Impact of Insertion Sequences and Recombination on the Population Structure of Staphylococcus haemolyticus.

PubMed

Bouchami, Ons; de Lencastre, Herminia; Miragaia, Maria

2016-01-01

Staphylococcus haemolyticus is one of the most common pathogens associated with medical-device related infections, but its molecular epidemiology is poorly explored. In the current study, we aimed to better understand the genetic mechanisms contributing to S. haemolyticus diversity in the hospital environment and their impact on the population structure and clinical relevant phenotypic traits. The analysis of a representative S. haemolyticus collection by multilocus sequence typing (MLST) has identified a single highly prevalent and diverse genetic lineage of nosocomial S. haemolyticus clonal complex (CC) 29 accounting for 91% of the collection of isolates disseminated worldwide. The examination of the sequence changes at MLST loci during clonal diversification showed that recombination had a higher impact than mutation in shaping the S. haemolyticus population. Also, we ascertained that another mechanism contributing significantly to clonal diversification and adaptation was mediated by insertion sequence (IS) elements. We found that all nosocomial S. haemolyticus, belonging to different STs, were rich in IS1272 copies, as determined by Southern hybridization of macrorestriction patterns. In particular, we observed that the chromosome of a S. haemolyticus strain within CC29 was highly unstable during serial growth in vitro which paralleled with IS1272 transposition events and changes in clinically relevant phenotypic traits namely, mannitol fermentation, susceptibility to beta-lactams, biofilm formation and hemolysis. Our results suggest that recombination and IS transposition might be a strategy of adaptation, evolution and pathogenicity of the major S. haemolyticus prevalent lineage in the hospital environment.

Impact of Insertion Sequences and Recombination on the Population Structure of Staphylococcus haemolyticus

PubMed Central

Bouchami, Ons; de Lencastre, Herminia; Miragaia, Maria

2016-01-01

Staphylococcus haemolyticus is one of the most common pathogens associated with medical-device related infections, but its molecular epidemiology is poorly explored. In the current study, we aimed to better understand the genetic mechanisms contributing to S. haemolyticus diversity in the hospital environment and their impact on the population structure and clinical relevant phenotypic traits. The analysis of a representative S. haemolyticus collection by multilocus sequence typing (MLST) has identified a single highly prevalent and diverse genetic lineage of nosocomial S. haemolyticus clonal complex (CC) 29 accounting for 91% of the collection of isolates disseminated worldwide. The examination of the sequence changes at MLST loci during clonal diversification showed that recombination had a higher impact than mutation in shaping the S. haemolyticus population. Also, we ascertained that another mechanism contributing significantly to clonal diversification and adaptation was mediated by insertion sequence (IS) elements. We found that all nosocomial S. haemolyticus, belonging to different STs, were rich in IS1272 copies, as determined by Southern hybridization of macrorestriction patterns. In particular, we observed that the chromosome of a S. haemolyticus strain within CC29 was highly unstable during serial growth in vitro which paralleled with IS1272 transposition events and changes in clinically relevant phenotypic traits namely, mannitol fermentation, susceptibility to beta-lactams, biofilm formation and hemolysis. Our results suggest that recombination and IS transposition might be a strategy of adaptation, evolution and pathogenicity of the major S. haemolyticus prevalent lineage in the hospital environment. PMID:27249649

Impact of Public Safety Policies on Human Immunodeficiency Virus Transmission Dynamics in Tijuana, Mexico.

PubMed

Mehta, Sanjay R; Chaillon, Antoine; Gaines, Tommi L; Gonzalez-Zuniga, Patricia E; Stockman, Jamila K; Almanza-Reyes, Horatio; Chavez, Jose Roman; Vera, Alicia; Wagner, Karla D; Patterson, Thomas L; Scott, Brianna; Smith, Davey M; Strathdee, Steffanie A

2018-02-10

North Tijuana, Mexico is home to many individuals at high risk for transmitting and acquiring human immunodeficiency virus (HIV). Recently, policy shifts by local government impacted how these individuals were handled by authorities. Here we examined how this affected regional HIV transmission dynamics. HIV pol sequences and associated demographic information were collected from 8 research studies enrolling persons in Tijuana and were used to infer viral transmission patterns. To evaluate the impact of recent policy changes on HIV transmission dynamics, qualitative interviews were performed on a subset of recently infected individuals. Between 2004 and 2016, 288 unique HIV pol sequences were obtained from individuals in Tijuana, including 46.4% from men who have sex with men, 42.1% from individuals reporting transactional sex, and 27.8% from persons who inject drugs (some individuals had >1 risk factor). Forty-two percent of sequences linked to at least 1 other sequence, forming 37 transmission clusters. Thirty-two individuals seroconverted during the observation period, including 8 between April and July 2016. Three of these individuals were putatively linked together. Qualitative interviews suggested changes in policing led individuals to shift locations of residence and injection drug use, leading to increased risk taking (eg, sharing needles). Near real-time molecular epidemiologic analyses identified a cluster of linked transmissions temporally associated with policy shifts. Interviews suggested these shifts may have led to increased risk taking among individuals at high risk for HIV acquisition. With all public policy shifts, downstream impacts need to be carefully considered, as even well-intentioned policies can have major public health consequences. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Investment in Communications and Transportation: Socio-economic Impacts on Rural Development.

ERIC Educational Resources Information Center

Hilewick, Carol Lee; And Others

Two rural counties served as model areas in a comparison of the size and sequence of socioeconomic changes that investment in communications, as opposed to investment in transportation networks, might stimulate. A series of communications, rail, and highway changes were simulated through the use of an econometric model. An Industrial Communication…

Land Reform and Social Change in Colombia.

ERIC Educational Resources Information Center

Hirschman, Albert O.; And Others

This conference report focuses on three major areas of interest: (1) land reform in Colombia, (2) social change in Popayan, and (3) implications for research in agrarian structure in Colombia. A case study dealing with Colombia's sequence of moves toward land reform over the last 40 years is reviewed. The impact of political factors and social…

The Unique Significance and Origin of the Cretaceous-Tertiary Boundary: Historical Context and Burdens of Proof

NASA Technical Reports Server (NTRS)

Ryder, Graham

1996-01-01

The abruptness and intensity of the Cretaceous-Tertiary boundary have been deemphasized by some authors over recent years, mainly by those skeptical of an impact origin for the boundary. However, it was recognized at the birth of stratigraphy as both abrupt and of major importance. It was used to define the change from the Mesozoic to the Cenozoic; the boundary has become continually more precisely defined and its global sequences more correlatable. It is now unique in being an event boundary marked by an iridium-bearing layer of global extent, rather than an arbitrary boundary in a sequence of little change. The Permian-Triassic boundary, in contrast, is arbitrary and the transition is not yet proven to be abrupt, the extinctions that define it perhaps having taken place in pulses over several millions of years. Some of those who have denied the importance (and in some cases even the existence) of an impact in the Cretaceous-Tertiary extinctions have placed burdens of proof on the impact hypothesis that they do not place on strictly terrestrial mechanisms. Terrestrial mechanisms have always been unsatisfactory (or at least unconvincing for global, massive, multienvironment faunal change) and are now even more so. Some authors have required of the impact hypothesis attributes that are not inherent in it, including particular patterns of extinction selectivity and timing.

IMPACT web portal: oncology database integrating molecular profiles with actionable therapeutics.

PubMed

Hintzsche, Jennifer D; Yoo, Minjae; Kim, Jihye; Amato, Carol M; Robinson, William A; Tan, Aik Choon

2018-04-20

With the advancement of next generation sequencing technology, researchers are now able to identify important variants and structural changes in DNA and RNA in cancer patient samples. With this information, we can now correlate specific variants and/or structural changes with actionable therapeutics known to inhibit these variants. We introduce the creation of the IMPACT Web Portal, a new online resource that connects molecular profiles of tumors to approved drugs, investigational therapeutics and pharmacogenetics associated drugs. IMPACT Web Portal contains a total of 776 drugs connected to 1326 target genes and 435 target variants, fusion, and copy number alterations. The online IMPACT Web Portal allows users to search for various genetic alterations and connects them to three levels of actionable therapeutics. The results are categorized into 3 levels: Level 1 contains approved drugs separated into two groups; Level 1A contains approved drugs with variant specific information while Level 1B contains approved drugs with gene level information. Level 2 contains drugs currently in oncology clinical trials. Level 3 provides pharmacogenetic associations between approved drugs and genes. IMPACT Web Portal allows for sequencing data to be linked to actionable therapeutics for translational and drug repurposing research. The IMPACT Web Portal online resource allows users to query genes and variants to approved and investigational drugs. We envision that this resource will be a valuable database for personalized medicine and drug repurposing. IMPACT Web Portal is freely available for non-commercial use at http://tanlab.ucdenver.edu/IMPACT .

Impact of peer review on reports of randomised trials published in open peer review journals: retrospective before and after study

PubMed Central

Collins, Gary S; Boutron, Isabelle; Yu, Ly-Mee; Cook, Jonathan; Shanyinde, Milensu; Wharton, Rose; Shamseer, Larissa; Altman, Douglas G

2014-01-01

Objective To investigate the effectiveness of open peer review as a mechanism to improve the reporting of randomised trials published in biomedical journals. Design Retrospective before and after study. Setting BioMed Central series medical journals. Sample 93 primary reports of randomised trials published in BMC-series medical journals in 2012. Main outcome measures Changes to the reporting of methodological aspects of randomised trials in manuscripts after peer review, based on the CONSORT checklist, corresponding peer reviewer reports, the type of changes requested, and the extent to which authors adhered to these requests. Results Of the 93 trial reports, 38% (n=35) did not describe the method of random sequence generation, 54% (n=50) concealment of allocation sequence, 50% (n=46) whether the study was blinded, 34% (n=32) the sample size calculation, 35% (n=33) specification of primary and secondary outcomes, 55% (n=51) results for the primary outcome, and 90% (n=84) details of the trial protocol. The number of changes between manuscript versions was relatively small; most involved adding new information or altering existing information. Most changes requested by peer reviewers had a positive impact on the reporting of the final manuscript—for example, adding or clarifying randomisation and blinding (n=27), sample size (n=15), primary and secondary outcomes (n=16), results for primary or secondary outcomes (n=14), and toning down conclusions to reflect the results (n=27). Some changes requested by peer reviewers, however, had a negative impact, such as adding additional unplanned analyses (n=15). Conclusion Peer reviewers fail to detect important deficiencies in reporting of the methods and results of randomised trials. The number of these changes requested by peer reviewers was relatively small. Although most had a positive impact, some were inappropriate and could have a negative impact on reporting in the final publication. PMID:24986891

Spatially explicit integrated modeling and economic valuation of climate driven land use change and its indirect effects.

PubMed

Bateman, Ian; Agarwala, Matthew; Binner, Amy; Coombes, Emma; Day, Brett; Ferrini, Silvia; Fezzi, Carlo; Hutchins, Michael; Lovett, Andrew; Posen, Paulette

2016-10-01

We present an integrated model of the direct consequences of climate change on land use, and the indirect effects of induced land use change upon the natural environment. The model predicts climate-driven shifts in the profitability of alternative uses of agricultural land. Both the direct impact of climate change and the induced shift in land use patterns will cause secondary effects on the water environment, for which agriculture is the major source of diffuse pollution. We model the impact of changes in such pollution on riverine ecosystems showing that these will be spatially heterogeneous. Moreover, we consider further knock-on effects upon the recreational benefits derived from water environments, which we assess using revealed preference methods. This analysis permits a multi-layered examination of the economic consequences of climate change, assessing the sequence of impacts from climate change through farm gross margins, land use, water quality and recreation, both at the individual and catchment scale. Copyright © 2016 Elsevier Ltd. All rights reserved.

Climate Change and Water Resources Management: A Federal Perspective

USGS Publications Warehouse

Brekke, Levi D.; Kiang, Julie E.; Olsen, J. Rolf; Pulwarty, Roger S.; Raff, David A.; Turnipseed, D. Phil; Webb, Robert S.; White, Kathleen D.

2009-01-01

Many challenges, including climate change, face the Nation's water managers. The Intergovernmental Panel on Climate Change (IPCC) has provided estimates of how climate may change, but more understanding of the processes driving the changes, the sequences of the changes, and the manifestation of these global changes at different scales could be beneficial. Since the changes will likely affect fundamental drivers of the hydrological cycle, climate change may have a large impact on water resources and water resources managers. The purpose of this interagency report prepared by the U.S. Geological Survey (USGS), U.S. Army Corps of Engineers (USACE), Bureau of Reclamation (Reclamation), and National Oceanic and Atmospheric Administration (NOAA) is to explore strategies to improve water management by tracking, anticipating, and responding to climate change. This report describes the existing and still needed underpinning science crucial to addressing the many impacts of climate change on water resources management.

Impact of a Regional Drought on Terrestrial Carbon Fluxes and Atmospheric Carbon: Results from a Coupled Carbon Cycle Model

NASA Technical Reports Server (NTRS)

Lee, Eunjee; Koster, Randal D.; Ott, Lesley E.; Weir, Brad; Mahanama, Sarith; Chang, Yehui; Zeng, Fan-Wei

2017-01-01

Understanding the underlying processes that control the carbon cycle is key to predicting future global change. Much of the uncertainty in the magnitude and variability of the atmospheric carbon dioxide (CO2) stems from uncertainty in terrestrial carbon fluxes, and the relative impacts of temperature and moisture variations on regional and global scales are poorly understood. Here we investigate the impact of a regional drought on terrestrial carbon fluxes and CO2 mixing ratios over North America using the NASA Goddard Earth Observing System (GEOS) Model. Results show a sequence of changes in carbon fluxes and atmospheric CO2, induced by the drought. The relative contributions of meteorological changes to the neighboring carbon dynamics are also presented. The coupled modeling approach allows a direct quantification of the impact of the regional drought on local and proximate carbon exchange at the land surface via the carbon-water feedback processes.

Localized structural frustration for evaluating the impact of sequence variants

PubMed Central

Kumar, Sushant; Clarke, Declan; Gerstein, Mark

2016-01-01

Population-scale sequencing is increasingly uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions of the genome. The rarity of these variants makes it challenging to evaluate their deleteriousness with conventional phenotype–genotype associations. Protein structures provide a way of addressing this challenge. Previous efforts have focused on globally quantifying the impact of SNVs on protein stability. However, local perturbations may severely impact protein functionality without strongly disrupting global stability (e.g. in relation to catalysis or allostery). Here, we describe a workflow in which localized frustration, quantifying unfavorable local interactions, is employed as a metric to investigate such effects. Using this workflow on the Protein Databank, we find that frustration produces many immediately intuitive results: for instance, disease-related SNVs create stronger changes in localized frustration than non-disease related variants, and rare SNVs tend to disrupt local interactions to a larger extent than common variants. Less obviously, we observe that somatic SNVs associated with oncogenes and tumor suppressor genes (TSGs) induce very different changes in frustration. In particular, those associated with TSGs change the frustration more in the core than the surface (by introducing loss-of-function events), whereas those associated with oncogenes manifest the opposite pattern, creating gain-of-function events. PMID:27915290

Elucidative analysis and sequencing of two respiratory health monitoring methods to study the impact of varying atmospheric composition on human health

NASA Astrophysics Data System (ADS)

Awasthi, Amit; Hothi, Navjot; Kaur, Prabhjot; Singh, Nirankar; Chakraborty, Monojit; Bansal, Sangeeta

2017-12-01

Atmospheric composition of ambient air consists of different gases in definite proportion that affect the earth's climate and its ecological system. Due to varied anthropogenic reasons, this composition is changed, which ultimately have an impact on the health of living beings. For survival, the human respiratory system is one of the sensitive systems, which is easily and closely affected by the change in atmospheric composition of an external environment. Many studies have been conducted to quantify the effects of atmospheric pollution on human health by using different approaches. This article presents different scenario of studies conducted to evaluate the effects on different human groups. Differences between the studies conducted using spirometry and survey methods are presented in this article to extract a better sequence between these two methodologies. Many studies have been conducted to measure the respiratory status by evaluating the respiratory symptoms and hospital admissions. Limited numbers of studies are found with repeated spirometry on the same subjects for long duration to nullify the error arising due to decrease in efforts by the same subjects during manoeuvre of pulmonary function tests. Present study reveals the importance of methodological sequencing in order to obtain more authentic and reliable results. This study suggests that impacts of deteriorating atmospheric composition on human health can be more significantly studied if spirometry is done after survey analysis. The article also proposes that efficiency and authenticity of surveys involving health impacts will increase, if medical data information of patients is saved in hospitals in a proper format.

