration is done entirely via inverse computation in reverse. The article is focused on detailed performance benchmarking to evaluate the runtime dynamics and performance effects, comparing reversible computation with checkpointing on both traditional CPU platforms and recent GPU accelerator platforms. For BLAS Level-1 subprograms, data indicates over an order of magnitude better speed of reversible computation compared to checkpointing. For BLAS Level-2 and Level-3, a more complex tradeoff is observed between reversible computation and checkpointing, depending on computational and memory complexities of the subprograms.« less

The walk is never random: subtle landscape effects shape gene flow in a continuous white-tailed deer population in the Midwestern United States

USGS Publications Warehouse

Robinson, Stacie J.; Samuel, Michael D.; Lopez, Davin L.; Shelton, Paul

2012-01-01

One of the pervasive challenges in landscape genetics is detecting gene flow patterns within continuous populations of highly mobile wildlife. Understanding population genetic structure within a continuous population can give insights into social structure, movement across the landscape and contact between populations, which influence ecological interactions, reproductive dynamics or pathogen transmission. We investigated the genetic structure of a large population of deer spanning the area of Wisconsin and Illinois, USA, affected by chronic wasting disease. We combined multiscale investigation, landscape genetic techniques and spatial statistical modelling to address the complex questions of landscape factors influencing population structure. We sampled over 2000 deer and used spatial autocorrelation and a spatial principal components analysis to describe the population genetic structure. We evaluated landscape effects on this pattern using a spatial autoregressive model within a model selection framework to test alternative hypotheses about gene flow. We found high levels of genetic connectivity, with gradients of variation across the large continuous population of white-tailed deer. At the fine scale, spatial clustering of related animals was correlated with the amount and arrangement of forested habitat. At the broader scale, impediments to dispersal were important to shaping genetic connectivity within the population. We found significant barrier effects of individual state and interstate highways and rivers. Our results offer an important understanding of deer biology and movement that will help inform the management of this species in an area where overabundance and disease spread are primary concerns.

Genetic Structures of Copy Number Variants Revealed by Genotyping Single Sperm

PubMed Central

Luo, Minjie; Cui, Xiangfeng; Fredman, David; Brookes, Anthony J.; Azaro, Marco A.; Greenawalt, Danielle M.; Hu, Guohong; Wang, Hui-Yun; Tereshchenko, Irina V.; Lin, Yong; Shentu, Yue; Gao, Richeng; Shen, Li; Li, Honghua

2009-01-01

Background Copy number variants (CNVs) occupy a significant portion of the human genome and may have important roles in meiotic recombination, human genome evolution and gene expression. Many genetic diseases may be underlain by CNVs. However, because of the presence of their multiple copies, variability in copy numbers and the diploidy of the human genome, detailed genetic structure of CNVs cannot be readily studied by available techniques. Methodology/Principal Findings Single sperm samples were used as the primary subjects for the study so that CNV haplotypes in the sperm donors could be studied individually. Forty-eight CNVs characterized in a previous study were analyzed using a microarray-based high-throughput genotyping method after multiplex amplification. Seventeen single nucleotide polymorphisms (SNPs) were also included as controls. Two single-base variants, either allelic or paralogous, could be discriminated for all markers. Microarray data were used to resolve SNP alleles and CNV haplotypes, to quantitatively assess the numbers and compositions of the paralogous segments in each CNV haplotype. Conclusions/Significance This is the first study of the genetic structure of CNVs on a large scale. Resulting information may help understand evolution of the human genome, gain insight into many genetic processes, and discriminate between CNVs and SNPs. The highly sensitive high-throughput experimental system with haploid sperm samples as subjects may be used to facilitate detailed large-scale CNV analysis. PMID:19384415

Vortex pairing and reverse cascade in a simulated two-dimensional rocket motor-like flow field

NASA Astrophysics Data System (ADS)

Chakravarthy, Kalyana; Chakraborty, Debasis

2017-07-01

Two-dimensional large eddy simulation of a flow experiment intended for studying and understanding transition and parietal vortex shedding has brought to light some interesting features that have never been seen in previous similar simulations and have implications for future computational work on combustion instabilities in rocket motors. The frequency spectrum of pressure at head end shows a peak at the expected value associated with parietal vortex shedding but an additional peak at half this frequency emerges at downstream location. Using vorticity spectra at various distances away from the wall, it is shown that the frequency halving is due to vortex pairing as hypothesized by Dunlap et al. ["Internal flow field studies in a simulated cylindrical port rocket chamber," J. Propul. Power 6(6), 690-704 (1990)] for a similar experiment. As the flow transitions to turbulence towards the nozzle end, inertial range with Kolmogorov scaling becomes evident in the velocity spectrum. Given that the simulation is two-dimensional, such a scaling could be associated with a reverse energy cascade as per Kraichnan-Leith-Bachelor theory. By filtering the simulated flow field and identifying where the energy backscatters into the filtered scales, the regions with a reverse cascade are identified. The implications of this finding on combustion modeling are discussed.

Genome-Wide Association Mapping Combined with Reverse Genetics Identifies New Effectors of Low Water Potential-Induced Proline Accumulation in Arabidopsis1[W][OPEN

PubMed Central

Verslues, Paul E.; Lasky, Jesse R.; Juenger, Thomas E.; Liu, Tzu-Wen; Kumar, M. Nagaraj

2014-01-01

Arabidopsis (Arabidopsis thaliana) exhibits natural genetic variation in drought response, including varying levels of proline (Pro) accumulation under low water potential. As Pro accumulation is potentially important for stress tolerance and cellular redox control, we conducted a genome-wide association (GWAS) study of low water potential-induced Pro accumulation using a panel of natural accessions and publicly available single-nucleotide polymorphism (SNP) data sets. Candidate genomic regions were prioritized for subsequent study using metrics considering both the strength and spatial clustering of the association signal. These analyses found many candidate regions likely containing gene(s) influencing Pro accumulation. Reverse genetic analysis of several candidates identified new Pro effector genes, including thioredoxins and several genes encoding Universal Stress Protein A domain proteins. These new Pro effector genes further link Pro accumulation to cellular redox and energy status. Additional new Pro effector genes found include the mitochondrial protease LON1, ribosomal protein RPL24A, protein phosphatase 2A subunit A3, a MADS box protein, and a nucleoside triphosphate hydrolase. Several of these new Pro effector genes were from regions with multiple SNPs, each having moderate association with Pro accumulation. This pattern supports the use of summary approaches that incorporate clusters of SNP associations in addition to consideration of individual SNP probability values. Further GWAS-guided reverse genetics promises to find additional effectors of Pro accumulation. The combination of GWAS and reverse genetics to efficiently identify new effector genes may be especially applicable for traits difficult to analyze by other genetic screening methods. PMID:24218491

Genetic Influences on the Development of Alcoholism

PubMed Central

Enoch, Mary-Anne

2014-01-01

Alcoholism has a substantial heritability yet the detection of specific genetic influences has largely proved elusive. The strongest findings are with genes encoding alcohol metabolizing enzymes. A few candidate genes such as GABRA2 have shown robust associations with alcoholism. Moreover, it has become apparent that variants in stress-related genes such as CRHR1, may only confer risk in individuals exposed to trauma, particularly in early life. Over the past decade there have been tremendous advances in large scale SNP genotyping technologies allowing for genome-wide associations studies (GWAS). As a result, it is now recognized that genetic risk for alcoholism is likely to be due to common variants in very many genes, each of small effect, although rare variants with large effects might also play a role. This has resulted in a paradigm shift away from gene centric studies towards analyses of gene interactions and gene networks within biologically relevant pathways. PMID:24091936

Genetic influences on the development of alcoholism.

PubMed

Enoch, Mary-Anne

2013-11-01

Alcoholism has a substantial heritability yet the detection of specific genetic influences has largely proved elusive. The strongest findings are with genes encoding alcohol metabolizing enzymes. A few candidate genes such as GABRA2 have shown robust associations with alcoholism. Moreover, it has become apparent that variants in stress-related genes such as CRHR1, may only confer risk in individuals exposed to trauma, particularly in early life. Over the past decade there have been tremendous advances in large scale SNP genotyping technologies allowing for genome-wide associations studies (GWAS). As a result, it is now recognized that genetic risk for alcoholism is likely to be due to common variants in very many genes, each of small effect, although rare variants with large effects might also play a role. This has resulted in a paradigm shift away from gene centric studies toward analyses of gene interactions and gene networks within biologically relevant pathways.

Gene targeting by TALEN-induced homologous recombination in goats directs production of β-lactoglobulin-free, high-human lactoferrin milk

PubMed Central

Cui, Chenchen; Song, Yujie; Liu, Jun; Ge, Hengtao; Li, Qian; Huang, Hui; Hu, Linyong; Zhu, Hongmei; Jin, Yaping; Zhang, Yong

2015-01-01

β-Lactoglobulin (BLG) is a major goat’s milk allergen that is absent in human milk. Engineered endonucleases, including transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases, enable targeted genetic modification in livestock. In this study, TALEN-mediated gene knockout followed by gene knock-in were used to generate BLG knockout goats as mammary gland bioreactors for large-scale production of human lactoferrin (hLF). We introduced precise genetic modifications in the goat genome at frequencies of approximately 13.6% and 6.09% for the first and second sequential targeting, respectively, by using targeting vectors that underwent TALEN-induced homologous recombination (HR). Analysis of milk from the cloned goats revealed large-scale hLF expression or/and decreased BLG levels in milk from heterozygous goats as well as the absence of BLG in milk from homozygous goats. Furthermore, the TALEN-mediated targeting events in somatic cells can be transmitted through the germline after SCNT. Our result suggests that gene targeting via TALEN-induced HR may expedite the production of genetically engineered livestock for agriculture and biomedicine. PMID:25994151

Gene targeting by TALEN-induced homologous recombination in goats directs production of β-lactoglobulin-free, high-human lactoferrin milk.

PubMed

Cui, Chenchen; Song, Yujie; Liu, Jun; Ge, Hengtao; Li, Qian; Huang, Hui; Hu, Linyong; Zhu, Hongmei; Jin, Yaping; Zhang, Yong

2015-05-21

β-Lactoglobulin (BLG) is a major goat's milk allergen that is absent in human milk. Engineered endonucleases, including transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases, enable targeted genetic modification in livestock. In this study, TALEN-mediated gene knockout followed by gene knock-in were used to generate BLG knockout goats as mammary gland bioreactors for large-scale production of human lactoferrin (hLF). We introduced precise genetic modifications in the goat genome at frequencies of approximately 13.6% and 6.09% for the first and second sequential targeting, respectively, by using targeting vectors that underwent TALEN-induced homologous recombination (HR). Analysis of milk from the cloned goats revealed large-scale hLF expression or/and decreased BLG levels in milk from heterozygous goats as well as the absence of BLG in milk from homozygous goats. Furthermore, the TALEN-mediated targeting events in somatic cells can be transmitted through the germline after SCNT. Our result suggests that gene targeting via TALEN-induced HR may expedite the production of genetically engineered livestock for agriculture and biomedicine.

Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells.

PubMed

Lokugamage, Nandadeva; Ikegami, Tetsuro

2017-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa which affects both ruminants and humans. RVF causes serious damage to the livestock industry and is also a threat to public health. The Rift Valley fever virus has a segmented negative-stranded RNA genome consisting of Large (L)-, Medium (M)-, and Small (S)-segments. The live-attenuated MP-12 vaccine is immunogenic in livestock and humans, and is conditionally licensed for veterinary use in the U.S. The MP-12 strain encodes 23 mutations (nine amino acid substitutions) and is attenuated through a combination of mutations in the L-, M-, and S-segments. Among them, the M-U795C, M-A3564G, and L-G3104A mutations contribute to viral attenuation through the L- and M-segments. The M-U795C, M-A3564G, L-U533C, and L-G3750A mutations are also independently responsible for temperature-sensitive (ts) phenotype. We hypothesized that a serial passage of the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP-12 vaccine and recombinant rMP12-ΔNSs16/198 were serially passaged 25 times. Droplet digital PCR analysis revealed that the reversion occurred at L-G3750A during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M-A3564G and L-U533C of rMP12-ΔNSs16/198 in Vero cells. Reversion mutations were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with encephalitis. This study characterized genetic stability of the MP-12 vaccine and the potential risk of reversion mutation at the L-G3750A ts mutation after excessive viral passages in culture cells.

Large-scale data integration framework provides a comprehensive view on glioblastoma multiforme.

PubMed

Ovaska, Kristian; Laakso, Marko; Haapa-Paananen, Saija; Louhimo, Riku; Chen, Ping; Aittomäki, Viljami; Valo, Erkka; Núñez-Fontarnau, Javier; Rantanen, Ville; Karinen, Sirkku; Nousiainen, Kari; Lahesmaa-Korpinen, Anna-Maria; Miettinen, Minna; Saarinen, Lilli; Kohonen, Pekka; Wu, Jianmin; Westermarck, Jukka; Hautaniemi, Sampsa

2010-09-07

Coordinated efforts to collect large-scale data sets provide a basis for systems level understanding of complex diseases. In order to translate these fragmented and heterogeneous data sets into knowledge and medical benefits, advanced computational methods for data analysis, integration and visualization are needed. We introduce a novel data integration framework, Anduril, for translating fragmented large-scale data into testable predictions. The Anduril framework allows rapid integration of heterogeneous data with state-of-the-art computational methods and existing knowledge in bio-databases. Anduril automatically generates thorough summary reports and a website that shows the most relevant features of each gene at a glance, allows sorting of data based on different parameters, and provides direct links to more detailed data on genes, transcripts or genomic regions. Anduril is open-source; all methods and documentation are freely available. We have integrated multidimensional molecular and clinical data from 338 subjects having glioblastoma multiforme, one of the deadliest and most poorly understood cancers, using Anduril. The central objective of our approach is to identify genetic loci and genes that have significant survival effect. Our results suggest several novel genetic alterations linked to glioblastoma multiforme progression and, more specifically, reveal Moesin as a novel glioblastoma multiforme-associated gene that has a strong survival effect and whose depletion in vitro significantly inhibited cell proliferation. All analysis results are available as a comprehensive website. Our results demonstrate that integrated analysis and visualization of multidimensional and heterogeneous data by Anduril enables drawing conclusions on functional consequences of large-scale molecular data. Many of the identified genetic loci and genes having significant survival effect have not been reported earlier in the context of glioblastoma multiforme. Thus, in addition to generally applicable novel methodology, our results provide several glioblastoma multiforme candidate genes for further studies.Anduril is available at http://csbi.ltdk.helsinki.fi/anduril/The glioblastoma multiforme analysis results are available at http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/

A 2-step penalized regression method for family-based next-generation sequencing association studies.

PubMed

Ding, Xiuhua; Su, Shaoyong; Nandakumar, Kannabiran; Wang, Xiaoling; Fardo, David W

2014-01-01

Large-scale genetic studies are often composed of related participants, and utilizing familial relationships can be cumbersome and computationally challenging. We present an approach to efficiently handle sequencing data from complex pedigrees that incorporates information from rare variants as well as common variants. Our method employs a 2-step procedure that sequentially regresses out correlation from familial relatedness and then uses the resulting phenotypic residuals in a penalized regression framework to test for associations with variants within genetic units. The operating characteristics of this approach are detailed using simulation data based on a large, multigenerational cohort.

Kernel methods for large-scale genomic data analysis

PubMed Central

Xing, Eric P.; Schaid, Daniel J.

2015-01-01

Machine learning, particularly kernel methods, has been demonstrated as a promising new tool to tackle the challenges imposed by today’s explosive data growth in genomics. They provide a practical and principled approach to learning how a large number of genetic variants are associated with complex phenotypes, to help reveal the complexity in the relationship between the genetic markers and the outcome of interest. In this review, we highlight the potential key role it will have in modern genomic data processing, especially with regard to integration with classical methods for gene prioritizing, prediction and data fusion. PMID:25053743

Biological safety concepts of genetically modified live bacterial vaccines.

PubMed

Frey, Joachim

2007-07-26

Live vaccines possess the advantage of having access to induce cell-mediated and antibody-mediated immunity; thus in certain cases they are able to prevent infection, and not only disease. Furthermore, live vaccines, particularly bacterial live vaccines, are relatively cheap to produce and easy to apply. Hence they are suitable to immunize large communities or herds. The induction of both cell-mediated immunity as well as antibody-mediated immunity, which is particularly beneficial in inducing mucosal immune responses, is obtained by the vaccine-strain's ability to colonize and multiply in the host without causing disease. For this reason, live vaccines require attenuation of virulence of the bacterium to which immunity must be induced. Traditionally attenuation was achieved simply by multiple passages of the microorganism on growth medium, in animals, eggs or cell cultures or by chemical or physical mutagenesis, which resulted in random mutations that lead to attenuation. In contrast, novel molecular methods enable the development of genetically modified organisms (GMOs) targeted to specific genes that are particularly suited to induce attenuation or to reduce undesirable effects in the tissue in which the vaccine strains can multiply and survive. Since live vaccine strains (attenuated by natural selection or genetic engineering) are potentially released into the environment by the vaccinees, safety issues concerning the medical as well as environmental aspects must be considered. These involve (i) changes in cell, tissue and host tropism, (ii) virulence of the carrier through the incorporation of foreign genes, (iii) reversion to virulence by acquisition of complementation genes, (iv) exchange of genetic information with other vaccine or wild-type strains of the carrier organism and (v) spread of undesired genes such as antibiotic resistance genes. Before live vaccines are applied, the safety issues must be thoroughly evaluated case-by-case. Safety assessment includes knowledge of the precise function and genetic location of the genes to be mutated, their genetic stability, potential reversion mechanisms, possible recombination events with dormant genes, gene transfer to other organisms as well as gene acquisition from other organisms by phage transduction, transposition or plasmid transfer and cis- or trans-complementation. For this, GMOs that are constructed with modern techniques of genetic engineering display a significant advantage over random mutagenesis derived live organisms. The selection of suitable GMO candidate strains can be made under in vitro conditions using basic knowledge on molecular mechanisms of pathogenicity of the corresponding bacterial species rather than by in vivo testing of large numbers of random mutants. This leads to a more targeted safety testing on volunteers and to a reduction in the use of animal experimentation.

Inherited XX sex reversal originating from wild medaka populations.

PubMed

Shinomiya, A; Otake, H; Hamaguchi, S; Sakaizumi, M

2010-11-01

The teleost fish, medaka (Oryzias latipes), has an XX/XY sex-determining mechanism. A Y-linked DM domain gene, DMY, has been isolated by positional cloning as the sex-determining gene in this species. Previously, we conducted a field survey of genotypic sex and found that approximately 1% of wild medaka are sex-reversed (XX males and XY females). Here, we performed genetic analyses of nine spontaneous XX sex-reversed males to elucidate its genetic basis. In all cases, the F(1) progeny were all females, whereas XX males reappeared in the backcross (BC) progeny, suggesting that XX sex reversal is a recessive trait. Although the incidences of sex reversal in the BC progeny were mostly low, 40% were males derived from one XX male. We performed linkage analysis using 55 BC males and located a single major factor, sda-1 (sex-determining autosomal factor-1), controlling sex reversal in an autosomal linkage group. Thus, genes involved in the sex-determining pathway can be isolated from spontaneous mutants in wild populations.

Evaluation of three herbicide resistance genes for use in genetic transformations and for potential crop protection in algae production.

PubMed

Brueggeman, Andrew J; Kuehler, Daniel; Weeks, Donald P

2014-09-01

Genes conferring resistance to the herbicides glyphosate, oxyfluorfen and norflurazon were developed and tested for use as dominant selectable markers in genetic transformation of Chlamydomonas reinhardtii and as potential tools for the protection of commercial-scale algal production facilities against contamination by organisms sensitive to these broad-spectrum herbicides. A synthetic glyphosate acetyltransferase (GAT) gene, when fitted with a strong Chlamydomonas promoter, conferred a 2.7×-fold increase in tolerance to the EPSPS inhibitor, glyphosate, in transgenic cells compared with progenitor WT cells. A mutant Chlamydomonas protoporphyrinogen oxidase (protox, PPO) gene previously shown to produce an enzyme insensitive to PPO-inhibiting herbicides, when genetically engineered, generated transgenic cells able to tolerate up to 136× higher levels of the PPO inhibitor, oxyfluorfen, than nontransformed cells. Genetic modification of the Chlamydomonas phytoene desaturase (PDS) gene-based gene sequences found in various norflurazon-resistant organisms allowed production of transgenic cells tolerant to 40× higher levels of norflurazon than nontransgenic cells. The high efficiency of all three herbicide resistance genes in producing transgenic cells demonstrated their suitability as dominant selectable markers for genetic transformation of Chlamydomonas and, potentially, other eukaryotic algae. However, the requirement for high concentrations of glyphosate and its associated negative effects on cell growth rates preclude its consideration for use in large-scale production facilities. In contrast, only low doses of norflurazon and oxyfluorfen (~1.5 μm and ~0.1 μm, respectively) are required for inhibition of cell growth, suggesting that these two herbicides may prove effective in large-scale algal production facilities in suppressing growth of organisms sensitive to these herbicides. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Predicting Hydrologic Function With Aquatic Gene Fragments

NASA Astrophysics Data System (ADS)

Good, S. P.; URycki, D. R.; Crump, B. C.

2018-03-01

Recent advances in microbiology techniques, such as genetic sequencing, allow for rapid and cost-effective collection of large quantities of genetic information carried within water samples. Here we posit that the unique composition of aquatic DNA material within a water sample contains relevant information about hydrologic function at multiple temporal scales. In this study, machine learning was used to develop discharge prediction models trained on the relative abundance of bacterial taxa classified into operational taxonomic units (OTUs) based on 16S rRNA gene sequences from six large arctic rivers. We term this approach "genohydrology," and show that OTU relative abundances can be used to predict river discharge at monthly and longer timescales. Based on a single DNA sample from each river, the average Nash-Sutcliffe efficiency (NSE) for predicted mean monthly discharge values throughout the year was 0.84, while the NSE for predicted discharge values across different return intervals was 0.67. These are considerable improvements over predictions based only on the area-scaled mean specific discharge of five similar rivers, which had average NSE values of 0.64 and -0.32 for seasonal and recurrence interval discharge values, respectively. The genohydrology approach demonstrates that genetic diversity within the aquatic microbiome is a large and underutilized data resource with benefits for prediction of hydrologic function.

Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology

PubMed Central

Brudey, Karine; Driscoll, Jeffrey R; Rigouts, Leen; Prodinger, Wolfgang M; Gori, Andrea; Al-Hajoj, Sahal A; Allix, Caroline; Aristimuño, Liselotte; Arora, Jyoti; Baumanis, Viesturs; Binder, Lothar; Cafrune, Patricia; Cataldi, Angel; Cheong, Soonfatt; Diel, Roland; Ellermeier, Christopher; Evans, Jason T; Fauville-Dufaux, Maryse; Ferdinand, Séverine; de Viedma, Dario Garcia; Garzelli, Carlo; Gazzola, Lidia; Gomes, Harrison M; Guttierez, M Cristina; Hawkey, Peter M; van Helden, Paul D; Kadival, Gurujaj V; Kreiswirth, Barry N; Kremer, Kristin; Kubin, Milan; Kulkarni, Savita P; Liens, Benjamin; Lillebaek, Troels; Ly, Ho Minh; Martin, Carlos; Martin, Christian; Mokrousov, Igor; Narvskaïa, Olga; Ngeow, Yun Fong; Naumann, Ludmilla; Niemann, Stefan; Parwati, Ida; Rahim, Zeaur; Rasolofo-Razanamparany, Voahangy; Rasolonavalona, Tiana; Rossetti, M Lucia; Rüsch-Gerdes, Sabine; Sajduda, Anna; Samper, Sofia; Shemyakin, Igor G; Singh, Urvashi B; Somoskovi, Akos; Skuce, Robin A; van Soolingen, Dick; Streicher, Elisabeth M; Suffys, Philip N; Tortoli, Enrico; Tracevska, Tatjana; Vincent, Véronique; Victor, Tommie C; Warren, Robin M; Yap, Sook Fan; Zaman, Khadiza; Portaels, Françoise; Rastogi, Nalin; Sola, Christophe

2006-01-01

Background The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. Results The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. Conclusion Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress. PMID:16519816

The Large-Scale Environment during the Tropical Cyclone Structure 2008 and THORPEX Pacific Asian Regional Campaign

DTIC Science & Technology

2009-03-01

earlier, Saji et al. (1999) stated that the changes in the state of the climate system associated with the seasonal monsoonal reversals are responsible...western North Pacific basin, in State of the Climate in 2008. To appear in Bull. Amer. Meteor. Soc., July 2009. Camargo, S. J., and A. H. Sobel

Cryptosporidium within-host genetic diversity: systematic bibliographical search and narrative overview.

PubMed

Grinberg, Alex; Widmer, Giovanni

2016-07-01

Knowledge of the within-host genetic diversity of a pathogen often has broad implications for disease management. Cryptosporidium protozoan parasites are among the most common causative agents of infectious diarrhoea. Current limitations of in vitro culture impose the use of uncultured isolates obtained directly from the hosts as operational units of Cryptosporidium genotyping. The validity of this practice is centred on the assumption of genetic homogeneity of the parasite within the host, and genetic studies often take little account of the within-host genetic diversity of Cryptosporidium. Yet, theory and experimental evidence contemplate genetic diversity of Cryptosporidium at the within-host scale, but this diversity is not easily identified by genotyping methods ill-suited for the resolution of DNA mixtures. We performed a systematic bibliographical search of the occurrence of within-host genetic diversity of Cryptosporidium parasites in epidemiological samples, between 2005 and 2015. Our results indicate that genetic diversity at the within-host scale, in the form of mixed species or intra-species diversity, has been identified in a large number (n=55) of epidemiological surveys of cryptosporidiosis in variable proportions, but has often been treated as a secondary finding and not analysed. As in malaria, there are indications that the scale of this diversity varies between geographical regions, perhaps depending on the prevailing transmission pathways. These results provide a significant knowledge base from which to draw alternative population genetic structure models, some of which are discussed in this paper. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Canal construction destroys the barrier between major European invasion lineages of the zebra mussel.

PubMed Central

Müller, Jakob C; Hidde, Dennis; Seitz, Alfred

2002-01-01

Since the mid-1980s the zebra mussel, Dreissena polymorpha, Pallas 1771, has become the protagonist of a spectacular freshwater invasion in North America due to its large economic and biological impact. Several genetic studies on American populations have failed to detect any large-scale geographical patterns. In western Europe, where D. polymorpha has been a classical invader from the Pontocaspian since the early 19th century, the situation is strikingly different. Here, we show with genetic markers that two major western European invasion lineages with lowered genetic variability within and among populations can be discriminated. These two invasion lineages correspond with two separate navigable waterways to western Europe. We found a rapid and asymmetrical genetic interchange of the two invasion lines after the construction of the Main-Danube canal in 1992, which interconnected the two waterways across the main watershed. PMID:12061957

Lassa Virus Reverse Genetics.

PubMed

Martínez-Sobrido, Luis; Paessler, Slobodan; de la Torre, Juan Carlos

2017-01-01

The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several hundred thousand people yearly in West Africa, resulting in high numbers of Lassa fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity and mortality. To date, no licensed vaccines are available to LASV infections, and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that is only partially effective. The development of reverse genetics has provided investigators with a novel and powerful approach for the investigation of the molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV minigenome (MG) systems has allowed examining the cis- and trans-acting factors involved in genome replication and gene transcription and the identification of novel drugable LASV targets. Likewise, it is now feasible to rescue infectious recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify antiviral drugs against LASV and the implementation of novel strategies to develop live-attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art experimental procedures for implementation of LASV reverse genetics. In addition, we will briefly discuss some significant translational research developments that have been made possible upon the development of LASV reverse genetics.

Reverse genetics in high throughput: rapid generation of complete negative strand RNA virus cDNA clones and recombinant viruses thereof.

PubMed

Nolden, T; Pfaff, F; Nemitz, S; Freuling, C M; Höper, D; Müller, T; Finke, Stefan

2016-04-05

Reverse genetics approaches are indispensable tools for proof of concepts in virus replication and pathogenesis. For negative strand RNA viruses (NSVs) the limited number of infectious cDNA clones represents a bottleneck as clones are often generated from cell culture adapted or attenuated viruses, with limited potential for pathogenesis research. We developed a system in which cDNA copies of complete NSV genomes were directly cloned into reverse genetics vectors by linear-to-linear RedE/T recombination. Rapid cloning of multiple rabies virus (RABV) full length genomes and identification of clones identical to field virus consensus sequence confirmed the approache's reliability. Recombinant viruses were recovered from field virus cDNA clones. Similar growth kinetics of parental and recombinant viruses, preservation of field virus characters in cell type specific replication and virulence in the mouse model were confirmed. Reduced titers after reporter gene insertion indicated that the low level of field virus replication is affected by gene insertions. The flexibility of the strategy was demonstrated by cloning multiple copies of an orthobunyavirus L genome segment. This important step in reverse genetics technology development opens novel avenues for the analysis of virus variability combined with phenotypical characterization of recombinant viruses at a clonal level.