Advancing Our Understanding of the Etiologies and Mutational Landscapes of Basal-Like, Luminal A, and Luminal B Breast Cancers

DTIC Science & Technology

2015-10-01

an additional 80 to 100 estrogen receptor positive (ER+) cases. In terms of the impact of this change on our specific aims, it impacts only Aims 1...This modification does not impact the work or budget of Dr. Chinnaiyan’s component of this project as there were never any plans to provide samples...increased speed and sequencing yield, months 7-60: We will optimize and incorporate improved methods for library construction, such as transposon based

A yoga program for cognitive enhancement.

PubMed

Brunner, Devon; Abramovitch, Amitai; Etherton, Joseph

2017-01-01

Recent studies suggest that yoga practice may improve cognitive functioning. Although preliminary data indicate that yoga improves working memory (WM), high-resolution information about the type of WM subconstructs, namely maintenance and manipulation, is not available. Furthermore, the association between cognitive enhancement and improved mindfulness as a result of yoga practice requires empirical examination. The aim of the present study is to assess the impact of a brief yoga program on WM maintenance, WM manipulation and attentive mindfulness. Measures of WM (Digit Span Forward, Backward, and Sequencing, and Letter-Number Sequencing) were administered prior to and following 6 sessions of yoga (N = 43). Additionally, the Mindfulness Attention Awareness Scale was administered to examine the potential impact of yoga practice on mindfulness, as well as the relationships among changes in WM and mindfulness. Analyses revealed significant improvement from pre- to post- training assessment on both maintenance WM (Digit Span Forward) and manipulation WM (Digit Span Backward and Letter-Number Sequencing). No change was found on Digit Span Sequencing. Improvement was also found on mindfulness scores. However, no correlation was observed between mindfulness and WM measures. A 6-session yoga program was associated with improvement on manipulation and maintenance WM measures as well as enhanced mindfulness scores. Additional research is needed to understand the extent of yoga-related cognitive enhancement and mechanisms by which yoga may enhance cognition, ideally by utilizing randomized controlled trials and more comprehensive neuropsychological batteries.

Somatic Mosaicism for Cancer Predisposition Genes and Pancreatic Cancer

DTIC Science & Technology

2017-07-01

cancer or had a strong family history of cancer. Thus far all tissues from 21 of these patients have undergone targeted sequencing using a 468 gene...major accomplishments, innovations , successes, or any change in practice or behavior that has come about as a result of the project relative to...What was the impact on technology transfer? What was the impact on society beyond science and technology ? Nothing to

Analysis of simple sequence repeat (SSR) structure and sequence within Epichloë endophyte genomes reveals impacts on gene structure and insights into ancestral hybridization events.

PubMed

Clayton, William; Eaton, Carla Jane; Dupont, Pierre-Yves; Gillanders, Tim; Cameron, Nick; Saikia, Sanjay; Scott, Barry

2017-01-01

Epichloë grass endophytes comprise a group of filamentous fungi of both sexual and asexual species. Known for the beneficial characteristics they endow upon their grass hosts, the identification of these endophyte species has been of great interest agronomically and scientifically. The use of simple sequence repeat loci and the variation in repeat elements has been used to rapidly identify endophyte species and strains, however, little is known of how the structure of repeat elements changes between species and strains, and where these repeat elements are located in the fungal genome. We report on an in-depth analysis of the structure and genomic location of the simple sequence repeat locus B10, commonly used for Epichloë endophyte species identification. The B10 repeat was found to be located within an exon of a putative bZIP transcription factor, suggesting possible impacts on polypeptide sequence and thus protein function. Analysis of this repeat in the asexual endophyte hybrid Epichloë uncinata revealed that the structure of B10 alleles reflects the ancestral species that hybridized to give rise to this species. Understanding the structure and sequence of these simple sequence repeats provides a useful set of tools for readily distinguishing strains and for gaining insights into the ancestral species that have undergone hybridization events.

Making sense of deep sequencing

PubMed Central

Goldman, D.; Domschke, K.

2016-01-01

This review, the first of an occasional series, tries to make sense of the concepts and uses of deep sequencing of polynucleic acids (DNA and RNA). Deep sequencing, synonymous with next-generation sequencing, high-throughput sequencing and massively parallel sequencing, includes whole genome sequencing but is more often and diversely applied to specific parts of the genome captured in different ways, for example the highly expressed portion of the genome known as the exome and portions of the genome that are epigenetically marked either by DNA methylation, the binding of proteins including histones, or that are in different configurations and thus more or less accessible to enzymes that cleave DNA. Deep sequencing of RNA (RNASeq) reverse-transcribed to complementary DNA is invaluable for measuring RNA expression and detecting changes in RNA structure. Important concepts in deep sequencing include the length and depth of sequence reads, mapping and assembly of reads, sequencing error, haplotypes, and the propensity of deep sequencing, as with other types of ‘big data’, to generate large numbers of errors, requiring monitoring for methodologic biases and strategies for replication and validation. Deep sequencing yields a unique genetic fingerprint that can be used to identify a person, and a trove of predictors of genetic medical diseases. Deep sequencing to identify epigenetic events including changes in DNA methylation and RNA expression can reveal the history and impact of environmental exposures. Because of the power of sequencing to identify and deliver biomedically significant information about a person and their blood relatives, it creates ethical dilemmas and practical challenges in research and clinical care, for example the decision and procedures to report incidental findings that will increasingly and frequently be discovered. PMID:24925306

Monitoring of Ebola Virus Makona Evolution through Establishment of Advanced Genomic Capability in Liberia.

PubMed

Kugelman, Jeffrey R; Wiley, Michael R; Mate, Suzanne; Ladner, Jason T; Beitzel, Brett; Fakoli, Lawrence; Taweh, Fahn; Prieto, Karla; Diclaro, Joseph W; Minogue, Timothy; Schoepp, Randal J; Schaecher, Kurt E; Pettitt, James; Bateman, Stacey; Fair, Joseph; Kuhn, Jens H; Hensley, Lisa; Park, Daniel J; Sabeti, Pardis C; Sanchez-Lockhart, Mariano; Bolay, Fatorma K; Palacios, Gustavo

2015-07-01

To support Liberia's response to the ongoing Ebola virus (EBOV) disease epidemic in Western Africa, we established in-country advanced genomic capabilities to monitor EBOV evolution. Twenty-five EBOV genomes were sequenced at the Liberian Institute for Biomedical Research, which provided an in-depth view of EBOV diversity in Liberia during September 2014-February 2015. These sequences were consistent with a single virus introduction to Liberia; however, shared ancestry with isolates from Mali indicated at least 1 additional instance of movement into or out of Liberia. The pace of change is generally consistent with previous estimates of mutation rate. We observed 23 nonsynonymous mutations and 1 nonsense mutation. Six of these changes are within known binding sites for sequence-based EBOV medical countermeasures; however, the diagnostic and therapeutic impact of EBOV evolution within Liberia appears to be low.

Monitoring of Ebola Virus Makona Evolution through Establishment of Advanced Genomic Capability in Liberia

PubMed Central

Kugelman, Jeffrey R.; Wiley, Michael R.; Mate, Suzanne; Ladner, Jason T.; Beitzel, Brett; Fakoli, Lawrence; Taweh, Fahn; Prieto, Karla; Diclaro, Joseph W.; Minogue, Timothy; Schoepp, Randal J.; Schaecher, Kurt E.; Pettitt, James; Bateman, Stacey; Fair, Joseph; Kuhn, Jens H.; Hensley, Lisa; Park, Daniel J.; Sabeti, Pardis C.; Sanchez-Lockhart, Mariano; Bolay, Fatorma K.

2015-01-01

To support Liberia’s response to the ongoing Ebola virus (EBOV) disease epidemic in Western Africa, we established in-country advanced genomic capabilities to monitor EBOV evolution. Twenty-five EBOV genomes were sequenced at the Liberian Institute for Biomedical Research, which provided an in-depth view of EBOV diversity in Liberia during September 2014–February 2015. These sequences were consistent with a single virus introduction to Liberia; however, shared ancestry with isolates from Mali indicated at least 1 additional instance of movement into or out of Liberia. The pace of change is generally consistent with previous estimates of mutation rate. We observed 23 nonsynonymous mutations and 1 nonsense mutation. Six of these changes are within known binding sites for sequence-based EBOV medical countermeasures; however, the diagnostic and therapeutic impact of EBOV evolution within Liberia appears to be low. PMID:26079255

Firing rate dynamics in the hippocampus induced by trajectory learning.

PubMed

Ji, Daoyun; Wilson, Matthew A

2008-04-30

The hippocampus is essential for spatial navigation, which may involve sequential learning. However, how the hippocampus encodes new sequences in familiar environments is unknown. To study the impact of novel spatial sequences on the activity of hippocampal neurons, we monitored hippocampal ensembles while rats learned to switch from two familiar trajectories to a new one in a familiar environment. Here, we show that this novel spatial experience induces two types of changes in firing rates, but not locations of hippocampal place cells. First, place-cell firing rates on the two familiar trajectories start to change before the actual behavioral switch to the new trajectory. Second, repeated exposure on the new trajectory is associated with an increased dependence of place-cell firing rates on immediate past locations. The result suggests that sequence encoding in the hippocampus may involve integration of information about the recent past into current state.

Firing Rate Dynamics in the Hippocampus Induced by Trajectory Learning

PubMed Central

Wilson, Matthew A.

2008-01-01

The hippocampus is essential for spatial navigation, which may involve sequential learning. However, how the hippocampus encodes new sequences in familiar environments is unknown. To study the impact of novel spatial sequences on the activity of hippocampal neurons, we monitored hippocampal ensembles while rats learned to switch from two familiar trajectories to a new one in a familiar environment. Here, we show that this novel spatial experience induces two types of changes in firing rates, but not locations of hippocampal place cells. First, place-cell firing rates on the two familiar trajectories start to change before the actual behavioral switch to the new trajectory. Second, repeated exposure on the new trajectory is associated with an increased dependence of place-cell firing rates on immediate past locations. The result suggests that sequence encoding in the hippocampus may involve integration of information about the recent past into current state. PMID:18448645

Supervised analysis of drug prescription sequences.

PubMed

Ficheur, Grégoire; Chazard, Emmanuel; Merlin, Béatrice; Ferret, Laurie; Luyckx, Michel; Beuscart, Régis

2013-01-01

Hospitals have at their disposal large databases that may be considered for reuse. The objective of this work is to evaluate the impact of a drug on a specific laboratory result by analyzing these data. This analysis first involves building a record of temporal patterns, including medical context, of drug prescriptions. Changes in outcome due to these patterns of drug prescription are assessed using short phases of the inpatient stay compared to monotonous changes in the laboratory result. To illustrate this technique, we investigated potassium chloride supplementation and its impact on kalemia. This method enables us to assess the impact of a drug (in its frequent context of prescription) on a laboratory result. This kind of analysis could play a role in post-marketing studies.

Localized structural frustration for evaluating the impact of sequence variants.

PubMed

Kumar, Sushant; Clarke, Declan; Gerstein, Mark

2016-12-01

Population-scale sequencing is increasingly uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions of the genome. The rarity of these variants makes it challenging to evaluate their deleteriousness with conventional phenotype-genotype associations. Protein structures provide a way of addressing this challenge. Previous efforts have focused on globally quantifying the impact of SNVs on protein stability. However, local perturbations may severely impact protein functionality without strongly disrupting global stability (e.g. in relation to catalysis or allostery). Here, we describe a workflow in which localized frustration, quantifying unfavorable local interactions, is employed as a metric to investigate such effects. Using this workflow on the Protein Databank, we find that frustration produces many immediately intuitive results: for instance, disease-related SNVs create stronger changes in localized frustration than non-disease related variants, and rare SNVs tend to disrupt local interactions to a larger extent than common variants. Less obviously, we observe that somatic SNVs associated with oncogenes and tumor suppressor genes (TSGs) induce very different changes in frustration. In particular, those associated with TSGs change the frustration more in the core than the surface (by introducing loss-of-function events), whereas those associated with oncogenes manifest the opposite pattern, creating gain-of-function events. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Assessing the impact of fungicide enostroburin application on bacterial community in wheat phyllosphere.

PubMed

Gu, Likun; Bai, Zhihui; Jin, Bo; Hu, Qing; Wang, Huili; Zhuang, Guoqiang; Zhang, Hongxun

2010-01-01

Fungicides have been used extensively for controlling fungal pathogens of plants. However, little is known regarding the effects that fungicides upon the indigenous bacterial communities within the plant phyllosphere. The aims of this study were to assess the impact of fungicide enostroburin upon bacterial communities in wheat phyllosphere. Culture-independent methodologies of 16S rDNA clone library and 16S rDNA directed polymerase chain reaction with denaturing gradient gel electrophoresis (PCR-DGGE) were used for monitoring the change of bacterial community. The 16S rDNA clone library and PCR-DGGE analysis both confirmed the microbial community of wheat plant phyllosphere were predominantly of the gamma-Proteobacteria phyla. Results from PCR-DGGE analysis indicated a significant change in bacterial community structure within the phyllosphere following fungicide enostroburin application. Bands sequenced within control cultures were predominantly of Pseudomonas genus, but those bands sequenced in the treated samples were predominantly strains of Pantoea genus and Pseudomonas genus. Of interest was the appearance of two DGGE bands following fungicide treatment, one of which had sequence similarities (98%) to Pantoea sp. which might be a competitor of plant pathogens. This study revealed the wheat phyllosphere bacterial community composition and a shift in the bacterial community following fungicide enostroburin application.

Frontostriatal and Mediotemporal Lobe Contributions to Implicit Higher-Order Spatial Sequence Learning Declines in Aging and Parkinson’s Disease

PubMed Central

Schendan, Haline E.; Tinaz, Sule; Maher, Stephen M.; Stern, Chantal E.

2015-01-01

Sequence learning depends on the striatal system, but recent findings also implicate the mediotemporal lobe (MTL) system. Schendan, Searl, Melrose, & Stern (2003) found higher-order associative, learning-related activation in the striatum, dorsolateral prefrontal cortex, and the MTL during the early acquisition phase of both implicit and explicit variants of a serial response time task. This functional magnetic resonance imaging (fMRI) study capitalized on this task to determine how changes in MTL function observed in aging and compromised frontostriatal function characteristic of Parkinson’s disease (PD) patients impacts sequence learning and memory under implicit instructions. Brain activity was compared between “Sequence” and “Random” conditions in 12 non-demented PD patients and education and gender matched healthy control participants of whom 12 were age matched (MC) and 14 were younger (YC). Behaviorally, sequence-specific learning of higher-order associations was reduced with aging and changed further with PD and resulted primarily in implicit knowledge in the older participants. FMRI revealed reduced intensity and extent of sequence learning-related activation in older relative to younger people in frontostriatal circuits and the MTL. This was because signal was greater for the Sequence than Random condition in younger people, whereas older people, especially those with PD, showed the opposite pattern. Both older groups also showed increased activation to the task itself relative to baseline fixation. In addition, right MTL showed hypoactivation and left MTL hyperactivation in PD relative to the MC group. The results suggest changes in frontostriatal and MTL activity occur during aging that affect task-related activity and the initial acquisition phase of implicit higher-order sequence learning. In addition, the results suggest that Parkinson’s disease adversely affects processes in the MTL including sequence learning and memory. PMID:23565935

Molecular sequence data of hepatitis B virus and genetic diversity after vaccination.

PubMed

van Ballegooijen, W Marijn; van Houdt, Robin; Bruisten, Sylvia M; Boot, Hein J; Coutinho, Roel A; Wallinga, Jacco

2009-12-15

The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.

PubMed

Stark, Zornitza; Tan, Tiong Y; Chong, Belinda; Brett, Gemma R; Yap, Patrick; Walsh, Maie; Yeung, Alison; Peters, Heidi; Mordaunt, Dylan; Cowie, Shannon; Amor, David J; Savarirayan, Ravi; McGillivray, George; Downie, Lilian; Ekert, Paul G; Theda, Christiane; James, Paul A; Yaplito-Lee, Joy; Ryan, Monique M; Leventer, Richard J; Creed, Emma; Macciocca, Ivan; Bell, Katrina M; Oshlack, Alicia; Sadedin, Simon; Georgeson, Peter; Anderson, Charlotte; Thorne, Natalie; Melbourne Genomics Health Alliance; Gaff, Clara; White, Susan M

2016-11-01

To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease. Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated. Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies. This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.Genet Med 18 11, 1090-1096.

‘Someday it will be the norm’: physician perspectives on the utility of genome sequencing for patient care in the MedSeq Project

PubMed Central

Vassy, Jason L; Christensen, Kurt D; Slashinski, Melody J; Lautenbach, Denise M; Raghavan, Sridharan; Robinson, Jill Oliver; Blumenthal-Barby, Jennifer; Feuerman, Lindsay Zausmer; Lehmann, Lisa Soleymani; Murray, Michael F; Green, Robert C; McGuire, Amy L

2015-01-01

Aim To describe practicing physicians’ perceived clinical utility of genome sequencing. Materials & methods We conducted a mixed-methods analysis of data from 18 primary care physicians and cardiologists in a study of the clinical integration of whole-genome sequencing. Physicians underwent brief genomics continuing medical education before completing surveys and semi-structured interviews. Results Physicians described sequencing as currently lacking clinical utility because of its uncertain interpretation and limited impact on clinical decision-making, but they expressed the idea that its clinical integration was inevitable. Potential clinical uses for sequencing included complementing other clinical information, risk stratification, motivating patient behavior change and pharmacogenetics. Conclusion Physicians given genomics continuing medical education use the language of both evidence-based and personalized medicine in describing the utility of genome-wide testing in patient care. PMID:25642274

Effects of changes in climate variability and extremes on the exceedance of critical algal bloom thresholds

NASA Astrophysics Data System (ADS)

Hecht, J. S.; Zia, A.; Beckage, B.; Winter, J.; Schroth, A. W.; Bomblies, A.; Clemins, P. J.; Rizzo, D. M.

2017-12-01

Identifying critical thresholds associated with algal blooms in freshwater lakes is important for avoiding persistent eutrophic conditions and their undesirable ecological, recreational and drinking water impacts. Recent Integrated Assessment Model (IAM) and Bayesian network studies have demonstrated that future climatic changes could increase the duration and intensity of these blooms. Yet, few studies have systematically examined the sensitivity of algal blooms to projected changes in precipitation and temperature variability and extremes at storm-event to seasonal timescales. We employ an IAM, which couples downscaled Global Climate Model (GCM) output with hydrologic and water quality models, to examine the sensitivity of algal blooms in Lake Champlain's shallow Missisquoi Bay to potential future climate changes. We first identify a set of statistically downscaled GCMs from the Coupled Model Intercomparison Project Phase 5 (CMIP5) that reproduce recent historical daily temperature and precipitation observations well in the Lake Champlain basin. Then, we identify plausible covarying changes in the (i) mean and variance of seasonal precipitation and temperature distributions and (ii) frequency and magnitude of individual storm events. We assess the response of water quality indicators (e.g. chlorophyll a concentrations, Trophic State Index) and societal impacts to sequences of daily meteorological series generated from distributions that account for these covarying changes. We also discuss strategies for examining the sensitivity of bloom impacts to different weather sequences generated from a single set of precipitation and temperature distributions with a limited number of computationally intensive IAM simulations. We then evaluate the implications of modeling these changes in climate variability and extreme precipitation events for nutrient management. Finally, we consider the generalizability of our findings for water bodies with different physical and climatic characteristics and address the extent to which climate-driven alterations to terrestrial hydrologic processes, such as evapotranspiration and soil moisture storage, mediate changes to lake water quality.

TU-H-CAMPUS-JeP3-05: Adaptive Determination of Needle Sequence HDR Prostate Brachytherapy with Divergent Needle-By-Needle Delivery

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

Borot de Battisti, M; Maenhout, M; Lagendijk, J J W

Purpose: To develop a new method which adaptively determines the optimal needle insertion sequence for HDR prostate brachytherapy involving divergent needle-by-needle dose delivery by e.g. a robotic device. A needle insertion sequence is calculated at the beginning of the intervention and updated after each needle insertion with feedback on needle positioning errors. Methods: Needle positioning errors and anatomy changes may occur during HDR brachytherapy which can lead to errors in the delivered dose. A novel strategy was developed to calculate and update the needle sequence and the dose plan after each needle insertion with feedback on needle positioning errors. Themore » dose plan optimization was performed by numerical simulations. The proposed needle sequence determination optimizes the final dose distribution based on the dose coverage impact of each needle. This impact is predicted stochastically by needle insertion simulations. HDR procedures were simulated with varying number of needle insertions (4 to 12) using 11 patient MR data-sets with PTV, prostate, urethra, bladder and rectum delineated. Needle positioning errors were modeled by random normally distributed angulation errors (standard deviation of 3 mm at the needle’s tip). The final dose parameters were compared in the situations where the needle with the largest vs. the smallest dose coverage impact was selected at each insertion. Results: Over all scenarios, the percentage of clinically acceptable final dose distribution improved when the needle selected had the largest dose coverage impact (91%) compared to the smallest (88%). The differences were larger for few (4 to 6) needle insertions (maximum difference scenario: 79% vs. 60%). The computation time of the needle sequence optimization was below 60s. Conclusion: A new adaptive needle sequence determination for HDR prostate brachytherapy was developed. Coupled to adaptive planning, the selection of the needle with the largest dose coverage impact increases chances of reaching the clinical constraints. M. Borot de Battisti is funded by Philips Medical Systems Nederland B.V.; M. Moerland is principal investigator on a contract funded by Philips Medical Systems Nederland B.V.; G. Hautvast and D. Binnekamp are fulltime employees of Philips Medical Systems Nederland B.V.« less

Variation in multiring basic structures as a function of impact angle

NASA Technical Reports Server (NTRS)

Wichman, R. W.; Schultz, P. H.

1992-01-01

Previous studies have demonstrated that the impact process in the laboratory varies as a function of impact angle. This variation is attributed to changes in energy partitioning and projectile failure during the impact and, in simple craters, produces a sequence of progressively smaller and more asymmetric crater forms as impact angle decreases from approximately 20 degrees. Variations in impact angle can produce differences in the appearance of multiring impact basins. Comparisons of Orientale to the more oblique impact structure at Crisium also suggests that these differences primarily reflect the degree of cavity collapse. The relative changes in massif ring topography, basin scarp relief, and the distribution of peripheral mare units are consistent with a reduction in degree of cavity collapse with decreasing impact angle. The prominent uprange basin scarps and the restriction of tectonically derived peripheral mare units along uprange ring structures also may indicate an uprange enhancement of failure during cavity collapse. Finally, although basin ring faults appear to be preferred pathways for mare volcanism, fault-controlled peripheral mare volcanism occurs most readily uprange of an oblique impact; elsewhere such volcanism apparently requires superposition of an impact structure on the ring fault.

Differential working memory correlates for implicit sequence performance in young and older adults.

PubMed

Bo, Jin; Jennett, S; Seidler, R D

2012-09-01

Our recent work has revealed that visuospatial working memory (VSWM) relates to the rate of explicit motor sequence learning (Bo and Seidler in J Neurophysiol 101:3116-3125, 2009) and implicit sequence performance (Bo et al. in Exp Brain Res 214:73-81, 2011a) in young adults (YA). Although aging has a detrimental impact on many cognitive functions, including working memory, older adults (OA) still rely on their declining working memory resources in an effort to optimize explicit motor sequence learning. Here, we evaluated whether age-related differences in VSWM and/or verbal working memory (VWM) performance relates to implicit performance change in the serial reaction time (SRT) sequence task in OA. Participants performed two computerized working memory tasks adapted from change detection working memory assessments (Luck and Vogel in Nature 390:279-281, 1997), an implicit SRT task and several neuropsychological tests. We found that, although OA exhibited an overall reduction in both VSWM and VWM, both OA and YA showed similar performance in the implicit SRT task. Interestingly, while VSWM and VWM were significantly correlated with each other in YA, there was no correlation between these two working memory scores in OA. In YA, the rate of SRT performance change (exponential fit to the performance curve) was significantly correlated with both VSWM and VWM, while in contrast, OA's performance was only correlated with VWM, and not VSWM. These results demonstrate differential reliance on VSWM and VWM for SRT performance between YA and OA. OA may utilize VWM to maintain optimized performance of second-order conditional sequences.

Resilience of arctic mycorrhizal fungal communities after wildfire facilitated by resprouting shrubs

Treesearch

Rebecca E. Hewitt; Elizabeth Bent; Teresa N. Hollingsworth; F. Stuart Chapin; D. Lee Taylor

2013-01-01

Climate-induced changes in the tundra fire regime are expected to alter shrub abundance and distribution across the Arctic. However, little is known about how fire may indirectly impact shrub performance by altering mycorrhizal symbionts. We used molecular tools, including ARISA and ITS sequencing, to characterize the mycorrhizal communities on resprouting ...

Elementary Social Studies: Trite, Disjointed, and in Need of Reform?

ERIC Educational Resources Information Center

Duplass, James A.

2007-01-01

Elementary social studies has used the same scope and sequence for more than a half century despite significant changes in society. Efforts to reform the curriculum are adversely impacted by inertia, tradition, the culture wars, traditional state autonomy in setting curriculum, publishers, and competition between disciplines for space within the…

Expansion of inverted repeat does not decrease substitution rates in Pelargonium plastid genomes.

PubMed

Weng, Mao-Lun; Ruhlman, Tracey A; Jansen, Robert K

2017-04-01

For species with minor inverted repeat (IR) boundary changes in the plastid genome (plastome), nucleotide substitution rates were previously shown to be lower in the IR than the single copy regions (SC). However, the impact of large-scale IR expansion/contraction on plastid nucleotide substitution rates among closely related species remains unclear. We included plastomes from 22 Pelargonium species, including eight newly sequenced genomes, and used both pairwise and model-based comparisons to investigate the impact of the IR on sequence evolution in plastids. Ten types of plastome organization with different inversions or IR boundary changes were identified in Pelargonium. Inclusion in the IR was not sufficient to explain the variation of nucleotide substitution rates. Instead, the rate heterogeneity in Pelargonium plastomes was a mixture of locus-specific, lineage-specific and IR-dependent effects. Our study of Pelargonium plastomes that vary in IR length and gene content demonstrates that the evolutionary consequences of retaining these repeats are more complicated than previously suggested. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Exploring the impact of an automated prescription-filling device on community pharmacy technician workflow.

PubMed

Walsh, Kristin E; Chui, Michelle Anne; Kieser, Mara A; Williams, Staci M; Sutter, Susan L; Sutter, John G

2011-01-01

To explore community pharmacy technician workflow change after implementation of an automated robotic prescription-filling device. At an independent community pharmacy in rural Mayville, WI, pharmacy technicians were observed before and 3 months after installation of an automated robotic prescription-filling device. The main outcome measures were sequences and timing of technician workflow steps, workflow interruptions, automation surprises, and workarounds. Of the 77 and 80 observations made before and 3 months after robot installation, respectively, 17 different workflow sequences were observed before installation and 38 after installation. Average prescription filling time was reduced by 40 seconds per prescription with use of the robot. Workflow interruptions per observation increased from 1.49 to 1.79 (P = 0.11), and workarounds increased from 10% to 36% after robot use. Although automated prescription-filling devices can increase efficiency, workflow interruptions and workarounds may negate that efficiency. Assessing changes in workflow and sequencing of tasks that may result from the use of automation can help uncover opportunities for workflow policy and procedure redesign.

Projecting climate change impacts on hydrology: the potential role of daily GCM output

NASA Astrophysics Data System (ADS)

Maurer, E. P.; Hidalgo, H. G.; Das, T.; Dettinger, M. D.; Cayan, D.

2008-12-01

A primary challenge facing resource managers in accommodating climate change is determining the range and uncertainty in regional and local climate projections. This is especially important for assessing changes in extreme events, which will drive many of the more severe impacts of a changed climate. Since global climate models (GCMs) produce output at a spatial scale incompatible with local impact assessment, different techniques have evolved to downscale GCM output so locally important climate features are expressed in the projections. We compared skill and hydrologic projections using two statistical downscaling methods and a distributed hydrology model. The downscaling methods are the constructed analogues (CA) and the bias correction and spatial downscaling (BCSD). CA uses daily GCM output, and can thus capture GCM projections for changing extreme event occurrence, while BCSD uses monthly output and statistically generates historical daily sequences. We evaluate the hydrologic impacts projected using downscaled climate (from the NCEP/NCAR reanalysis as a surrogate GCM) for the late 20th century with both methods, comparing skill in projecting soil moisture, snow pack, and streamflow at key locations in the Western United States. We include an assessment of a new method for correcting for GCM biases in a hybrid method combining the most important characteristics of both methods.

Chloroplast genomes: diversity, evolution, and applications in genetic engineering

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

Daniell, Henry; Lin, Choun -Sea; Yu, Ming

Chloroplasts play a crucial role in sustaining life on earth. The availability of over 800 sequenced chloroplast genomes from a variety of land plants has enhanced our understanding of chloroplast biology, intracellular gene transfer, conservation, diversity, and the genetic basis by which chloroplast transgenes can be engineered to enhance plant agronomic traits or to produce high-value agricultural or biomedical products. In this review, we discuss the impact of chloroplast genome sequences on understanding the origins of economically important cultivated species and changes that have taken place during domestication. Here, we also discuss the potential biotechnological applications of chloroplast genomes.

Chloroplast genomes: diversity, evolution, and applications in genetic engineering

DOE PAGES

Daniell, Henry; Lin, Choun -Sea; Yu, Ming; ...

2016-06-23

Chloroplasts play a crucial role in sustaining life on earth. The availability of over 800 sequenced chloroplast genomes from a variety of land plants has enhanced our understanding of chloroplast biology, intracellular gene transfer, conservation, diversity, and the genetic basis by which chloroplast transgenes can be engineered to enhance plant agronomic traits or to produce high-value agricultural or biomedical products. In this review, we discuss the impact of chloroplast genome sequences on understanding the origins of economically important cultivated species and changes that have taken place during domestication. Here, we also discuss the potential biotechnological applications of chloroplast genomes.

Climate change, fisheries management and fishing aptitude affecting spatial and temporal distributions of the Barents Sea cod fishery.

PubMed

Eide, Arne

2017-12-01

Climate change is expected to influence spatial and temporal distributions of fish stocks. The aim of this paper is to compare climate change impact on a fishery with other factors impacting the performance of fishing fleets. The fishery in question is the Northeast Arctic cod fishery, a well-documented fishery where data on spatial and temporal distributions are available. A cellular automata model is developed for the purpose of mimicking possible distributional patterns and different management alternatives are studied under varying assumptions on the fleets' fishing aptitude. Fisheries management and fishing aptitude, also including technological development and local knowledge, turn out to have the greatest impact on the spatial distribution of the fishing effort, when comparing the IPCC's SRES A1B scenario with repeated sequences of the current environmental situation over a period of 45 years. In both cases, the highest profits in the simulation period of 45 years are obtained at low exploitation levels and moderate fishing aptitude.