Development of a PCR-Based Reverse Genetics System for an Attenuated Duck Tembusu Virus Strain

PubMed Central

Wu, Xiaogang; Shi, Ying; Yan, Dawei; Li, Xuesong; Yan, Pixi; Gao, Xuyuan; Zhang, Yuee; Yu, Lei; Ren, Chaochao; Li, Guoxin; Yan, Liping; Teng, Qiaoyang; Li, Zejun

2016-01-01

The infectious disease caused by the duck Tembusu virus (DTMUV) has resulted in massive economic losses to the Chinese duck industry in China since 2010. Research on the molecular basis of DTMUV pathogenicity has been hampered by the lack of a reliable reverse genetics system for this virus. Here we developed a PCR-based reverse genetics system with high fidelity for the attenuated DTMUV strain FX2010-180P. The rescued virus was characterized by using both indirect immunofluorescence assays (IFA) and whole genome sequencing. The rescued virus (rFX2010-180P) grew to similar titers as compared with the wild-type virus in DF-1 cells, and had similar replication and immunogenicity properties in ducks. To determine whether exogenous proteins could be expressed from DTMUV, both an internal ribosomal entry site (IRES) and the enhanced green fluorescent protein (eGFP) gene were introduced between the NS5 gene and the 3' non-coding sequence of FX2010-180P. A recombinant DTMUV expressing eGFP was rescued, but eGFP expression was unstable after 4 passages in DF-1 cells due to a deletion of 1,294 nucleotides. The establishment of a reliable reverse genetics system for FX2010-180P provides a foundation for future studies of DTMUV. PMID:27248497

Development of a PCR-Based Reverse Genetics System for an Attenuated Duck Tembusu Virus Strain.

PubMed

Wu, Xiaogang; Shi, Ying; Yan, Dawei; Li, Xuesong; Yan, Pixi; Gao, Xuyuan; Zhang, Yuee; Yu, Lei; Ren, Chaochao; Li, Guoxin; Yan, Liping; Teng, Qiaoyang; Li, Zejun

2016-01-01

The infectious disease caused by the duck Tembusu virus (DTMUV) has resulted in massive economic losses to the Chinese duck industry in China since 2010. Research on the molecular basis of DTMUV pathogenicity has been hampered by the lack of a reliable reverse genetics system for this virus. Here we developed a PCR-based reverse genetics system with high fidelity for the attenuated DTMUV strain FX2010-180P. The rescued virus was characterized by using both indirect immunofluorescence assays (IFA) and whole genome sequencing. The rescued virus (rFX2010-180P) grew to similar titers as compared with the wild-type virus in DF-1 cells, and had similar replication and immunogenicity properties in ducks. To determine whether exogenous proteins could be expressed from DTMUV, both an internal ribosomal entry site (IRES) and the enhanced green fluorescent protein (eGFP) gene were introduced between the NS5 gene and the 3' non-coding sequence of FX2010-180P. A recombinant DTMUV expressing eGFP was rescued, but eGFP expression was unstable after 4 passages in DF-1 cells due to a deletion of 1,294 nucleotides. The establishment of a reliable reverse genetics system for FX2010-180P provides a foundation for future studies of DTMUV.

Genetic screens for mutations affecting development of Xenopus tropicalis.

PubMed

Goda, Tadahiro; Abu-Daya, Anita; Carruthers, Samantha; Clark, Matthew D; Stemple, Derek L; Zimmerman, Lyle B

2006-06-01

We present here the results of forward and reverse genetic screens for chemically-induced mutations in Xenopus tropicalis. In our forward genetic screen, we have uncovered 77 candidate phenotypes in diverse organogenesis and differentiation processes. Using a gynogenetic screen design, which minimizes time and husbandry space expenditures, we find that if a phenotype is detected in the gynogenetic F2 of a given F1 female twice, it is highly likely to be a heritable abnormality (29/29 cases). We have also demonstrated the feasibility of reverse genetic approaches for obtaining carriers of mutations in specific genes, and have directly determined an induced mutation rate by sequencing specific exons from a mutagenized population. The Xenopus system, with its well-understood embryology, fate map, and gain-of-function approaches, can now be coupled with efficient loss-of-function genetic strategies for vertebrate functional genomics and developmental genetics.

Finite element analysis and genetic algorithm optimization design for the actuator placement on a large adaptive structure

NASA Astrophysics Data System (ADS)

Sheng, Lizeng

The dissertation focuses on one of the major research needs in the area of adaptive/intelligent/smart structures, the development and application of finite element analysis and genetic algorithms for optimal design of large-scale adaptive structures. We first review some basic concepts in finite element method and genetic algorithms, along with the research on smart structures. Then we propose a solution methodology for solving a critical problem in the design of a next generation of large-scale adaptive structures---optimal placements of a large number of actuators to control thermal deformations. After briefly reviewing the three most frequently used general approaches to derive a finite element formulation, the dissertation presents techniques associated with general shell finite element analysis using flat triangular laminated composite elements. The element used here has three nodes and eighteen degrees of freedom and is obtained by combining a triangular membrane element and a triangular plate bending element. The element includes the coupling effect between membrane deformation and bending deformation. The membrane element is derived from the linear strain triangular element using Cook's transformation. The discrete Kirchhoff triangular (DKT) element is used as the plate bending element. For completeness, a complete derivation of the DKT is presented. Geometrically nonlinear finite element formulation is derived for the analysis of adaptive structures under the combined thermal and electrical loads. Next, we solve the optimization problems of placing a large number of piezoelectric actuators to control thermal distortions in a large mirror in the presence of four different thermal loads. We then extend this to a multi-objective optimization problem of determining only one set of piezoelectric actuator locations that can be used to control the deformation in the same mirror under the action of any one of the four thermal loads. A series of genetic algorithms, GA Version 1, 2 and 3, were developed to find the optimal locations of piezoelectric actuators from the order of 1021 ˜ 1056 candidate placements. Introducing a variable population approach, we improve the flexibility of selection operation in genetic algorithms. Incorporating mutation and hill climbing into micro-genetic algorithms, we are able to develop a more efficient genetic algorithm. Through extensive numerical experiments, we find that the design search space for the optimal placements of a large number of actuators is highly multi-modal and that the most distinct nature of genetic algorithms is their robustness. They give results that are random but with only a slight variability. The genetic algorithms can be used to get adequate solution using a limited number of evaluations. To get the highest quality solution, multiple runs including different random seed generators are necessary. The investigation time can be significantly reduced using a very coarse grain parallel computing. Overall, the methodology of using finite element analysis and genetic algorithm optimization provides a robust solution approach for the challenging problem of optimal placements of a large number of actuators in the design of next generation of adaptive structures.

Genetic and pharmacological reactivation of the mammalian inactive X chromosome

PubMed Central

Bhatnagar, Sanchita; Zhu, Xiaochun; Ou, Jianhong; Lin, Ling; Chamberlain, Lynn; Zhu, Lihua J.; Wajapeyee, Narendra; Green, Michael R.

2014-01-01

X-chromosome inactivation (XCI), the random transcriptional silencing of one X chromosome in somatic cells of female mammals, is a mechanism that ensures equal expression of X-linked genes in both sexes. XCI is initiated in cis by the noncoding Xist RNA, which coats the inactive X chromosome (Xi) from which it is produced. However, trans-acting factors that mediate XCI remain largely unknown. Here, we perform a large-scale RNA interference screen to identify trans-acting XCI factors (XCIFs) that comprise regulators of cell signaling and transcription, including the DNA methyltransferase, DNMT1. The expression pattern of the XCIFs explains the selective onset of XCI following differentiation. The XCIFs function, at least in part, by promoting expression and/or localization of Xist to the Xi. Surprisingly, we find that DNMT1, which is generally a transcriptional repressor, is an activator of Xist transcription. Small-molecule inhibitors of two of the XCIFs can reversibly reactivate the Xi, which has implications for treatment of Rett syndrome and other dominant X-linked diseases. A homozygous mouse knockout of one of the XCIFs, stanniocalcin 1 (STC1), has an expected XCI defect but surprisingly is phenotypically normal. Remarkably, X-linked genes are not overexpressed in female Stc1−/− mice, revealing the existence of a mechanism(s) that can compensate for a persistent XCI deficiency to regulate X-linked gene expression. PMID:25136103

MetaRanker 2.0: a web server for prioritization of genetic variation data

PubMed Central

Pers, Tune H.; Dworzyński, Piotr; Thomas, Cecilia Engel; Lage, Kasper; Brunak, Søren

2013-01-01

MetaRanker 2.0 is a web server for prioritization of common and rare frequency genetic variation data. Based on heterogeneous data sets including genetic association data, protein–protein interactions, large-scale text-mining data, copy number variation data and gene expression experiments, MetaRanker 2.0 prioritizes the protein-coding part of the human genome to shortlist candidate genes for targeted follow-up studies. MetaRanker 2.0 is made freely available at www.cbs.dtu.dk/services/MetaRanker-2.0. PMID:23703204

MetaRanker 2.0: a web server for prioritization of genetic variation data.

PubMed

Pers, Tune H; Dworzyński, Piotr; Thomas, Cecilia Engel; Lage, Kasper; Brunak, Søren

2013-07-01

MetaRanker 2.0 is a web server for prioritization of common and rare frequency genetic variation data. Based on heterogeneous data sets including genetic association data, protein-protein interactions, large-scale text-mining data, copy number variation data and gene expression experiments, MetaRanker 2.0 prioritizes the protein-coding part of the human genome to shortlist candidate genes for targeted follow-up studies. MetaRanker 2.0 is made freely available at www.cbs.dtu.dk/services/MetaRanker-2.0.

Extreme antagonistic pleiotropy effects of DGAT1 on fat, milk and protein yields

USDA-ARS?s Scientific Manuscript database

A large-scale analysis using 294,079 first lactation Holstein cows, as well as a group of contemporary Holsteins and a Holstein line unselected since 1964, were used to study the genetic architecture associated with a mutation in the DGAT1 gene that has large effects on milk production. The ‘G’ alle...

Functional annotation of HOT regions in the human genome: implications for human disease and cancer

PubMed Central

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-01-01

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy. PMID:26113264

Functional annotation of HOT regions in the human genome: implications for human disease and cancer.

PubMed

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-06-26

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy.

Advances in Dyslexia Genetics-New Insights Into the Role of Brain Asymmetries.

PubMed

Paracchini, S; Diaz, R; Stein, J

2016-01-01

Dyslexia is a common condition affecting up to 10% school-aged children. There is strong evidence that genetics plays an important role in dyslexia and is expected to be complex in nature. Few specific susceptibility factors have been identified so far, but their functional characterization has provided novel insights into the biology of dyslexia. In particular, they point to an unexpected role of candidate genes for dyslexia in the biology of cilia, cellular organelles required in many processes including the establishment of left-right asymmetries early in development. This observation has brought back into the spotlight the old idea of a link between dyslexia and handedness. Yet much of the genetics contributing to dyslexia remains unexplained. The lack of biological markers, clear diagnostic criteria, and homogeneous assessment strategies are just some of the factors preventing the collection of the cohorts powered enough for large-scale genetic studies. While the technology and methods to generate and handle large-scale data have reached unprecedented potential, the main challenge remains in establishing universal guidelines to collect suitable phenotype information across independent studies. These difficulties reflect the complex nature of dyslexia which is highly heterogeneous and often co-occurs with other neurodevelopmental disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Converging evolution leads to near maximal junction diversity through parallel mechanisms in B and T cell receptors

NASA Astrophysics Data System (ADS)

Benichou, Jennifer I. C.; van Heijst, Jeroen W. J.; Glanville, Jacob; Louzoun, Yoram

2017-08-01

T and B cell receptor (TCR and BCR) complementarity determining region 3 (CDR3) genetic diversity is produced through multiple diversification and selection stages. Potential holes in the CDR3 repertoire were argued to be linked to immunodeficiencies and diseases. In contrast with BCRs, TCRs have practically no Dβ germline genetic diversity, and the question emerges as to whether they can produce a diverse CDR3 repertoire. In order to address the genetic diversity of the adaptive immune system, appropriate quantitative measures for diversity and large-scale sequencing are required. Such a diversity method should incorporate the complex diversification mechanisms of the adaptive immune response and the BCR and TCR loci structure. We combined large-scale sequencing and diversity measures to show that TCRs have a near maximal CDR3 genetic diversity. Specifically, TCR have a larger junctional and V germline diversity, which starts more 5‧ in Vβ than BCRs. Selection decreases the TCR repertoire diversity, but does not affect BCR repertoire. As a result, TCR is as diverse as BCR repertoire, with a biased CDR3 length toward short TCRs and long BCRs. These differences suggest parallel converging evolutionary tracks to reach the required diversity to avoid holes in the CDR3 repertoire.

Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.

PubMed

Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak

2013-01-08

Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.

Construction of a general human chromosome jumping library, with application to cystic fibrosis

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

Collins, F.S.; Drumm, M.L.; Cole, J.L.

1987-02-27

In many genetic disorders, the responsible gene and its protein product are unknown. The technique known as reverse genetics, in which chromosomal map positions and genetically linked DNA markers are used to identify and clone such genes, is complicated by the fact that the molecular distances from the closest DNA markers to the gene itself are often too large to traverse by standard cloning techniques. To address this situation, a general human chromosome jumping library was constructed that allows the cloning of DNA sequences approximately 100 kilobases away from any starting point in genomic DNA. As an illustration of itsmore » usefulness, this library was searched for a jumping clone, starting at the met oncogene, which is a marker tightly linked to the cystic fibrosis gene that is located on human chromosome 7. Mapping of the new genomic fragment by pulsed field gel electrophoresis confirmed that it resides on chromosome 7 within 240 kilobases downstream of the met gene. The use of chromosome jumping should be applicable to any genetic locus for which a closely linked DNA marker is available.« less

Genetically Predicted Body Mass Index and Alzheimer’s Disease Related Phenotypes in Three Large Samples: Mendelian Randomization Analyses

PubMed Central

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

2015-01-01

Observational research shows that higher body mass index (BMI) increases Alzheimer’s disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian Randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9,613 controls), the Health and Retirement Study (HRS: 8,403 participants with algorithm-predicted dementia status) and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3,177 AD cases and 7,277 controls). No evidence from individual SNPs or polygenic scores indicated BMI increased AD risk. Mendelian Randomization effect estimates per BMI point (95% confidence intervals) were: ADGC OR=0.95 (0.90, 1.01); HRS OR=1.00 (0.75, 1.32); GERAD1 OR=0.96 (0.87, 1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk. PMID:26079416

Breast and Prostate Cancer and Hormone-Related Gene Variant Study

Cancer.gov

The Breast and Prostate Cancer and Hormone-Related Gene Variant Study allows large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism.

Big Data Analytics for Genomic Medicine

PubMed Central

He, Karen Y.; Ge, Dongliang; He, Max M.

2017-01-01

Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients’ genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy. In this paper, we review the challenges of manipulating large-scale next-generation sequencing (NGS) data and diverse clinical data derived from the EHRs for genomic medicine. We introduce possible solutions for different challenges in manipulating, managing, and analyzing genomic and clinical data to implement genomic medicine. Additionally, we also present a practical Big Data toolset for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs. PMID:28212287

Big Data Analytics for Genomic Medicine.

PubMed

He, Karen Y; Ge, Dongliang; He, Max M

2017-02-15

Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients' genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy. In this paper, we review the challenges of manipulating large-scale next-generation sequencing (NGS) data and diverse clinical data derived from the EHRs for genomic medicine. We introduce possible solutions for different challenges in manipulating, managing, and analyzing genomic and clinical data to implement genomic medicine. Additionally, we also present a practical Big Data toolset for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs.

Genetics of migraine.

PubMed

Anttila, Verneri; Wessman, Maija; Kallela, Mikko; Palotie, Aarno

2018-01-01

Genetics of migraine has recently undergone a major shift, moving in the space of a few years from having only a few known genes for rare Mendelian forms to 47 known common variant loci affecting the susceptibility of the common forms of migraine. This has largely been achieved by rapidly increasing sample sizes for genomewide association studies (GWAS), soon to be followed by the first wave of large-scale exome-sequencing studies. The large number of detected loci, chief among them TRPM8, PRDM16, and LRP1, have enabled a number of in silico analyses, which have shed light on the functional and tissue-level aspects of the common risk variants for migraine, including evidence for involvement of both vascular and neuronal mechanisms. Polygenic risk scores and other measures of genetic variance based on GWAS information are further opening the door to dissecting pharmacogenetics, functional etiology, and comorbidity. Heritability-based analyses are demonstrating strong links between migraine and other neuropsychiatric disorders and brain phenotypes, highlighting genetic links between migraine and major depressive disorder and attention-deficit hyperactivity disorder, among others. These recent successes in migraine genetics are starting to be mature enough to provide robust evidence of specific quantifiable genetic factors in common migraine. Copyright © 2018 Elsevier B.V. All rights reserved.

Large-Scale Interaction Effects Reveal Missing Heritability in Schizophrenia, Bipolar Disorder and Posttraumatic Stress Disorder

DTIC Science & Technology

2017-04-11

polymorphisms (SNPs) reached genome-wide significance. In contrast, when SNPs were selected in groups ( containing up to thousands each) and the collective...the underlying genetic factors has been challen- ging because of high polygenicity, necessitating large sample sizes in meta-analyses.4 Possible ways...partners simultaneously considered beyond SNP pairs by using the regularized inference of high -dimensional interactions within large SNP groups. Over

Large-scale gene discovery in the pea aphid Acyrthosiphon pisum (Hemiptera)

PubMed Central

Sabater-Muñoz, Beatriz; Legeai, Fabrice; Rispe, Claude; Bonhomme, Joël; Dearden, Peter; Dossat, Carole; Duclert, Aymeric; Gauthier, Jean-Pierre; Ducray, Danièle Giblot; Hunter, Wayne; Dang, Phat; Kambhampati, Srini; Martinez-Torres, David; Cortes, Teresa; Moya, Andrès; Nakabachi, Atsushi; Philippe, Cathy; Prunier-Leterme, Nathalie; Rahbé, Yvan; Simon, Jean-Christophe; Stern, David L; Wincker, Patrick; Tagu, Denis

2006-01-01

Aphids are the leading pests in agricultural crops. A large-scale sequencing of 40,904 ESTs from the pea aphid Acyrthosiphon pisum was carried out to define a catalog of 12,082 unique transcripts. A strong AT bias was found, indicating a compositional shift between Drosophila melanogaster and A. pisum. An in silico profiling analysis characterized 135 transcripts specific to pea-aphid tissues (relating to bacteriocytes and parthenogenetic embryos). This project is the first to address the genetics of the Hemiptera and of a hemimetabolous insect. PMID:16542494

Genetics of coronary artery disease: discovery, biology and clinical translation

PubMed Central

Khera, Amit V.; Kathiresan, Sekar

2018-01-01

Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked about 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forward, genetic testing could enable precision medicine approaches, by identifying subgroups of patients at increased risk of CAD or those with a specific driving pathophysiology in whom a therapeutic or preventive approach is most useful. PMID:28286336

Discovery and mapping of a new expressed sequence tag-single nucleotide polymorphism and simple sequence repeat panel for large-scale genetic studies and breeding of Theobroma cacao L.

PubMed Central

Allegre, Mathilde; Argout, Xavier; Boccara, Michel; Fouet, Olivier; Roguet, Yolande; Bérard, Aurélie; Thévenin, Jean Marc; Chauveau, Aurélie; Rivallan, Ronan; Clement, Didier; Courtois, Brigitte; Gramacho, Karina; Boland-Augé, Anne; Tahi, Mathias; Umaharan, Pathmanathan; Brunel, Dominique; Lanaud, Claire

2012-01-01

Theobroma cacao is an economically important tree of several tropical countries. Its genetic improvement is essential to provide protection against major diseases and improve chocolate quality. We discovered and mapped new expressed sequence tag-single nucleotide polymorphism (EST-SNP) and simple sequence repeat (SSR) markers and constructed a high-density genetic map. By screening 149 650 ESTs, 5246 SNPs were detected in silico, of which 1536 corresponded to genes with a putative function, while 851 had a clear polymorphic pattern across a collection of genetic resources. In addition, 409 new SSR markers were detected on the Criollo genome. Lastly, 681 new EST-SNPs and 163 new SSRs were added to the pre-existing 418 co-dominant markers to construct a large consensus genetic map. This high-density map and the set of new genetic markers identified in this study are a milestone in cocoa genomics and for marker-assisted breeding. The data are available at http://tropgenedb.cirad.fr. PMID:22210604

Reversing flow causes passive shark scale actuation in a separating turbulent boundary layer

NASA Astrophysics Data System (ADS)

Lang, Amy; Gemmell, Bradford; Motta, Phil; Habegger, Laura; Du Clos, Kevin; Devey, Sean; Stanley, Caleb; Santos, Leo

2017-11-01

Control of flow separation by shortfin mako skin in experiments has been demonstrated, but the mechanism is still poorly understood yet must be to some extent Re independent. The hypothesized mechanisms inherent in the shark skin for controlling flow separation are: (1) the scales, which are capable of being bristled only by reversing flow, inhibit flow reversal events from further development into larger-scale separation and (2) the cavities formed when scales bristle induces mixing of high momentum flow towards the wall thus energizing the flow close to the surface. Two studies were carried out to measure passive scale actuation caused by reversing flow. A small flow channel induced an unsteady, wake flow over the scales prompting reversing flow events and scale actuation. To resolve the flow and scale movements simultaneously we used specialized optics at high magnification (1 mm field of view) at 50,000 fps. In another study, 3D printed models of shark scales, or microflaps (bristling capability up to 50 degrees), were set into a flat plate. Using a tripped, turbulent boundary layer grown over the long flat plate and a localized adverse pressure gradient, a separation bubble was generated within which the microflaps were placed. Passive flow actuation of both shark scales and microflaps by reversing flow was observed. Funding from Army Research Office and NSF REU site Grant.

Population Explosion in the Yellow-Spined Bamboo Locust Ceracris kiangsu and Inferences for the Impact of Human Activity

PubMed Central

Fan, Zhou; Jiang, Guo-Fang; Liu, Yu-Xiang; He, Qi-Xin; Blanchard, Benjamin

2014-01-01

Geographic distance and geographical barriers likely play a considerable role in structuring genetic variation in species, although some migratory species may have less phylogeographic structure on a smaller spatial scale. Here, genetic diversity and the phylogenetic structure among geographical populations of the yellow-spined bamboo locust, Ceracris kiangsu, were examined with 16S rDNA and amplified fragment length polymorphisms (AFLPs). In this study, no conspicuous phylogeographical structure was discovered from either Maximum parsimony (MP) and Neighbor-joining (NJ) phylogenetic analyses. The effect of geographical isolation was not conspicuous on a large spatial scale.At smaller spatial scales local diversity of some populations within mountainous areas were detected using Nei's genetic distance and AMOVA. There is a high level of genetic diversity and a low genetic differentiation among populations in the C. kiangsu of South and Southeast China. Our analyses indicate that C. kiangsu is a monophyletic group. Our results also support the hypothesis that the C. kiangsu population is in a primary differentiation stage. Given the mismatch distribution, it is likely that a population expansion in C. kiangsu occurred about 0.242 Ma during the Quaternary interglaciation. Based on historical reports, we conjecture that human activities had significant impacts on the C. kiangsu gene flow. PMID:24603526

Reverse Genetics of Newcastle Disease Virus.

PubMed

Cardenas-Garcia, Stivalis; Afonso, Claudio L

2017-01-01

Reverse genetics allows for the generation of recombinant viruses or vectors used in functional studies, vaccine development, and gene therapy. This technique enables genetic manipulation and cloning of viral genomes, gene mutation through site-directed mutagenesis, along with gene insertion or deletion, among other studies. An in vitro infection-based system including the highly attenuated vaccinia virus Ankara strain expressing the T7 RNA polymerase from bacteriophage T7, with co-transfection of three helper plasmids and a full-length cDNA plasmid, was successfully developed to rescue genetically modified Newcastle disease viruses in 1999. In this chapter, the materials and the methods involved in rescuing Newcastle disease virus (NDV) from cDNA, utilizing site-directed mutagenesis and gene replacement techniques, are described in detail.

Characterization of Arabidopsis thaliana mismatch specific endonucleases: application to mutation discovery by TILLING in pea.

PubMed

Triques, Karine; Sturbois, Bénédicte; Gallais, Stéphane; Dalmais, Marion; Chauvin, Stéphanie; Clepet, Christian; Aubourg, Sébastien; Rameau, Catherine; Caboche, Michel; Bendahmane, Abdelhafid

2007-09-01

Scanning DNA sequences for mutations and polymorphisms has become one of the most challenging, often expensive and time-consuming obstacles in many molecular genetic applications, including reverse genetic and clinical diagnostic applications. Enzymatic mutation detection methods are based on the cleavage of heteroduplex DNA at the mismatch sites. These methods are often limited by the availability of a mismatch-specific endonuclease, their sensitivity in detecting one allele in a pool of DNA and their costs. Here, we present detailed biochemical analysis of five Arabidopsis putative mismatch-specific endonucleases. One of them, ENDO1, is presented as the first endonuclease that recognizes and cleaves all types of mismatches with high efficiency. We report on a very simple protocol for the expression and purification of ENDO1. The ENDO1 system could be exploited in a wide range of mutation diagnostic tools. In particular, we report the use of ENDO1 for discovery of point mutations in the gibberellin 3beta-hydrolase gene of Pisum sativum. Twenty-one independent mutants were isolated, five of these were characterized and two new mutations affecting internodes length were identified. To further evaluate the quality of the mutant population we screened for mutations in four other genes and identified 5-21 new alleles per target. Based on the frequency of the obtained alleles we concluded that the pea population described here would be suitable for use in a large reverse-genetics project.

Differentially expressed genes during the imbibition of dormant and after-ripened seeds - a reverse genetics approach.

PubMed

Yazdanpanah, Farzaneh; Hanson, Johannes; Hilhorst, Henk W M; Bentsink, Leónie

2017-09-11

Seed dormancy, defined as the incapability of a viable seed to germinate under favourable conditions, is an important trait in nature and agriculture. Despite extensive research on dormancy and germination, many questions about the molecular mechanisms controlling these traits remain unanswered, likely due to its genetic complexity and the large environmental effects which are characteristic of these quantitative traits. To boost research towards revealing mechanisms in the control of seed dormancy and germination we depend on the identification of genes controlling those traits. We used transcriptome analysis combined with a reverse genetics approach to identify genes that are prominent for dormancy maintenance and germination in imbibed seeds of Arabidopsis thaliana. Comparative transcriptomics analysis was employed on freshly harvested (dormant) and after-ripened (AR; non-dormant) 24-h imbibed seeds of four different DELAY OF GERMINATION near isogenic lines (DOGNILs) and the Landsberg erecta (Ler) wild type with varying levels of primary dormancy. T-DNA knock-out lines of the identified genes were phenotypically investigated for their effect on dormancy and AR. We identified conserved sets of 46 and 25 genes which displayed higher expression in seeds of all dormant and all after-ripened DOGNILs and Ler, respectively. Knock-out mutants in these genes showed dormancy and germination related phenotypes. Most of the identified genes had not been implicated in seed dormancy or germination. This research will be useful to further decipher the molecular mechanisms by which these important ecological and commercial traits are regulated.

A genetically stable rooting protocol for propagating a threatened medicinal plant—Celastrus paniculatus

PubMed Central

Phulwaria, Mahendra; Rai, Manoj K.; Patel, Ashok Kumar; Kataria, Vinod; Shekhawat, N. S.

2012-01-01

Celastrus paniculatus, belonging to the family Celastraceae, is an important medicinal plant of India. Owing to the ever-increasing demand from the pharmaceutical industry, the species is being overexploited, thereby threatening its stock in the wild. Poor seed viability coupled with low germination restricts its propagation through sexual means. Thus, alternative approaches such as in vitro techniques are highly desirable for large-scale propagation of this medicinally important plant. Nodal segments, obtained from a 12-year-old mature plant, were used as explants for multiple shoot induction. Shoot multiplication was achieved by repeated transfer of mother explants and subculturing of in vitro produced shoot clumps on Murashige and Skoog's (MS) medium supplemented with various concentrations of 6-benzylaminopurine (BAP) alone or in combination with auxin (indole-3-acetic acid (IAA) or α-naphthalene acetic acid (NAA)). The maximum number of shoots (47.75 ± 2.58) was observed on MS medium supplemented with BAP (0.5 mg L−1) and IAA (0.1 mg L−1). In vitro raised shoots were rooted under ex vitro conditions after treating them with indole-3-butyric acid (300 mg L−1) for 3 min. Over 95 % of plantlets acclimatized successfully. The genetic fidelity of the regenerated plants was assessed using random amplified polymorphic DNA. No polymorphism was detected in regenerated plants and the mother plant, revealing the genetic fidelity of the in vitro raised plantlets. The protocol discussed could be effectively employed for large-scale multiplication of C. paniculatus. Its commercial application could be realized for the large-scale multiplication and supply to the State Forest Department.

Sensitivity of Female Inbreds of Cucumis sativus to Sex Reversion by Gibberellin.

PubMed

Shifriss, O; George, W L

1964-03-27

Two female inbred cucumbers were developed by substituting gene Acr for acr in the genetic backgrounds of the monoecious races Marketer and Tokyo, which exhibit weak and strong male tendency respectively. Marketer females are resistant and Tokyo females are sensitive to sex reversion in response to treatments with gibberellin A(3). Resistance and sensitivity of this type appear to depend upon the genetic system which controls sex tendency.

Reverse Genetics for Newcastle Disease Virus as a Vaccine Vector.

PubMed

Kim, Shin-Hee; Samal, Siba K

2018-02-22

Newcastle disease virus (NDV) is an economically important pathogen in the poultry industry worldwide. Recovery of infectious NDV from cDNA using reverse genetics has made it possible to manipulate the genome of NDV. This has greatly contributed to our understanding of the molecular biology and pathogenesis of NDV. Furthermore, NDV has modular genome and accommodates insertion of a foreign gene as a transcriptional unit, thus enabling NDV as a vaccine vector against diseases of humans and animals. Avirulent NDV strains (e.g., LaSota and B1) have been commonly used as vaccine vectors. In this protocol, we have described reverse genetics of NDV to be used as a vaccine vector by exemplifying the recovery of NDV vectored avian influenza virus vaccine. Specifically, cloning and recovery of NDV expressing the hemagglutinin protein of highly pathogenic influenza virus were explained. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Continental-level population differentiation and environmental adaptation in the mushroom Suillus brevipes

PubMed Central

Branco, Sara; Bi, Ke; Liao, Hui-Ling; Gladieux, Pierre; Badouin, Hélène; Ellison, Christopher E.; Nguyen, Nhu H.; Vilgalys, Rytas; Peay, Kabir G.; Taylor, John W.; Bruns, Thomas D.

2016-01-01

Recent advancements in sequencing technology allowed researchers to better address the patterns and mechanisms involved in microbial environmental adaptation at large spatial scales. Here we investigated the genomic basis of adaptation to climate at the continental scale in Suillus brevipes, an ectomycorrhizal fungus symbiotically associated with the roots of pine trees. We used genomic data from 55 individuals in seven locations across North America to perform genome scans to detect signatures of positive selection and assess whether temperature and precipitation were associated with genetic differentiation. We found that S. brevipes exhibited overall strong population differentiation, with potential admixture in Canadian populations. This species also displayed genomic signatures of positive selection as well as genomic sites significantly associated with distinct climatic regimes and abiotic environmental parameters. These genomic regions included genes involved in transmembrane transport of substances and helicase activity potentially involved in cold stress response. Our study sheds light on large-scale environmental adaptation in fungi by identifying putative adaptive genes and providing a framework to further investigate the genetic basis of fungal adaptation. PMID:27761941

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens.

PubMed

Pan, Joshua; Meyers, Robin M; Michel, Brittany C; Mashtalir, Nazar; Sizemore, Ann E; Wells, Jonathan N; Cassel, Seth H; Vazquez, Francisca; Weir, Barbara A; Hahn, William C; Marsh, Joseph A; Tsherniak, Aviad; Kadoch, Cigall

2018-05-23

Protein complexes are assemblies of subunits that have co-evolved to execute one or many coordinated functions in the cellular environment. Functional annotation of mammalian protein complexes is critical to understanding biological processes, as well as disease mechanisms. Here, we used genetic co-essentiality derived from genome-scale RNAi- and CRISPR-Cas9-based fitness screens performed across hundreds of human cancer cell lines to assign measures of functional similarity. From these measures, we systematically built and characterized functional similarity networks that recapitulate known structural and functional features of well-studied protein complexes and resolve novel functional modules within complexes lacking structural resolution, such as the mammalian SWI/SNF complex. Finally, by integrating functional networks with large protein-protein interaction networks, we discovered novel protein complexes involving recently evolved genes of unknown function. Taken together, these findings demonstrate the utility of genetic perturbation screens alone, and in combination with large-scale biophysical data, to enhance our understanding of mammalian protein complexes in normal and disease states. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Time scales of supercooled water and implications for reversible polyamorphism

NASA Astrophysics Data System (ADS)

Limmer, David T.; Chandler, David

2015-09-01

Deeply supercooled water exhibits complex dynamics with large density fluctuations, ice coarsening and characteristic time scales extending from picoseconds to milliseconds. Here, we discuss implications of these time scales as they pertain to two-phase coexistence and to molecular simulations of supercooled water. Specifically, we argue that it is possible to discount liquid-liquid criticality because the time scales imply that correlation lengths for such behaviour would be bounded by no more than a few nanometres. Similarly, it is possible to discount two-liquid coexistence because the time scales imply a bounded interfacial free energy that cannot grow in proportion to a macroscopic surface area. From time scales alone, therefore, we see that coexisting domains of differing density in supercooled water can be no more than nanoscale transient fluctuations.

XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing.

PubMed

Piton, Amélie; Redin, Claire; Mandel, Jean-Louis

2013-08-08

Because of the unbalanced sex ratio (1.3-1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past. Such information is now available thanks to large-scale sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project, which provides variation information on 10,563 X chromosomes from the general population. We used this NHLBI cohort to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. We particularly question the implication in XLID of ten of them (AGTR2, MAGT1, ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which truncating variants or previously published mutations are observed at a relatively high frequency within this cohort. We also highlight 15 other genes (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3, RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted. We propose that similar reassessment of reported mutations (and genes) with the use of data from large-scale human exome sequencing would be relevant for a wide range of other genetic diseases. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Complex spatial dynamics maintain northern leopard frog (Lithobates pipiens) genetic diversity in a temporally varying landscape

USGS Publications Warehouse

Mushet, David M.; Euliss, Ned H.; Chen, Yongjiu; Stockwell, Craig A.

2013-01-01

In contrast to most local amphibian populations, northeastern populations of the Northern Leopard Frog (Lithobates pipiens) have displayed uncharacteristically high levels of genetic diversity that have been attributed to large, stable populations. However, this widely distributed species also occurs in areas known for great climatic fluctuations that should be reflected in corresponding fluctuations in population sizes and reduced genetic diversity. To test our hypothesis that Northern Leopard Frog genetic diversity would be reduced in areas subjected to significant climate variability, we examined the genetic diversity of L. pipiens collected from 12 sites within the Prairie Pothole Region of North Dakota. Despite the region's fluctuating climate that includes periods of recurring drought and deluge, we found unexpectedly high levels of genetic diversity approaching that of northeastern populations. Further, genetic structure at a landscape scale was strikingly homogeneous; genetic differentiation estimates (Dest) averaged 0.10 (SD = 0.036) across the six microsatellite loci we studied, and two Bayesian assignment tests (STRUCTURE and BAPS) failed to reveal the development of significant population structure across the 68 km breadth of our study area. These results suggest that L. pipiens in the Prairie Pothole Region consists of a large, panmictic population capable of maintaining high genetic diversity in the face of marked climate variability.

Isolation by environment in the highly mobile olive ridley turtle (Lepidochelys olivacea) in the eastern Pacific.

PubMed

Rodríguez-Zárate, Clara J; Sandoval-Castillo, Jonathan; van Sebille, Erik; Keane, Robert G; Rocha-Olivares, Axayácatl; Urteaga, Jose; Beheregaray, Luciano B

2018-05-16

Spatial and temporal scales at which processes modulate genetic diversity over the landscape are usually overlooked, impacting the design of conservation management practices for widely distributed species. We examine processes shaping population divergence in highly mobile species by re-assessing the case of panmixia in the iconic olive ridley turtle from the eastern Pacific. We implemented a biophysical model of connectivity and a seascape genetic analysis based on nuclear DNA variation of 634 samples collected from 27 nesting areas. Two genetically distinct populations largely isolated during reproductive migrations and mating were detected, each composed of multiple nesting sites linked by high connectivity. This pattern was strongly associated with a steep environmental gradient and also influenced by ocean currents. These findings relate to meso-scale features of a dynamic oceanographic interface in the eastern tropical Pacific (ETP) region, a scenario that possibly provides different cost-benefit solutions and selective pressures for sea turtles during both the mating and migration periods. We reject panmixia and propose a new paradigm for olive ridley turtles where reproductive isolation due to assortative mating is linked to its environment. Our study demonstrates the relevance of integrative approaches for assessing the role of environmental gradients and oceanographic currents as drivers of genetic differentiation in widely distributed marine species. This is relevant for the conservation management of species of highly mobile behaviour, and assists the planning and development of large-scale conservation strategies for the threatened olive ridley turtles in the ETP. © 2018 The Author(s).

Multi-Genetic Marker Approach and Spatio-Temporal Analysis Suggest There Is a Single Panmictic Population of Swordfish Xiphias gladius in the Indian Ocean

PubMed Central

Muths, Delphine; Le Couls, Sarah; Evano, Hugues; Grewe, Peter; Bourjea, Jerome

2013-01-01

Genetic population structure of swordfish Xiphias gladius was examined based on 2231 individual samples, collected mainly between 2009 and 2010, among three major sampling areas within the Indian Ocean (IO; twelve distinct sites), Atlantic (two sites) and Pacific (one site) Oceans using analysis of nineteen microsatellite loci (n = 2146) and mitochondrial ND2 sequences (n = 2001) data. Sample collection was stratified in time and space in order to investigate the stability of the genetic structure observed with a special focus on the South West Indian Ocean. Significant AMOVA variance was observed for both markers indicating genetic population subdivision was present between oceans. Overall value of F-statistics for ND2 sequences confirmed that Atlantic and Indian Oceans swordfish represent two distinct genetic stocks. Indo-Pacific differentiation was also significant but lower than that observed between Atlantic and Indian Oceans. However, microsatellite F-statistics failed to reveal structure even at the inter-oceanic scale, indicating that resolving power of our microsatellite loci was insufficient for detecting population subdivision. At the scale of the Indian Ocean, results obtained from both markers are consistent with swordfish belonging to a single unique panmictic population. Analyses partitioned by sampling area, season, or sex also failed to identify any clear structure within this ocean. Such large spatial and temporal homogeneity of genetic structure, observed for such a large highly mobile pelagic species, suggests as satisfactory to consider swordfish as a single panmictic population in the Indian Ocean. PMID:23717447

Genetic variation in the prostaglandin E2 pathway is associated with primary graft dysfunction.

PubMed

Diamond, Joshua M; Akimova, Tatiana; Kazi, Altaf; Shah, Rupal J; Cantu, Edward; Feng, Rui; Levine, Matthew H; Kawut, Steven M; Meyer, Nuala J; Lee, James C; Hancock, Wayne W; Aplenc, Richard; Ware, Lorraine B; Palmer, Scott M; Bhorade, Sangeeta; Lama, Vibha N; Weinacker, Ann; Orens, Jonathan; Wille, Keith; Crespo, Maria; Lederer, David J; Arcasoy, Selim; Demissie, Ejigayehu; Christie, Jason D

2014-03-01

Biologic pathways with significant genetic conservation across human populations have been implicated in the pathogenesis of primary graft dysfunction (PGD). The evaluation of the role of recipient genetic variation in PGD has thus far been limited to single, candidate gene analyses. We sought to identify genetic variants in lung transplant recipients that are responsible for increased risk of PGD using a two-phase large-scale genotyping approach. Phase 1 was a large-scale candidate gene association study of the multicenter, prospective Lung Transplant Outcomes Group cohort. Phase 2 included functional evaluation of selected variants and a bioinformatics screening of variants identified in phase 1. After genetic data quality control, 680 lung transplant recipients were included in the analysis. In phase 1, a total of 17 variants were significantly associated with PGD, four of which were in the prostaglandin E2 family of genes. Among these were a coding variant in the gene encoding prostaglandin E2 synthase (PTGES2; P = 9.3 × 10(-5)) resulting in an arginine to histidine substitution at amino acid position 298, and three variants in a block containing the 5' promoter and first intron of the PTGER4 gene (encoding prostaglandin E2 receptor subtype 4; all P < 5 × 10(-5)). Functional evaluation in regulatory T cells identified that rs4434423A in the PTGER4 gene was associated with differential suppressive function of regulatory T cells. Further research aimed at replication and additional functional insight into the role played by genetic variation in prostaglandin E2 synthetic and signaling pathways in PGD is warranted.

Genetic effects of a large-scale Spartina alterniflora (smooth cordgrass) dieback and recovery in the northern Gulf of Mexico

USGS Publications Warehouse

Edwards, K.R.; Travis, S.E.; Proffitt, C.E.

2005-01-01

A large-scale dieback event struck marshes along the northwestern Gulf of Mexico coast during summer 2000, in apparent response to a prolonged and severe drought. Along the Louisiana coast, large areas of the dominant marsh species, Spartina alterniflora, turned brown, followed by death of at least the aboveground structures or entire plant mortality. Key ecological and genetic measures were studied in a dieback-affected marsh in southwest Louisiana (C83 marsh, Sabine National Wildlife Refuge), for which existed predieback ecologic and genetic datasets. Effects on genetic diversity only were studied in a second set of sites in southeastern Louisiana (near Bay Junop), where the dieback was more widespread. We hypothesized that stem density, live aboveground biomass, and genetic diversity would be significantly reduced compared to predieback conditions and to nearby unaffected marshes. Stem densities and biomass levels approached predieback conditions 14 months after first observance of the dieback in the Sabine marsh and were similar to or exceeded the same measures for a nearby unaffected marsh. DNA extracted from leaf samples in the Sabine and Bay Junop sites was used to construct genotype profiles using AFLPs and analyzed using the complement of Simpson's Index (1-D), the richness measure G/N, average heterozygosity ???H???, and the estimated proportion of polymorphic genes ???P???. Genetic diversity was relatively unaffected by the dieback at either the Sabine or Bay Junop sites. Evidence from field observations and the results of the genetic analyses suggest that seedling recruitment is an important factor in the recovery of both the Bay Junop and C83 sites, although re-growth from surviving below-ground rhizomes appeared to dominate recovery at the latter site. Survival of below-ground structures, leading to the rapid recovery observed, indicates a high level of resilience of the Sabine marsh to drought-induced stress. Still, the genetic diversity of S. alterniflora- dominated marshes may be promoted by occasional disturbance events, which produce open areas in which seedling recruitment can occur. ?? 2005 Estuarine Research Federation.

Quantitative measures of sexual selection reveal no evidence for sex-role reversal in a sea spider with prolonged paternal care.

PubMed

Barreto, Felipe S; Avise, John C

2010-10-07

Taxa in which males alone invest in postzygotic care of offspring are often considered good models for investigating the proffered relationships between sexual selection and mating systems. In the pycnogonid sea spider Pycnogonum stearnsi, males carry large egg masses on their bodies for several weeks, so this species is a plausible candidate for sex-role reversal (greater intensity of sexual selection on females than on males). Here, we couple a microsatellite-based assessment of the mating system in a natural population with formal quantitative measures of genetic fitness to investigate the direction of sexual selection in P. stearnsi. Both sexes proved to be highly polygamous and showed similar standardized variances in reproductive and mating successes. Moreover, the fertility (number of progeny) of males and females appeared to be equally and highly dependent on mate access, as shown by similar Bateman gradients for the two sexes. The absence of sex-role reversal in this population of P. stearnsi is probably attributable to the fact that males are not limited by brooding space but have evolved an ability to carry large numbers of progeny. Body length was not a good predictor of male mating or reproductive success, so the aim of future studies should be to determine what traits are the targets of sexual selection in this species.

Reversible Redox Chemistry of Azo Compounds for Sodium-Ion Batteries.

PubMed

Luo, Chao; Xu, Gui-Liang; Ji, Xiao; Hou, Singyuk; Chen, Long; Wang, Fei; Jiang, Jianjun; Chen, Zonghai; Ren, Yang; Amine, Khalil; Wang, Chunsheng

2018-03-05

Sustainable sodium-ion batteries (SSIBs) using renewable organic electrodes are promising alternatives to lithium-ion batteries for the large-scale renewable energy storage. However, the lack of high-performance anode material impedes the development of SSIBs. Herein, we report a new type of organic anode material based on azo group for SSIBs. Azobenzene-4,4'-dicarboxylic acid sodium salt is used as a model to investigate the electrochemical behaviors and reaction mechanism of azo compound. It exhibits a reversible capacity of 170 mAh g -1 at 0.2C. When current density is increased to 20C, the reversible capacities of 98 mAh g -1 can be retained for 2000 cycles, demonstrating excellent cycling stability and high rate capability. The detailed characterizations reveal that azo group acts as an electrochemical active site to reversibly bond with Na + . The reversible redox chemistry between azo compound and Na ions offer opportunities for developing long-cycle-life and high-rate SSIBs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An empirical evaluation of genetic distance statistics using microsatellite data from bear (Ursidae) populations.

PubMed

Paetkau, D; Waits, L P; Clarkson, P L; Craighead, L; Strobeck, C

1997-12-01

A large microsatellite data set from three species of bear (Ursidae) was used to empirically test the performance of six genetic distance measures in resolving relationships at a variety of scales ranging from adjacent areas in a continuous distribution to species that diverged several million years ago. At the finest scale, while some distance measures performed extremely well, statistics developed specifically to accommodate the mutational processes of microsatellites performed relatively poorly, presumably because of the relatively higher variance of these statistics. At the other extreme, no statistic was able to resolve the close sister relationship of polar bears and brown bears from more distantly related pairs of species. This failure is most likely due to constraints on allele distributions at microsatellite loci. At intermediate scales, both within continuous distributions and in comparisons to insular populations of late Pleistocene origin, it was not possible to define the point where linearity was lost for each of the statistics, except that it is clearly lost after relatively short periods of independent evolution. All of the statistics were affected by the amount of genetic diversity within the populations being compared, significantly complicating the interpretation of genetic distance data.

An Empirical Evaluation of Genetic Distance Statistics Using Microsatellite Data from Bear (Ursidae) Populations

PubMed Central

Paetkau, D.; Waits, L. P.; Clarkson, P. L.; Craighead, L.; Strobeck, C.

1997-01-01

A large microsatellite data set from three species of bear (Ursidae) was used to empirically test the performance of six genetic distance measures in resolving relationships at a variety of scales ranging from adjacent areas in a continuous distribution to species that diverged several million years ago. At the finest scale, while some distance measures performed extremely well, statistics developed specifically to accommodate the mutational processes of microsatellites performed relatively poorly, presumably because of the relatively higher variance of these statistics. At the other extreme, no statistic was able to resolve the close sister relationship of polar bears and brown bears from more distantly related pairs of species. This failure is most likely due to constraints on allele distributions at microsatellite loci. At intermediate scales, both within continuous distributions and in comparisons to insular populations of late Pleistocene origin, it was not possible to define the point where linearity was lost for each of the statistics, except that it is clearly lost after relatively short periods of independent evolution. All of the statistics were affected by the amount of genetic diversity within the populations being compared, significantly complicating the interpretation of genetic distance data. PMID:9409849

Experimental design for estimating unknown groundwater pumping using genetic algorithm and reduced order model

NASA Astrophysics Data System (ADS)

Ushijima, Timothy T.; Yeh, William W.-G.

2013-10-01

An optimal experimental design algorithm is developed to select locations for a network of observation wells that provide maximum information about unknown groundwater pumping in a confined, anisotropic aquifer. The design uses a maximal information criterion that chooses, among competing designs, the design that maximizes the sum of squared sensitivities while conforming to specified design constraints. The formulated optimization problem is non-convex and contains integer variables necessitating a combinatorial search. Given a realistic large-scale model, the size of the combinatorial search required can make the problem difficult, if not impossible, to solve using traditional mathematical programming techniques. Genetic algorithms (GAs) can be used to perform the global search; however, because a GA requires a large number of calls to a groundwater model, the formulated optimization problem still may be infeasible to solve. As a result, proper orthogonal decomposition (POD) is applied to the groundwater model to reduce its dimensionality. Then, the information matrix in the full model space can be searched without solving the full model. Results from a small-scale test case show identical optimal solutions among the GA, integer programming, and exhaustive search methods. This demonstrates the GA's ability to determine the optimal solution. In addition, the results show that a GA with POD model reduction is several orders of magnitude faster in finding the optimal solution than a GA using the full model. The proposed experimental design algorithm is applied to a realistic, two-dimensional, large-scale groundwater problem. The GA converged to a solution for this large-scale problem.

Giant reversible anisotropy changes at room temperature in a (La,Sr)MnO3/Pb(Mg,Nb,Ti)O3 magneto-electric heterostructure

PubMed Central

Chopdekar, Rajesh Vilas; Buzzi, Michele; Jenkins, Catherine; Arenholz, Elke; Nolting, Frithjof; Takamura, Yayoi

2016-01-01

In a model artificial multiferroic system consisting of a (011)-oriented ferroelectric Pb(Mg,Nb,Ti)O3 substrate intimately coupled to an epitaxial ferromagnetic (La,Sr)MnO3 film, electric field pulse sequences of less than 6 kV/cm induce large, reversible, and bistable remanent strains. The magnetic anisotropy symmetry reversibly switches from a highly anisotropic two-fold state to a more isotropic one, with concomitant changes in resistivity. Anisotropy changes at the scale of a single ferromagnetic domain were measured using X-ray microscopy, with electric-field dependent magnetic domain reversal showing that the energy barrier for magnetization reversal is drastically lowered. Free energy calculations confirm this barrier lowering by up to 70% due to the anisotropic strain changes generated by the substrate. Thus, we demonstrate that an electric field pulse can be used to ‘set’ and ‘reset’ the magnetic anisotropy orientation and resistive state in the film, as well as to lower the magnetization reversal barrier, showing a promising route towards electric-field manipulation of multifunctional nanostructures at room temperature. PMID:27271984

Giant reversible anisotropy changes at room temperature in a (La,Sr)MnO 3/Pb(Mg,Nb,Ti)O 3 magneto-electric heterostructure

DOE PAGES

Chopdekar, Rajesh Vilas; Buzzi, Michele; Jenkins, Catherine; ...

2016-06-08

In a model artificial multiferroic system consisting of a (011)-oriented ferroelectric Pb(Mg,Nb,Ti)O 3 substrate intimately coupled to an epitaxial ferromagnetic (La,Sr)MnO 3 film, electric field pulse sequences of less than 6 kV/cm induce large, reversible, and bistable remanent strains. The magnetic anisotropy symmetry reversibly switches from a highly anisotropic two-fold state to a more isotropic one, with concomitant changes in resistivity. Anisotropy changes at the scale of a single ferromagnetic domain were measured using X-ray microscopy, with electric-field dependent magnetic domain reversal showing that the energy barrier for magnetization reversal is drastically lowered. Free energy calculations confirm this barrier loweringmore » by up to 70% due to the anisotropic strain changes generated by the substrate. Thus, we demonstrate that an electric field pulse can be used to 'set' and 'reset' the magnetic anisotropy orientation and resistive state in the film, as well as to lower the magnetization reversal barrier, showing a promising route towards electric-field manipulation of multifunctional nanostructures at room temperature.« less

Genetics of Triglycerides and the Risk of Atherosclerosis.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2017-07-01

Plasma triglycerides are routinely measured with a lipid profile, and elevated plasma triglycerides are commonly encountered in the clinic. The confounded nature of this trait, which is correlated with numerous other metabolic perturbations, including depressed high-density lipoprotein cholesterol (HDL-C), has thwarted efforts to directly implicate triglycerides as causal in atherogenesis. Human genetic approaches involving large-scale populations and high-throughput genomic assessment under a Mendelian randomization framework have undertaken to sort out questions of causality. We review recent large-scale meta-analyses of cohorts and population-based sequencing studies designed to address whether common and rare variants in genes whose products are determinants of plasma triglycerides are also associated with clinical cardiovascular endpoints. The studied loci include genes encoding lipoprotein lipase and proteins that interact with it, such as apolipoprotein (apo) A-V, apo C-III and angiopoietin-like proteins 3 and 4, and common polymorphisms identified in genome-wide association studies. Triglyceride-raising variant alleles of these genes showed generally strong associations with clinical cardiovascular endpoints. However, in most cases, a second lipid disturbance-usually depressed HDL-C-was concurrently associated. While the findings collectively shift our understanding towards a potential causal role for triglycerides, we still cannot rule out the possibilities that triglycerides are a component of a joint phenotype with low HDL-C or that they are but markers of deeper causal metabolic disturbances that are not routinely measured in epidemiological-scale genetic studies.

Eco-evolutionary dynamics in urbanized landscapes: evolution, species sorting and the change in zooplankton body size along urbanization gradients.

PubMed

Brans, Kristien I; Govaert, Lynn; Engelen, Jessie M T; Gianuca, Andros T; Souffreau, Caroline; De Meester, Luc

2017-01-19

Urbanization causes both changes in community composition and evolutionary responses, but most studies focus on these responses in isolation. We performed an integrated analysis assessing the relative contribution of intra- and interspecific trait turnover to the observed change in zooplankton community body size in 83 cladoceran communities along urbanization gradients quantified at seven spatial scales (50-3200 m radii). We also performed a quantitative genetic analysis on 12 Daphnia magna populations along the same urbanization gradient. Body size in zooplankton communities generally declined with increasing urbanization, but the opposite was observed for communities dominated by large species. The contribution of intraspecific trait variation to community body size turnover with urbanization strongly varied with the spatial scale considered, and was highest for communities dominated by large cladoceran species and at intermediate spatial scales. Genotypic size at maturity was smaller for urban than for rural D. magna populations and for animals cultured at 24°C compared with 20°C. While local genetic adaptation likely contributed to the persistence of D. magna in the urban heat islands, buffering for the phenotypic shift to larger body sizes with increasing urbanization, community body size turnover was mainly driven by non-genetic intraspecific trait change.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

Eco-evolutionary dynamics in urbanized landscapes: evolution, species sorting and the change in zooplankton body size along urbanization gradients

PubMed Central

Souffreau, Caroline

2017-01-01

Urbanization causes both changes in community composition and evolutionary responses, but most studies focus on these responses in isolation. We performed an integrated analysis assessing the relative contribution of intra- and interspecific trait turnover to the observed change in zooplankton community body size in 83 cladoceran communities along urbanization gradients quantified at seven spatial scales (50–3200 m radii). We also performed a quantitative genetic analysis on 12 Daphnia magna populations along the same urbanization gradient. Body size in zooplankton communities generally declined with increasing urbanization, but the opposite was observed for communities dominated by large species. The contribution of intraspecific trait variation to community body size turnover with urbanization strongly varied with the spatial scale considered, and was highest for communities dominated by large cladoceran species and at intermediate spatial scales. Genotypic size at maturity was smaller for urban than for rural D. magna populations and for animals cultured at 24°C compared with 20°C. While local genetic adaptation likely contributed to the persistence of D. magna in the urban heat islands, buffering for the phenotypic shift to larger body sizes with increasing urbanization, community body size turnover was mainly driven by non-genetic intraspecific trait change. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences’. PMID:27920375

Disordering Chain Motions in Fluoropolymers

NASA Astrophysics Data System (ADS)

Holt, David B.; Farmer, Barry L.

1998-03-01

Rotational and conformational disorder play important roles in the solid state phases of fluoropolymers such as polytetrafluoro- ethylene (PTFE). Modeling disordering processes and transitions which occur in fluoropolymers has been hampered due to a lack of force field parameters that adequately describe both the intra- and intermolecular characteristics (conformations and distances) of these polymers in the solid state. A force field has been developed which overcomes these inadequacies and has been utilized in molecular dynamics simulations on a system of PTFE oligomers to investigate two of the primary disordering processes that occur in the solid phases: rotations of chains about their helical axes and the formation and subsequent behavior of helix reversals. The simulation results confirm helix reversal activity at low temperatures and demonstrate correlations between chain segment rotations or librations and helix reversal motion. A mechanism for large scale chain segment rotations is proposed.