A unique assemblage of cosmopolitan freshwater bacteria and higher community diversity differentiate an urbanized estuary from oligotrophic Lake Michigan

PubMed Central

Newton, Ryan J.; McLellan, Sandra L.

2015-01-01

Water quality is impacted significantly by urbanization. The delivery of increased nutrient loads to waterways is a primary characteristic of this land use change. Despite the recognized effects of nutrient loading on aquatic systems, the influence of urbanization on the bacterial community composition of these systems is not understood. We used massively-parallel sequencing of bacterial 16S rRNA genes to examine the bacterial assemblages in transect samples spanning the heavily urbanized estuary of Milwaukee, WI to the relatively un-impacted waters of Lake Michigan. With this approach, we found that genera and lineages common to freshwater lake epilimnia were common and abundant in both the high nutrient, urban-impacted waterways, and the low nutrient Lake Michigan. Although the two environments harbored many taxa in common, we identified a significant change in the community assemblage across the urban-influence gradient, and three distinct community features drove this change. First, we found the urban-influenced waterways harbored significantly greater bacterial richness and diversity than Lake Michigan (i.e., taxa augmentation). Second, we identified a shift in the relative abundance among common freshwater lineages, where acI, acTH1, Algoriphagus and LD12, had decreased representation and Limnohabitans, Polynucleobacter, and Rhodobacter had increased representation in the urban estuary. Third, by oligotyping 18 common freshwater genera/lineages, we found that oligotypes (highly resolved sequence clusters) within many of these genera/lineages had opposite preferences for the two environments. With these data, we suggest many of the defined cosmopolitan freshwater genera/lineages contain both oligotroph and more copiotroph species or populations, promoting the idea that within-genus lifestyle specialization, in addition to shifts in the dominance among core taxa and taxa augmentation, drive bacterial community change in urbanized waters. PMID:26483766

Connecting Common Genetic Polymorphisms to Protein Function: A Modular Project Sequence for Lecture or Lab

ERIC Educational Resources Information Center

Berndsen, Christopher E.; Young, Byron H.; McCormick, Quinlin J.; Enke, Raymond A.

2016-01-01

Single nucleotide polymorphisms (SNPs) in DNA can result in phenotypes where the biochemical basis may not be clear due to the lack of protein structures. With the growing number of modeling and simulation software available on the internet, students can now participate in determining how small changes in genetic information impact cellular…

Quantifying the evolution of individual scientific impact.

PubMed

Sinatra, Roberta; Wang, Dashun; Deville, Pierre; Song, Chaoming; Barabási, Albert-László

2016-11-04

Despite the frequent use of numerous quantitative indicators to gauge the professional impact of a scientist, little is known about how scientific impact emerges and evolves in time. Here, we quantify the changes in impact and productivity throughout a career in science, finding that impact, as measured by influential publications, is distributed randomly within a scientist's sequence of publications. This random-impact rule allows us to formulate a stochastic model that uncouples the effects of productivity, individual ability, and luck and unveils the existence of universal patterns governing the emergence of scientific success. The model assigns a unique individual parameter Q to each scientist, which is stable during a career, and it accurately predicts the evolution of a scientist's impact, from the h-index to cumulative citations, and independent recognitions, such as prizes. Copyright © 2016, American Association for the Advancement of Science.

The Embedding Problem for Markov Models of Nucleotide Substitution

PubMed Central

Verbyla, Klara L.; Yap, Von Bing; Pahwa, Anuj; Shao, Yunli; Huttley, Gavin A.

2013-01-01

Continuous-time Markov processes are often used to model the complex natural phenomenon of sequence evolution. To make the process of sequence evolution tractable, simplifying assumptions are often made about the sequence properties and the underlying process. The validity of one such assumption, time-homogeneity, has never been explored. Violations of this assumption can be found by identifying non-embeddability. A process is non-embeddable if it can not be embedded in a continuous time-homogeneous Markov process. In this study, non-embeddability was demonstrated to exist when modelling sequence evolution with Markov models. Evidence of non-embeddability was found primarily at the third codon position, possibly resulting from changes in mutation rate over time. Outgroup edges and those with a deeper time depth were found to have an increased probability of the underlying process being non-embeddable. Overall, low levels of non-embeddability were detected when examining individual edges of triads across a diverse set of alignments. Subsequent phylogenetic reconstruction analyses demonstrated that non-embeddability could impact on the correct prediction of phylogenies, but at extremely low levels. Despite the existence of non-embeddability, there is minimal evidence of violations of the local time homogeneity assumption and consequently the impact is likely to be minor. PMID:23935949

Transcriptome Wide Annotation of Eukaryotic RNase III Reactivity and Degradation Signals

PubMed Central

Gagnon, Jules; Lavoie, Mathieu; Catala, Mathieu; Malenfant, Francis; Elela, Sherif Abou

2015-01-01

Detection and validation of the RNA degradation signals controlling transcriptome stability are essential steps for understanding how cells regulate gene expression. Here we present complete genomic and biochemical annotations of the signals required for RNA degradation by the dsRNA specific ribonuclease III (Rnt1p) and examine its impact on transcriptome expression. Rnt1p cleavage signals are randomly distributed in the yeast genome, and encompass a wide variety of sequences, indicating that transcriptome stability is not determined by the recurrence of a fixed cleavage motif. Instead, RNA reactivity is defined by the sequence and structural context in which the cleavage sites are located. Reactive signals are often associated with transiently expressed genes, and their impact on RNA expression is linked to growth conditions. Together, the data suggest that Rnt1p reactivity is triggered by malleable RNA degradation signals that permit dynamic response to changes in growth conditions. PMID:25680180

Dissecting genetic and environmental mutation signatures with model organisms.

PubMed

Segovia, Romulo; Tam, Annie S; Stirling, Peter C

2015-08-01

Deep sequencing has impacted on cancer research by enabling routine sequencing of genomes and exomes to identify genetic changes associated with carcinogenesis. Researchers can now use the frequency, type, and context of all mutations in tumor genomes to extract mutation signatures that reflect the driving mutational processes. Identifying mutation signatures, however, may not immediately suggest a mechanism. Consequently, several recent studies have employed deep sequencing of model organisms exposed to discrete genetic or environmental perturbations. These studies exploit the simpler genomes and availability of powerful genetic tools in model organisms to analyze mutation signatures under controlled conditions, forging mechanistic links between mutational processes and signatures. We discuss the power of this approach and suggest that many such studies may be on the horizon. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts

PubMed Central

Saini, Natalie; Chan, Kin; Grimm, Sara A.; Dai, Shuangshuang; Fargo, David C.; Kaufmann, William K.; Taylor, Jack A.; Lee, Eunjung; Cortes-Ciriano, Isidro; Park, Peter J.; Schurman, Shepherd H.; Malc, Ewa P.; Mieczkowski, Piotr A.

2016-01-01

Accumulation of somatic changes, due to environmental and endogenous lesions, in the human genome is associated with aging and cancer. Understanding the impacts of these processes on mutagenesis is fundamental to understanding the etiology, and improving the prognosis and prevention of cancers and other genetic diseases. Previous methods relying on either the generation of induced pluripotent stem cells, or sequencing of single-cell genomes were inherently error-prone and did not allow independent validation of the mutations. In the current study we eliminated these potential sources of error by high coverage genome sequencing of single-cell derived clonal fibroblast lineages, obtained after minimal propagation in culture, prepared from skin biopsies of two healthy adult humans. We report here accurate measurement of genome-wide magnitude and spectra of mutations accrued in skin fibroblasts of healthy adult humans. We found that every cell contains at least one chromosomal rearrangement and 600–13,000 base substitutions. The spectra and correlation of base substitutions with epigenomic features resemble many cancers. Moreover, because biopsies were taken from body parts differing by sun exposure, we can delineate the precise contributions of environmental and endogenous factors to the accrual of genetic changes within the same individual. We show here that UV-induced and endogenous DNA damage can have a comparable impact on the somatic mutation loads in skin fibroblasts. Trial Registration ClinicalTrials.gov NCT01087307 PMID:27788131

Interactive effects of multiple stressors revealed by sequencing total (DNA) and active (RNA) components of experimental sediment microbial communities.

PubMed

Birrer, Simone C; Dafforn, Katherine A; Simpson, Stuart L; Kelaher, Brendan P; Potts, Jaimie; Scanes, Peter; Johnston, Emma L

2018-05-15

Coastal waterways are increasingly exposed to multiple stressors, e.g. contaminants that can be delivered via pulse or press exposures. Therefore, it is crucial that ecological impacts can be differentiated among stressors to manage ecosystem threats. We investigated microbial community development in sediments exposed to press and pulse stressors. Press exposures were created with in situ mesocosm sediments containing a range of 'metal' concentrations (sediment contaminated with multiple metal(loid)s) and organic enrichment (fertiliser), while the pulse exposure was simulated by a single dose of organic fertiliser. All treatments and exposure concentrations were crossed in a fully factorial field experiment. We used amplicon sequencing to compare the sensitivity of the 1) total (DNA) and active (RNA) component of 2) bacterial (16S rRNA) and eukaryotic (18S rRNA) communities to contaminant exposures. Overall microbial community change was greater when exposed to press than pulse stressors, with the bacterial community responding more strongly than the eukaryotes. The total bacterial community represents a more time-integrated measure of change and proved to be more sensitive to multiple stressors than the active community. Metals and organic enrichment treatments interacted such that the effect of metals was weaker when the sediment was organically enriched. Taxa-level analyses revealed that press enrichment resulted in potential functional changes, mainly involving nitrogen cycling. Furthermore, enrichment generally reduced the abundance of active eukaryotes in the sediment. As well as demonstrating interactive impacts of metals and organic enrichment, this study highlights the sensitivity of next-generation sequencing for ecosystem biomonitoring of interacting stressors and identifies opportunities for more targeted application. Copyright © 2018 Elsevier B.V. All rights reserved.

Looking for Broken TAD Boundaries and Changes on DNA Interactions: Clinical Guide to 3D Chromatin Change Analysis in Complex Chromosomal Rearrangements and Chromothripsis.

PubMed

Yauy, Kevin; Gatinois, Vincent; Guignard, Thomas; Sati, Satish; Puechberty, Jacques; Gaillard, Jean Baptiste; Schneider, Anouck; Pellestor, Franck

2018-01-01

Apparition of next-generation sequencing (NGS) was a breakthrough on knowledge of genome structure. Bioinformatic tools are a key point to analyze this huge amount of data from NGS and characterize the three-dimensional organization of chromosomes. This chapter describes usage of different browsers to explore publicly available online data and to search for possible 3D chromatin changes involved during complex chromosomal rearrangements as chromothripsis. Their pathogenic impact on clinical phenotype and gene misexpression can also be evaluated with annotated databases.

Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing

PubMed Central

2012-01-01

Background RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods. Results Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices. Conclusions This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates. PMID:22985019

Efficient experimental design and analysis strategies for the detection of differential expression using RNA-Sequencing.

PubMed

Robles, José A; Qureshi, Sumaira E; Stephen, Stuart J; Wilson, Susan R; Burden, Conrad J; Taylor, Jennifer M

2012-09-17

RNA sequencing (RNA-Seq) has emerged as a powerful approach for the detection of differential gene expression with both high-throughput and high resolution capabilities possible depending upon the experimental design chosen. Multiplex experimental designs are now readily available, these can be utilised to increase the numbers of samples or replicates profiled at the cost of decreased sequencing depth generated per sample. These strategies impact on the power of the approach to accurately identify differential expression. This study presents a detailed analysis of the power to detect differential expression in a range of scenarios including simulated null and differential expression distributions with varying numbers of biological or technical replicates, sequencing depths and analysis methods. Differential and non-differential expression datasets were simulated using a combination of negative binomial and exponential distributions derived from real RNA-Seq data. These datasets were used to evaluate the performance of three commonly used differential expression analysis algorithms and to quantify the changes in power with respect to true and false positive rates when simulating variations in sequencing depth, biological replication and multiplex experimental design choices. This work quantitatively explores comparisons between contemporary analysis tools and experimental design choices for the detection of differential expression using RNA-Seq. We found that the DESeq algorithm performs more conservatively than edgeR and NBPSeq. With regard to testing of various experimental designs, this work strongly suggests that greater power is gained through the use of biological replicates relative to library (technical) replicates and sequencing depth. Strikingly, sequencing depth could be reduced as low as 15% without substantial impacts on false positive or true positive rates.

Measurement of student attitudes in first year engineering - A mixed methods approach

NASA Astrophysics Data System (ADS)

Malik, Qaiser Hameed

This research study focused on freshman attitudes towards engineering in a newly implemented cornerstone sequence that emphasized holistic design experiences. The students' initial attitudes and changes in these attitudes were examined with the explanatory mixed methods approach that allows a sequential examination of the target population with two methods, using two sets of data, to investigate the treatment effects. In the quantitative phase, the study compared changes in freshman attitude towards engineering, between the new 'design sequence' group (composed of freshmen in the cornerstone sequence) and the prior 'traditional sequence' group (composed of all other freshmen), over the course of one semester. The data were collected in fall 2008 at two time intervals and changes in the two groups' attitudes were examined with repeated measures analysis of covariance models. The analyses reported here include data from 389 students out of the total population of 722 freshmen. The analyses revealed that engineering freshmen joined the program with positive or strongly positive attitudes towards engineering. Those strong attitudes were durable and resistant to change. Students in the design sequence group had higher ACT scores, enjoyed math and science the most, and did not believe engineering to be an exact science. However, no appreciable time-group interaction was observed. To validate the quantitative results, an interview protocol was developed to investigate initial freshman attitudes and changes, if any, that took place as a result of the new cornerstone sequence. One-on-one interviews with a sample of ten students out of the population of 272 freshmen revealed that freshmen in the cornerstone sequence entered the program full of enthusiasm and idealism, and with strongly positive attitudes towards engineering. The strong motivational factors included parental/teacher influences, childhood motivations, and high school extra-curricular experiences. The participants appreciated the team work and problem solving aspects of engineering; however, they reported negative experiences in the cornerstone sequence. Interestingly, their overall perception about engineering was not affected by any of the negative experiences. The qualitative phase substantiated the belief that strong attitudes are harder to change; they are durable, they have impact, and they are not significantly affected by a short treatment. The results of this mixed methods study indicate that changing student attitudes may not be an easy task. One must develop a better understanding of student attitudes in order to improve understanding of the fine-grained details of curriculum and its implementation to be able to develop more effective cornerstone design courses. Clearly, tight and focused quantitative studies complemented with a qualitative component provide a much broader and deeper insight into the learning that takes place in freshman courses. This research also documents the use of a longitudinal study to track the design sequence group and observe their performance in their junior and senior years. This would provide a better understanding of the long term effects of the new sequence.

Static-stress impact of the 1992 Landers earthquake sequence on nucleation and slip at the site of the 1999 M=7.1 Hector Mine earthquake, southern California

USGS Publications Warehouse

Parsons, Tom; Dreger, Douglas S.

2000-01-01

The proximity in time (∼7 years) and space (∼20 km) between the 1992 M=7.3 Landers earthquake and the 1999 M=7.1 Hector Mine event suggests a possible link between the quakes. We thus calculated the static stress changes following the 1992 Joshua Tree/Landers/Big Bear earthquake sequence on the 1999 M=7.1 Hector Mine rupture plane in southern California. Resolving the stress tensor into rake-parallel and fault-normal components and comparing with changes in the post-Landers seismicity rate allows us to estimate a coefficient of friction on the Hector Mine plane. Seismicity following the 1992 sequence increased at Hector Mine where the fault was unclamped. This increase occurred despite a calculated reduction in right-lateral shear stress. The dependence of seismicity change primarily on normal stress change implies a high coefficient of static friction (µ≥0.8). We calculated the Coulomb stress change using µ=0.8 and found that the Hector Mine hypocenter was mildly encouraged (0.5 bars) by the 1992 earthquake sequence. In addition, the region of peak slip during the Hector Mine quake occurred where Coulomb stress is calculated to have increased by 0.5–1.5 bars. In general, slip was more limited where Coulomb stress was reduced, though there was some slip where the strongest stress decrease was calculated. Interestingly, many smaller earthquakes nucleated at or near the 1999 Hector Mine hypocenter after 1992, but only in 1999 did an event spread to become a M=7.1 earthquake.