Functional wiring of the yeast kinome revealed by global analysis of genetic network motifs

PubMed Central

Sharifpoor, Sara; van Dyk, Dewald; Costanzo, Michael; Baryshnikova, Anastasia; Friesen, Helena; Douglas, Alison C.; Youn, Ji-Young; VanderSluis, Benjamin; Myers, Chad L.; Papp, Balázs; Boone, Charles; Andrews, Brenda J.

2012-01-01

A combinatorial genetic perturbation strategy was applied to interrogate the yeast kinome on a genome-wide scale. We assessed the global effects of gene overexpression or gene deletion to map an integrated genetic interaction network of synthetic dosage lethal (SDL) and loss-of-function genetic interactions (GIs) for 92 kinases, producing a meta-network of 8700 GIs enriched for pathways known to be regulated by cognate kinases. Kinases most sensitive to dosage perturbations had constitutive cell cycle or cell polarity functions under standard growth conditions. Condition-specific screens confirmed that the spectrum of kinase dosage interactions can be expanded substantially in activating conditions. An integrated network composed of systematic SDL, negative and positive loss-of-function GIs, and literature-curated kinase–substrate interactions revealed kinase-dependent regulatory motifs predictive of novel gene-specific phenotypes. Our study provides a valuable resource to unravel novel functional relationships and pathways regulated by kinases and outlines a general strategy for deciphering mutant phenotypes from large-scale GI networks. PMID:22282571

Cardiovascular genetics: technological advancements and applicability for dilated cardiomyopathy.

PubMed

Kummeling, G J M; Baas, A F; Harakalova, M; van der Smagt, J J; Asselbergs, F W

2015-07-01

Genetics plays an important role in the pathophysiology of cardiovascular diseases, and is increasingly being integrated into clinical practice. Since 2008, both capacity and cost-efficiency of mutation screening of DNA have been increased magnificently due to the technological advancement obtained by next-generation sequencing. Hence, the discovery rate of genetic defects in cardiovascular genetics has grown rapidly and the financial threshold for gene diagnostics has been lowered, making large-scale DNA sequencing broadly accessible. In this review, the genetic variants, mutations and inheritance models are briefly introduced, after which an overview is provided of current clinical and technological applications in gene diagnostics and research for cardiovascular disease and in particular, dilated cardiomyopathy. Finally, a reflection on the future perspectives in cardiogenetics is given.

Polarization Reversal Over Flooded Regions and Applications to Large-Scale Flood Mapping with Spaceborne Scatterometers

NASA Technical Reports Server (NTRS)

Nghiem, Son V.; Liu, W. Timothy; Xie, Xiao-Su

1999-01-01

We present the polarization reversal in backscatter over flooded land regions, and demonstrate for the first time the utility of spaceborne Ku-band scatterometer for large-scale flood mapping. Scatterometer data were collected over the globe by the NASA Scatterometer (NSCAT) operated at 14 GHz on the Japanese ADEOS spacecraft from September 1996 to June 1997. During this time span, several severe floods occurred. Over most land surface, vertical polarization backscatter (Sigma(sub upsilon(upsilon)) is larger than horizontal polarization backscatter (sigma(sub hh)). Such polarization characteristics is reversed and sigma(sub upsilon(upsilon)) is smaller than sigma(sub hh) over flooded regions, except under a dense forest canopy. The total backscatter from the flooded landscape consists of direct backscatter and boundary-interaction backscatter. The direct term is contributed by direct backscattering from objects protruding above the water surface, and by backscattering from waves on the water surface. The boundary-interaction term is contributed by the forward scattering from the protruding objects and then reflected from the water surface, and also by the forward scattering from these objects after the water-surface reflection. Over flooded regions, the boundary-interaction term is dominant at large incidence angles and the strong water-surface reflection is much larger for horizontal polarization than the vertical one due to the Brewster effect in transverse-magnetic waves. These scattering mechanisms cause the polarization reversal over flooded regions. An example obtained with the Analytic Wave Theory is used to illustrate the scattering mechanisms leading to the polarization reversal. We then demonstrate the utility of spaceborne Ku-band scatterometer for large-scale flood mapping. We process NSCAT data to obtain the polarization ratio sigma(sub hh)/sigma(sub upsilon(upsilon)) with colocated data at incidence angles larger than 40 deg. The results over Asian summer monsoon regions in September-October 1996 indicate flooded areas in many countries such as Bangladesh, India, Lao, Vietnam, Cambodia, and China. Reports documented by the United Nation Department of Humanitarian Affairs (now called UN Office for the Coordination of Humanitarian Affairs) show loss of many lives and severe flood related damages which affected many million people in the corresponding flooded areas. We also map the NSCAT polarization ratio over the same regions in the "dry season" in January 1997 as a reference to confirm our results. Furthermore, we obtain concurrent ocean wind fields also derived from NSCAT data, and Asia topographic data (USGS GTOPO30) to investigate the flooded area. The results show that winds during summer monsoon season blowing inland, which perplex flood problems. Overlaying the topographic map over NSCAT results reveals an excellent correspondence between the confinement of flooded area within the relevant topographic features, which very well illustrates the value of topographic wetness index. Finally, we discuss the applications of future spaceborne scatterometers, including QuikSCAT and Seawinds, for flood mapping over the globe.

Contributions of historical and contemporary geographic and environmental factors to phylogeographic structure in a Tertiary relict species, Emmenopterys henryi (Rubiaceae)

PubMed Central

Zhang, Yong-Hua; Wang, Ian J.; Comes, Hans Peter; Peng, Hua; Qiu, Ying-Xiong

2016-01-01

Examining how historical and contemporary geographic and environmental factors contribute to genetic divergence at different evolutionary scales is a central yet largely unexplored question in ecology and evolution. Here, we examine this key question by investigating how environmental and geographic factors across different epochs have driven genetic divergence at deeper (phylogeographic) and shallower (landscape genetic) evolutionary scales in the Chinese Tertiary relict tree Emmenopterys henryi. We found that geography played a predominant role at all levels – phylogeographic clades are broadly geographically structured, the deepest levels of divergence are associated with major geological or pre-Quaternary climatic events, and isolation by distance (IBD) primarily explained population genetic structure. However, environmental factors are clearly also important – climatic fluctuations since the Last Interglacial (LIG) have likely contributed to phylogeographic structure, and the population genetic structure (in our AFLP dataset) was partly explained by isolation by environment (IBE), which may have resulted from natural selection in environments with divergent climates. Thus, historical and contemporary geography and historical and contemporary environments have all shaped patterns of genetic structure in E. henryi, and, in fact, changes in the landscape through time have also been critical factors. PMID:27137438

Contributions of historical and contemporary geographic and environmental factors to phylogeographic structure in a Tertiary relict species, Emmenopterys henryi (Rubiaceae).

PubMed

Zhang, Yong-Hua; Wang, Ian J; Comes, Hans Peter; Peng, Hua; Qiu, Ying-Xiong

2016-05-03

Examining how historical and contemporary geographic and environmental factors contribute to genetic divergence at different evolutionary scales is a central yet largely unexplored question in ecology and evolution. Here, we examine this key question by investigating how environmental and geographic factors across different epochs have driven genetic divergence at deeper (phylogeographic) and shallower (landscape genetic) evolutionary scales in the Chinese Tertiary relict tree Emmenopterys henryi. We found that geography played a predominant role at all levels - phylogeographic clades are broadly geographically structured, the deepest levels of divergence are associated with major geological or pre-Quaternary climatic events, and isolation by distance (IBD) primarily explained population genetic structure. However, environmental factors are clearly also important - climatic fluctuations since the Last Interglacial (LIG) have likely contributed to phylogeographic structure, and the population genetic structure (in our AFLP dataset) was partly explained by isolation by environment (IBE), which may have resulted from natural selection in environments with divergent climates. Thus, historical and contemporary geography and historical and contemporary environments have all shaped patterns of genetic structure in E. henryi, and, in fact, changes in the landscape through time have also been critical factors.

On the early emergence of reverse transcription: theoretical basis and experimental evidence

NASA Technical Reports Server (NTRS)

Lazcano, A.; Valverde, V.; Hernandez, G.; Gariglio, P.; Fox, G. E.; Oro, J.

1992-01-01

Reverse transcriptase (RT) was first discovered as an essential catalyst in the biological cycle of retroviruses. However, in the past years evidence has accumulated showing that RTs are involved in a surprisingly large number of RNA-mediated transpositional events that include both viral and nonviral genetic entities. Although it is probable that some RT-bearing genetic elements like the different types of AIDS viruses and the mammalian LINE family have arisen in recent geological times, the possibility that reverse transcription first took place in the early Archean is supported by (1) the hypothesis that RNA preceded DNA as cellular genetic material; (2) the existence of homologous regions of the subunit tau of the E. coli DNA polymerase III with the simian immunodeficiency virus RT, the hepatitis B virus RT, and the beta' subunit of the E. coli RNA polymerase (McHenry et al. 1988); (3) the presence of several conserved motifs, including a 14-amino-acid segment that consists of an Asp-Asp pair flanked by hydrophobic amino acids, which are found in all RTs and in most cellular and viral RNA polymerases. However, whether extant RTs descend from the primitive polymerase involved in the RNA-to-DNA transition remains unproven. Substrate specificity of the AMV and HIV-1 RTs can be modified in the presence of Mn2+, a cation which allows them to add ribonucleotides to an oligo (dG) primer in a template-dependent reaction. This change in specificity is comparable to that observed under similar conditions in other nucleic acid polymerases. This experimentally induced change in RT substrate specificity may explain previous observations on the misincorporation of ribonucleotides by the Maloney murine sarcoma virus RT in the minus and plus DNA of this retrovirus (Chen and Temin 1980). Our results also suggest that HIV-infected macrophages and T-cell cells may contain mixed polynucleotides containing both ribo- and deoxyribonucleotides. The evolutionary significance of these changes in substrate specificities of nucleic acid polymerases is also discussed.

Forward and reverse mutagenesis in C. elegans

PubMed Central

Kutscher, Lena M.; Shaham, Shai

2014-01-01

Mutagenesis drives natural selection. In the lab, mutations allow gene function to be deciphered. C. elegans is highly amendable to functional genetics because of its short generation time, ease of use, and wealth of available gene-alteration techniques. Here we provide an overview of historical and contemporary methods for mutagenesis in C. elegans, and discuss principles and strategies for forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific mutagenesis) genetic studies in this animal. PMID:24449699

Recovery of infectious classical swine fever virus (CSFV) from full-length genomic cDNA clones by a swine kidney cell line expressing bacteriophage T7 RNA polymerase.

PubMed

van Gennip, H G; van Rijn, P A; Widjojoatmodjo, M N; Moormann, R J

1999-03-01

A new method for the recovery of infectious classical swine fever virus (CSFV) from full-length genomic cDNA clones of the C-strain was developed. Classical reverse genetics is based on transfection of in vitro transcribed RNA to target cells to recover RNA viruses. However, the specific infectivity of such in vitro transcribed RNA in swine kidney cells is usually low. To improve reverse genetics for CSFV, a stable swine kidney cell line was established that expresses cytoplasmic bacteriophage T7 RNA polymerase (SK6.T7). A 200-fold increased virus titre was obtained from SK6.T7 cells transfected with linearized full-length cDNA compared to in vitro transcribed RNA, whereas transfection of circular full-length cDNA resulted in 20-fold increased virus titres. Viruses generated on the SK6.T7 cells are indistinguishable from the viruses generated by the classical reverse genetic procedures. These results show the improved recovery of infectious CSFV directly from full-length cDNAs. Furthermore, the reverse genetic procedures are simplified to a faster, one step protocol. We conclude that the SK6.T7 cell line will be a valuable tool for recovering mutant CSFV and will contribute to future pestivirus research.

Dispersal in the sub-Antarctic: king penguins show remarkably little population genetic differentiation across their range.

PubMed

Clucas, Gemma V; Younger, Jane L; Kao, Damian; Rogers, Alex D; Handley, Jonathan; Miller, Gary D; Jouventin, Pierre; Nolan, Paul; Gharbi, Karim; Miller, Karen J; Hart, Tom

2016-10-13

Seabirds are important components of marine ecosystems, both as predators and as indicators of ecological change, being conspicuous and sensitive to changes in prey abundance. To determine whether fluctuations in population sizes are localised or indicative of large-scale ecosystem change, we must first understand population structure and dispersal. King penguins are long-lived seabirds that occupy a niche across the sub-Antarctic zone close to the Polar Front. Colonies have very different histories of exploitation, population recovery, and expansion. We investigated the genetic population structure and patterns of colonisation of king penguins across their current range using a dataset of 5154 unlinked, high-coverage single nucleotide polymorphisms generated via restriction site associated DNA sequencing (RADSeq). Despite breeding at a small number of discrete, geographically separate sites, we find only very slight genetic differentiation among colonies separated by thousands of kilometers of open-ocean, suggesting migration among islands and archipelagos may be common. Our results show that the South Georgia population is slightly differentiated from all other colonies and suggest that the recently founded Falkland Island colony is likely to have been established by migrants from the distant Crozet Islands rather than nearby colonies on South Georgia, possibly as a result of density-dependent processes. The observed subtle differentiation among king penguin colonies must be considered in future conservation planning and monitoring of the species, and demographic models that attempt to forecast extinction risk in response to large-scale climate change must take into account migration. It is possible that migration could buffer king penguins against some of the impacts of climate change where colonies appear panmictic, although it is unlikely to protect them completely given the widespread physical changes projected for their Southern Ocean foraging grounds. Overall, large-scale population genetic studies of marine predators across the Southern Ocean are revealing more interconnection and migration than previously supposed.

Mortality and Morbidity Risks and Economic Behavior

PubMed Central

Stoler, Avraham; Meltzer, David

2012-01-01

There are theoretical reasons to expect that high risk of mortality or morbidity during young adulthood decreases investment in human capital. However, investigation of this hypothesis is complicated by a variety of empirical challenges, including difficulties in inferring causation due to omitted variables and reverse causation. For example, to compare two groups with substantially different mortality rates, one typically has to use samples from different countries or time periods, making it difficult to control for other relevant variables. Reverse causation is important because human capital investment can affect mortality and morbidity. To counter these problems, we collected data on human capital investments, fertility decisions, and other economic choices of people at risk for Huntington’s disease. Huntington’s disease is a fatal genetic disorder that introduces a large and exogenous risk of early mortality and morbidity. We find a strong negative relation between mortality and morbidity risks and human capital investment. PMID:22308067

Kinetics of matching.

PubMed

Mark, T A; Gallistel, C R

1994-01-01

Rats responded on concurrent variable interval schedules of brain stimulation reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the relative rate of reward. In successive, narrow time windows, the authors compared the ratio of the times spent on the 2 levers to the ratio of the rewards received. Time-allocation ratios tracked wide, random fluctuations in the reward ratio. The adjustment to the midsession reversal in relative rate of reward was largely completed within 1 interreward interval on the leaner schedule. Both results were unaffected by a 16-fold change in the combined rates of reward. The large, rapid, scale-invariant shifts in time-allocation ratios that underlie matching behavior imply that the subjective relative rate of reward can be determined by a very few of the most recent interreward intervals and that this estimate can directly determine the ratio of the expected stay durations.

Fabrication and characterization of controllable grain boundary arrays in solution-processed small molecule organic semiconductor films

NASA Astrophysics Data System (ADS)

Wo, Songtao; Headrick, Randall L.; Anthony, John E.

2012-04-01

We have produced solution-processed thin films of 6,13-bis(tri-isopropyl-silylethynyl) pentacene with grain sizes from a few micrometers up to millimeter scale by lateral crystallization from a rectangular stylus. Grains are oriented along the crystallization direction, and the grain size transverse to the crystallization direction depends inversely on the writing speed, hence forming a regular array of oriented grain boundaries with controllable spacing. We utilize these controllable arrays to systematically study the role of large-angle grain boundaries in carrier transport and charge trapping in thin film transistors. The effective mobility scales with the grain size, leading to an estimate of the potential drop at individual large-angle grain boundaries of more than 1 volt. This result indicates that the structure of grain boundaries is not molecularly abrupt, which may be a general feature of solution-processed small molecule organic semiconductor thin films, where relatively high energy grain boundaries are typically formed. Transient measurements after switching from positive to negative gate bias or between large and small negative gate bias reveal reversible charge trapping, with time constants on the order of 10 s and trap densities that are correlated with grain boundary density. We suggest that charge diffusion along grain boundaries and other defects is the rate-determining mechanism of the reversible trapping.

A reverse engineering algorithm for neural networks, applied to the subthalamopallidal network of basal ganglia.

PubMed

Floares, Alexandru George

2008-01-01

Modeling neural networks with ordinary differential equations systems is a sensible approach, but also very difficult. This paper describes a new algorithm based on linear genetic programming which can be used to reverse engineer neural networks. The RODES algorithm automatically discovers the structure of the network, including neural connections, their signs and strengths, estimates its parameters, and can even be used to identify the biophysical mechanisms involved. The algorithm is tested on simulated time series data, generated using a realistic model of the subthalamopallidal network of basal ganglia. The resulting ODE system is highly accurate, and results are obtained in a matter of minutes. This is because the problem of reverse engineering a system of coupled differential equations is reduced to one of reverse engineering individual algebraic equations. The algorithm allows the incorporation of common domain knowledge to restrict the solution space. To our knowledge, this is the first time a realistic reverse engineering algorithm based on linear genetic programming has been applied to neural networks.

PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics.

PubMed

Chantreau, Maxime; Grec, Sébastien; Gutierrez, Laurent; Dalmais, Marion; Pineau, Christophe; Demailly, Hervé; Paysant-Leroux, Christine; Tavernier, Reynald; Trouvé, Jean-Paul; Chatterjee, Manash; Guillot, Xavier; Brunaud, Véronique; Chabbert, Brigitte; van Wuytswinkel, Olivier; Bendahmane, Abdelhafid; Thomasset, Brigitte; Hawkins, Simon

2013-10-15

Flax (Linum usitatissimum L.) is an economically important fiber and oil crop that has been grown for thousands of years. The genome has been recently sequenced and transcriptomics are providing information on candidate genes potentially related to agronomically-important traits. In order to accelerate functional characterization of these genes we have generated a flax EMS mutant population that can be used as a TILLinG (Targeting Induced Local Lesions in Genomes) platform for forward and reverse genetics. A population of 4,894 M2 mutant seed families was generated using 3 different EMS concentrations (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and 1,552 families (38.5%) showed a visual developmental phenotype (stem size and diameter, plant architecture, flower-related). The majority of these families showed more than one phenotype. Mutant phenotype data are organised in a database and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb). Preliminary screens were also performed for atypical fiber and seed phenotypes. Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to validate the collection for reverse genetics, DNA pools were screened for two genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations in the C3H and CAD genes, respectively. The average mutation rate was calculated as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five out of the 52 flax cad mutant families containing missense or codon stop mutations showed the typical orange-brown xylem phenotype observed in CAD down-regulated/mutant plants in other species. We have developed a flax mutant population that can be used as an efficient forward and reverse genetics tool. The collection has an extremely high mutation rate that enables the detection of large numbers of independant mutant families by screening a comparatively low number of M2 families. The population will prove to be a valuable resource for both fundamental research and the identification of agronomically-important genes for crop improvement in flax.

PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics

PubMed Central

2013-01-01

Background Flax (Linum usitatissimum L.) is an economically important fiber and oil crop that has been grown for thousands of years. The genome has been recently sequenced and transcriptomics are providing information on candidate genes potentially related to agronomically-important traits. In order to accelerate functional characterization of these genes we have generated a flax EMS mutant population that can be used as a TILLinG (Targeting Induced Local Lesions in Genomes) platform for forward and reverse genetics. Results A population of 4,894 M2 mutant seed families was generated using 3 different EMS concentrations (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and 1,552 families (38.5%) showed a visual developmental phenotype (stem size and diameter, plant architecture, flower-related). The majority of these families showed more than one phenotype. Mutant phenotype data are organised in a database and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb). Preliminary screens were also performed for atypical fiber and seed phenotypes. Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to validate the collection for reverse genetics, DNA pools were screened for two genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations in the C3H and CAD genes, respectively. The average mutation rate was calculated as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five out of the 52 flax cad mutant families containing missense or codon stop mutations showed the typical orange-brown xylem phenotype observed in CAD down-regulated/mutant plants in other species. Conclusions We have developed a flax mutant population that can be used as an efficient forward and reverse genetics tool. The collection has an extremely high mutation rate that enables the detection of large numbers of independant mutant families by screening a comparatively low number of M2 families. The population will prove to be a valuable resource for both fundamental research and the identification of agronomically-important genes for crop improvement in flax. PMID:24128060

PS-b-PEO/Silica Films with Regular and Reverse Mesostructures of Large Characteristic Length Scales Prepared by Solvent Evaporation-Induced Self-Assembly

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

YU,KUI; BRINKER,C. JEFFREY; HURD,ALAN J.

2000-11-22

Since the discovery of surfactant-templated silica by Mobil scientists in 1992, mesostructured silica has been synthesized in various forms including thin films, powders, particles, and fibers. In general, mesostructured silica has potential applications, such as in separation, catalysis, sensors, and fluidic microsystems. In respect to these potential applications, mesostructured silica in the form of thin films is perhaps one of the most promising candidates. The preparation of mesostructured silica films through preferential solvent evaporation-induced self-assembly (EISA) has recently received much attention in the laboratories. However, no amphiphile/silica films with reverse mesophases have ever been made through this EISA procedure. Furthermore,more » templates employed to date have been either surfactants or poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymers, such as pluronic P-123, both of which are water-soluble and alcohol-soluble. Due to their relatively low molecular weight, the templated silica films with mesoscopic order have been limited to relatively small characteristic length scales. In the present communication, the authors report a novel synthetic method to prepare mesostructured amphiphilic/silica films with regular and reverse mesophases of large characteristic length scales. This method involves evaporation-induced self-assembly (EISA) of amphiphilic polystyrene-block-poly(ethylene oxide) (PS-b-PEO) diblock copolymers. In the present study, the PS-b-PEO diblocks are denoted as, for example, PS(215)-b-PEO(100), showing that this particular sample contains 215 S repeat units and 100 EO repeat units. This PS(215)-b-PEO(100) diblock possesses high molecular weight and does not directly mix with water or alcohol. To the authors knowledge, no studies have reported the use of water-insoluble and alcohol-insoluble amphiphilic diblocks as structure-directing agents in the synthesis of mesostructured silica films through EISA. It is believed that the present system is the first to yield amphiphile/silica films with regular and reverse mesophases, as well as curved multi-bilayer mesostructures, through EISA. The ready formation of the diblock/silica films with multi-bilayer vesicular mesostructures is discussed.« less

Genetic diversity and structure related to expansion history and habitat isolation: stone marten populating rural-urban habitats.

PubMed

Wereszczuk, Anna; Leblois, Raphaël; Zalewski, Andrzej

2017-12-22

Population genetic diversity and structure are determined by past and current evolutionary processes, among which spatially limited dispersal, genetic drift, and shifts in species distribution boundaries have major effects. In most wildlife species, environmental modifications by humans often lead to contraction of species' ranges and/or limit their dispersal by acting as environmental barriers. However, in species well adapted to anthropogenic habitat or open landscapes, human induced environmental changes may facilitate dispersal and range expansions. In this study, we analysed whether isolation by distance and deforestation, among other environmental features, promotes or restricts dispersal and expansion in stone marten (Martes foina) populations. We genotyped 298 martens from eight sites at twenty-two microsatellite loci to characterize the genetic variability, population structure and demographic history of stone martens in Poland. At the landscape scale, limited genetic differentiation between sites in a mosaic of urban, rural and forest habitats was mostly influenced by isolation by distance. Statistical clustering and multivariate analyses showed weak genetic structuring with two to four clusters and a high rate of gene flow between them. Stronger genetic differentiation was detected for one stone marten population (NE1) located inside a large forest complex. Genetic differentiation between this site and all others was 20% higher than between other sites separated by similar distances. The genetic uniqueness index of NE1 was also twofold higher than in other sites. Past demographic history analyses showed recent expansion of this species in north-eastern Poland. A decrease in genetic diversity from south to north, and MIGRAINE analyses indicated the direction of expansion of stone marten. Our results showed that two processes, changes in species distribution boundaries and limited dispersal associated with landscape barriers, affect genetic diversity and structure in stone marten. Analysis of local barriers that reduced dispersal and large scale analyses of genetic structure and demographic history highlight the importance of isolation by distance and forest cover for the past colonization of central Europe by stone marten. This confirmed the hypothesis that human-landscape changes (deforestation) accelerated stone marten expansion, to which climate warming probably has also been contributing over the last few decades.

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice

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

Wang, Diane R.; Wolfrum, Edward J.; Virk, Parminder

Rice plants ( Oryza sativa) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, establishedmore » an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. Lastly, we find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice.« less

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice

PubMed Central

Wang, Diane R.; Wolfrum, Edward J.; Virk, Parminder; Ismail, Abdelbagi; Greenberg, Anthony J.; McCouch, Susan R.

2016-01-01

Rice plants (Oryza sativa) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, established an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. We find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice. PMID:27707775

Robust phenotyping strategies for evaluation of stem non-structural carbohydrates (NSC) in rice

DOE PAGES

Wang, Diane R.; Wolfrum, Edward J.; Virk, Parminder; ...

2016-10-05

Rice plants ( Oryza sativa) accumulate excess photoassimilates in the form of non-structural carbohydrates (NSCs) in their stems prior to heading that can later be mobilized to supplement photosynthate production during grain-filling. Despite longstanding interest in stem NSC for rice improvement, the dynamics of NSC accumulation, remobilization, and re-accumulation that have genetic potential for optimization have not been systematically investigated. Here we conducted three pilot experiments to lay the groundwork for large-scale diversity studies on rice stem NSC. We assessed the relationship of stem NSC components with 21 agronomic traits in large-scale, tropical yield trials using 33 breeder-nominated lines, establishedmore » an appropriate experimental design for future genetic studies using a Bayesian framework to sample sub-datasets from highly replicated greenhouse data using 36 genetically diverse genotypes, and used 434 phenotypically divergent rice stem samples to develop two partial least-squares (PLS) models using near-infrared (NIR) spectra for accurate, rapid prediction of rice stem starch, sucrose, and total non-structural carbohydrates. Lastly, we find evidence that stem reserves are most critical for short-duration varieties and suggest that pre-heading stem NSC is worthy of further experimentation for breeding early maturing rice.« less

Epilepsy Genetics—Past, Present, and Future

PubMed Central

Poduri, Annapurna; Lowenstein, Daniel

2014-01-01

Human epilepsy is a common and heterogeneous condition in which genetics play an important etiological role. We begin by reviewing the past history of epilepsy genetics, a field that has traditionally included studies of pedigrees with epilepsy caused by defects in ion channels and neurotransmitters. We highlight important recent discoveries that have expanded the field beyond the realm of channels and neurotransmitters and that have challenged the notion that single genes produce single disorders. Finally, we project toward an exciting future for epilepsy genetics as large-scale collaborative phenotyping studies come face to face with new technologies in genomic medicine. PMID:21277190

The art and design of genetic screens: maize

USDA-ARS?s Scientific Manuscript database

Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible...

Clinical application of pharmacogenetics: focusing on practical issues.

PubMed

Chang, Matthew T; McCarthy, Jeanette J; Shin, Jaekyu

2015-01-01

Recent large-scale genetic-based studies have transformed the field of pharmacogenetics to identify, characterize and leverage genetic information to inform patient care. Genetic testing can be used to alter drug selection, optimize drug dosing and prevent unnecessary adverse events. As precision medicine becomes the mainstay in the clinic, it becomes critical for clinicians to utilize pharmacogenetics to guide patient care. One primary challenge is identifying patients where genetic tests that can potentially impact patient care. To address this challenge, our review highlights many practical issues clinicians may encounter: identifying candidate patients and clinical laboratories for pharmacogenetic testing, selecting highly curated resources to help asses test validity, reimbursing costs of pharmacogenetic tests, and interpreting of pharmacogenetic test results.

Fine-scale genetic structure and cryptic associations reveal evidence of kin-based sociality in the African forest elephant.

PubMed

Schuttler, Stephanie G; Philbrick, Jessica A; Jeffery, Kathryn J; Eggert, Lori S

2014-01-01

Spatial patterns of relatedness within animal populations are important in the evolution of mating and social systems, and have the potential to reveal information on species that are difficult to observe in the wild. This study examines the fine-scale genetic structure and connectivity of groups within African forest elephants, Loxodonta cyclotis, which are often difficult to observe due to forest habitat. We tested the hypothesis that genetic similarity will decline with increasing geographic distance, as we expect kin to be in closer proximity, using spatial autocorrelation analyses and Tau K(r) tests. Associations between individuals were investigated through a non-invasive genetic capture-recapture approach using network models, and were predicted to be more extensive than the small groups found in observational studies, similar to fission-fusion sociality found in African savanna (Loxodonta africana) and Asian (Elephas maximus) species. Dung samples were collected in Lopé National Park, Gabon in 2008 and 2010 and genotyped at 10 microsatellite loci, genetically sexed, and sequenced at the mitochondrial DNA control region. We conducted analyses on samples collected at three different temporal scales: a day, within six-day sampling sessions, and within each year. Spatial autocorrelation and Tau K(r) tests revealed genetic structure, but results were weak and inconsistent between sampling sessions. Positive spatial autocorrelation was found in distance classes of 0-5 km, and was strongest for the single day session. Despite weak genetic structure, individuals within groups were significantly more related to each other than to individuals between groups. Social networks revealed some components to have large, extensive groups of up to 22 individuals, and most groups were composed of individuals of the same matriline. Although fine-scale population genetic structure was weak, forest elephants are typically found in groups consisting of kin and based on matrilines, with some individuals having more associates than observed from group sizes alone.

Temporal and spatial scaling of the genetic structure of a vector-borne plant pathogen.

PubMed

Coletta-Filho, Helvécio D; Francisco, Carolina S; Almeida, Rodrigo P P

2014-02-01

The ecology of plant pathogens of perennial crops is affected by the long-lived nature of their immobile hosts. In addition, changes to the genetic structure of pathogen populations may affect disease epidemiology and management practices; examples include local adaptation of more fit genotypes or introduction of novel genotypes from geographically distant areas via human movement of infected plant material or insect vectors. We studied the genetic structure of Xylella fastidiosa populations causing disease in sweet orange plants in Brazil at multiple scales using fast-evolving molecular markers (simple-sequence DNA repeats). Results show that populations of X. fastidiosa were regionally isolated, and that isolation was maintained for populations analyzed a decade apart from each other. However, despite such geographic isolation, local populations present in year 2000 were largely replaced by novel genotypes in 2009 but not as a result of migration. At a smaller spatial scale (individual trees), results suggest that isolates within plants originated from a shared common ancestor. In summary, new insights on the ecology of this economically important plant pathogen were obtained by sampling populations at different spatial scales and two different time points.

A Toolkit for bulk PCR-based marker design from next-generation sequence data: application for development of a framework linkage map in bulb onion (Allium cepa L.)

PubMed Central

2012-01-01

Background Although modern sequencing technologies permit the ready detection of numerous DNA sequence variants in any organisms, converting such information to PCR-based genetic markers is hampered by a lack of simple, scalable tools. Onion is an example of an under-researched crop with a complex, heterozygous genome where genome-based research has previously been hindered by limited sequence resources and genetic markers. Results We report the development of generic tools for large-scale web-based PCR-based marker design in the Galaxy bioinformatics framework, and their application for development of next-generation genetics resources in a wide cross of bulb onion (Allium cepa L.). Transcriptome sequence resources were developed for the homozygous doubled-haploid bulb onion line ‘CUDH2150’ and the genetically distant Indian landrace ‘Nasik Red’, using 454™ sequencing of normalised cDNA libraries of leaf and shoot. Read mapping of ‘Nasik Red’ reads onto ‘CUDH2150’ assemblies revealed 16836 indel and SNP polymorphisms that were mined for portable PCR-based marker development. Tools for detection of restriction polymorphisms and primer set design were developed in BioPython and adapted for use in the Galaxy workflow environment, enabling large-scale and targeted assay design. Using PCR-based markers designed with these tools, a framework genetic linkage map of over 800cM spanning all chromosomes was developed in a subset of 93 F2 progeny from a very large F2 family developed from the ‘Nasik Red’ x ‘CUDH2150’ inter-cross. The utility of tools and genetic resources developed was tested by designing markers to transcription factor-like polymorphic sequences. Bin mapping these markers using a subset of 10 progeny confirmed the ability to place markers within 10 cM bins, enabling increased efficiency in marker assignment and targeted map refinement. The major genetic loci conditioning red bulb colour (R) and fructan content (Frc) were located on this map by QTL analysis. Conclusions The generic tools developed for the Galaxy environment enable rapid development of sets of PCR assays targeting sequence variants identified from Illumina and 454 sequence data. They enable non-specialist users to validate and exploit large volumes of next-generation sequence data using basic equipment. PMID:23157543

A toolkit for bulk PCR-based marker design from next-generation sequence data: application for development of a framework linkage map in bulb onion (Allium cepa L.).

PubMed

Baldwin, Samantha; Revanna, Roopashree; Thomson, Susan; Pither-Joyce, Meeghan; Wright, Kathryn; Crowhurst, Ross; Fiers, Mark; Chen, Leshi; Macknight, Richard; McCallum, John A

2012-11-19

Although modern sequencing technologies permit the ready detection of numerous DNA sequence variants in any organisms, converting such information to PCR-based genetic markers is hampered by a lack of simple, scalable tools. Onion is an example of an under-researched crop with a complex, heterozygous genome where genome-based research has previously been hindered by limited sequence resources and genetic markers. We report the development of generic tools for large-scale web-based PCR-based marker design in the Galaxy bioinformatics framework, and their application for development of next-generation genetics resources in a wide cross of bulb onion (Allium cepa L.). Transcriptome sequence resources were developed for the homozygous doubled-haploid bulb onion line 'CUDH2150' and the genetically distant Indian landrace 'Nasik Red', using 454™ sequencing of normalised cDNA libraries of leaf and shoot. Read mapping of 'Nasik Red' reads onto 'CUDH2150' assemblies revealed 16836 indel and SNP polymorphisms that were mined for portable PCR-based marker development. Tools for detection of restriction polymorphisms and primer set design were developed in BioPython and adapted for use in the Galaxy workflow environment, enabling large-scale and targeted assay design. Using PCR-based markers designed with these tools, a framework genetic linkage map of over 800cM spanning all chromosomes was developed in a subset of 93 F(2) progeny from a very large F(2) family developed from the 'Nasik Red' x 'CUDH2150' inter-cross. The utility of tools and genetic resources developed was tested by designing markers to transcription factor-like polymorphic sequences. Bin mapping these markers using a subset of 10 progeny confirmed the ability to place markers within 10 cM bins, enabling increased efficiency in marker assignment and targeted map refinement. The major genetic loci conditioning red bulb colour (R) and fructan content (Frc) were located on this map by QTL analysis. The generic tools developed for the Galaxy environment enable rapid development of sets of PCR assays targeting sequence variants identified from Illumina and 454 sequence data. They enable non-specialist users to validate and exploit large volumes of next-generation sequence data using basic equipment.

The Effects of Meiosis/Genetics Integration and Instructional Sequence on College Biology Student Achievement in Genetics.

ERIC Educational Resources Information Center

Browning, Mark

The purpose of the research was to manipulate two aspects of genetics instruction in order to measure their effects on college, introductory biology students' achievement in genetics. One instructional sequence that was used dealt first with monohybrid autosomal inheritance patterns, then sex-linkage. The alternate sequence was the reverse.…

Hierarchical Genetic Analysis of German Cockroach (Blattella germanica) Populations from within Buildings to across Continents

PubMed Central

Vargo, Edward L.; Crissman, Jonathan R.; Booth, Warren; Santangelo, Richard G.; Mukha, Dmitry V.; Schal, Coby

2014-01-01

Understanding the population structure of species that disperse primarily by human transport is essential to predicting and controlling human-mediated spread of invasive species. The German cockroach (Blattella germanica) is a widespread urban invader that can actively disperse within buildings but is spread solely by human-mediated dispersal over longer distances; however, its population structure is poorly understood. Using microsatellite markers we investigated population structure at several spatial scales, from populations within single apartment buildings to populations from several cities across the U.S. and Eurasia. Both traditional measures of genetic differentiation and Bayesian clustering methods revealed increasing levels of genetic differentiation at greater geographic scales. Our results are consistent with active dispersal of cockroaches largely limited to movement within a building. Their low levels of genetic differentiation, yet limited active spread between buildings, suggests a greater likelihood of human-mediated dispersal at more local scales (within a city) than at larger spatial scales (within and between continents). About half the populations from across the U.S. clustered together with other U.S. populations, and isolation by distance was evident across the U.S. Levels of genetic differentiation among Eurasian cities were greater than those in the U.S. and greater than those between the U.S. and Eurasia, but no clear pattern of structure at the continent level was detected. MtDNA sequence variation was low and failed to reveal any geographical structure. The weak genetic structure detected here is likely due to a combination of historical admixture among populations and periodic population bottlenecks and founder events, but more extensive studies are needed to determine whether signatures of global movement may be present in this species. PMID:25020136

Negative density-dependent dispersal in the American black bear (Ursus americanus) revealed by noninvasive sampling and genotyping

PubMed Central

Roy, Justin; Yannic, Glenn; Côté, Steeve D; Bernatchez, Louis

2012-01-01

Although the dispersal of animals is influenced by a variety of factors, few studies have used a condition-dependent approach to assess it. The mechanisms underlying dispersal are thus poorly known in many species, especially in large mammals. We used 10 microsatellite loci to examine population density effects on sex-specific dispersal behavior in the American black bear, Ursus americanus. We tested whether dispersal increases with population density in both sexes. Fine-scale genetic structure was investigated in each of four sampling areas using Mantel tests and spatial autocorrelation analyses. Our results revealed male-biased dispersal pattern in low-density areas. As population density increased, females appeared to exhibit philopatry at smaller scales. Fine-scale genetic structure for males at higher densities may indicate reduced dispersal distances and delayed dispersal by subadults. PMID:22822432

Common genetic architecture underlying young children's food fussiness and liking for vegetables and fruit.

PubMed

Fildes, Alison; van Jaarsveld, Cornelia H M; Cooke, Lucy; Wardle, Jane; Llewellyn, Clare H

2016-04-01

Food fussiness (FF) is common in early childhood and is often associated with the rejection of nutrient-dense foods such as vegetables and fruit. FF and liking for vegetables and fruit are likely all heritable phenotypes; the genetic influence underlying FF may explain the observed genetic influence on liking for vegetables and fruit. Twin analyses make it possible to get a broad-based estimate of the extent of the shared genetic influence that underlies these traits. We quantified the extent of the shared genetic influence that underlies FF and liking for vegetables and fruit in early childhood with the use of a twin design. Data were from the Gemini cohort, which is a population-based sample of twins born in England and Wales in 2007. Parents of 3-y-old twins (n= 1330 pairs) completed questionnaire measures of their children's food preferences (liking for vegetables and fruit) and the FF scale from the Children's Eating Behavior Questionnaire. Multivariate quantitative genetic modeling was used to estimate common genetic influences that underlie FF and liking for vegetables and fruit. Genetic correlations were significant and moderate to large in size between FF and liking for both vegetables (-0.65) and fruit (-0.43), which indicated that a substantial proportion of the genes that influence FF also influence liking. Common genes that underlie FF and liking for vegetables and fruit largely explained the observed phenotypic correlations between them (68-70%). FF and liking for fruit and vegetables in young children share a large proportion of common genetic factors. The genetic influence on FF may determine why fussy children typically reject fruit and vegetables.

An evolutionary theory of large-scale human warfare: Group-structured cultural selection.

PubMed

Zefferman, Matthew R; Mathew, Sarah

2015-01-01

When humans wage war, it is not unusual for battlefields to be strewn with dead warriors. These warriors typically were men in their reproductive prime who, had they not died in battle, might have gone on to father more children. Typically, they are also genetically unrelated to one another. We know of no other animal species in which reproductively capable, genetically unrelated individuals risk their lives in this manner. Because the immense private costs borne by individual warriors create benefits that are shared widely by others in their group, warfare is a stark evolutionary puzzle that is difficult to explain. Although several scholars have posited models of the evolution of human warfare, these models do not adequately explain how humans solve the problem of collective action in warfare at the evolutionarily novel scale of hundreds of genetically unrelated individuals. We propose that group-structured cultural selection explains this phenomenon. © 2015 Wiley Periodicals, Inc.

Synthetic Botany.

PubMed

Boehm, Christian R; Pollak, Bernardo; Purswani, Nuri; Patron, Nicola; Haseloff, Jim

2017-07-05

Plants are attractive platforms for synthetic biology and metabolic engineering. Plants' modular and plastic body plans, capacity for photosynthesis, extensive secondary metabolism, and agronomic systems for large-scale production make them ideal targets for genetic reprogramming. However, efforts in this area have been constrained by slow growth, long life cycles, the requirement for specialized facilities, a paucity of efficient tools for genetic manipulation, and the complexity of multicellularity. There is a need for better experimental and theoretical frameworks to understand the way genetic networks, cellular populations, and tissue-wide physical processes interact at different scales. We highlight new approaches to the DNA-based manipulation of plants and the use of advanced quantitative imaging techniques in simple plant models such as Marchantia polymorpha. These offer the prospects of improved understanding of plant dynamics and new approaches to rational engineering of plant traits. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Reverse genetics: Its origins and prospects

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

Berg, P.

1991-04-01

The nucleotide sequence of a gene and its flanking segments alone will not tell us how its expression is regulated during development and differentiation, or in response to environmental changes. To comprehend the physiological significance of the molecular details requires biological analysis. Recombinant DNA techniques provide a powerful experimental approach. A strategy termed reverse genetics' utilizes the analysis of the activities of mutant and normal genes and experimentally constructed mutants to explore the relationship between gene structure and function thereby helping elucidate the relationship between genotype and phenotype.

Large scale variation in DNA copy number in chicken breeds

USDA-ARS?s Scientific Manuscript database

Background Detecting genetic variation is a critical step in elucidating the molecular mechanisms underlying phenotypic diversity. Until recently, such detection has mostly focused on single nucleotide polymorphisms (SNPs) because of the ease in screening complete genomes. Another type of variant, c...

Epigenetic supersimilarity of monozygotic twin pairs

USDA-ARS?s Scientific Manuscript database

Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity. Here, by analyzing data from a genome-scale stud...

Elucidating the genetic architecture of reproductive ageing in the Japanese population.

PubMed

Horikoshi, Momoko; Day, Felix R; Akiyama, Masato; Hirata, Makoto; Kamatani, Yoichiro; Matsuda, Koichi; Ishigaki, Kazuyoshi; Kanai, Masahiro; Wright, Hollis; Toro, Carlos A; Ojeda, Sergio R; Lomniczi, Alejandro; Kubo, Michiaki; Ong, Ken K; Perry, John R B

2018-05-17

Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, we report 26 loci (all P < 5 × 10 -8 ) for reproductive ageing, i.e. puberty timing or age at menopause, in a non-European population (up to 67,029 women of Japanese ancestry). Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause. For puberty timing, we demonstrate an aetiological role for receptor-like protein tyrosine phosphatases by combining evidence across population genetics and pre- and peri-pubertal changes in hypothalamic gene expression in rodent and primate models. Furthermore, our findings demonstrate widespread differences in allele frequencies and effect estimates between Japanese and European associated variants, highlighting the benefits and challenges of large-scale trans-ethnic approaches.

Learning directed acyclic graphs from large-scale genomics data.

PubMed

Nikolay, Fabio; Pesavento, Marius; Kritikos, George; Typas, Nassos

2017-09-20

In this paper, we consider the problem of learning the genetic interaction map, i.e., the topology of a directed acyclic graph (DAG) of genetic interactions from noisy double-knockout (DK) data. Based on a set of well-established biological interaction models, we detect and classify the interactions between genes. We propose a novel linear integer optimization program called the Genetic-Interactions-Detector (GENIE) to identify the complex biological dependencies among genes and to compute the DAG topology that matches the DK measurements best. Furthermore, we extend the GENIE program by incorporating genetic interaction profile (GI-profile) data to further enhance the detection performance. In addition, we propose a sequential scalability technique for large sets of genes under study, in order to provide statistically significant results for real measurement data. Finally, we show via numeric simulations that the GENIE program and the GI-profile data extended GENIE (GI-GENIE) program clearly outperform the conventional techniques and present real data results for our proposed sequential scalability technique.

Lake-specific variation in growth, migration timing and survival of juvenile sockeye salmon Oncorhynchus nerka: separating environmental from genetic influences.

PubMed

Reed, T E; Martinek, G; Quinn, T P

2010-08-01

Time series on juvenile life-history traits obtained from sockeye salmon Oncorhynchus nerka were analysed to assess lake-specific environmental influences on juvenile migration timing, size and survival of fish from a common gene pool. Every year for the past two decades, O. nerka have been spawned at a hatchery facility, and the progeny released into two lakes that differ in average summer temperatures, limnological attributes and growth opportunities. Juveniles reared in the warmer, more productive Crosswind Lake were larger and heavier as smolts compared to those from the cooler, less productive Summit Lake and had higher in-lake and subsequent marine survival. Crosswind Lake smolts migrated from the lake to sea slightly earlier in the season but the migration timing distributions overlapped considerably across years. Fry stocking density had a negative effect on smolt length for both lakes, and a negative effect on in-lake survival in Summit Lake. Taken together, the results revealed a strong effect of lake-rearing environment on the expression of life-history variation in O. nerka. The stocking of these lakes each year with juveniles from a single mixed-source population provided a large-scale reverse common-garden experiment, where the same gene pool was exposed to different environments, rather than the different gene pools in the same environment approach typical of evolutionary ecology studies. Other researchers are encouraged to seek and exploit similar serendipitous situations, which might allow environmental and genetic influences on ecologically important traits to be distinguished in natural or semi-natural settings.

Practical applications of insects' sexual development for pest control.

PubMed

Koukidou, M; Alphey, L

2014-01-01

Elucidation of the sex differentiation pathway in insects offers an opportunity to understand key aspects of evolutionary developmental biology. In addition, it provides the understanding necessary to manipulate insects in order to develop new synthetic genetics-based tools for the control of pest insects. Considerable progress has been made in this, especially in improvements to the sterile insect technique (SIT). Large scale sex separation is considered highly desirable or essential for most SIT targets. This separation can be provided by genetic methods based on sex-specific gene expression. Investigation of sex determination by many groups has provided molecular components and methods for this. Though the primary sex determination signal varies considerably, key regulatory genes and mechanisms remain surprisingly similar. In most cases studied so far, a primary signal is transmitted to a basal gene at the bottom of the hierarchy (dsx) through an alternative splicing cascade; dsx is itself differentially spliced in males and females. A sex-specific alternative splicing system therefore offers an attractive route to achieve female-specific expression. Experience has shown that alternative splicing modules can be developed with cross-species function; modularity and standardisation and re-use of parts are key principles of synthetic biology. Both female-killing and sex reversal (XX females to phenotypic males) can in principle also be used as efficient alternatives to sterilisation in SIT-like methods. Sexual maturity is yet another area where understanding of sexual development may be applied to insect control programmes. Further detailed understanding of this crucial aspect of insect biology will undoubtedly continue to underpin innovative practical applications. © 2014 S. Karger AG, Basel.

Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof-of-concept and roadmap for future studies

PubMed Central

Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne YW; Martin, Nicholas G; Wright, Margaret J

2016-01-01

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current study provides proof-of-concept (albeit based on a limited set of structural brain measures), and defines a roadmap for future studies investigating the genetic covariance between structural/functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.

PubMed

Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne Yw; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F

2016-03-01

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

Large reversible magnetocaloric effect in a Ni-Co-Mn-In magnetic shape memory alloy

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

Huang, L.; Cong, D. Y.; Ma, L.

Reversibility of the magnetocaloric effect in materials with first-order magnetostructural transformation is of vital significance for practical magnetic refrigeration applications. Here, we report a large reversible magnetocaloric effect in a Ni49.8Co1.2Mn33.5In15.5 magnetic shape memory alloy. A large reversible magnetic entropy change of 14.6 J/(kg K) and a broad operating temperature window of 18 K under 5 T were simultaneously achieved, correlated with the low thermal hysteresis (-8 K) and large magnetic-field-induced shift of transformation temperatures (4.9 K/T) that lead to a narrow magnetic hysteresis (1.1 T) and small average magnetic hysteresis loss (48.4 J/kg under 5 T) as well. Furthermore,more » a large reversible effective refrigeration capacity (76.6 J/kg under 5 T) was obtained, as a result of the large reversible magnetic entropy change, broad operating temperature window, and small magnetic hysteresis loss. The large reversible magnetic entropy change and large reversible effective refrigeration capacity are important for improving the magnetocaloric performance, and the small magnetic hysteresis loss is beneficial to reducing energy dissipation during magnetic field cycle in potential applications.« less

Setaria viridis as a Model System to Advance Millet Genetics and Genomics

PubMed Central

Huang, Pu; Shyu, Christine; Coelho, Carla P.; Cao, Yingying; Brutnell, Thomas P.

2016-01-01

Millet is a common name for a group of polyphyletic, small-seeded cereal crops that include pearl, finger and foxtail millet. Millet species are an important source of calories for many societies, often in developing countries. Compared to major cereal crops such as rice and maize, millets are generally better adapted to dry and hot environments. Despite their food security value, the genetic architecture of agronomically important traits in millets, including both morphological traits and climate resilience remains poorly studied. These complex traits have been challenging to dissect in large part because of the lack of sufficient genetic tools and resources. In this article, we review the phylogenetic relationship among various millet species and discuss the value of a genetic model system for millet research. We propose that a broader adoption of green foxtail (Setaria viridis) as a model system for millets could greatly accelerate the pace of gene discovery in the millets, and summarize available and emerging resources in S. viridis and its domesticated relative S. italica. These resources have value in forward genetics, reverse genetics and high throughput phenotyping. We describe methods and strategies to best utilize these resources to facilitate the genetic dissection of complex traits. We envision that coupling cutting-edge technologies and the use of S. viridis for gene discovery will accelerate genetic research in millets in general. This will enable strategies and provide opportunities to increase productivity, especially in the semi-arid tropics of Asia and Africa where millets are staple food crops. PMID:27965689

Setaria viridis as a Model System to Advance Millet Genetics and Genomics.

PubMed

Huang, Pu; Shyu, Christine; Coelho, Carla P; Cao, Yingying; Brutnell, Thomas P

2016-01-01

Millet is a common name for a group of polyphyletic, small-seeded cereal crops that include pearl, finger and foxtail millet. Millet species are an important source of calories for many societies, often in developing countries. Compared to major cereal crops such as rice and maize, millets are generally better adapted to dry and hot environments. Despite their food security value, the genetic architecture of agronomically important traits in millets, including both morphological traits and climate resilience remains poorly studied. These complex traits have been challenging to dissect in large part because of the lack of sufficient genetic tools and resources. In this article, we review the phylogenetic relationship among various millet species and discuss the value of a genetic model system for millet research. We propose that a broader adoption of green foxtail ( Setaria viridis ) as a model system for millets could greatly accelerate the pace of gene discovery in the millets, and summarize available and emerging resources in S. viridis and its domesticated relative S. italica . These resources have value in forward genetics, reverse genetics and high throughput phenotyping. We describe methods and strategies to best utilize these resources to facilitate the genetic dissection of complex traits. We envision that coupling cutting-edge technologies and the use of S. viridis for gene discovery will accelerate genetic research in millets in general. This will enable strategies and provide opportunities to increase productivity, especially in the semi-arid tropics of Asia and Africa where millets are staple food crops.

GHEP-ISFG collaborative simulated exercise for DVI/MPI: Lessons learned about large-scale profile database comparisons.

PubMed

Vullo, Carlos M; Romero, Magdalena; Catelli, Laura; Šakić, Mustafa; Saragoni, Victor G; Jimenez Pleguezuelos, María Jose; Romanini, Carola; Anjos Porto, Maria João; Puente Prieto, Jorge; Bofarull Castro, Alicia; Hernandez, Alexis; Farfán, María José; Prieto, Victoria; Alvarez, David; Penacino, Gustavo; Zabalza, Santiago; Hernández Bolaños, Alejandro; Miguel Manterola, Irati; Prieto, Lourdes; Parsons, Thomas

2016-03-01

The GHEP-ISFG Working Group has recognized the importance of assisting DNA laboratories to gain expertise in handling DVI or missing persons identification (MPI) projects which involve the need for large-scale genetic profile comparisons. Eleven laboratories participated in a DNA matching exercise to identify victims from a hypothetical conflict with 193 missing persons. The post mortem database was comprised of 87 skeletal remain profiles from a secondary mass grave displaying a minimal number of 58 individuals with evidence of commingling. The reference database was represented by 286 family reference profiles with diverse pedigrees. The goal of the exercise was to correctly discover re-associations and family matches. The results of direct matching for commingled remains re-associations were correct and fully concordant among all laboratories. However, the kinship analysis for missing persons identifications showed variable results among the participants. There was a group of laboratories with correct, concordant results but nearly half of the others showed discrepant results exhibiting likelihood ratio differences of several degrees of magnitude in some cases. Three main errors were detected: (a) some laboratories did not use the complete reference family genetic data to report the match with the remains, (b) the identity and/or non-identity hypotheses were sometimes wrongly expressed in the likelihood ratio calculations, and (c) many laboratories did not properly evaluate the prior odds for the event. The results suggest that large-scale profile comparisons for DVI or MPI is a challenge for forensic genetics laboratories and the statistical treatment of DNA matching and the Bayesian framework should be better standardized among laboratories. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

From sexless to sexy: Why it is time for human genetics to consider and report analyses of sex.

PubMed

Powers, Matthew S; Smith, Phillip H; McKee, Sherry A; Ehringer, Marissa A

2017-01-01

Science has come a long way with regard to the consideration of sex differences in clinical and preclinical research, but one field remains behind the curve: human statistical genetics. The goal of this commentary is to raise awareness and discussion about how to best consider and evaluate possible sex effects in the context of large-scale human genetic studies. Over the course of this commentary, we reinforce the importance of interpreting genetic results in the context of biological sex, establish evidence that sex differences are not being considered in human statistical genetics, and discuss how best to conduct and report such analyses. Our recommendation is to run stratified analyses by sex no matter the sample size or the result and report the findings. Summary statistics from stratified analyses are helpful for meta-analyses, and patterns of sex-dependent associations may be hidden in a combined dataset. In the age of declining sequencing costs, large consortia efforts, and a number of useful control samples, it is now time for the field of human genetics to appropriately include sex in the design, analysis, and reporting of results.

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

PubMed Central

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

2014-01-01

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

Genetics Home Reference: nephronophthisis

MedlinePlus

... which can include liver fibrosis, heart abnormalities, or mirror image reversal of the position of one or ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related ...

The reverse of social anxiety is not always the opposite: the reverse-scored items of the social interaction anxiety scale do not belong.

PubMed

Rodebaugh, Thomas L; Woods, Carol M; Heimberg, Richard G

2007-06-01

Although well-used and empirically supported, the Social Interaction Anxiety Scale (SIAS) has a questionable factor structure and includes reverse-scored items with questionable utility. Here, using samples of undergraduates and a sample of clients with social anxiety disorder, we extend previous work that opened the question of whether the reverse-scored items belong on the scale. First, we successfully confirmed the factor structure obtained in previous samples. Second, we found the reverse-scored items to show consistently weaker relationships with a variety of comparison measures. Third, we demonstrated that removing the reverse-scored questions generally helps rather than hinders the psychometric performance of the SIAS total score. Fourth, we found that the reverse-scored items show a strong relationship with the normal personality characteristic of extraversion, suggesting that the reverse-scored items may primarily assess extraversion. Given the above results, we suggest investigators consider performing data analyses using only the straightforwardly worded items of the SIAS.

Genetic Variation in the Prostaglandin E2 Pathway Is Associated with Primary Graft Dysfunction

PubMed Central

Akimova, Tatiana; Kazi, Altaf; Shah, Rupal J.; Cantu, Edward; Feng, Rui; Levine, Matthew H.; Kawut, Steven M.; Meyer, Nuala J.; Lee, James C.; Hancock, Wayne W.; Aplenc, Richard; Ware, Lorraine B.; Palmer, Scott M.; Bhorade, Sangeeta; Lama, Vibha N.; Weinacker, Ann; Orens, Jonathan; Wille, Keith; Crespo, Maria; Lederer, David J.; Arcasoy, Selim; Demissie, Ejigayehu; Christie, Jason D.