Impact of Mutation Type and Amplicon Characteristics on Genetic Diversity Measures Generated Using a High-Resolution Melting Diversity Assay

PubMed Central

Cousins, Matthew M.; Donnell, Deborah; Eshleman, Susan H.

2013-01-01

We adapted high-resolution melting (HRM) technology to measure genetic diversity without sequencing. Diversity is measured as a single numeric HRM score. Herein, we determined the impact of mutation types and amplicon characteristics on HRM diversity scores. Plasmids were generated with single-base changes, insertions, and deletions. Different primer sets were used to vary the position of mutations within amplicons. Plasmids and plasmid mixtures were analyzed to determine the impact of mutation type, position, and concentration on HRM scores. The impact of amplicon length and G/C content on HRM scores was also evaluated. Different mutation types affected HRM scores to varying degrees (1-bp deletion < 1-bp change < 3-bp insertion < 9-bp insertion). The impact of mutations on HRM scores was influenced by amplicon length and the position of the mutation within the amplicon. Mutations were detected at concentrations of 5% to 95%, with the greatest impact at 50%. The G/C content altered melting temperature values of amplicons but had no impact on HRM scores. These data are relevant to the design of assays that measure genetic diversity using HRM technology. PMID:23178437

Assessing the Impact of Curricular Reform--Measures of Course Efficiency and Effectiveness. AIR 1999 Annual Forum Paper.

ERIC Educational Resources Information Center

Andrade, Sally J.

This paper proposes an alternative curriculum assessment model to the traditional approach of examining semester course grades as a measure of curricular or instructional change. The alternative model focuses on the academic success of students in the next course in a curricular sequence and was applied with a gateway mathematics course…

Expressing genes do not forget their LINEs: transposable elements and gene expression

PubMed Central

Kines, Kristine J.; Belancio, Victoria P.

2012-01-01

1. ABSTRACT Historically the accumulated mass of mammalian transposable elements (TEs), particularly those located within gene boundaries, was viewed as a genetic burden potentially detrimental to the genomic landscape. This notion has been strengthened by the discovery that transposable sequences can alter the architecture of the transcriptome, not only through insertion, but also long after the integration process is completed. Insertions previously considered harmless are now known to impact the expression of host genes via modification of the transcript quality or quantity, transcriptional interference, or by the control of pathways that affect the mRNA life-cycle. Conversely, several examples of the evolutionary advantageous impact of TEs on the host gene structure that diversified the cellular transcriptome are reported. TE-induced changes in gene expression can be tissue-or disease-specific, raising the possibility that the impact of TE sequences may vary during development, among normal cell types, and between normal and disease-affected tissues. The understanding of the rules and abundance of TE-interference with gene expression is in its infancy, and its contribution to human disease and/or evolution remains largely unexplored. PMID:22201807

DNA methylation at hepatitis B viral integrants is associated with methylation at flanking human genomic sequences

PubMed Central

Watanabe, Yoshiyuki; Yamamoto, Hiroyuki; Oikawa, Ritsuko; Toyota, Minoru; Yamamoto, Masakazu; Kokudo, Norihiro; Tanaka, Shinji; Arii, Shigeki; Yotsuyanagi, Hiroshi; Koike, Kazuhiko; Itoh, Fumio

2015-01-01

Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)–related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis. PMID:25653310

PknB remains an essential and a conserved target for drug development in susceptible and MDR strains of M. Tuberculosis.

PubMed

Gupta, Anamika; Pal, Sudhir K; Pandey, Divya; Fakir, Najneen A; Rathod, Sunita; Sinha, Dhiraj; SivaKumar, S; Sinha, Pallavi; Periera, Mycal; Balgam, Shilpa; Sekar, Gomathi; UmaDevi, K R; Anupurba, Shampa; Nema, Vijay

2017-08-18

The Mycobacterium tuberculosis (M.tb) protein kinase B (PknB) which is now proved to be essential for the growth and survival of M.tb, is a transmembrane protein with a potential to be a good drug target. However it is not known if this target remains conserved in otherwise resistant isolates from clinical origin. The present study describes the conservation analysis of sequences covering the inhibitor binding domain of PknB to assess if it remains conserved in susceptible and resistant clinical strains of mycobacteria picked from three different geographical areas of India. A total of 116 isolates from North, South and West India were used in the study with a variable profile of their susceptibilities towards streptomycin, isoniazid, rifampicin, ethambutol and ofloxacin. Isolates were also spoligotyped in order to find if the conservation pattern of pknB gene remain consistent or differ with different spoligotypes. The impact of variation as found in the study was analyzed using Molecular dynamics simulations. The sequencing results with 115/116 isolates revealed the conserved nature of pknB sequences irrespective of their susceptibility status and spoligotypes. The only variation found was in one strains wherein pnkB sequence had G to A mutation at 664 position translating into a change of amino acid, Valine to Isoleucine. After analyzing the impact of this sequence variation using Molecular dynamics simulations, it was observed that the variation is causing no significant change in protein structure or the inhibitor binding. Hence, the study endorses that PknB is an ideal target for drug development and there is no pre-existing or induced resistance with respect to the sequences involved in inhibitor binding. Also if the mutation that we are reporting for the first time is found again in subsequent work, it should be checked with phenotypic profile before drawing the conclusion that it would affect the activity in any way. Bioinformatics analysis in our study says that it has no significant effect on the binding and hence the activity of the protein.

MACARON: A python framework to identify and re-annotate multi-base affected codons in whole genome/exome sequence data.

PubMed

Khan, Waqasuddin; Saripella, Ganapathi Varma-; Ludwig, Thomas; Cuppens, Tania; Thibord, Florian; Génin, Emmanuelle; Deleuze, Jean-Francois; Trégouët, David-Alexandre

2018-05-03

Predicted deleteriousness of coding variants is a frequently used criterion to filter out variants detected in next-generation sequencing projects and to select candidates impacting on the risk of human diseases. Most available dedicated tools implement a base-to-base annotation approach that could be biased in presence of several variants in the same genetic codon. We here proposed the MACARON program that, from a standard VCF file, identifies, re-annotates and predicts the amino acid change resulting from multiple single nucleotide variants (SNVs) within the same genetic codon. Applied to the whole exome dataset of 573 individuals, MACARON identifies 114 situations where multiple SNVs within a genetic codon induce an amino acid change that is different from those predicted by standard single SNV annotation tool. Such events are not uncommon and deserve to be studied in sequencing projects with inconclusive findings. MACARON is written in python with codes available on the GENMED website (www.genmed.fr). david-alexandre.tregouet@inserm.fr. Supplementary data are available at Bioinformatics online.

Exploring the impact of an automated prescription-filling device on community pharmacy technician workflow

PubMed Central

Walsh, Kristin E.; Chui, Michelle Anne; Kieser, Mara A.; Williams, Staci M.; Sutter, Susan L.; Sutter, John G.

2012-01-01

Objective To explore community pharmacy technician workflow change after implementation of an automated robotic prescription-filling device. Methods At an independent community pharmacy in rural Mayville, WI, pharmacy technicians were observed before and 3 months after installation of an automated robotic prescription-filling device. The main outcome measures were sequences and timing of technician workflow steps, workflow interruptions, automation surprises, and workarounds. Results Of the 77 and 80 observations made before and 3 months after robot installation, respectively, 17 different workflow sequences were observed before installation and 38 after installation. Average prescription filling time was reduced by 40 seconds per prescription with use of the robot. Workflow interruptions per observation increased from 1.49 to 1.79 (P = 0.11), and workarounds increased from 10% to 36% after robot use. Conclusion Although automated prescription-filling devices can increase efficiency, workflow interruptions and workarounds may negate that efficiency. Assessing changes in workflow and sequencing of tasks that may result from the use of automation can help uncover opportunities for workflow policy and procedure redesign. PMID:21896459

[Research on soil bacteria under the impact of sealed CO2 leakage by high-throughput sequencing technology].

PubMed

Tian, Di; Ma, Xin; Li, Yu-E; Zha, Liang-Song; Wu, Yang; Zou, Xiao-Xia; Liu, Shuang

2013-10-01

Carbon dioxide Capture and Storage has provided a new option for mitigating global anthropogenic CO2 emission with its unique advantages. However, there is a risk of the sealed CO2 leakage, bringing a serious threat to the ecology system. It is widely known that soil microorganisms are closely related to soil health, while the study on the impact of sequestered CO2 leakage on soil microorganisms is quite deficient. In this study, the leakage scenarios of sealed CO2 were constructed and the 16S rRNA genes of soil bacteria were sequenced by Illumina high-throughput sequencing technology on Miseq platform, and related biological analysis was conducted to explore the changes of soil bacterial abundance, diversity and structure. There were 486,645 reads for 43,017 OTUs of 15 soil samples and the results of biological analysis showed that there were differences in the abundance, diversity and community structure of soil bacterial community under different CO, leakage scenarios while the abundance and diversity of the bacterial community declined with the amplification of CO2 leakage quantity and leakage time, and some bacteria species became the dominant bacteria species in the bacteria community, therefore the increase of Acidobacteria species would be a biological indicator for the impact of sealed CO2 leakage on soil ecology system.

The Cretaceous-Paleogene transition and Chicxulub impact ejecta in the northwestern Gulf of Mexico: Paleoenvironments, sequence stratigraphic setting and target lithologies

NASA Astrophysics Data System (ADS)

Schulte, Peter

2003-07-01

The Cretaceous-Paleogene (K-P) transition is characterized by a period of mass extinctions, the Chicxulub impact event, sea-level changes, and considerable climate changes (e.g., cooling). The Gulf of Mexico region is a key area for addressing these issues, specifically because of the proximity to the large Chicxulub impact structure in southern Mexico, and because of its shallow shelf areas throughout the Maastrichtian to Danian period. This study presents the results of a multidisciplinary investigation of Chicxulub impact ejecta and marine sediments from the K-P transition in the western Gulf of Mexico. Sedimentological, mineralogical, and geochemical aspects of K-P sections and cores from northeastern Mexico, Texas, and Alabama have been by studied with focus on Chicxulub ejecta, long- or short-term facies change, and sequence stratigraphic setting. CHICXULUB EJECTA: The Chicxulub ejecta (or impact spherule) deposits from northeastern Mexico and Texas revealed an unexpected complex and localized ejecta composition. Fe-Mg-rich chlorite- as well as Si-Al-K-rich glass-spherules are the predominant silicic ejecta components in northeastern Mexico, whereas in Texas, spherules of Mg-rich smectite compositions were encountered. Spherules contain Fe-Ti-K-rich schlieren, Fe-Mg-rich globules, and rare µm-sized metallic and sulfidic Ni-Co-(Ir-?) rich inclusions. This composition provides evidence for a distinct range of target rocks of mafic to intermediate composition, presumably situated in the northwestern sector of the Chicxulub impact structure, in addition to the possibility of contamination by meteoritic material. The absence of spinels and the ubiquitous presence of hematite and goethite points to high oxygen fugacity during the impact process. Besides these silicic phases, the most prominent ejecta component is carbonate.! Carbonate is found in ejecta deposits as unshocked clasts, accretionary lapilli-like grains, melt globules (often with quenching textures), and as microspar, suggesting that this area received ejecta mainly from shallow, carbonate-rich lithologies at the impact site on the Yucatán carbonate platform. Albeit the ejecta spherules are mostly altered to clay minerals and iron oxides, the microfacies and internal textures of the ejecta particles show a variety of distinct features, including welding and fusing of components and evidence for liquid immiscibility between silicic-silicic and carbonate-silicic melts. No evidence for binary mixing of ejecta phases was found. Therefore, it is assumed that ejecta in northeastern Mexico derived from less energetic parts of the ejecta curtain. The welding features of ejecta particles suggest an initial ground surge-like ejecta-dispersion mode. The specific morphological features and the compositional range of Chicxulub ejecta, as well as the results of petrological and rock magnetic characteristics reveal similarities to Chicxulub ejecta from K-P sections in the Gulf of Mexico area, the Caribbean, the Atlantic, the Pacific, and Northern America (Western Interior). In addition, Mg-rich smectite, K-feldspar, and iron oxide-rich microspherules are characteristic for the K-P boundary clay layer in sections from the Atlantic and Tethyan realm, suggestive of a relationship between the Chicxulub impact event and the basal K-P boundary clay layer. EJECTA DEPOSITS: The Chicxulub ejecta deposits are commonly associated with an event deposit that shows a complex succession of deposition from high-energetic (channelized) debris flows or turbidity currents derived from multiple source areas, followed by a period of decreasing current energy and intermittent periods of reworking. The uppermost parts of these deposits are often bioturbated, pointing to longer periods of deposition, as also sustained by the complex internal subdivision of the K-P event deposits. In northeastern Mexico, Chicxulub ejecta is also locally embedded within latest Maastrichtian marls, though common soft-sediment deformation opposes a clear age assignation of these deposits. However, individual spherule layers in the slumped and in the channelized spherule deposits are of similar petrological, mineralogical, and geochemical composition with no size-sorting and abrasion of ejecta, hence pointing to an origin from a single impact event (Chicxulub) and providing no evidence for extended periods between reworking of individual spherule layers. In the Brazos core from Texas, a m-thick shale interval, almost devoid of micro- and macrofossils and therefore of unclear stratigraphic age, is sandwiched between Chicxulub impact ejecta and the first appearance of Paleocene microfossils, indicating a period (of enhanced reworking?) between these two events. However, no mm-thick ferruginous layer with Ni-rich spinels, smectite spherules, and shocked quartz that defines the K-P boundary in the Global Stratotype Section and Point (GSSP) at El Kef, Tunisia, and elsewhere has been observed in any of the sections and cores studied. Therefore, an unequivocal positioning of the K-P boundary is difficult for the northwestern Gulf of Mexico region. PALEOCLIMATE RECORD: The long-term record of clay mineral species during the K-P transition of northeastern Mexico, Texas, and Alabama shows remarkably localized compositional patterns, indicating local sediment influx from topographically, petrologically, and probably climatically distinct source regions. Chlorite-illite-dominated clay assemblages in northwestern Mexico indicate mafic source rocks, predominance of physical weathering, and cooler climates, probably associated with the uplift of the Sierra Madre Oriental, whereas a smectite-dominated clay assemblage in Texas indicates semiarid-humid climates. In central Alabama, a distinct trend from tropically humid and warm climates to more seasonal and drier climate that already started in the late Maastrichtian was inferred from a prominent change of a kaolinite- to a smectite-dominated clay mineral assemblage. Hence, no unique climate conditions and distinct climate trends can be inferred for the northwestern Gulf of Mexico area from the data provided by this study. SEQUENCE STRATIGRAPHY: The sequence stratigraphic setting of the Maastrichtian to Danian strata in northeastern Mexico, Texas, and Alabama is also quite complex. The deep-water marls in northeastern Mexico were not amenable to a clear sequence stratigraphic subdivision, though the similar mineralogical (and geochemical) composition of the Maastrichtian to Danian marls provided no evidence for a distinct major facies change during this interval. In Texas, no facies change was observed for the (highstand) shale interval that includes the event bed, though a gradual sea-level lowering took place upon the appearance of the earliest Paleocene microfossils. A sequence boundary is present in the earliest Danian and overlain by transgressive systems tract. In central Alabama, a pronounced sea-level shallowing was recognized during a highstand systems tract in the late Maastrichtian, topped by a sequence boundary and subsequent (strongly) rising sea level throughout the latest Maastrichtian and the early Danian. Rapid and intense water-depth fluctuations are inferred from middle Danian carbonate-rich strata concomitant to a change from a mixed siliciclastic-carbonate depositional system to a more stable carbonate platform in central Alabama during this period. In summary, no universal pattern of facies and related sea-level changes was obtained from the northwestern Gulf of Mexico area, and particularly, no evidence for adverse an- or dysoxic sedimentary conditions were observed for the Maastrichtian to Danian interval governed by this study.