2014-01-01

Rationale: Biologic pathways with significant genetic conservation across human populations have been implicated in the pathogenesis of primary graft dysfunction (PGD). The evaluation of the role of recipient genetic variation in PGD has thus far been limited to single, candidate gene analyses. Objectives: We sought to identify genetic variants in lung transplant recipients that are responsible for increased risk of PGD using a two-phase large-scale genotyping approach. Methods: Phase 1 was a large-scale candidate gene association study of the multicenter, prospective Lung Transplant Outcomes Group cohort. Phase 2 included functional evaluation of selected variants and a bioinformatics screening of variants identified in phase 1. Measurements and Main Results: After genetic data quality control, 680 lung transplant recipients were included in the analysis. In phase 1, a total of 17 variants were significantly associated with PGD, four of which were in the prostaglandin E2 family of genes. Among these were a coding variant in the gene encoding prostaglandin E2 synthase (PTGES2; P = 9.3 × 10−5) resulting in an arginine to histidine substitution at amino acid position 298, and three variants in a block containing the 5′ promoter and first intron of the PTGER4 gene (encoding prostaglandin E2 receptor subtype 4; all P < 5 × 10−5). Functional evaluation in regulatory T cells identified that rs4434423A in the PTGER4 gene was associated with differential suppressive function of regulatory T cells. Conclusions: Further research aimed at replication and additional functional insight into the role played by genetic variation in prostaglandin E2 synthetic and signaling pathways in PGD is warranted. PMID:24467603

Genetic and molecular alterations across medulloblastoma subgroups.

PubMed

Skowron, Patryk; Ramaswamy, Vijay; Taylor, Michael D

2015-10-01

Medulloblastoma is the most common malignant brain tumour diagnosed in children. Over the last few decades, advances in radiation and chemotherapy have significantly improved the odds of survival. Nevertheless, one third of all patients still succumb to their disease, and many long-term survivors are afflicted with neurocognitive sequelae. Large-scale multi-institutional efforts have provided insight into the transcriptional and genetic landscape of medulloblastoma. Four distinct subgroups of medulloblastoma have been identified, defined by distinct transcriptomes, genetics, demographics and outcomes. Integrated genomic profiling of each of these subgroups has revealed distinct genetic alterations, driving pathways and in some instances cells of origin. In this review, we highlight, in a subgroup-specific manner, our current knowledge of the genetic and molecular alterations in medulloblastoma and underscore the possible avenues for future therapeutic intervention.

Large effect of columnar defects on the thermodynamic properties of Bi2Sr2CaCu2O8 single crystals

NASA Astrophysics Data System (ADS)

van der Beek, C. J.; Konczykowski, M.; Li, T. W.; Kes, P. H.; Benoit, W.

1996-07-01

The introduction of columnar defects by irradiation with 5.8-GeV Pb ions is shown to affect significantly the reversible magnetic properties of Bi2Sr2CaCu2O8+δ single crystals. Notably, the suppression of superconducting fluctuations on length scales greater than the separation between columns leads to the disappearance of the ``crossing point'' in the critical fluctuation regime. At lower temperatures, the strong modification of the vortex energy due to pinning leads to an important change of the reversible magnetization. The analysis of the latter permits the direct determination of the pinning energy.

Simultaneous separation by reversed-phase high-performance liquid chromatography and mass spectral identification of anthocyanins and flavonols in Shiraz grape skin.

PubMed

Downey, Mark O; Rochfort, Simone

2008-08-01

A limitation of large-scale viticultural trials is the time and cost of comprehensive compositional analysis of the fruit by high-performance liquid chromatography (HPLC). In addition, separate methods have generally been required to identify and quantify different classes of metabolites. To address these shortcomings a reversed-phase HPLC method was developed to simultaneously separate the anthocyanins and flavonols present in grape skins. The method employs a methanol and water gradient acidified with 10% formic acid with a run-time of 48 min including re-equilibration. Identity of anthocyanins and flavonols in Shiraz (Vitis vinifera L.) skin was confirmed by mass spectral analysis.

Synthesis and electrochemical property of few-layer molybdenum disulfide nanosheets

NASA Astrophysics Data System (ADS)

Fu, Yanjue; Wang, Chunrui; Wang, Linlin; Peng, Xia; Wu, Binhe; Sun, Xingqu; Chen, Xiaoshuang

2016-12-01

Large-scale few-layer MoS2 nanosheets have been fabricated via a simple hydrothermal route using molybdenum powder as precursors. The as-prepared MoS2 samples were characterized by X-ray powder diffraction (XRD) analysis, transmission electron microscopy (TEM), and Raman and photoluminescence (PL) spectral analyses at room temperature. The results confirm that the as-prepared MoS2 displays a sheet-like morphology with a thickness of few (bi- to tri-) layers. Electrochemical measurements showed that the as-prepared few-layer MoS2 exhibited the highest reversible capacity of 1127 mAh g-1 and a stable reversible capacity of 1057 mAh g-1 after 30 cycles.

Landscape genetic approaches to guide native plant restoration in the Mojave Desert

USGS Publications Warehouse

Shryock, Daniel F.; Havrilla, Caroline A.; DeFalco, Lesley; Esque, Todd C.; Custer, Nathan; Wood, Troy E.

2016-01-01

Restoring dryland ecosystems is a global challenge due to synergistic drivers of disturbance coupled with unpredictable environmental conditions. Dryland plant species have evolved complex life-history strategies to cope with fluctuating resources and climatic extremes. Although rarely quantified, local adaptation is likely widespread among these species and potentially influences restoration outcomes. The common practice of reintroducing propagules to restore dryland ecosystems, often across large spatial scales, compels evaluation of adaptive divergence within these species. Such evaluations are critical to understanding the consequences of large-scale manipulation of gene flow and to predicting success of restoration efforts. However, genetic information for species of interest can be difficult and expensive to obtain through traditional common garden experiments. Recent advances in landscape genetics offer marker-based approaches for identifying environmental drivers of adaptive genetic variability in non-model species, but tools are still needed to link these approaches with practical aspects of ecological restoration. Here, we combine spatially-explicit landscape genetics models with flexible visualization tools to demonstrate how cost-effective evaluations of adaptive genetic divergence can facilitate implementation of different seed sourcing strategies in ecological restoration. We apply these methods to Amplified Fragment Length Polymorphism (AFLP) markers genotyped in two Mojave Desert shrub species of high restoration importance: the long-lived, wind-pollinated gymnosperm Ephedra nevadensis, and the short-lived, insect-pollinated angiosperm Sphaeralcea ambigua. Mean annual temperature was identified as an important driver of adaptive genetic divergence for both species. Ephedra showed stronger adaptive divergence with respect to precipitation variability, while temperature variability and precipitation averages explained a larger fraction of adaptive divergence in Sphaeralcea. We describe multivariate statistical approaches for interpolating spatial patterns of adaptive divergence while accounting for potential bias due to neutral genetic structure. Through a spatial bootstrapping procedure, we also visualize patterns in the magnitude of model uncertainty. Finally, we introduce an interactive, distance-based mapping approach that explicitly links marker-based models of adaptive divergence with local or admixture seed sourcing strategies, promoting effective native plant restoration.

Role of evolutionary and ecological factors in the reproductive success and the spatial genetic structure of the temperate gorgonian Paramuricea clavata

PubMed Central

Mokhtar-Jamaï, Kenza; Coma, Rafel; Wang, Jinliang; Zuberer, Frederic; Féral, Jean-Pierre; Aurelle, Didier

2013-01-01

Dispersal and mating features strongly influence the evolutionary dynamics and the spatial genetic structure (SGS) of marine populations. For the first time in a marine invertebrate, we examined individual reproductive success, by conducting larval paternity assignments after a natural spawning event, combined with a small-scale SGS analysis within a population of the gorgonian Paramuricea clavata. Thirty four percent of the larvae were sired by male colonies surrounding the brooding female colonies, revealing that the bulk of the mating was accomplished by males from outside the studied area. Male success increased with male height and decreased with increasing male to female distance. The parentage analyses, with a strong level of self-recruitment (25%), unveiled the occurrence of a complex family structure at a small spatial scale, consistent with the limited larval dispersal of this species. However, no evidence of small scale SGS was revealed despite this family structure. Furthermore, temporal genetic structure was not observed, which appears to be related to the rather large effective population size. The low level of inbreeding found suggests a pattern of random mating in this species, which disagrees with expectations that limited larval dispersal should lead to biparental inbreeding. Surface brooding and investment in sexual reproduction in P. clavata contribute to multiple paternity (on average 6.4 fathers were assigned per brood), which enhance genetic diversity of the brood. Several factors may have contributed to the lack of biparental inbreeding in our study such as (i) the lack of sperm limitation at a small scale, (ii) multiple paternity, and (iii) the large effective population size. Thus, our results indicate that limited larval dispersal and complex family structure do not necessarily lead to biparental inbreeding and SGS. In the framework of conservation purposes, our results suggested that colony size, proximity among colonies and the population size should be taken into consideration for restoration projects. PMID:23789084

Population Genetics of the Aquatic Fungus Tetracladium marchalianum over Space and Time

PubMed Central

Anderson, Jennifer L.; Shearer, Carol A.

2011-01-01

Aquatic hyphomycete fungi are fundamental mediators of energy flow and nutrient spiraling in rivers. These microscopic fungi are primarily dispersed in river currents, undergo substantial annual fluctuations in abundance, and reproduce either predominantly or exclusively asexually. These aspects of aquatic hyphomycete biology are expected to influence levels and distributions of genetic diversity over both spatial and temporal scales. In this study, we investigated the spatiotemporal distribution of genotypic diversity in the representative aquatic hyphomycete Tetracladium marchalianum. We sampled populations of this fungus from seven sites, three sites each in two rivers in Illinois, USA, and one site in a Wisconsin river, USA, and repeatedly sampled one population over two years to track population genetic parameters through two seasonal cycles. The resulting fungal isolates (N = 391) were genotyped at eight polymorphic microsatellite loci. In spite of seasonal reductions in the abundance of this species, genotypic diversity was consistently very high and allele frequencies remarkably stable over time. Likewise, genotypic diversity was very high at all sites. Genetic differentiation was only observed between the most distant rivers (∼450 km). Clear evidence that T. marchalianum reproduces sexually in nature was not observed. Additionally, we used phylogenetic analysis of partial β-tubulin gene sequences to confirm that the fungal isolates studied here represent a single species. These results suggest that populations of T. marchalianum may be very large and highly connected at local scales. We speculate that large population sizes and colonization of alternate substrates in both terrestrial and aquatic environments may effectively buffer the aquatic populations from in-stream population fluctuations and facilitate stability in allele frequencies over time. These data also suggest that overland dispersal is more important for structuring populations of T. marchalianum over geographic scales than expected. PMID:21264239

Speciation reversal and biodiversity dynamics with hybridization in changing environments.

PubMed

Seehausen, Ole; Takimoto, Gaku; Roy, Denis; Jokela, Jukka

2008-01-01

A considerable fraction of the world's biodiversity is of recent evolutionary origin and has evolved as a by-product of, and is maintained by, divergent adaptation in heterogeneous environments. Conservationists have paid attention to genetic homogenization caused by human-induced translocations (e.g. biological invasions and stocking), and to the importance of environmental heterogeneity for the ecological coexistence of species. However, far less attention has been paid to the consequences of loss of environmental heterogeneity to the genetic coexistence of sympatric species. Our review of empirical observations and our theoretical considerations on the causes and consequences of interspecific hybridization suggest that a loss of environmental heterogeneity causes a loss of biodiversity through increased genetic admixture, effectively reversing speciation. Loss of heterogeneity relaxes divergent selection and removes ecological barriers to gene flow between divergently adapted species, promoting interspecific introgressive hybridization. Since heterogeneity of natural environments is rapidly deteriorating in most biomes, the evolutionary ecology of speciation reversal ought to be fully integrated into conservation biology.

GM foods: is there a way forward?

PubMed

Jones, Huw D

2015-08-01

There are many quality targets in cereals that could generate step-change improvements in nutritional or food-processing characteristics. For instance, levels of acrylamide, soluble and insoluble fibre, antioxidants, allergens and intolerance factors in food are, to a large extent, determined by the genetics of the raw materials used. However, improvements to these traits pose significant challenges to plant breeders. For some traits, this is because the underlying genetic and biochemical basis of the traits is not fully understood but for others, there is simply a lack of natural genetic variation in commercially useful germplasm. One strategy to overcome the latter hindrance is to use wide crosses with more exotic germplasm; however, this can bring other difficulties such as yield loss and linkage drag of deleterious alleles. As DNA sequencing becomes cheaper and faster, it drives the research fields of reverse genetics and functional genomics which in turn will enable the incorporation of desirable traits into crop varieties via molecular breeding and biotechnology. I will discuss the evolution of these techniques from conventional genetic modification to more recent developments in targeted gene editing and the potential of biotechnology to complement conventional breeding methods. I will also discuss the role of risk assessment and regulation in the commercialisation of GM crops.

Discrete Event Modeling and Massively Parallel Execution of Epidemic Outbreak Phenomena

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

Perumalla, Kalyan S; Seal, Sudip K

2011-01-01

In complex phenomena such as epidemiological outbreaks, the intensity of inherent feedback effects and the significant role of transients in the dynamics make simulation the only effective method for proactive, reactive or post-facto analysis. The spatial scale, runtime speed, and behavioral detail needed in detailed simulations of epidemic outbreaks make it necessary to use large-scale parallel processing. Here, an optimistic parallel execution of a new discrete event formulation of a reaction-diffusion simulation model of epidemic propagation is presented to facilitate in dramatically increasing the fidelity and speed by which epidemiological simulations can be performed. Rollback support needed during optimistic parallelmore » execution is achieved by combining reverse computation with a small amount of incremental state saving. Parallel speedup of over 5,500 and other runtime performance metrics of the system are observed with weak-scaling execution on a small (8,192-core) Blue Gene / P system, while scalability with a weak-scaling speedup of over 10,000 is demonstrated on 65,536 cores of a large Cray XT5 system. Scenarios representing large population sizes exceeding several hundreds of millions of individuals in the largest cases are successfully exercised to verify model scalability.« less

A SPECTRAL GRAPH APPROACH TO DISCOVERING GENETIC ANCESTRY1

PubMed Central

Lee, Ann B.; Luca, Diana; Roeder, Kathryn

2010-01-01

Mapping human genetic variation is fundamentally interesting in fields such as anthropology and forensic inference. At the same time, patterns of genetic diversity confound efforts to determine the genetic basis of complex disease. Due to technological advances, it is now possible to measure hundreds of thousands of genetic variants per individual across the genome. Principal component analysis (PCA) is routinely used to summarize the genetic similarity between subjects. The eigenvectors are interpreted as dimensions of ancestry. We build on this idea using a spectral graph approach. In the process we draw on connections between multidimensional scaling and spectral kernel methods. Our approach, based on a spectral embedding derived from the normalized Laplacian of a graph, can produce more meaningful delineation of ancestry than by using PCA. The method is stable to outliers and can more easily incorporate different similarity measures of genetic data than PCA. We illustrate a new algorithm for genetic clustering and association analysis on a large, genetically heterogeneous sample. PMID:20689656

FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans.

PubMed

Bhardwaj, Ashwani; Thapliyal, Saurabh; Dahiya, Yogesh; Babu, Kavita

2018-05-16

Animal behavior is critically dependent on the activity of neuropeptides. Reversals, one of the most conspicuous behaviors in Caenorhabditis elegans , plays an important role in determining the navigation strategy of the animal. Our experiments on hermaphrodite C. elegans show the involvement of a neuropeptide FLP-18 in modulating reversal length in these hermaphrodites. We show that FLP-18 controls the reversal length by regulating the activity of AVA interneurons through the G-protein-coupled neuropeptide receptors, NPR-4 and NPR-1. We go on to show that the site of action of these receptors is the AVA interneuron for NPR-4 and the ASE sensory neurons for NPR-1. We further show that mutants in the neuropeptide, flp-18 , and its receptors show increased reversal lengths. Consistent with the behavioral data, calcium levels in the AVA neuron of freely reversing C. elegans were significantly higher and persisted for longer durations in flp-18 , npr-1 , npr-4 , and npr-1 npr-4 genetic backgrounds compared with wild-type control animals. Finally, we show that increasing FLP-18 levels through genetic and physiological manipulations causes shorter reversal lengths. Together, our analysis suggests that the FLP-18/NPR-1/NPR-4 signaling is a pivotal point in the regulation of reversal length under varied genetic and environmental conditions. SIGNIFICANCE STATEMENT In this study, we elucidate the circuit and molecular machinery required for normal reversal behavior in hermaphrodite Caenorhabditis elegans We delineate the circuit and the neuropeptide receptors required for maintaining reversal length in C. elegans Our work sheds light on the importance of a single neuropeptide, FLP-18, and how change in levels in this one peptide could allow the animal to change the length of its reversal, thereby modulating how the C. elegans explores its environment. We also go on to show that FLP-18 functions to maintain reversal length through the neuropeptide receptors NPR-4 and NPR-1. Our study will allow for a better understanding of the complete repertoire of behaviors shown by freely moving animals as they explore their environment. Copyright © 2018 the authors 0270-6474/18/384641-14$15.00/0.

Integrative approaches for large-scale transcriptome-wide association studies

PubMed Central

Gusev, Alexander; Ko, Arthur; Shi, Huwenbo; Bhatia, Gaurav; Chung, Wonil; Penninx, Brenda W J H; Jansen, Rick; de Geus, Eco JC; Boomsma, Dorret I; Wright, Fred A; Sullivan, Patrick F; Nikkola, Elina; Alvarez, Marcus; Civelek, Mete; Lusis, Aldons J.; Lehtimäki, Terho; Raitoharju, Emma; Kähönen, Mika; Seppälä, Ilkka; Raitakari, Olli T.; Kuusisto, Johanna; Laakso, Markku; Price, Alkes L.; Pajukanta, Päivi; Pasaniuc, Bogdan

2016-01-01

Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance levels of one or multiple proteins. Here, we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated to complex traits. We leverage expression imputation to perform a transcriptome wide association scan (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ~3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 novel genes significantly associated to obesity-related traits (BMI, lipids, and height). Many of the novel genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits. PMID:26854917

Resolving the ancestry of Austronesian-speaking populations.

PubMed

Soares, Pedro A; Trejaut, Jean A; Rito, Teresa; Cavadas, Bruno; Hill, Catherine; Eng, Ken Khong; Mormina, Maru; Brandão, Andreia; Fraser, Ross M; Wang, Tse-Yi; Loo, Jun-Hun; Snell, Christopher; Ko, Tsang-Ming; Amorim, António; Pala, Maria; Macaulay, Vincent; Bulbeck, David; Wilson, James F; Gusmão, Leonor; Pereira, Luísa; Oppenheimer, Stephen; Lin, Marie; Richards, Martin B

2016-03-01

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion.

Hybrid algorithms for fuzzy reverse supply chain network design.

PubMed

Che, Z H; Chiang, Tzu-An; Kuo, Y C; Cui, Zhihua

2014-01-01

In consideration of capacity constraints, fuzzy defect ratio, and fuzzy transport loss ratio, this paper attempted to establish an optimized decision model for production planning and distribution of a multiphase, multiproduct reverse supply chain, which addresses defects returned to original manufacturers, and in addition, develops hybrid algorithms such as Particle Swarm Optimization-Genetic Algorithm (PSO-GA), Genetic Algorithm-Simulated Annealing (GA-SA), and Particle Swarm Optimization-Simulated Annealing (PSO-SA) for solving the optimized model. During a case study of a multi-phase, multi-product reverse supply chain network, this paper explained the suitability of the optimized decision model and the applicability of the algorithms. Finally, the hybrid algorithms showed excellent solving capability when compared with original GA and PSO methods.

Hybrid Algorithms for Fuzzy Reverse Supply Chain Network Design

PubMed Central

Che, Z. H.; Chiang, Tzu-An; Kuo, Y. C.

2014-01-01

In consideration of capacity constraints, fuzzy defect ratio, and fuzzy transport loss ratio, this paper attempted to establish an optimized decision model for production planning and distribution of a multiphase, multiproduct reverse supply chain, which addresses defects returned to original manufacturers, and in addition, develops hybrid algorithms such as Particle Swarm Optimization-Genetic Algorithm (PSO-GA), Genetic Algorithm-Simulated Annealing (GA-SA), and Particle Swarm Optimization-Simulated Annealing (PSO-SA) for solving the optimized model. During a case study of a multi-phase, multi-product reverse supply chain network, this paper explained the suitability of the optimized decision model and the applicability of the algorithms. Finally, the hybrid algorithms showed excellent solving capability when compared with original GA and PSO methods. PMID:24892057

The strains recommended for use in the bacterial reverse mutation test (OECD guideline 471) can be certified as non-genetically modified organisms.

PubMed

Sugiyama, Kei-Ichi; Yamada, Masami; Awogi, Takumi; Hakura, Atsushi

2016-01-01

The bacterial reverse mutation test, commonly called Ames test, is used worldwide. In Japan, the genetically modified organisms (GMOs) are regulated under the Cartagena Domestic Law, and organisms obtained by self-cloning and/or natural occurrence would be exempted from the law case by case. The strains of Salmonella typhimurium and Escherichia coli recommended for use in the bacterial reverse mutation test (OECD guideline 471), have been considered as non-GMOs because they can be constructed by self-cloning or naturally occurring bacterial strains, or do not disturb the biological diversity. The present article explains the reasons why these tester strains should be classified as non-GMOs.

Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica

PubMed Central

Vercken, Elodie; Fontaine, Michael C.; Gladieux, Pierre; Hood, Michael E.; Jonot, Odile; Giraud, Tatiana

2010-01-01

Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization patterns. PMID:21187901

Implementation and verification of a four-probe motion error measurement system for a large-scale roll lathe used in hybrid manufacturing

NASA Astrophysics Data System (ADS)

Chen, Yuan-Liu; Niu, Zengyuan; Matsuura, Daiki; Lee, Jung Chul; Shimizu, Yuki; Gao, Wei; Oh, Jeong Seok; Park, Chun Hong

2017-10-01

In this paper, a four-probe measurement system is implemented and verified for the carriage slide motion error measurement of a large-scale roll lathe used in hybrid manufacturing where a laser machining probe and a diamond cutting tool are placed on two sides of a roll workpiece for manufacturing. The motion error of the carriage slide of the roll lathe is composed of two straightness motion error components and two parallelism motion error components in the vertical and horizontal planes. Four displacement measurement probes, which are mounted on the carriage slide with respect to four opposing sides of the roll workpiece, are employed for the measurement. Firstly, based on the reversal technique, the four probes are moved by the carriage slide to scan the roll workpiece before and after a 180-degree rotation of the roll workpiece. Taking into consideration the fact that the machining accuracy of the lathe is influenced by not only the carriage slide motion error but also the gravity deformation of the large-scale roll workpiece due to its heavy weight, the vertical motion error is thus characterized relating to the deformed axis of the roll workpiece. The horizontal straightness motion error can also be synchronously obtained based on the reversal technique. In addition, based on an error separation algorithm, the vertical and horizontal parallelism motion error components are identified by scanning the rotating roll workpiece at the start and the end positions of the carriage slide, respectively. The feasibility and reliability of the proposed motion error measurement system are demonstrated by the experimental results and the measurement uncertainty analysis.

Spatio-temporal population structuring and genetic diversity retention in depleted Atlantic Bluefin tuna of the Mediterranean Sea

PubMed Central

Riccioni, Giulia; Landi, Monica; Ferrara, Giorgia; Milano, Ilaria; Cariani, Alessia; Zane, Lorenzo; Sella, Massimo; Barbujani, Guido; Tinti, Fausto

2010-01-01

Fishery genetics have greatly changed our understanding of population dynamics and structuring in marine fish. In this study, we show that the Atlantic Bluefin tuna (ABFT, Thunnus thynnus), an oceanic predatory species exhibiting highly migratory behavior, large population size, and high potential for dispersal during early life stages, displays significant genetic differences over space and time, both at the fine and large scales of variation. We compared microsatellite variation of contemporary (n = 256) and historical (n = 99) biological samples of ABFTs of the central-western Mediterranean Sea, the latter dating back to the early 20th century. Measures of genetic differentiation and a general heterozygote deficit suggest that differences exist among population samples, both now and 96–80 years ago. Thus, ABFTs do not represent a single panmictic population in the Mediterranean Sea. Statistics designed to infer changes in population size, both from current and past genetic variation, suggest that some Mediterranean ABFT populations, although still not severely reduced in their genetic potential, might have suffered from demographic declines. The short-term estimates of effective population size are straddled on the minimum threshold (effective population size = 500) indicated to maintain genetic diversity and evolutionary potential across several generations in natural populations. PMID:20080643

A 454 multiplex sequencing method for rapid and reliable genotyping of highly polymorphic genes in large-scale studies.

PubMed

Galan, Maxime; Guivier, Emmanuel; Caraux, Gilles; Charbonnel, Nathalie; Cosson, Jean-François

2010-05-11

High-throughput sequencing technologies offer new perspectives for biomedical, agronomical and evolutionary research. Promising progresses now concern the application of these technologies to large-scale studies of genetic variation. Such studies require the genotyping of high numbers of samples. This is theoretically possible using 454 pyrosequencing, which generates billions of base pairs of sequence data. However several challenges arise: first in the attribution of each read produced to its original sample, and second, in bioinformatic analyses to distinguish true from artifactual sequence variation. This pilot study proposes a new application for the 454 GS FLX platform, allowing the individual genotyping of thousands of samples in one run. A probabilistic model has been developed to demonstrate the reliability of this method. DNA amplicons from 1,710 rodent samples were individually barcoded using a combination of tags located in forward and reverse primers. Amplicons consisted in 222 bp fragments corresponding to DRB exon 2, a highly polymorphic gene in mammals. A total of 221,789 reads were obtained, of which 153,349 were finally assigned to original samples. Rules based on a probabilistic model and a four-step procedure, were developed to validate sequences and provide a confidence level for each genotype. The method gave promising results, with the genotyping of DRB exon 2 sequences for 1,407 samples from 24 different rodent species and the sequencing of 392 variants in one half of a 454 run. Using replicates, we estimated that the reproducibility of genotyping reached 95%. This new approach is a promising alternative to classical methods involving electrophoresis-based techniques for variant separation and cloning-sequencing for sequence determination. The 454 system is less costly and time consuming and may enhance the reliability of genotypes obtained when high numbers of samples are studied. It opens up new perspectives for the study of evolutionary and functional genetics of highly polymorphic genes like major histocompatibility complex genes in vertebrates or loci regulating self-compatibility in plants. Important applications in biomedical research will include the detection of individual variation in disease susceptibility. Similarly, agronomy will benefit from this approach, through the study of genes implicated in productivity or disease susceptibility traits.

Sex-specific genetic analysis indicates low correlation between demographic and genetic connectivity in the Scandinavian brown bear (Ursus arctos).

PubMed

Schregel, Julia; Kopatz, Alexander; Eiken, Hans Geir; Swenson, Jon E; Hagen, Snorre B

2017-01-01

The degree of gene flow within and among populations, i.e. genetic population connectivity, may closely track demographic population connectivity. Alternatively, the rate of gene flow may change relative to the rate of dispersal. In this study, we explored the relationship between genetic and demographic population connectivity using the Scandinavian brown bear as model species, due to its pronounced male dispersal and female philopatry. Thus, we expected that females would shape genetic structure locally, whereas males would act as genetic mediators among regions. To test this, we used eight validated microsatellite markers on 1531 individuals sampled noninvasively during country-wide genetic population monitoring in Sweden and Norway from 2006 to 2013. First, we determined sex-specific genetic structure and substructure across the study area. Second, we compared genetic differentiation, migration/gene flow patterns, and spatial autocorrelation results between the sexes both within and among genetic clusters and geographic regions. Our results indicated that demographic connectivity was not a reliable indicator of genetic connectivity. Among regions, we found no consistent difference in long-term gene flow and estimated current migration rates between males and females. Within regions/genetic clusters, only females consistently displayed significant positive spatial autocorrelation, indicating male-biased small-scale dispersal. In one cluster, however, males showed a dispersal pattern similar to females. The Scandinavian brown bear population has experienced substantial recovery over the last decades; however, our results did not show any changes in its large-scale population structure compared to previous studies, suggesting that an increase in population size and dispersal of individuals does not necessary lead to increased genetic connectivity. Thus, we conclude that both genetic and demographic connectivity should be estimated, so as not to make false assumptions about the reality of wildlife populations.

Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset | Office of Cancer Genomics

Cancer.gov

Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset.

Privacy Challenges of Genomic Big Data.

PubMed

Shen, Hong; Ma, Jian

2017-01-01

With the rapid advancement of high-throughput DNA sequencing technologies, genomics has become a big data discipline where large-scale genetic information of human individuals can be obtained efficiently with low cost. However, such massive amount of personal genomic data creates tremendous challenge for privacy, especially given the emergence of direct-to-consumer (DTC) industry that provides genetic testing services. Here we review the recent development in genomic big data and its implications on privacy. We also discuss the current dilemmas and future challenges of genomic privacy.

Insights into population ecology and sexual selection in snakes through the application of DNA-based genetic markers.

PubMed

Gibbs, H L; Weatherhead, P J

2001-01-01

Hypervariable genetic markers have revolutionized studies of kinship, behavioral ecology, and population biology in vertebrate groups such as birds, but their use in snakes remains limited. To illustrate the value of such markers in snakes, we review studies that have used microsatellite DNA loci to analyze local population differentiation and parentage in snakes. Four ecologically distinct species of snakes all show evidence for differentiation at small spatial scales (2-15 km), but with substantial differences among species. This result highlights how genetic analysis can reveal hidden aspects of the natural history of difficult-to-observe taxa, and it raises important questions about the ecological factors that may contribute to restricted gene flow. A 3-year study of genetic parentage in marked populations of the northern water snake showed that (1) participation in mating aggregations was a poor predictor of genetic-based measures of reproductive success; (2) multiple paternity was high, yet there was no detectable fitness advantage to multiple mating by females; and (3) the opportunity for selection was far higher in males than in females due to a larger variance in male reproductive success, and yet this resulted in no detectable selection on morphological variation in males. Thus genetic markers have provided accurate measures of individual reproductive success in this species, an important step toward resolving the adaptive significance of key features including multiple paternity and reversed sexual size dimorphism. Overall these studies illustrate how genetic analyses of snakes provide previously unobtainable information of long-standing interest to behavioral ecologists.

Genetic Variability Under the Seedbank Coalescent.

PubMed

Blath, Jochen; González Casanova, Adrián; Eldon, Bjarki; Kurt, Noemi; Wilke-Berenguer, Maite

2015-07-01

We analyze patterns of genetic variability of populations in the presence of a large seedbank with the help of a new coalescent structure called the seedbank coalescent. This ancestral process appears naturally as a scaling limit of the genealogy of large populations that sustain seedbanks, if the seedbank size and individual dormancy times are of the same order as those of the active population. Mutations appear as Poisson processes on the active lineages and potentially at reduced rate also on the dormant lineages. The presence of "dormant" lineages leads to qualitatively altered times to the most recent common ancestor and nonclassical patterns of genetic diversity. To illustrate this we provide a Wright-Fisher model with a seedbank component and mutation, motivated from recent models of microbial dormancy, whose genealogy can be described by the seedbank coalescent. Based on our coalescent model, we derive recursions for the expectation and variance of the time to most recent common ancestor, number of segregating sites, pairwise differences, and singletons. Estimates (obtained by simulations) of the distributions of commonly employed distance statistics, in the presence and absence of a seedbank, are compared. The effect of a seedbank on the expected site-frequency spectrum is also investigated using simulations. Our results indicate that the presence of a large seedbank considerably alters the distribution of some distance statistics, as well as the site-frequency spectrum. Thus, one should be able to detect from genetic data the presence of a large seedbank in natural populations. Copyright © 2015 by the Genetics Society of America.

Large-scale image-based profiling of single-cell phenotypes in arrayed CRISPR-Cas9 gene perturbation screens.

PubMed

de Groot, Reinoud; Lüthi, Joel; Lindsay, Helen; Holtackers, René; Pelkmans, Lucas

2018-01-23

High-content imaging using automated microscopy and computer vision allows multivariate profiling of single-cell phenotypes. Here, we present methods for the application of the CISPR-Cas9 system in large-scale, image-based, gene perturbation experiments. We show that CRISPR-Cas9-mediated gene perturbation can be achieved in human tissue culture cells in a timeframe that is compatible with image-based phenotyping. We developed a pipeline to construct a large-scale arrayed library of 2,281 sequence-verified CRISPR-Cas9 targeting plasmids and profiled this library for genes affecting cellular morphology and the subcellular localization of components of the nuclear pore complex (NPC). We conceived a machine-learning method that harnesses genetic heterogeneity to score gene perturbations and identify phenotypically perturbed cells for in-depth characterization of gene perturbation effects. This approach enables genome-scale image-based multivariate gene perturbation profiling using CRISPR-Cas9. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Population genomic analysis suggests strong influence of river network on spatial distribution of genetic variation in invasive saltcedar across the southwestern United States

USGS Publications Warehouse

Lee, Soo-Rang; Jo, Yeong-Seok; Park, Chan-Ho; Friedman, Jonathan M.; Olson, Matthew S.

2018-01-01

Understanding the complex influences of landscape and anthropogenic elements that shape the population genetic structure of invasive species provides insight into patterns of colonization and spread. The application of landscape genomics techniques to these questions may offer detailed, previously undocumented insights into factors influencing species invasions. We investigated the spatial pattern of genetic variation and the influences of landscape factors on population similarity in an invasive riparian shrub, saltcedar (Tamarix L.) by analysing 1,997 genomewide SNP markers for 259 individuals from 25 populations collected throughout the southwestern United States. Our results revealed a broad-scale spatial genetic differentiation of saltcedar populations between the Colorado and Rio Grande river basins and identified potential barriers to population similarity along both river systems. River pathways most strongly contributed to population similarity. In contrast, low temperature and dams likely served as barriers to population similarity. We hypothesize that large-scale geographic patterns in genetic diversity resulted from a combination of early introductions from distinct populations, the subsequent influence of natural selection, dispersal barriers and founder effects during range expansion.

Hiding in Plain Sight: A Case for Cryptic Metapopulations in Brook Trout (Salvelinus fontinalis)

PubMed Central

Kazyak, David C.; Hilderbrand, Robert H.; King, Tim L.; Keller, Stephen R.; Chhatre, Vikram E.

2016-01-01

A fundamental issue in the management and conservation of biodiversity is how to define a population. Spatially contiguous fish occupying a stream network have often been considered to represent a single, homogenous population. However, they may also represent multiple discrete populations, a single population with genetic isolation-by-distance, or a metapopulation. We used microsatellite DNA and a large-scale mark-recapture study to assess population structure in a spatially contiguous sample of Brook Trout (Salvelinus fontinalis), a species of conservation concern. We found evidence for limited genetic exchange across small spatial scales and in the absence of barriers to physical movement. Mark-recapture and stationary passive integrated transponder antenna records demonstrated that fish from two tributaries very seldom moved into the opposite tributary, but movements between the tributaries and mainstem were more common. Using Bayesian genetic clustering, we identified two genetic groups that exhibited significantly different growth rates over three years of study, yet survival rates were very similar. Our study highlights the importance of considering the possibility of multiple genetically distinct populations occurring within spatially contiguous habitats, and suggests the existence of a cryptic metapopulation: a spatially continuous distribution of organisms exhibiting metapopulation-like behaviors. PMID:26730588

A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities

PubMed Central

Vizeacoumar, Franco J; Arnold, Roland; Vizeacoumar, Frederick S; Chandrashekhar, Megha; Buzina, Alla; Young, Jordan T F; Kwan, Julian H M; Sayad, Azin; Mero, Patricia; Lawo, Steffen; Tanaka, Hiromasa; Brown, Kevin R; Baryshnikova, Anastasia; Mak, Anthony B; Fedyshyn, Yaroslav; Wang, Yadong; Brito, Glauber C; Kasimer, Dahlia; Makhnevych, Taras; Ketela, Troy; Datti, Alessandro; Babu, Mohan; Emili, Andrew; Pelletier, Laurence; Wrana, Jeff; Wainberg, Zev; Kim, Philip M; Rottapel, Robert; O'Brien, Catherine A; Andrews, Brenda; Boone, Charles; Moffat, Jason

2013-01-01

Improved efforts are necessary to define the functional product of cancer mutations currently being revealed through large-scale sequencing efforts. Using genome-scale pooled shRNA screening technology, we mapped negative genetic interactions across a set of isogenic cancer cell lines and confirmed hundreds of these interactions in orthogonal co-culture competition assays to generate a high-confidence genetic interaction network of differentially essential or differential essentiality (DiE) genes. The network uncovered examples of conserved genetic interactions, densely connected functional modules derived from comparative genomics with model systems data, functions for uncharacterized genes in the human genome and targetable vulnerabilities. Finally, we demonstrate a general applicability of DiE gene signatures in determining genetic dependencies of other non-isogenic cancer cell lines. For example, the PTEN−/− DiE genes reveal a signature that can preferentially classify PTEN-dependent genotypes across a series of non-isogenic cell lines derived from the breast, pancreas and ovarian cancers. Our reference network suggests that many cancer vulnerabilities remain to be discovered through systematic derivation of a network of differentially essential genes in an isogenic cancer cell model. PMID:24104479

Hiding in Plain Sight: A Case for Cryptic Metapopulations in Brook Trout (Salvelinus fontinalis).

PubMed

Kazyak, David C; Hilderbrand, Robert H; King, Tim L; Keller, Stephen R; Chhatre, Vikram E

2016-01-01

A fundamental issue in the management and conservation of biodiversity is how to define a population. Spatially contiguous fish occupying a stream network have often been considered to represent a single, homogenous population. However, they may also represent multiple discrete populations, a single population with genetic isolation-by-distance, or a metapopulation. We used microsatellite DNA and a large-scale mark-recapture study to assess population structure in a spatially contiguous sample of Brook Trout (Salvelinus fontinalis), a species of conservation concern. We found evidence for limited genetic exchange across small spatial scales and in the absence of barriers to physical movement. Mark-recapture and stationary passive integrated transponder antenna records demonstrated that fish from two tributaries very seldom moved into the opposite tributary, but movements between the tributaries and mainstem were more common. Using Bayesian genetic clustering, we identified two genetic groups that exhibited significantly different growth rates over three years of study, yet survival rates were very similar. Our study highlights the importance of considering the possibility of multiple genetically distinct populations occurring within spatially contiguous habitats, and suggests the existence of a cryptic metapopulation: a spatially continuous distribution of organisms exhibiting metapopulation-like behaviors.

Expectation propagation for large scale Bayesian inference of non-linear molecular networks from perturbation data.

PubMed

Narimani, Zahra; Beigy, Hamid; Ahmad, Ashar; Masoudi-Nejad, Ali; Fröhlich, Holger

2017-01-01

Inferring the structure of molecular networks from time series protein or gene expression data provides valuable information about the complex biological processes of the cell. Causal network structure inference has been approached using different methods in the past. Most causal network inference techniques, such as Dynamic Bayesian Networks and ordinary differential equations, are limited by their computational complexity and thus make large scale inference infeasible. This is specifically true if a Bayesian framework is applied in order to deal with the unavoidable uncertainty about the correct model. We devise a novel Bayesian network reverse engineering approach using ordinary differential equations with the ability to include non-linearity. Besides modeling arbitrary, possibly combinatorial and time dependent perturbations with unknown targets, one of our main contributions is the use of Expectation Propagation, an algorithm for approximate Bayesian inference over large scale network structures in short computation time. We further explore the possibility of integrating prior knowledge into network inference. We evaluate the proposed model on DREAM4 and DREAM8 data and find it competitive against several state-of-the-art existing network inference methods.

Ten-channel InP-based large-scale photonic integrated transmitter fabricated by SAG technology

NASA Astrophysics Data System (ADS)

Zhang, Can; Zhu, Hongliang; Liang, Song; Cui, Xiao; Wang, Huitao; Zhao, Lingjuan; Wang, Wei

2014-12-01

A 10-channel InP-based large-scale photonic integrated transmitter was fabricated by selective area growth (SAG) technology combined with butt-joint regrowth (BJR) technology. The SAG technology was utilized to fabricate the electroabsorption modulated distributed feedback (DFB) laser (EML) arrays at the same time. The design of coplanar electrodes for electroabsorption modulator (EAM) was used for the flip-chip bonding package. The lasing wavelength of DFB laser could be tuned by the integrated micro-heater to match the ITU grids, which only needs one electrode pad. The average output power of each channel is 250 μW with an injection current of 200 mA. The static extinction ratios of the EAMs for 10 channels tested are ranged from 15 to 27 dB with a reverse bias of 6 V. The frequencies of 3 dB bandwidth of the chip for each channel are around 14 GHz. The novel design and simple fabrication process show its enormous potential in reducing the cost of large-scale photonic integrated circuit (LS-PIC) transmitter with high chip yields.

SCOPA and META-SCOPA: software for the analysis and aggregation of genome-wide association studies of multiple correlated phenotypes.

PubMed

Mägi, Reedik; Suleimanov, Yury V; Clarke, Geraldine M; Kaakinen, Marika; Fischer, Krista; Prokopenko, Inga; Morris, Andrew P

2017-01-11

Genome-wide association studies (GWAS) of single nucleotide polymorphisms (SNPs) have been successful in identifying loci contributing genetic effects to a wide range of complex human diseases and quantitative traits. The traditional approach to GWAS analysis is to consider each phenotype separately, despite the fact that many diseases and quantitative traits are correlated with each other, and often measured in the same sample of individuals. Multivariate analyses of correlated phenotypes have been demonstrated, by simulation, to increase power to detect association with SNPs, and thus may enable improved detection of novel loci contributing to diseases and quantitative traits. We have developed the SCOPA software to enable GWAS analysis of multiple correlated phenotypes. The software implements "reverse regression" methodology, which treats the genotype of an individual at a SNP as the outcome and the phenotypes as predictors in a general linear model. SCOPA can be applied to quantitative traits and categorical phenotypes, and can accommodate imputed genotypes under a dosage model. The accompanying META-SCOPA software enables meta-analysis of association summary statistics from SCOPA across GWAS. Application of SCOPA to two GWAS of high-and low-density lipoprotein cholesterol, triglycerides and body mass index, and subsequent meta-analysis with META-SCOPA, highlighted stronger association signals than univariate phenotype analysis at established lipid and obesity loci. The META-SCOPA meta-analysis also revealed a novel signal of association at genome-wide significance for triglycerides mapping to GPC5 (lead SNP rs71427535, p = 1.1x10 -8 ), which has not been reported in previous large-scale GWAS of lipid traits. The SCOPA and META-SCOPA software enable discovery and dissection of multiple phenotype association signals through implementation of a powerful reverse regression approach.

Big Data in Medicine is Driving Big Changes

PubMed Central

Verspoor, K.

2014-01-01

Summary Objectives To summarise current research that takes advantage of “Big Data” in health and biomedical informatics applications. Methods Survey of trends in this work, and exploration of literature describing how large-scale structured and unstructured data sources are being used to support applications from clinical decision making and health policy, to drug design and pharmacovigilance, and further to systems biology and genetics. Results The survey highlights ongoing development of powerful new methods for turning that large-scale, and often complex, data into information that provides new insights into human health, in a range of different areas. Consideration of this body of work identifies several important paradigm shifts that are facilitated by Big Data resources and methods: in clinical and translational research, from hypothesis-driven research to data-driven research, and in medicine, from evidence-based practice to practice-based evidence. Conclusions The increasing scale and availability of large quantities of health data require strategies for data management, data linkage, and data integration beyond the limits of many existing information systems, and substantial effort is underway to meet those needs. As our ability to make sense of that data improves, the value of the data will continue to increase. Health systems, genetics and genomics, population and public health; all areas of biomedicine stand to benefit from Big Data and the associated technologies. PMID:25123716

Tough Self-Healing Elastomers by Molecular Enforced Integration of Covalent and Reversible Networks.

PubMed

Wu, Jinrong; Cai, Li-Heng; Weitz, David A

2017-10-01

Self-healing polymers crosslinked by solely reversible bonds are intrinsically weaker than common covalently crosslinked networks. Introducing covalent crosslinks into a reversible network would improve mechanical strength. It is challenging, however, to apply this concept to "dry" elastomers, largely because reversible crosslinks such as hydrogen bonds are often polar motifs, whereas covalent crosslinks are nonpolar motifs. These two types of bonds are intrinsically immiscible without cosolvents. Here, we design and fabricate a hybrid polymer network by crosslinking randomly branched polymers carrying motifs that can form both reversible hydrogen bonds and permanent covalent crosslinks. The randomly branched polymer links such two types of bonds and forces them to mix on the molecular level without cosolvents. This enables a hybrid "dry" elastomer that is very tough with fracture energy 13500 Jm -2 comparable to that of natural rubber. Moreover, the elastomer can self-heal at room temperature with a recovered tensile strength 4 MPa, which is 30% of its original value, yet comparable to the pristine strength of existing self-healing polymers. The concept of forcing covalent and reversible bonds to mix at molecular scale to create a homogenous network is quite general and should enable development of tough, self-healing polymers of practical usage. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Psychometric testing of the decisional conflict scale: genetic testing hereditary breast and ovarian cancer.

PubMed

Katapodi, Maria C; Munro, Michelle L; Pierce, Penny F; Williams, Reg A

2011-01-01

: Hereditary breast and ovarian cancer (HBOC) syndrome is attributed mostly to mutations in the Breast Cancer 1 and Breast Cancer 2 genes (BRCA1/2). Mutation carriers of BRCA1/2 genes have significantly higher risk for developing breast cancer compared with the general population (55%-85% vs. 12%) and for developing ovarian cancer (20%-60% vs. 1.5%). The availability of genetic testing enables mutation carriers to make informed decisions about managing their cancer risk (e.g., risk-reducing surgery). However, uptake of testing for HBOC among high-risk individuals is low, indicating the need to better understand and measure the decisional conflict associated with this process. : The aim of this study was to evaluate the reliability and validity of the modified Decisional Conflict Scale for use in decisions associated with genetic testing for HBOC. : This cross-sectional cohort study, recruited women who pursued genetic testing for HBOC in two genetic risk assessment clinics affiliated with a large comprehensive cancer center and one of their female relatives who did not pursue testing. The final sample consisted of 342 women who completed all 16 items of the Decisional Conflict Scale. The psychometric properties of the scale were assessed using tests of reliability and validity, including face, content, construct, contrast, convergent, divergent, and predictive validity. : Factor analysis using principal axis factoring with oblimin rotation elicited a three-factor structure: (a) Lack of Knowledge About the Decision (α = .97), (b) Lack of Autonomy in Decision Making (α = .94), and (c) Lack of Confidence in Decision Making (α = .87). These factors explained 82% of the variance in decisional conflict about genetic testing. Cronbach's alpha coefficient was .96. : The instrument is an important tool for researchers and healthcare providers working with women at risk for HBOC who are deciding whether genetic testing is the right choice for them.

Spatial genetic structuring of baobab (Adansonia digitata, Malvaceae) in the traditional agroforestry systems of West Africa.

PubMed

Kyndt, Tina; Assogbadjo, Achille E; Hardy, Olivier J; Glele Kakaï, Romain; Sinsin, Brice; Van Damme, Patrick; Gheysen, Godelieve

2009-05-01

This study evaluates the spatial genetic structure of baobab (Adansonia digitata) populations from West African agroforestry systems at different geographical scales using AFLP fingerprints. Eleven populations from four countries (Benin, Ghana, Burkina Faso, and Senegal) had comparable levels of genetic diversity, although the two populations in the extreme west (Senegal) had less diversity. Pairwise F(ST) ranged from 0.02 to 0.28 and increased with geographic distance, even at a regional scale. Gene pools detected by Bayesian clustering seem to be a byproduct of the isolation-by-distance pattern rather than representing actual discrete entities. The organization of genetic diversity appears to result essentially from spatially restricted gene flow, with some influences of human seed exchange. Despite the potential for relatively long-distance pollen and seed dispersal by bats within populations, statistically significant spatial genetic structuring within populations (SGS) was detected and gave a mean indirect estimate of neighborhood size of ca. 45. This study demonstrated that relatively high levels of genetic structuring are present in baobab at both large and within-population level, which was unexpected in regard to its dispersal by bats and the influence of human exchange of seeds. Implications of these results for the conservation of baobab populations are discussed.

[Research progress on molecular genetics of forest musk deer].

PubMed

Jie, Hang; Zheng, Cheng-li; Wang, Jian-ming; Feng, Xiao-lan; Zeng, De-jun; Zhao, Gui-jun

2015-11-01

Forest musk deer is one of the large-scale farming musk deer animals with the largest population at the same time. The male musk deer can secrete valuable medicines, which has high medicinal and economic value. Due to the loss of habitat and indiscriminate hunting, the numbers of wild population specie and the distribution have been drastically reduced. Therefore, in-depth understanding of the molecular genetics progress of forest musk deer will pave a way for musk deer protection and breeding. In this review, the progress associated with the molecular marker, genetic classification, artificial breeding, musk secretion and disease in past decades were reviewed, in order to provide a theoretical basis for subsequent molecular genetic researches in forest musk deer.

Molecular cytogenetic mapping of 24 CEPH YACs and 24 gene-specific large insert probes to chromosome 17.

PubMed

Bärlund, M; Nupponen, N N; Karhu, R; Tanner, M M; Paavola, P; Kallioniemi, O P; Kallioniemi, A

1998-01-01

Defining boundaries of chromosomal rearrangements at the molecular level would benefit from landmarks that link the cytogenetic map to physical, genetic, and transcript maps, as well as from large-insert FISH probes for such loci to detect numerical and structural rearrangements in metaphase or interphase cells. Here, we determined the locations of 24 genetically mapped CEPH-Mega YACs along the FLpter scale (fractional length from p-telomere) by quantitative fluorescence in situ hybridization analysis. This generated a set of cytogenetically mapped probes for chromosome 17 with an average spacing of about 5 cM. We then developed large-insert YAC, BAC, PAC, or P1 clones to the following 24 known genes, and determined refined map locations along the same FLpter scale: pter-TP53-TOP3-cen-TNFAIP1-ERBB2-TOP2A- BRCA1-TCF11-NME1-HLF-ZNF147/CL N80-BCL5/MPO/SFRS1-TBX2-PECAM1-DDX5/ PRKCA-ICAM2-GH1/PRKAR1A-GRB2-CDK3 /FKHL13-qter. Taken together, these 48 cytogenetically mapped large-insert probes provide tools for the molecular analysis of chromosome 17 rearrangements, such as mapping amplification, deletion, and translocation breakpoints in this chromosome, in cancer and other diseases.

Reversible immortalization of Nestin-positive precursor cells from pancreas and differentiation into insulin-secreting cells

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

Wei, Pei; Li, Li; Qi, Hui

2012-02-10

Highlights: Black-Right-Pointing-Pointer The NPPCs from mouse pancreas were isolated. Black-Right-Pointing-Pointer Tet-on system for SV40 large in NPPCs was used to get RINPPCs. Black-Right-Pointing-Pointer The RINPPCs can undergo at least 80 population doublings without senescence. Black-Right-Pointing-Pointer The RINPPCs can be induced to differentiate into insulin-producing cells. Black-Right-Pointing-Pointer The combination of GLP-1 and sodium butyrate promoted the differentiation process. -- Abstract: Pancreatic stem cells or progenitor cells posses the ability of directed differentiation into pancreatic {beta} cells. However, these cells usually have limited proliferative capacity and finite lifespan in vitro. In the present study, Nestin-positive progenitor cells (NPPCs) from mouse pancreas thatmore » expressed the pancreatic stem cells or progenitor cell marker Nestin were isolated to obtain a sufficient number of differentiated pancreatic {beta} cells. Tet-on system for SV40 large T-antigen expression in NPPCs was used to achieve reversible immortalization. The reversible immortal Nestin-positive progenitor cells (RINPPCs) can undergo at least 80 population doublings without senescence in vitro while maintaining their biological and genetic characteristics. RINPPCs can be efficiently induced to differentiate into insulin-producing cells that contain a combination of glucagon-like peptide-1 (GLP-1) and sodium butyrate. The results of the present study can be used to explore transplantation therapy of type I diabetes mellitus.« less

Osteosarcoma Genetics and Epigenetics: Emerging Biology and Candidate Therapies

PubMed Central

Morrow, James J.; Khanna, Chand

2016-01-01

Osteosarcoma is the most common primary malignancy of bone, typically presenting in the first or second decade of life. Unfortunately, clinical outcomes for osteosarcoma patients have not substantially improved in over 30 years. This stagnation in therapeutic advances is perhaps explained by the genetic, epigenetic, and biological complexities of this rare tumor. In this review we provide a general background on the biology of osteosarcoma and the clinical status quo. We go on to enumerate the genetic and epigenetic defects identified in osteosarcoma. Finally, we discuss ongoing large-scale studies in the field and potential new therapies that are currently under investigation. PMID:26349415

The ENCODE project: implications for psychiatric genetics.

PubMed

Kavanagh, D H; Dwyer, S; O'Donovan, M C; Owen, M J

2013-05-01

The ENCyclopedia Of DNA Elements (ENCODE) project is a public research consortium that aims to identify all functional elements of the human genome sequence. The project comprised 1640 data sets, from 147 different cell type and the findings were released in a coordinated set of 34 publications across several journals. The ENCODE publications report that 80.4% of the human genome displays some functionality. These data have important implications for interpreting results from large-scale genetics studies. We reviewed some of the key findings from the ENCODE publications and discuss how they can influence or inform further investigations into the genetic factors contributing to neuropsychiatric disorders.

Novel Hantavirus in the Flat-Skulled Shrew (Sorex roboratus)

PubMed Central

Kang, Hae Ji; Arai, Satoru; Hope, Andrew G.; Cook, Joseph A.

2010-01-01

Abstract Genetically distinct hantaviruses have been identified recently in multiple species of shrews (Order Soricomorpha, Family Soricidae) in Eurasia and North America. To corroborate decades-old reports of hantaviral antigens in shrews from Russia, archival liver and lung tissues from 4 Siberian large-toothed shrews (Sorex daphaenodon), 5 Eurasian least shrews (Sorex minutissimus), 12 flat-skulled shrews (Sorex roboratus), and 18 tundra shrews (Sorex tundrensis), captured in the Sakha Republic in northeastern Siberia during July and August 2006, were analyzed for hantavirus RNA by reverse transcription–polymerase chain reaction. A novel hantavirus, named Kenkeme virus, was detected in a flat-skulled shrew. Sequence analysis of the full-length S and partial M and L segments indicated that Kenkeme virus was genetically and phylogenetically distinct from Seewis virus harbored by the Eurasian common shrew (Sorex araneus), as well as all other rodent-, soricid-, and talpid-borne hantaviruses. PMID:20426682

Genome-Scale Metabolic Reconstructions and Theoretical Investigation of Methane Conversion in Methylomicrobium buryatense Strain 5G(B1)

DOE PAGES

de la Torre, Andrea; Metivier, Aisha; Chu, Frances; ...

2015-11-25

Methane-utilizing bacteria (methanotrophs) are capable of growth on methane and are attractive systems for bio-catalysis. However, the application of natural methanotrophic strains to large-scale production of value-added chemicals/biofuels requires a number of physiological and genetic alterations. An accurate metabolic model coupled with flux balance analysis can provide a solid interpretative framework for experimental data analyses and integration.

Engineering and Scaling the Spontaneous Magnetization Reversal of Faraday Induced Magnetic Relaxation in Nano-Sized Amorphous Ni Coated on Crystalline Au.

PubMed

Li, Wen-Hsien; Lee, Chi-Hung; Kuo, Chen-Chen

2016-05-28

We report on the generation of large inverse remanent magnetizations in nano-sized core/shell structure of Au/Ni by turning off the applied magnetic field. The remanent magnetization is very sensitive to the field reduction rate as well as to the thermal and field processes before the switching off of the magnetic field. Spontaneous reversal in direction and increase in magnitude of the remanent magnetization in subsequent relaxations over time were found. All of the various types of temporal relaxation curves of the remanent magnetizations are successfully scaled by a stretched exponential decay profile, characterized by two pairs of relaxation times and dynamic exponents. The relaxation time is used to describe the reduction rate, while the dynamic exponent describes the dynamical slowing down of the relaxation through time evolution. The key to these effects is to have the induced eddy current running beneath the amorphous Ni shells through Faraday induction.

Analysis of genetic diversity using SNP markers in oat

USDA-ARS?s Scientific Manuscript database

A large-scale single nucleotide polymorphism (SNP) discovery was carried out in cultivated oat using Roche 454 sequencing methods. DNA sequences were generated from cDNAs originating from a panel of 20 diverse oat cultivars, and from Diversity Array Technology (DArT) genomic complexity reductions fr...

Dual redox catalysts for oxygen reduction and evolution reactions: towards a redox flow Li-O2 battery.

PubMed

Zhu, Yun Guang; Jia, Chuankun; Yang, Jing; Pan, Feng; Huang, Qizhao; Wang, Qing

2015-06-11

A redox flow lithium-oxygen battery (RFLOB) by using soluble redox catalysts with good performance was demonstrated for large-scale energy storage. The new device enables the reversible formation and decomposition of Li2O2 via redox targeting reactions in a gas diffusion tank, spatially separated from the electrode, which obviates the passivation and pore clogging of the cathode.