Techniques for automatic large scale change analysis of temporal multispectral imagery

NASA Astrophysics Data System (ADS)

Mercovich, Ryan A.

Change detection in remotely sensed imagery is a multi-faceted problem with a wide variety of desired solutions. Automatic change detection and analysis to assist in the coverage of large areas at high resolution is a popular area of research in the remote sensing community. Beyond basic change detection, the analysis of change is essential to provide results that positively impact an image analyst's job when examining potentially changed areas. Present change detection algorithms are geared toward low resolution imagery, and require analyst input to provide anything more than a simple pixel level map of the magnitude of change that has occurred. One major problem with this approach is that change occurs in such large volume at small spatial scales that a simple change map is no longer useful. This research strives to create an algorithm based on a set of metrics that performs a large area search for change in high resolution multispectral image sequences and utilizes a variety of methods to identify different types of change. Rather than simply mapping the magnitude of any change in the scene, the goal of this research is to create a useful display of the different types of change in the image. The techniques presented in this dissertation are used to interpret large area images and provide useful information to an analyst about small regions that have undergone specific types of change while retaining image context to make further manual interpretation easier. This analyst cueing to reduce information overload in a large area search environment will have an impact in the areas of disaster recovery, search and rescue situations, and land use surveys among others. By utilizing a feature based approach founded on applying existing statistical methods and new and existing topological methods to high resolution temporal multispectral imagery, a novel change detection methodology is produced that can automatically provide useful information about the change occurring in large area and high resolution image sequences. The change detection and analysis algorithm developed could be adapted to many potential image change scenarios to perform automatic large scale analysis of change.

Application of wavelet analysis in determining the periodicity of global warming

NASA Astrophysics Data System (ADS)

Feng, Xiao

2018-04-01

In the last two decades of the last century, the global average temperature has risen by 0.48 ° C over 100 years ago. Since then, global warming has become a hot topic. Global warming will have complex and potential impacts on humans and the Earth. However, the negative impacts far outweigh the positive impacts. The most obvious external manifestation of global warming is temperature. Therefore, this study uses wavelet analysis study the characteristics of temperature time series, solve the periodicity of the sequence, find out the trend of temperature change and predict the extent of global warming in the future, so as to take the necessary precautionary measures.

RNA-Seq reveals complex genetic response to Deepwater Horizon oil release in Fundulus grandis.

PubMed

Garcia, Tzintzuni I; Shen, Yingjia; Crawford, Douglas; Oleksiak, Marjorie F; Whitehead, Andrew; Walter, Ronald B

2012-09-12

The release of oil resulting from the blowout of the Deepwater Horizon (DH) drilling platform was one of the largest in history discharging more than 189 million gallons of oil and subject to widespread application of oil dispersants. This event impacted a wide range of ecological habitats with a complex mix of pollutants whose biological impact is still not yet fully understood. To better understand the effects on a vertebrate genome, we studied gene expression in the salt marsh minnow Fundulus grandis, which is local to the northern coast of the Gulf of Mexico and is a sister species of the ecotoxicological model Fundulus heteroclitus. To assess genomic changes, we quantified mRNA expression using high throughput sequencing technologies (RNA-Seq) in F. grandis populations in the marshes and estuaries impacted by DH oil release. This application of RNA-Seq to a non-model, wild, and ecologically significant organism is an important evaluation of the technology to quickly assess similar events in the future. Our de novo assembly of RNA-Seq data produced a large set of sequences which included many duplicates and fragments. In many cases several of these could be associated with a common reference sequence using blast to query a reference database. This reduced the set of significant genes to 1,070 down-regulated and 1,251 up-regulated genes. These genes indicate a broad and complex genomic response to DH oil exposure including the expected AHR-mediated response and CYP genes. In addition a response to hypoxic conditions and an immune response are also indicated. Several genes in the choriogenin family were down-regulated in the exposed group; a response that is consistent with AH exposure. These analyses are in agreement with oligonucleotide-based microarray analyses, and describe only a subset of significant genes with aberrant regulation in the exposed set. RNA-Seq may be successfully applied to feral and extremely polymorphic organisms that do not have an underlying genome sequence assembly to address timely environmental problems. Additionally, the observed changes in a large set of transcript expression levels are indicative of a complex response to the varied petroleum components to which the fish were exposed.

"Maxillary lateral incisor partial anodontia sequence": a clinical entity with epigenetic origin.

PubMed

Consolaro, Alberto; Cardoso, Maurício Almeida; Consolaro, Renata Bianco

2017-01-01

The relationship between maxillary lateral incisor anodontia and the palatal displacement of unerupted maxillary canines cannot be considered as a multiple tooth abnormality with defined genetic etiology in order to be regarded as a "syndrome". Neither were the involved genes identified and located in the human genome, nor was it presumed on which chromosome the responsible gene would be located. The palatal maxillary canine displacement in cases of partial anodontia of the maxillary lateral incisor is potentially associated with environmental changes caused by its absence in its place of formation and eruption, which would characterize an epigenetic etiology. The lack of the maxillary lateral incisor in the canine region means removing one of the reference guides for the eruptive trajectory of the maxillary canine, which would therefore, not erupt and /or impact on the palate. Consequently, and in sequence, it would lead to malocclusion, maxillary atresia, transposition, prolonged retention of the deciduous canine and resorption in the neighboring teeth. Thus, we can say that we are dealing with a set of anomalies and multiple sequential changes known as sequential development anomalies or, simply, sequence. Once the epigenetics and sequential condition is accepted for this clinical picture, it could be called "Maxillary Lateral Incisor Partial Anodontia Sequence."

MutaBind estimates and interprets the effects of sequence variants on protein-protein interactions.

PubMed

Li, Minghui; Simonetti, Franco L; Goncearenco, Alexander; Panchenko, Anna R

2016-07-08

Proteins engage in highly selective interactions with their macromolecular partners. Sequence variants that alter protein binding affinity may cause significant perturbations or complete abolishment of function, potentially leading to diseases. There exists a persistent need to develop a mechanistic understanding of impacts of variants on proteins. To address this need we introduce a new computational method MutaBind to evaluate the effects of sequence variants and disease mutations on protein interactions and calculate the quantitative changes in binding affinity. The MutaBind method uses molecular mechanics force fields, statistical potentials and fast side-chain optimization algorithms. The MutaBind server maps mutations on a structural protein complex, calculates the associated changes in binding affinity, determines the deleterious effect of a mutation, estimates the confidence of this prediction and produces a mutant structural model for download. MutaBind can be applied to a large number of problems, including determination of potential driver mutations in cancer and other diseases, elucidation of the effects of sequence variants on protein fitness in evolution and protein design. MutaBind is available at http://www.ncbi.nlm.nih.gov/projects/mutabind/. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Conifer genomics and adaptation: at the crossroads of genetic diversity and genome function.

PubMed

Prunier, Julien; Verta, Jukka-Pekka; MacKay, John J

2016-01-01

Conifers have been understudied at the genomic level despite their worldwide ecological and economic importance but the situation is rapidly changing with the development of next generation sequencing (NGS) technologies. With NGS, genomics research has simultaneously gained in speed, magnitude and scope. In just a few years, genomes of 20-24 gigabases have been sequenced for several conifers, with several others expected in the near future. Biological insights have resulted from recent sequencing initiatives as well as genetic mapping, gene expression profiling and gene discovery research over nearly two decades. We review the knowledge arising from conifer genomics research emphasizing genome evolution and the genomic basis of adaptation, and outline emerging questions and knowledge gaps. We discuss future directions in three areas with potential inputs from NGS technologies: the evolutionary impacts of adaptation in conifers based on the adaptation-by-speciation model; the contributions of genetic variability of gene expression in adaptation; and the development of a broader understanding of genetic diversity and its impacts on genome function. These research directions promise to sustain research aimed at addressing the emerging challenges of adaptation that face conifer trees. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

The Effect of Defense Contracting Requirements on Just-In-Time Implementation

DTIC Science & Technology

1988-12-01

and purchasing efforts negatively impacted. The role of I11 contract uncertainty was weakest and had mixed effects. Difficult negotiations prior to...they recommend differs somewhat. Shingo stresses the use of setup reduction and layout changes early in his sequence with production leveling occurring...consciousness toward quality improvement, and use of foolproof mechanisms to prevent errors), higher level government quality standards stress separate

Sequence variations of the partially dominant DELLA gene Rht-B1c in wheat and their functional impacts

PubMed Central

Ma, Zhengqiang

2013-01-01

Rht-B1c, allelic to the DELLA protein-encoding gene Rht-B1a, is a natural mutation documented in common wheat (Triticum aestivum). It confers variation to a number of traits related to cell and plant morphology, seed dormancy, and photosynthesis. The present study was conducted to examine the sequence variations of Rht-B1c and their functional impacts. The results showed that Rht-B1c was partially dominant or co-dominant for plant height, and exhibited an increased dwarfing effect. At the sequence level, Rht-B1c differed from Rht-B1a by one 2kb Veju retrotransposon insertion, three coding region single nucleotide polymorphisms (SNPs), one 197bp insertion, and four SNPs in the 1kb upstream sequence. Haplotype investigations, association analyses, transient expression assays, and expression profiling showed that the Veju insertion was primarily responsible for the extreme dwarfing effect. It was found that the Veju insertion changed processing of the Rht-B1c transcripts and resulted in DELLA motif primary structure disruption. Expression assays showed that Rht-B1c caused reduction of total Rht-1 transcript levels, and up-regulation of GATA-like transcription factors and genes positively regulated by these factors, suggesting that one way in which Rht-1 proteins affect plant growth and development is through GATA-like transcription factor regulation. PMID:23918966

Sequence stratigraphic controls on reservoir characterization and architecture: case study of the Messinian Abu Madi incised-valley fill, Egypt

NASA Astrophysics Data System (ADS)

Abdel-Fattah, Mohamed I.; Slatt, Roger M.

2013-12-01

Understanding sequence stratigraphy architecture in the incised-valley is a crucial step to understanding the effect of relative sea level changes on reservoir characterization and architecture. This paper presents a sequence stratigraphic framework of the incised-valley strata within the late Messinian Abu Madi Formation based on seismic and borehole data. Analysis of sand-body distribution reveals that fluvial channel sandstones in the Abu Madi Formation in the Baltim Fields, offshore Nile Delta, Egypt, are not randomly distributed but are predictable in their spatial and stratigraphic position. Elucidation of the distribution of sandstones in the Abu Madi incised-valley fill within a sequence stratigraphic framework allows a better understanding of their characterization and architecture during burial. Strata of the Abu Madi Formation are interpreted to comprise two sequences, which are the most complex stratigraphically; their deposits comprise a complex incised valley fill. The lower sequence (SQ1) consists of a thick incised valley-fill of a Lowstand Systems Tract (LST1)) overlain by a Transgressive Systems Tract (TST1) and Highstand Systems Tract (HST1). The upper sequence (SQ2) contains channel-fill and is interpreted as a LST2 which has a thin sandstone channel deposits. Above this, channel-fill sandstone and related strata with tidal influence delineates the base of TST2, which is overlain by a HST2. Gas reservoirs of the Abu Madi Formation (present-day depth ˜3552 m), the Baltim Fields, Egypt, consist of fluvial lowstand systems tract (LST) sandstones deposited in an incised valley. LST sandstones have a wide range of porosity (15 to 28%) and permeability (1 to 5080mD), which reflect both depositional facies and diagenetic controls. This work demonstrates the value of constraining and evaluating the impact of sequence stratigraphic distribution on reservoir characterization and architecture in incised-valley deposits, and thus has an important impact on reservoir quality evolution in hydrocarbon exploration in such settings.

Action starring narratives and events: Structure and inference in visual narrative comprehension

PubMed Central

Cohn, Neil; Wittenberg, Eva

2015-01-01

Studies of discourse have long placed focus on the inference generated by information that is not overtly expressed, and theories of visual narrative comprehension similarly focused on the inference generated between juxtaposed panels. Within the visual language of comics, star-shaped “flashes” commonly signify impacts, but can be enlarged to the size of a whole panel that can omit all other representational information. These “action star” panels depict a narrative culmination (a “Peak”), but have content which readers must infer, thereby posing a challenge to theories of inference generation in visual narratives that focus only on the semantic changes between juxtaposed images. This paper shows that action stars demand more inference than depicted events, and that they are more coherent in narrative sequences than scrambled sequences (Experiment 1). In addition, action stars play a felicitous narrative role in the sequence (Experiment 2). Together, these results suggest that visual narratives use conventionalized depictions that demand the generation of inferences while retaining narrative coherence of a visual sequence. PMID:26709362

Action starring narratives and events: Structure and inference in visual narrative comprehension.

PubMed

Cohn, Neil; Wittenberg, Eva

Studies of discourse have long placed focus on the inference generated by information that is not overtly expressed, and theories of visual narrative comprehension similarly focused on the inference generated between juxtaposed panels. Within the visual language of comics, star-shaped "flashes" commonly signify impacts, but can be enlarged to the size of a whole panel that can omit all other representational information. These "action star" panels depict a narrative culmination (a "Peak"), but have content which readers must infer, thereby posing a challenge to theories of inference generation in visual narratives that focus only on the semantic changes between juxtaposed images. This paper shows that action stars demand more inference than depicted events, and that they are more coherent in narrative sequences than scrambled sequences (Experiment 1). In addition, action stars play a felicitous narrative role in the sequence (Experiment 2). Together, these results suggest that visual narratives use conventionalized depictions that demand the generation of inferences while retaining narrative coherence of a visual sequence.

Effects of dispense equipment sequence on process start-up defects

NASA Astrophysics Data System (ADS)

Brakensiek, Nick; Sevegney, Michael

2013-03-01

Photofluid dispense systems within coater/developer tools have been designed with the intent to minimize cost of ownership to the end user. Waste and defect minimization, dispense quality and repeatability, and ease of use are all desired characteristics. One notable change within commercially available systems is the sequence in which process fluid encounters dispense pump and filtration elements. Traditionally, systems adopted a pump-first sequence, where fluid is "pushed through" a point-of-use filter just prior to dispensing on the wafer. Recently, systems configured in a pump-last scheme have become available, where fluid is "pulled through" the filter, into the pump, and then is subsequently dispensed. The present work constitutes a comparative evaluation of the two equipment sequences with regard to the aforementioned characteristics that impact cost of ownership. Additionally, removal rating and surface chemistry (i.e., hydrophilicity) of the point-of-use filter are varied in order to evaluate their influence on system start-up and defects.

Experimental and analytical study of high velocity impact on Kevlar/Epoxy composite plates

NASA Astrophysics Data System (ADS)

Sikarwar, Rahul S.; Velmurugan, Raman; Madhu, Velmuri

2012-12-01

In the present study, impact behavior of Kevlar/Epoxy composite plates has been carried out experimentally by considering different thicknesses and lay-up sequences and compared with analytical results. The effect of thickness, lay-up sequence on energy absorbing capacity has been studied for high velocity impact. Four lay-up sequences and four thickness values have been considered. Initial velocities and residual velocities are measured experimentally to calculate the energy absorbing capacity of laminates. Residual velocity of projectile and energy absorbed by laminates are calculated analytically. The results obtained from analytical study are found to be in good agreement with experimental results. It is observed from the study that 0/90 lay-up sequence is most effective for impact resistance. Delamination area is maximum on the back side of the plate for all thickness values and lay-up sequences. The delamination area on the back is maximum for 0/90/45/-45 laminates compared to other lay-up sequences.

Determining the impacts of climate change and catchment development on future water availability in Tasmania, Australia

NASA Astrophysics Data System (ADS)

Post, David

2010-05-01

In a water-scarce country such as Australia, detailed, accurate and reliable assessments of current and future water availability are essential in order to adequately manage the limited water resource. This presentation describes a recently completed study which provided an assessment of current water availability in Tasmania, Australia, and also determined how this water availability would be impacted by climate change and proposed catchment development by the year 2030. The Tasmania Sustainable Yields Project (http://www.csiro.au/partnerships/TasSY.html) assessed current water availability through the application of rainfall-runoff models, river models, and recharge and groundwater models. These were calibrated to streamflow records and parameterised using estimates of current groundwater and surface water extractions and use. Having derived a credible estimate of current water availability, the impacts of future climate change on water availability were determined through deriving changes in rainfall and potential evapotranspiration from 15 IPCC AR4 global climate models. These changes in rainfall were then dynamically downscaled using the CSIRO-CCAM model over the relatively small study area (50,000 square km). A future climate sequence was derived by modifying the historical 84-year climate sequence based on these changes in rainfall and potential evapotranspiration. This future climate sequence was then run through the rainfall-runoff, river, recharge and groundwater models to give an estimate of water availability under future climate. To estimate the impacts of future catchment development on water availability, the models were modified and re-run to reflect projected increases in development. Specifically, outputs from the rainfall-runoff and recharge models were reduced over areas of projected future plantation forestry. Conversely, groundwater recharge was increased over areas of new irrigated agriculture and new extractions of water for irrigation were implemented in the groundwater and river models. Results indicate that historical average water availability across the project area was 21,815 GL/year. Of this, 636 GL/year of surface water and 38 GL/year of groundwater are currently extracted for use. By 2030, rainfall is projected to decrease by an average of 3% over the project area. This decrease in rainfall and concurrent increase in potential evapotranspiration leads to a decrease in water availability of 5% by 2030. As a result of lower streamflows, under current cease-to-take rules, currently licensed extractions are projected to decrease by 3% (19 GL/year). This however is offset by an additional 120 GL/year of extractions for proposed new irrigated agriculture. These new extractions, along with the increase in commercial forest plantations lead to a reduction in total surface water of 1% in addition to the 5% reduction due to climate change. Results from this study are being used by the Tasmanian and Australian governments to guide the development of a sustainable irrigated agriculture industry in Tasmania. In part, this is necessary to offset the loss of irrigated agriculture from the southern Murray-Darling Basin where climate change induced reductions in rainfall are projected to be far worse.

Peptide de novo sequencing of mixture tandem mass spectra

PubMed Central

Hotta, Stéphanie Yuki Kolbeck; Verano‐Braga, Thiago; Kjeldsen, Frank

2016-01-01

The impact of mixture spectra deconvolution on the performance of four popular de novo sequencing programs was tested using artificially constructed mixture spectra as well as experimental proteomics data. Mixture fragmentation spectra are recognized as a limitation in proteomics because they decrease the identification performance using database search engines. De novo sequencing approaches are expected to be even more sensitive to the reduction in mass spectrum quality resulting from peptide precursor co‐isolation and thus prone to false identifications. The deconvolution approach matched complementary b‐, y‐ions to each precursor peptide mass, which allowed the creation of virtual spectra containing sequence specific fragment ions of each co‐isolated peptide. Deconvolution processing resulted in equally efficient identification rates but increased the absolute number of correctly sequenced peptides. The improvement was in the range of 20–35% additional peptide identifications for a HeLa lysate sample. Some correct sequences were identified only using unprocessed spectra; however, the number of these was lower than those where improvement was obtained by mass spectral deconvolution. Tight candidate peptide score distribution and high sensitivity to small changes in the mass spectrum introduced by the employed deconvolution method could explain some of the missing peptide identifications. PMID:27329701

Holocene alluvium around Lefkosia (Nicosia), Cyprus: An archive of land-use, tectonic processes, and climate change

USGS Publications Warehouse

Newell, Wayne L.; Stone, B.; Harrison, R.; ,

2004-01-01

Holocene alluvium of the Pedhicos River around Lefkosia (Nicosia), Cyprus, was studied. Alluvial stratigraphy was found to present serial flood deposits underlying river terraces and an extensive alluvial fan. It was found that the stratigraphy and geomorphology of the alluvium can be interpreted to distinguish not only the effects of climate change, but also land-use change, and the impact of particular engineering works. It was suggested that details of the physical properties of the flood deposit sequences and paleosols can contribute to modeling various geophysical and engineering properties and in predicting response to vertical acceleration during earthquakes.

Sedimentology, Petrography and Microfacies of the Paleogene Carbonate Sequence - Yaxcopoil-1 Borehole (Chicxulub, Yucatan)

NASA Astrophysics Data System (ADS)

Escobar-Sanchez, E.; Fucugauchi, J. U.

2013-05-01

Chicxulub crater is one the three largest known impact craters on Earth, formed 66 Ma-old, with multi-ring basin morphology. Crater is located in northwestern Yucatan, southern Gulf of Mexico, with rim diameter of 200 km and crater center at Chicxulub Perto in the coastline. It is buried beneath the carbonate and evaporitic Cenozoic sequence. Study of the structure requires geophysics and drilling, with several boreholes drilled in the peninsula. The Yaxcopoil-1 borehole was drilled south of Merida, about 62 km from center, as part of the Chicxulub Scientific Drilling Program. One of the main objectives was to determine the role of the Chicxulub impact event in the K/Pg mass extinction and boundary events. We present a sedimentological and petrological study of the carbonate sequence in the interval from 404 m to 792 m overlying the K/Pg boundary. The well reached a depth of 1510.6 m. In this interval, we identified twelve units marked by different lithological and sedimentological changes, and supplemented by thin section analysis. Facies are composed mainly of marls, argillaceous, limestones, dolomitized limestones, calcareous breccias and calcarenites with shales thin beds. From the microfacies study we observed several major changes in the microfacies. From bottom of the sequence several textural changes cyclic from mudstone to bioclastic planktic foraminiferal wackestone, bioclastic packstone and some bioclastic grainstone. Two textures dominated in the calcareous sequence: bioclastic wackestone and packstone microfacies. From the microfacies study, we derived inferences on stable environmental conditions. We observed benthic and planktic foraminiferal layers. The benthic foraminifera strongly depend on environmental parameters, such as nutrient supply or oxygenation of the sea bottom water in the Paleocene and Eocene. Changes suggest occurrence of a progradational event, with a relative increase in sea level very slowly, with the sediment enough to overcome the elevation. In the last meters of Unit 2 (778-772 m), a series of thin layers of marl and calcareous shale interbedded with wackestone are interpreted as a transgressive event. In the first few meters of Unit 3 provides greater energy currents causing variations in the grain size. Petrographic observations show that planktonic and benthic facies are arranged as intermittent flows in parts of the unit, which points to flow currents. Predominance of coarse-grained facies rich in carbonates possibly indicates a prograding event into deep areas. In the sequence several possible changes in sea level are recorded, especially from Unit 5 to 8 Unit, where a possible limit between the Paleocene and Eocene is located between Unit 6 and Unit 7, at about 660 m. Biostratigraphy was obtained by zones corresponding to P4 and P5. In Unit 8 contains the first record of turbidite or storm deposits outer shelf environments that could be related to platform progradation. The Paleocene-Eocene thermal maximum represents a period of global warming and sea level rise. The sedimentological and micropaleontological changes may be correlated with the faunal turnover in the Gulf of Mexico, providing a complementary tool for biostratigraphic inferences.

Interbasin water transfer, riverine connectivity, and spatial controls on fish biodiversity

USGS Publications Warehouse

Grant, Evan H. Campbell; Lynch, Heather J.; Muneepeerakul, Rachata; Muthukumarasamy, Arunachalam; Rodríguez-Iturbe, Ignacio; Fagan, William F.

2012-01-01

Background Large-scale inter-basin water transfer (IBWT) projects are commonly proposed as solutions to water distribution and supply problems. These problems are likely to intensify under future population growth and climate change scenarios. Scarce data on the distribution of freshwater fishes frequently limits the ability to assess the potential implications of an IBWT project on freshwater fish communities. Because connectivity in habitat networks is expected to be critical to species' biogeography, consideration of changes in the relative isolation of riverine networks may provide a strategy for controlling impacts of IBWTs on freshwater fish communities Methods/Principal Findings Using empirical data on the current patterns of freshwater fish biodiversity for rivers of peninsular India, we show here how the spatial changes alone under an archetypal IBWT project will (1) reduce freshwater fish biodiversity system-wide, (2) alter patterns of local species richness, (3) expand distributions of widespread species throughout peninsular rivers, and (4) decrease community richness by increasing inter-basin similarity (a mechanism for the observed decrease in biodiversity). Given the complexity of the IBWT, many paths to partial or full completion of the project are possible. We evaluate two strategies for step-wise implementation of the 11 canals, based on economic or ecological considerations. We find that for each step in the project, the impacts on freshwater fish communities are sensitive to which canal is added to the network. Conclusions/Significance Importantly, ecological impacts can be reduced by associating the sequence in which canals are added to characteristics of the links, except for the case when all 11 canals are implemented simultaneously (at which point the sequence of canal addition is inconsequential). By identifying the fundamental relationship between the geometry of riverine networks and freshwater fish biodiversity, our results will aid in assessing impacts of IBWT projects and balancing ecosystem and societal demands for freshwater, even in cases where biodiversity data are limited.

Interbasin Water Transfer, Riverine Connectivity, and Spatial Controls on Fish Biodiversity

PubMed Central

Grant, Evan H. Campbell; Lynch, Heather J.; Muneepeerakul, Rachata; Arunachalam, Muthukumarasamy; Rodríguez-Iturbe, Ignacio; Fagan, William F.

2012-01-01

Background Large-scale inter-basin water transfer (IBWT) projects are commonly proposed as solutions to water distribution and supply problems. These problems are likely to intensify under future population growth and climate change scenarios. Scarce data on the distribution of freshwater fishes frequently limits the ability to assess the potential implications of an IBWT project on freshwater fish communities. Because connectivity in habitat networks is expected to be critical to species' biogeography, consideration of changes in the relative isolation of riverine networks may provide a strategy for controlling impacts of IBWTs on freshwater fish communities. Methods/Principal Findings Using empirical data on the current patterns of freshwater fish biodiversity for rivers of peninsular India, we show here how the spatial changes alone under an archetypal IBWT project will (1) reduce freshwater fish biodiversity system-wide, (2) alter patterns of local species richness, (3) expand distributions of widespread species throughout peninsular rivers, and (4) decrease community richness by increasing inter-basin similarity (a mechanism for the observed decrease in biodiversity). Given the complexity of the IBWT, many paths to partial or full completion of the project are possible. We evaluate two strategies for step-wise implementation of the 11 canals, based on economic or ecological considerations. We find that for each step in the project, the impacts on freshwater fish communities are sensitive to which canal is added to the network. Conclusions/Significance Importantly, ecological impacts can be reduced by associating the sequence in which canals are added to characteristics of the links, except for the case when all 11 canals are implemented simultaneously (at which point the sequence of canal addition is inconsequential). By identifying the fundamental relationship between the geometry of riverine networks and freshwater fish biodiversity, our results will aid in assessing impacts of IBWT projects and balancing ecosystem and societal demands for freshwater, even in cases where biodiversity data are limited. PMID:22470533

Interbasin water transfer, riverine connectivity, and spatial controls on fish biodiversity.

PubMed

Grant, Evan H Campbell; Lynch, Heather J; Muneepeerakul, Rachata; Arunachalam, Muthukumarasamy; Rodríguez-Iturbe, Ignacio; Fagan, William F

2012-01-01

Large-scale inter-basin water transfer (IBWT) projects are commonly proposed as solutions to water distribution and supply problems. These problems are likely to intensify under future population growth and climate change scenarios. Scarce data on the distribution of freshwater fishes frequently limits the ability to assess the potential implications of an IBWT project on freshwater fish communities. Because connectivity in habitat networks is expected to be critical to species' biogeography, consideration of changes in the relative isolation of riverine networks may provide a strategy for controlling impacts of IBWTs on freshwater fish communities. Using empirical data on the current patterns of freshwater fish biodiversity for rivers of peninsular India, we show here how the spatial changes alone under an archetypal IBWT project will (1) reduce freshwater fish biodiversity system-wide, (2) alter patterns of local species richness, (3) expand distributions of widespread species throughout peninsular rivers, and (4) decrease community richness by increasing inter-basin similarity (a mechanism for the observed decrease in biodiversity). Given the complexity of the IBWT, many paths to partial or full completion of the project are possible. We evaluate two strategies for step-wise implementation of the 11 canals, based on economic or ecological considerations. We find that for each step in the project, the impacts on freshwater fish communities are sensitive to which canal is added to the network. Importantly, ecological impacts can be reduced by associating the sequence in which canals are added to characteristics of the links, except for the case when all 11 canals are implemented simultaneously (at which point the sequence of canal addition is inconsequential). By identifying the fundamental relationship between the geometry of riverine networks and freshwater fish biodiversity, our results will aid in assessing impacts of IBWT projects and balancing ecosystem and societal demands for freshwater, even in cases where biodiversity data are limited.

Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data.

PubMed

Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne-Vibeke; Kruse, Torben A; Larsen, Martin Jakob

2016-01-01

Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths.

Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data

PubMed Central

Krøigård, Anne Bruun; Thomassen, Mads; Lænkholm, Anne-Vibeke; Kruse, Torben A.; Larsen, Martin Jakob

2016-01-01

Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths. PMID:27002637

How to use sequence analysis for life course epidemiology? An example on HIV-positive Sub-Saharan migrants in France.

PubMed

Gosselin, Anne; Desgrées du Loû, Annabel; Lelièvre, Eva

2018-06-01

Life course epidemiology is now an established field in social epidemiology; in sociodemography, the quantitative analysis of biographies recently experienced significant trend from event history analysis to sequence analysis. The purpose of this article is to introduce and adapt this methodology to a social epidemiology question, taking the example of the impact of HIV diagnosis on Sub-Saharan migrants' residential trajectories in the Paris region. The sample consists of 640 migrants born in Sub-Saharan Africa receiving HIV care. They were interviewed in healthcare facilities in the Paris region within the PARCOURS project, conducted from 2012 to 2013, using life event history calendars, which recorded year by year their health, family and residential histories. We introduce a two-step methodological approach consisting of (1) sequence analysis by optimal matching to build a typology of migrants' residential pathways before and after diagnosis, and (2) a Cox model of the probability to experience changes in the residential situation. The seven-clusters typology shows that for a majority, the HIV diagnosis did not entail changes in residential situation. However 30% of the migrants experienced a change in their residential situation at time of diagnosis. The Cox model analysis reveals that this residential change was in fact moving in with one's partner (HR 2.99, P<0.000) rather than network rejection. This original combination of sequence analysis and Cox models is a powerful process that could be applied to other themes and constitutes a new approach in the life course epidemiology toolbox. NCT02566148. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of the impact of refrigeration on next generation sequencing-based assessment of the canine and feline fecal microbiota.

PubMed

Weese, J Scott; Jalali, Mohammad

2014-09-30

Evaluation of factors that might impact microbiota assessment is important to avoid spurious results, particularly in field and multicenter studies where sample collection may occur distant from the laboratory. This study evaluated the impact of refrigeration on next generation sequence-based assessment of the canine and feline fecal microbiota. Fecal samples were collected from seven dogs and ten cats, and analysed at baseline and after 3, 7, 10 and 14 days of storage at 4°C. There were no differences in community membership or population structure between timepoints for either dogs or cats, nor were there any differences in richness, diversity and evenness. There were few differences in relative abundance of phyla or predominant genera, with the only differences being significant increases in Actinobacteria between Days 0-14 (P = 0.0184) and 1-14 (P = 0.0182) for canine samples, and a decrease in Erysipelotrichaceae incertae sedis between Day 0 and Day 7 (median 4.9 vs 2.2%, P = 0.046) in feline samples. Storage for at least 14 days at 4°C has limited impact on culture-independent assessment of the canine and feline fecal microbiota, although changes in some individual groups may occur.