Facile Synthesis of Layer Structured GeP3/C with Stable Chemical Bonding for Enhanced Lithium-Ion Storage

NASA Astrophysics Data System (ADS)

Qi, Wen; Zhao, Haihua; Wu, Ying; Zeng, Hong; Tao, Tao; Chen, Chao; Kuang, Chunjiang; Zhou, Shaoxiong; Huang, Yunhui

2017-02-01

Recently, metal phosphides have been investigated as potential anode materials because of higher specific capacity compared with those of carbonaceous materials. However, the rapid capacity fade upon cycling leads to poor durability and short cycle life, which cannot meet the need of lithium-ion batteries with high energy density. Herein, we report a layer-structured GeP3/C nanocomposite anode material with high performance prepared by a facial and large-scale ball milling method via in-situ mechanical reaction. The P-O-C bonds are formed in the composite, leading to close contact between GeP3 and carbon. As a result, the GeP3/C anode displays excellent lithium storage performance with a high reversible capacity up to 1109 mA h g-1 after 130 cycles at a current density of 0.1 A g-1. Even at high current densities of 2 and 5 A g-1, the reversible capacities are still as high as 590 and 425 mA h g-1, respectively. This suggests that the GeP3/C composite is promising to achieve high-energy lithium-ion batteries and the mechanical milling is an efficient method to fabricate such composite electrode materials especially for large-scale application.

Radiative Reverse Shock Laser Experiments Relevant to Accretion Processes in Cataclysmic Variables

NASA Astrophysics Data System (ADS)

Krauland, Christine

2012-10-01

We present results from experiments that explore radiative reverse shock waves and their contribution to the evolving dynamics of the cataclysmic variable (CV) system in which they reside. CVs are close binary star systems containing a white dwarf (WD) that accretes matter from its late-type main sequence companion star. In the process of accretion, a reverse shock forms when the supersonic infalling plasma is impeded. It provides the main source of radiation in the binary systems. In the case of a non-magnetic CV, the impact on an accretion disk produces this ``hot spot,'' where the flow obliquely strikes the rotating accretion disk. This collision region has many ambiguities as a radiation hydrodynamic system, but shock development in the infalling flow can be modeled [1]. We discuss the production of radiative reverse shocks in experiments at the Omega-60 laser facility. The ability of this high-intensity laser to create large energy densities in targets having millimeter-scale volumes makes it feasible to create supersonic plasma flows. Obtaining a radiative reverse shock in the laboratory requires a sufficiently fast flow (> 60 km/s) within a material whose opacity is large enough to produce energetically significant emission from experimentally achievable layers. We will show the radiographic and emission data from three campaigns on Omega-60 with accompanying CRASH [2] simulations, and will discuss the implications in the context of the CV system. [4pt] [1] Armitage, P. J. and Livio, M., ApJ, 493, 898 (1998).[0pt] [2] van der Holst, B., Toth, G., Sokolov, I.V., et al., ApJS, 194, 23 (2011).

Monitoring Local Changes in Granite Rock Under Biaxial Test: A Spatiotemporal Imaging Application With Diffuse Waves

NASA Astrophysics Data System (ADS)

Xie, Fan; Ren, Yaqiong; Zhou, Yongsheng; Larose, Eric; Baillet, Laurent

2018-03-01

Diffuse acoustic or seismic waves are highly sensitive to detect changes of mechanical properties in heterogeneous geological materials. In particular, thanks to acoustoelasticity, we can quantify stress changes by tracking acoustic or seismic relative velocity changes in the material at test. In this paper, we report on a small-scale laboratory application of an innovative time-lapse tomography technique named Locadiff to image spatiotemporal mechanical changes on a granite sample under biaxial loading, using diffuse waves at ultrasonic frequencies (300 kHz to 900 kHz). We demonstrate the ability of the method to image reversible stress evolution and deformation process, together with the development of reversible and irreversible localized microdamage in the specimen at an early stage. Using full-field infrared thermography, we visualize stress-induced temperature changes and validate stress images obtained from diffuse ultrasound. We demonstrate that the inversion with a good resolution can be achieved with only a limited number of receivers distributed around a single source, all located at the free surface of the specimen. This small-scale experiment is a proof of concept for frictional earthquake-like failure (e.g., stick-slip) research at laboratory scale as well as large-scale seismic applications, potentially including active fault monitoring.

Shared genetic basis for migraine and ischemic stroke

PubMed Central

Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S.; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G.; Terwindt, Gisela M.; Sturm, Jonathan; Bis, Joshua C.; Hopewell, Jemma C.; Ferrari, Michel D.; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F.; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I.; Mitchell, Braxton D.; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T.; Kurth, Tobias; Ikram, M. Arfan; Reiner, Alex P.; Longstreth, W.T.; Rothwell, Peter M.; Strachan, David P.; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B.; Davey Smith, George; van Duijn, Cornelia M.; Stefansson, Kari; Worrall, Bradford B.; Nyholt, Dale R.; Markus, Hugh S.; van den Maagdenberg, Arn M.J.M.; Cotsapas, Chris; Zwart, John A.; Palotie, Aarno

2015-01-01

Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10−28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10−20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. PMID:25934857

Aetiology for the covariation between combined type ADHD and reading difficulties in a family study: the role of IQ

PubMed Central

Cheung, Celeste H.M.; Wood, Alexis C.; Paloyelis, Yannis; Arias-Vasquez, Alejandro; Buitelaar, Jan K.; Franke, Barbara; Miranda, Ana; Mulas, Fernando; Rommelse, Nanda; Sergeant, Joseph A.; Sonuga-Barke, Edmund J.; Faraone, Stephen V.; Asherson, Philip; Kuntsi, Jonna

2012-01-01

Background Twin studies using both clinical and population-based samples suggest that the frequent co-occurrence of attention deficit hyperactivity disorder (ADHD) and reading ability/disability (RD) is largely driven by shared genetic influences. While both disorders are associated with lower IQ, recent twin data suggest that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genetic influences contributing to general cognitive ability. The current study aimed to extend the previous findings that were based on rating scale measures in a population sample by examining the generalizability of the findings to a clinical population, and by measuring reading difficulties both with a rating scale and with an objective task. We therefore investigated the familial relationships between ADHD, reading difficulties and IQ in a sample of individuals diagnosed with ADHD combined type, their siblings and control sibling pairs. Methods We ran multivariate familial models on data from 1789 individuals at ages 6 to 19. Reading difficulties were measured with both rating scale and an objective task. IQ was obtained using the Wechsler Intelligence Scales (WISC-III / WAIS-III). Results Significant phenotypic (0.2–0.4) and familial (0.3–0.5) correlations were observed among ADHD, reading difficulties and IQ. Yet 53% to 72% of the overlapping familial influences between ADHD and reading difficulties were not shared with IQ. Conclusions Our finding that familial influences shared with general cognitive ability, though present, do not account for the majority of the overlapping familial influences on ADHD and reading difficulties extends previous findings from a population-based study to a clinically-ascertained sample with combined type ADHD. PMID:22324316

Genetic correlations and the evolution of photoperiodic time measurement within a local population of the pitcher-plant mosquito, Wyeomyia smithii

PubMed Central

Bradshaw, W E; Emerson, K J; Holzapfel, C M

2012-01-01

The genetic relationship between the daily circadian clock and the seasonal photoperiodic timer remains a subject of intense controversy. In Wyeomyia smithii, the critical photoperiod (an overt expression of the photoperiodic timer) evolves independently of the rhythmic response to the Nanda–Hamner protocol (an overt expression of the daily circadian clock) over a wide geographical range in North America. Herein, we focus on these two processes within a single local population in which there is a negative genetic correlation between them. We show that antagonistic selection against this genetic correlation rapidly breaks it down and, in fact, reverses its sign, showing that the genetic correlation is due primarily to linkage and not to pleiotropy. This rapid reversal of the genetic correlation within a small, single population means that it is difficult to argue that circadian rhythmicity forms the necessary, causal basis for the adaptive divergence of photoperiodic time measurement within populations or for the evolution of photoperiodic time measurement among populations over a broad geographical gradient of seasonal selection. PMID:22072069

The morphing of geographical features by Fourier transformation.

PubMed

Li, Jingzhong; Liu, Pengcheng; Yu, Wenhao; Cheng, Xiaoqiang

2018-01-01

This paper presents a morphing model of vector geographical data based on Fourier transformation. This model involves three main steps. They are conversion from vector data to Fourier series, generation of intermediate function by combination of the two Fourier series concerning a large scale and a small scale, and reverse conversion from combination function to vector data. By mirror processing, the model can also be used for morphing of linear features. Experimental results show that this method is sensitive to scale variations and it can be used for vector map features' continuous scale transformation. The efficiency of this model is linearly related to the point number of shape boundary and the interceptive value n of Fourier expansion. The effect of morphing by Fourier transformation is plausible and the efficiency of the algorithm is acceptable.

Dispersal ability and habitat requirements determine landscape-level genetic patterns in desert aquatic insects.

PubMed

Phillipsen, Ivan C; Kirk, Emily H; Bogan, Michael T; Mims, Meryl C; Olden, Julian D; Lytle, David A

2015-01-01

Species occupying the same geographic range can exhibit remarkably different population structures across the landscape, ranging from highly diversified to panmictic. Given limitations on collecting population-level data for large numbers of species, ecologists seek to identify proximate organismal traits-such as dispersal ability, habitat preference and life history-that are strong predictors of realized population structure. We examined how dispersal ability and habitat structure affect the regional balance of gene flow and genetic drift within three aquatic insects that represent the range of dispersal abilities and habitat requirements observed in desert stream insect communities. For each species, we tested for linear relationships between genetic distances and geographic distances using Euclidean and landscape-based metrics of resistance. We found that the moderate-disperser Mesocapnia arizonensis (Plecoptera: Capniidae) has a strong isolation-by-distance pattern, suggesting migration-drift equilibrium. By contrast, population structure in the flightless Abedus herberti (Hemiptera: Belostomatidae) is influenced by genetic drift, while gene flow is the dominant force in the strong-flying Boreonectes aequinoctialis (Coleoptera: Dytiscidae). The best-fitting landscape model for M. arizonensis was based on Euclidean distance. Analyses also identified a strong spatial scale-dependence, where landscape genetic methods only performed well for species that were intermediate in dispersal ability. Our results highlight the fact that when either gene flow or genetic drift dominates in shaping population structure, no detectable relationship between genetic and geographic distances is expected at certain spatial scales. This study provides insight into how gene flow and drift interact at the regional scale for these insects as well as the organisms that share similar habitats and dispersal abilities. © 2014 John Wiley & Sons Ltd.

Understanding Coral's Short-term Adaptive Ability to Changing Environment

NASA Astrophysics Data System (ADS)

Tisthammer, K.; Richmond, R. H.

2016-02-01

Corals in Maunalua Bay, Hawaii are under chronic pressures from sedimentation and terrestrial runoffs containing multiple pollutants as a result of large scale urbanization that has taken place in the last 100 years. However, some individual corals thrive despite the prolonged exposure to these environmental stressors, which suggests that these individuals may have adapted to withstand such stressors. A recent survey showed that the lobe coral Porites lobata from the `high-stress' nearshore site had an elevated level of stress ixnduced proteins, compared to those from the `low-stress,' less polluted offshore site. To understand the genetic basis for the observed differential stress responses between the nearshore and offshore P. lobata populations, an analysis of the lineage-scale population genetic structure, as well as a reciprocal transplant experiment were conducted. The result of the genetic analysis revealed a clear genetic differentiation between P. lobata from the nearshore site and the offshore site. Following the 30- day reciprocal transplant experiment, protein expression profiles and other stress-related physiological characteristics were compared between the two populations. The experimental results suggest that the nearshore genotype can cope better with sedimentation/pollutants than the offshore genotype. This indicates that the observed genetic differentiation is due to selection for tolerance to these environmental stressors. Understanding the little-known, linage-scale genetic variation in corals offers a critical insight into their short-term adaptive ability, which is indispensable for protecting corals from impending environmental and climate change. The results of this study also offer a valuable tool for resource managers to make effective decisions on coral reef conservation, such as designing marine protected areas that incorporate and maintain such genetic diversity, and establishing acceptable pollution run-off levels.

Spin diffusion from an inhomogeneous quench in an integrable system.

PubMed

Ljubotina, Marko; Žnidarič, Marko; Prosen, Tomaž

2017-07-13

Generalized hydrodynamics predicts universal ballistic transport in integrable lattice systems when prepared in generic inhomogeneous initial states. However, the ballistic contribution to transport can vanish in systems with additional discrete symmetries. Here we perform large scale numerical simulations of spin dynamics in the anisotropic Heisenberg XXZ spin 1/2 chain starting from an inhomogeneous mixed initial state which is symmetric with respect to a combination of spin reversal and spatial reflection. In the isotropic and easy-axis regimes we find non-ballistic spin transport which we analyse in detail in terms of scaling exponents of the transported magnetization and scaling profiles of the spin density. While in the easy-axis regime we find accurate evidence of normal diffusion, the spin transport in the isotropic case is clearly super-diffusive, with the scaling exponent very close to 2/3, but with universal scaling dynamics which obeys the diffusion equation in nonlinearly scaled time.

Optimisation Of a Magnetostrictive Wave Energy Converter

NASA Astrophysics Data System (ADS)

Mundon, T. R.; Nair, B.

2014-12-01

Oscilla Power, Inc. (OPI) is developing a patented magnetostrictive wave energy converter aimed at reducing the cost of grid-scale electricity from ocean waves. Designed to operate cost-effectively across a wide range of wave conditions, this will be the first use of reverse magnetostriction for large-scale energy production. The device architecture is a straightforward two-body, point absorbing system that has been studied at length by various researchers. A large surface float is anchored to a submerged heave (reaction) plate by multiple taut tethers that are largely made up of discrete, robust power takeoff modules that house the magnetostrictive generators. The unique generators developed by OPI utilize the phenomenon of reverse magnetostriction, which through the application of load to a specific low cost alloy, can generate significant magnetic flux changes, and thus create power through electromagnetic induction. Unlike traditional generators, the mode of operation is low-displacement, high-force, high damping which in combination with the specific multi-tether configuration creates some unique effects and interesting optimization challenges. Using an empirical approach with a combination of numerical tools, such as ORCAFLEX, and physical models, we investigated the properties and sensitivities of this system arrangement, including various heave plate geometries, with the overall goal of identifying the mass and hydrodynamic parameters required for optimum performance. Furthermore, through a detailed physical model test program at the University of New Hampshire, we were able to study in more detail how the heave plate geometry affects the drag and added mass coefficients. In presenting this work we will discuss how alternate geometries could be used to optimize the hydrodynamic parameters of the heave plate, allowing maximum inertial forces in operational conditions, while simultaneously minimizing the forces generated in extreme waves. This presentation will cover the significant findings from this research, including physical model results and identified sensitivity parameters. In addition, we will discuss some preliminary results from our large-scale ocean trial conducted in August & September of this year.

Statistical genetics concepts and approaches in schizophrenia and related neuropsychiatric research.

PubMed

Schork, Nicholas J; Greenwood, Tiffany A; Braff, David L

2007-01-01

Statistical genetics is a research field that focuses on mathematical models and statistical inference methodologies that relate genetic variations (ie, naturally occurring human DNA sequence variations or "polymorphisms") to particular traits or diseases (phenotypes) usually from data collected on large samples of families or individuals. The ultimate goal of such analysis is the identification of genes and genetic variations that influence disease susceptibility. Although of extreme interest and importance, the fact that many genes and environmental factors contribute to neuropsychiatric diseases of public health importance (eg, schizophrenia, bipolar disorder, and depression) complicates relevant studies and suggests that very sophisticated mathematical and statistical modeling may be required. In addition, large-scale contemporary human DNA sequencing and related projects, such as the Human Genome Project and the International HapMap Project, as well as the development of high-throughput DNA sequencing and genotyping technologies have provided statistical geneticists with a great deal of very relevant and appropriate information and resources. Unfortunately, the use of these resources and their interpretation are not straightforward when applied to complex, multifactorial diseases such as schizophrenia. In this brief and largely nonmathematical review of the field of statistical genetics, we describe many of the main concepts, definitions, and issues that motivate contemporary research. We also provide a discussion of the most pressing contemporary problems that demand further research if progress is to be made in the identification of genes and genetic variations that predispose to complex neuropsychiatric diseases.

Sockeye salmon (Oncorhynchus nerka) return after an absence of nearly 90 years: A case of reversion to anadromy

USGS Publications Warehouse

Godbout, L.; Wood, C.C.; Withler, R.E.; Latham, S.; Nelson, R.J.; Wetzel, L.; Barnett-Johnson, R.; Grove, M.J.; Schmitt, A.K.; McKeegan, K.D.

2011-01-01

We document the recent reappearance of anadromous sockeye salmon (Oncorhynchus nerka) that were thought to have been extirpated by the construction of hydroelectric dams on the Coquitlam and Alouette rivers in British Columbia, Canada, in 1914 and 1927, respectively. Unexpected downstream migrations of juveniles during experimental water releases into both rivers in 2005 and 2006 preceded upstream return migrations of adults in 2007 and 2008. Genetic (microsatellite and mitochondrial DNA) markers and stable isotope (??34S and 87Sr/86Sr) patterns in otoliths confirm that both the juvenile downstream migrants and adult upstream migrants were progeny of nonanadromous sockeye salmon (kokanee) that inhabit Coquitlam and Alouette reservoirs. Low genetic diversity and evidence of genetic bottlenecks suggest that the kokanee populations in both reservoirs originated from relatively few anadromous individuals that residualized after downstream migration was largely prevented by the construction of dams. Once given an opportunity for upstream and downstream migration, both populations appear capable of reverting to a successful anadromous form, even after 25 generations.

Mutagenicity of fractionated test material from the synthetic fuel technology with bacterial systems

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

Rao, T.K.; Young, J.A.; Hardigree, A.A.

1978-01-01

The predictive value of short-term genetic tests, such as the Salmonella and Escherichia coli (K-12, 343/113) systems including microsomal activation, is well documented. We have applied the short-term testing to various crude products and effluents from the synthetic fuel technologies. Class fractionation and column chromatography of the test materials and the coupled bioassays can be used to identify the most active fractions (collaborative effort with Analytical Chemistry Division). Reversion at the histidine locus for Salmonella was assayed with each fraction and the results are expressed in units of revertants (strain TA98) per milligram of the starting material (organic content) includingmore » metabolic activation with a crude rat liver preparation. Results obtained with the Salmonella system were validated by employing E. coli strains auxotrophic for arginine. Genetic activity is seen with a variety of fractions, largely the basic and neutral (PAH) components. Total activity varies from process to process, thus, the short-term genetic test can be considered a useful prescreen for potential biohazard of various effluents both in plants and in the immediate plant environment.« less

Moving into a new era of periodontal genetic studies: relevance of large case-control samples using severe phenotypes for genome-wide association studies.

PubMed

Vaithilingam, R D; Safii, S H; Baharuddin, N A; Ng, C C; Cheong, S C; Bartold, P M; Schaefer, A S; Loos, B G

2014-12-01

Studies to elucidate the role of genetics as a risk factor for periodontal disease have gone through various phases. In the majority of cases, the initial 'hypothesis-dependent' candidate-gene polymorphism studies did not report valid genetic risk loci. Following a large-scale replication study, these initially positive results are believed to be caused by type 1 errors. However, susceptibility genes, such as CDKN2BAS (Cyclin Dependend KiNase 2B AntiSense RNA; alias ANRIL [ANtisense Rna In the Ink locus]), glycosyltransferase 6 domain containing 1 (GLT6D1) and cyclooxygenase 2 (COX2), have been reported as conclusive risk loci of periodontitis. The search for genetic risk factors accelerated with the advent of 'hypothesis-free' genome-wide association studies (GWAS). However, despite many different GWAS being performed for almost all human diseases, only three GWAS on periodontitis have been published - one reported genome-wide association of GLT6D1 with aggressive periodontitis (a severe phenotype of periodontitis), whereas the remaining two, which were performed on patients with chronic periodontitis, were not able to find significant associations. This review discusses the problems faced and the lessons learned from the search for genetic risk variants of periodontitis. Current and future strategies for identifying genetic variance in periodontitis, and the importance of planning a well-designed genetic study with large and sufficiently powered case-control samples of severe phenotypes, are also discussed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Computational reverse shoulder prosthesis model: Experimental data and verification.

PubMed

Martins, A; Quental, C; Folgado, J; Ambrósio, J; Monteiro, J; Sarmento, M

2015-09-18

The reverse shoulder prosthesis aims to restore the stability and function of pathological shoulders, but the biomechanical aspects of the geometrical changes induced by the implant are yet to be fully understood. Considering a large-scale musculoskeletal model of the upper limb, the aim of this study is to evaluate how the Delta reverse shoulder prosthesis influences the biomechanical behavior of the shoulder joint. In this study, the kinematic data of an unloaded abduction in the frontal plane and an unloaded forward flexion in the sagittal plane were experimentally acquired through video-imaging for a control group, composed of 10 healthy shoulders, and a reverse shoulder group, composed of 3 reverse shoulders. Synchronously, the EMG data of 7 superficial muscles were also collected. The muscle force sharing problem was solved through the minimization of the metabolic energy consumption. The evaluation of the shoulder kinematics shows an increase in the lateral rotation of the scapula in the reverse shoulder group, and an increase in the contribution of the scapulothoracic joint to the shoulder joint. Regarding the muscle force sharing problem, the musculoskeletal model estimates an increased activity of the deltoid, teres minor, clavicular fibers of the pectoralis major, and coracobrachialis muscles in the reverse shoulder group. The comparison between the muscle forces predicted and the EMG data acquired revealed a good correlation, which provides further confidence in the model. Overall, the shoulder joint reaction force was lower in the reverse shoulder group than in the control group. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic Based Plant Resistance and Susceptibility Traits to Herbivory Influence Needle and Root Litter Nutrient Dynamics

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

Classen, Aimee T; Chapman, Samantha K.; Whitham, Thomas G

2007-01-01

It is generally assumed that leaf and root litter decomposition have similar drivers and that nutrient release from these substrates is synchronized. Few studies have examined these assumptions, and none has examined how plant genetics (i.e., plant susceptibility to herbivory) could affect these relationships. Here we examine the effects of herbivore susceptibility and resistance on needle and fine root litter decomposition of pi on pine, Pinus edulis. The study population consists of individual trees that are either susceptible or resistant to herbivory by the pi on needle scale, Matsucoccus acalyptus, or the stem-boring moth, Dioryctria albovittella. Genetic analyses and experimentalmore » removals and additions of these insects have identified trees that are naturally resistant and susceptible to these insects. These herbivores increase the chemical quality of litter inputs and alter soil microclimate, both of which are important decomposition drivers. Our research leads to four major conclusions: Herbivore susceptibility and resistance effects on 1) needle litter mass loss and phosphorus (P) retention in moth susceptible and resistant litter are governed by microclimate, 2) root litter nitrogen (N) and P retention, and needle litter N retention are governed by litter chemical quality, 3) net nutrient release from litter can reverse over time, 4) root and needle litter mass loss and nutrient release are determined by location (above- vs. belowground), suggesting that the regulators of needle and root decomposition differ at the local scale. Understanding of decomposition and nutrient retention in ecosystems requires consideration of herbivore effects on above- and belowground processes and how these effects may be governed by plant genotype. Because an underlying genetic component to herbivory is common to most ecosystems of the world and herbivory may increase in climatic change scenarios, it is important to evaluate the role of plant genetics in affecting carbon and nutrient fluxes.« less

Relating Silica Scaling in Reverse Osmosis to Membrane Surface Properties.

PubMed

Tong, Tiezheng; Zhao, Song; Boo, Chanhee; Hashmi, Sara M; Elimelech, Menachem

2017-04-18

We investigated the relationship between membrane surface properties and silica scaling in reverse osmosis (RO). The effects of membrane hydrophilicity, free energy for heterogeneous nucleation, and surface charge on silica scaling were examined by comparing thin-film composite polyamide membranes grafted with a variety of polymers. Results show that the rate of silica scaling was independent of both membrane hydrophilicity and free energy for heterogeneous nucleation. In contrast, membrane surface charge demonstrated a strong correlation with the extent of silica scaling (R 2 > 0.95, p < 0.001). Positively charged membranes significantly facilitated silica scaling, whereas a more negative membrane surface charge led to reduced scaling. This observation suggests that deposition of negatively charged silica species on the membrane surface plays a critical role in silica scale formation. Our findings provide fundamental insights into the mechanisms governing silica scaling in reverse osmosis and highlight the potential of membrane surface modification as a strategy to reduce silica scaling.

Flow path oscillations in transient ground-water simulations of large peatland systems

USGS Publications Warehouse

Reeve, A.S.; Evensen, R.; Glaser, P.H.; Siegel, D.I.; Rosenberry, D.

2006-01-01

Transient numerical simulations of the Glacial Lake Agassiz Peatland near the Red Lakes in Northern Minnesota were constructed to evaluate observed reversals in vertical ground-water flow. Seasonal weather changes were introduced to a ground-water flow model by varying evapotranspiration and recharge over time. Vertical hydraulic reversals, driven by changes in recharge and evapotranspiration were produced in the simulated peat layer. These simulations indicate that the high specific storage associated with the peat is an important control on hydraulic reversals. Seasonally driven vertical flow is on the order of centimeters in the deep peat, suggesting that seasonal vertical advective fluxes are not significant and that ground-water flow into the deep peat likely occurs on decadal or longer time scales. Particles tracked within the ground-water flow model oscillate over time, suggesting that seasonal flow reversals will enhance vertical mixing in the peat column. The amplitude of flow path oscillations increased with increasing peat storativity, with amplitudes of about 5 cm occurring when peat specific storativity was set to about 0.05 m-1. ?? 2005 Elsevier B.V. All rights reserved.

Stimulus-Responsive Nanoparticles and Associated (Reversible) Polymorphism via Polymerization Induced Self-assembly (PISA).

PubMed

Pei, Yiwen; Lowe, Andrew B; Roth, Peter J

2017-01-01

Polymerization-induced self-assembly (PISA) is an extremely versatile method for the in situ preparation of soft-matter nanoparticles of defined size and morphologies at high concentrations, suitable for large-scale production. Recently, certain PISA-prepared nanoparticles have been shown to exhibit reversible polymorphism ("shape-shifting"), typically between micellar, worm-like, and vesicular phases (order-order transitions), in response to external stimuli including temperature, pH, electrolytes, and chemical modification. This review summarises the literature to date and describes molecular requirements for the design of stimulus-responsive nano-objects. Reversible pH-responsive behavior is rationalised in terms of increased solvation of reversibly ionized groups. Temperature-triggered order-order transitions, conversely, do not rely on inherently thermo-responsive polymers, but are explained based on interfacial LCST or UCST behavior that affects the volume fractions of the core and stabilizer blocks. Irreversible morphology transitions, on the other hand, can result from chemical post-modification of reactive PISA-made particles. Emerging applications and future research directions of this "smart" nanoparticle behavior are reviewed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative maps of genetic interactions in yeast - comparative evaluation and integrative analysis.

PubMed

Lindén, Rolf O; Eronen, Ville-Pekka; Aittokallio, Tero

2011-03-24

High-throughput genetic screening approaches have enabled systematic means to study how interactions among gene mutations contribute to quantitative fitness phenotypes, with the aim of providing insights into the functional wiring diagrams of genetic interaction networks on a global scale. However, it is poorly known how well these quantitative interaction measurements agree across the screening approaches, which hinders their integrated use toward improving the coverage and quality of the genetic interaction maps in yeast and other organisms. Using large-scale data matrices from epistatic miniarray profiling (E-MAP), genetic interaction mapping (GIM), and synthetic genetic array (SGA) approaches, we carried out here a systematic comparative evaluation among these quantitative maps of genetic interactions in yeast. The relatively low association between the original interaction measurements or their customized scores could be improved using a matrix-based modelling framework, which enables the use of single- and double-mutant fitness estimates and measurements, respectively, when scoring genetic interactions. Toward an integrative analysis, we show how the detections from the different screening approaches can be combined to suggest novel positive and negative interactions which are complementary to those obtained using any single screening approach alone. The matrix approximation procedure has been made available to support the design and analysis of the future screening studies. We have shown here that even if the correlation between the currently available quantitative genetic interaction maps in yeast is relatively low, their comparability can be improved by means of our computational matrix approximation procedure, which will enable integrative analysis and detection of a wider spectrum of genetic interactions using data from the complementary screening approaches.