Sequence variation between 462 human individuals fine-tunes functional sites of RNA processing

NASA Astrophysics Data System (ADS)

Ferreira, Pedro G.; Oti, Martin; Barann, Matthias; Wieland, Thomas; Ezquina, Suzana; Friedländer, Marc R.; Rivas, Manuel A.; Esteve-Codina, Anna; Estivill, Xavier; Guigó, Roderic; Dermitzakis, Emmanouil; Antonarakis, Stylianos; Meitinger, Thomas; Strom, Tim M.; Palotie, Aarno; François Deleuze, Jean; Sudbrak, Ralf; Lerach, Hans; Gut, Ivo; Syvänen, Ann-Christine; Gyllensten, Ulf; Schreiber, Stefan; Rosenstiel, Philip; Brunner, Han; Veltman, Joris; Hoen, Peter A. C. T.; Jan van Ommen, Gert; Carracedo, Angel; Brazma, Alvis; Flicek, Paul; Cambon-Thomsen, Anne; Mangion, Jonathan; Bentley, David; Hamosh, Ada; Rosenstiel, Philip; Strom, Tim M.; Lappalainen, Tuuli; Guigó, Roderic; Sammeth, Michael

2016-09-01

Recent advances in the cost-efficiency of sequencing technologies enabled the combined DNA- and RNA-sequencing of human individuals at the population-scale, making genome-wide investigations of the inter-individual genetic impact on gene expression viable. Employing mRNA-sequencing data from the Geuvadis Project and genome sequencing data from the 1000 Genomes Project we show that the computational analysis of DNA sequences around splice sites and poly-A signals is able to explain several observations in the phenotype data. In contrast to widespread assessments of statistically significant associations between DNA polymorphisms and quantitative traits, we developed a computational tool to pinpoint the molecular mechanisms by which genetic markers drive variation in RNA-processing, cataloguing and classifying alleles that change the affinity of core RNA elements to their recognizing factors. The in silico models we employ further suggest RNA editing can moonlight as a splicing-modulator, albeit less frequently than genomic sequence diversity. Beyond existing annotations, we demonstrate that the ultra-high resolution of RNA-Seq combined from 462 individuals also provides evidence for thousands of bona fide novel elements of RNA processing—alternative splice sites, introns, and cleavage sites—which are often rare and lowly expressed but in other characteristics similar to their annotated counterparts.

Unique genetic responses revealed in RNA-seq of the spleen of chickens stimulated with lipopolysaccharide and short-term heat

PubMed Central

Van Goor, Angelica; Ashwell, Chris M.; Persia, Michael E.; Rothschild, Max F.; Schmidt, Carl J.

2017-01-01

Climate change and disease have large negative impacts on poultry production, but little is known about the interactions of responses to these stressors in chickens. Fayoumi (heat and disease resistant) and broiler (heat and disease susceptible) chicken lines were stimulated at 22 days of age, using a 2x2x2 factorial design including: breed (Fayoumi or broiler), inflammatory stimulus (lipopolysaccharide (LPS) or saline), and temperature (35°C or 25°C). Transcriptional changes in spleens were analyzed using RNA-sequencing on the Illumina HiSeq 2500. Thirty-two individual cDNA libraries were sequenced (four per treatment) and an average of 22 million reads were generated per library. Stimulation with LPS induced more differentially expressed genes (DEG, log2 fold change ≥ 2 and FDR ≤ 0.05) in the broiler (N = 283) than the Fayoumi (N = 85), whereas heat treatment resulted in fewer DEG in broiler (N = 22) compared to Fayoumi (N = 107). The double stimulus of LPS+heat induced the largest numbers of changes in gene expression, for which broiler had 567 DEG and Fayoumi had 1471 DEG of which 399 were shared between breeds. Further analysis of DEG revealed pathways impacted by these stressors such as Remodelling of Epithelial Adherens Junctions due to heat stress, Granulocyte Adhesion and Diapedesis due to LPS, and Hepatic Fibrosis/Hepatic Stellate Cell Activation due to LPS+heat. The genes and pathways identified provide deeper understanding of the response to the applied stressors and may serve as biomarkers for genetic selection for heat and disease tolerant chickens. PMID:28166270

Changes in the equine fecal microbiota associated with the use of systemic antimicrobial drugs.

PubMed

Costa, Marcio C; Stämpfli, Henry R; Arroyo, Luis G; Allen-Vercoe, Emma; Gomes, Roberta G; Weese, J Scott

2015-02-03

The intestinal tract is a rich and complex environment and its microbiota has been shown to have an important role in health and disease in the host. Several factors can cause disruption of the normal intestinal microbiota, including antimicrobial therapy, which is an important cause of diarrhea in horses. This study aimed to characterize changes in the fecal bacterial populations of healthy horses associated with the administration of frequently used antimicrobial drugs. Twenty-four adult mares were assigned to receive procaine penicillin intramuscularly (IM), ceftiofur sodium IM, trimethoprim sulfadiazine (TMS) orally or to a control group. Treatment was given for 5 consecutive days and fecal samples were collected before drug administration (Day 1), at the end of treatment (Days 5), and on Days 14 and 30 of the trial. High throughput sequencing of the V4 region of the 16S rRNA gene was performed using an Illumina MiSeq sequencer. Significant changes of population structure and community membership were observed after the use of all drugs. TMS caused the most marked changes on fecal microbiota even at higher taxonomic levels including a significant decrease of richness and diversity. Those changes were mainly due to a drastic decrease of Verrucomicrobia, specifically the "5 genus incertae sedis". Changes in structure and membership caused by antimicrobial administration were specific for each drug and may be predictable. Twenty-five days after the end of treatment, bacterial profiles were more similar to pre-treatment patterns indicating a recovery from changes caused by antimicrobial administration, but differences were still evident, especially regarding community membership. The use of systemic antimicrobials leads to changes in the intestinal microbiota, with different and specific responses to different antimicrobials. All antimicrobials tested here had some impact on the microbiota, but TMS significantly reduced bacterial species richness and diversity and had the greatest apparent impact on population structure, specifically targeting members of the Verrucomicrobia phylum.

SNPdbe: constructing an nsSNP functional impacts database.

PubMed

Schaefer, Christian; Meier, Alice; Rost, Burkhard; Bromberg, Yana

2012-02-15

Many existing databases annotate experimentally characterized single nucleotide polymorphisms (SNPs). Each non-synonymous SNP (nsSNP) changes one amino acid in the gene product (single amino acid substitution;SAAS). This change can either affect protein function or be neutral in that respect. Most polymorphisms lack experimental annotation of their functional impact. Here, we introduce SNPdbe-SNP database of effects, with predictions of computationally annotated functional impacts of SNPs. Database entries represent nsSNPs in dbSNP and 1000 Genomes collection, as well as variants from UniProt and PMD. SAASs come from >2600 organisms; 'human' being the most prevalent. The impact of each SAAS on protein function is predicted using the SNAP and SIFT algorithms and augmented with experimentally derived function/structure information and disease associations from PMD, OMIM and UniProt. SNPdbe is consistently updated and easily augmented with new sources of information. The database is available as an MySQL dump and via a web front end that allows searches with any combination of organism names, sequences and mutation IDs. http://www.rostlab.org/services/snpdbe.

Deep Illumina-Based Shotgun Sequencing Reveals Dietary Effects on the Structure and Function of the Fecal Microbiome of Growing Kittens

PubMed Central

Deusch, Oliver; O’Flynn, Ciaran; Colyer, Alison; Morris, Penelope; Allaway, David; Jones, Paul G.; Swanson, Kelly S.

2014-01-01

Background Previously, we demonstrated that dietary protein:carbohydrate ratio dramatically affects the fecal microbial taxonomic structure of kittens using targeted 16S gene sequencing. The present study, using the same fecal samples, applied deep Illumina shotgun sequencing to identify the diet-associated functional potential and analyze taxonomic changes of the feline fecal microbiome. Methodology & Principal Findings Fecal samples from kittens fed one of two diets differing in protein and carbohydrate content (high–protein, low–carbohydrate, HPLC; and moderate-protein, moderate-carbohydrate, MPMC) were collected at 8, 12 and 16 weeks of age (n = 6 per group). A total of 345.3 gigabases of sequence were generated from 36 samples, with 99.75% of annotated sequences identified as bacterial. At the genus level, 26% and 39% of reads were annotated for HPLC- and MPMC-fed kittens, with HPLC-fed cats showing greater species richness and microbial diversity. Two phyla, ten families and fifteen genera were responsible for more than 80% of the sequences at each taxonomic level for both diet groups, consistent with the previous taxonomic study. Significantly different abundances between diet groups were observed for 324 genera (56% of all genera identified) demonstrating widespread diet-induced changes in microbial taxonomic structure. Diversity was not affected over time. Functional analysis identified 2,013 putative enzyme function groups were different (p<0.000007) between the two dietary groups and were associated to 194 pathways, which formed five discrete clusters based on average relative abundance. Of those, ten contained more (p<0.022) enzyme functions with significant diet effects than expected by chance. Six pathways were related to amino acid biosynthesis and metabolism linking changes in dietary protein with functional differences of the gut microbiome. Conclusions These data indicate that feline feces-derived microbiomes have large structural and functional differences relating to the dietary protein:carbohydrate ratio and highlight the impact of diet early in life. PMID:25010839

Correlation between high resolution sequence stratigraphy and mechanical stratigraphy for enhanced fracture characteristic prediction

NASA Astrophysics Data System (ADS)

Al Kharusi, Laiyyan M.

Sequence stratigraphy relates changes in vertical and lateral facies distribution to relative changes in sea level. These relative changes in carbonates effect early diagenesis, types of pores, cementation and dissolution patterns. As a result, in carbonates, relative changes in sea level significantly impact the lithology, porosity, diagenesis, bed and bounding surfaces which are all factors that control fracture patterns. This study explores these relationships by integrating stratigraphy with fracture analysis and petrophysical properties. A special focus is given to the relationship between mechanical boundaries and sequence stratigraphic boundaries in three different settings: (1) Mississippian strata in Sheep Mountain Anticline, Wyoming, (2) Mississippian limestones in St. Louis, Missouri, and (3) Pennsylvanian limestones intermixed with elastics in the Paradox Basin, Utah. The analysis of these sections demonstrate that a fracture hierarchy exists in relation to the sequence stratigraphic hierarchy. The majority of fractures (80%) terminate at genetic unit boundaries or the internal flooding surface that separates the transgressive from regressive hemicycle. Fractures (20%) that do not terminate at genetic unit boundaries or their internal flooding surface terminate at lower order sequence stratigraphic boundaries or their internal flooding surfaces. Secondly, the fracture spacing relates well to bed thickness in mechanical units no greater than 0.5m in thickness but with increasing bed thickness a scatter from the linear trend is observed. In the Paradox Basin the influence of strain on fracture density is illustrated by two sections measured in different strain regimes. The folded strata at Raplee Anticline has higher fracture densities than the flat-lying beds at the Honaker Trail. Cemented low porosity rocks in the Paradox Basin do not show a correlation between fracture pattern and porosity. However velocity and rock stiffness moduli's display a slight correlation to fracture spacing. Furthermore, bed thickness is found to be only one factor in determining fracture density but with increasing strain, internal bedforms and rock petrophysical heterogeneities influence fracture density patterns. This study illustrates how integrating sedimentologic and sequence stratigraphic interpretations with data on structural kinematics can lead to refined predictive understanding of fracture attributes.

Testing a Weather Generator for Downscaling Climate Change Projections over Switzerland

NASA Astrophysics Data System (ADS)

Keller, Denise E.; Fischer, Andreas M.; Liniger, Mark A.; Appenzeller, Christof; Knutti, Reto

2016-04-01

Climate information provided by global or regional climate models (RCMs) are often too coarse and prone to substantial biases, making it impossible to directly use daily time-series of the RCMs for local assessments and in climate impact models. Hence, statistical downscaling becomes necessary. For the Swiss National Climate Change Initiative (CH2011), a delta-change approach was used to provide daily climate projections at the local scale. This data have the main limitations that changes in variability, extremes and in the temporal structure, such as changes in the wet day frequency, are not reproduced. The latter is a considerable downside of the delta-change approach for many impact applications. In this regard, stochastic weather generators (WGs) are an appealing technique that allow the simulation of multiple realizations of synthetic weather sequences consistent with the locally observed weather statistics and its future changes. Here, we analyse a Richardson-type weather generator (WG) as an alternative method to downscale daily precipitation, minimum and maximum temperature. The WG is calibrated for 26 Swiss stations and the reference period 1980-2009. It is perturbed with change factors derived from 12 RCMs (ENSEMBLES) to represent the climate of 2070-2099 assuming the SRES A1B emission scenario. The WG can be run in multi-site mode, making it especially attractive for impact-modelers that rely on a realistic spatial structure in downscaled time-series. The results from the WG are benchmarked against the original delta-change approach that applies mean additive or multiplicative adjustments to the observations. According to both downscaling methods, the results reveal area-wide mean temperature increases and a precipitation decrease in summer, consistent with earlier studies. For the summer drying, the WG indicates primarily a decrease in wet-day frequency and correspondingly an increase in mean dry spell length by around 18% - 40% at low-elevation stations. By construction, these potential changes cannot be represented by a delta-change approach. In winter, both methods project a shortening of the frost period (-30 to -60 days) and a decrease of snow days (-20% to -100%). The WG demonstrates though, that almost present-day conditions in snow-days could still occur in the future. As expected, both methods have difficulties in representing extremes. If users focus on changes in temporal sequences and need a large number of future realizations that are spatially consistent, it is recommended to use data from a WG instead of a delta-change approach.

Solar System Chaos and its climatic and biogeochemical consequences

NASA Astrophysics Data System (ADS)

Ikeda, M.; Tada, R.; Ozaki, K.; Olsen, P. E.

2017-12-01

Insolation changes caused by changes in Earth's orbital parameters are the main driver of climatic variations, whose pace has been used for astronomically-calibrated geologic time scales of high accuracy to understand Earth system dynamics. However, the astrophysical models beyond several tens of million years ago have large uncertainty due to chaotic behavior of the Solar System, and its impact on amplitude modulation of multi-Myr-scale orbital variations and consequent climate changes has become the subject of debate. Here we show the geologic constraints on the past chaotic behavior of orbital cycles from early Mesozoic monsoon-related records; the 30-Myr-long lake level records of the lacustrine sequence in Newark-Hartford basins (North America) and 70-Myr-long biogenic silica (BSi) burial flux record of pelagic deep-sea chert sequence in Inuyama area (Japan). BSi burial flux of chert could be considered as proportional to the dissolved Si (DSi) input from chemical weathering on timescales longer than the residence time of DSi ( 100 kyr), because chert could represent a major sink for oceanic dissolved silica (Ikeda et al., 2017).These geologic records show multi-Myr cycles with similar frequency modulations of eccentricity solution of astronomical model La2010d (Laskar et al., 2011) compared with other astronomical solutions, but not exactly same. Our geologic records provide convincing evidence for the past chaotic dynamical behaviour of the Solar System and new and challenging additional constraints for astrophysical models. In addition, we find that ˜10 Myr cycle detected in monsoon proxies and their amplitude modulation of ˜2 Myr cycle may be related to the amplitude modulation of ˜2 Myr eccentricity cycle through non-linear process(es) of Earth system dynamics, suggesting possible impact of the chaotic behavior of Solar planets on climate change. Further impact of multi-Myr orbital cycles on global biogeochemical cycles will be discussed.

Climate change and physical disturbance manipulations result in distinct biological soil crust communities.

PubMed

Steven, Blaire; Kuske, Cheryl R; Gallegos-Graves, La Verne; Reed, Sasha C; Belnap, Jayne

2015-11-01

Biological soil crusts (biocrusts) colonize plant interspaces in many drylands and are critical to soil nutrient cycling. Multiple climate change and land use factors have been shown to detrimentally impact biocrusts on a macroscopic (i.e., visual) scale. However, the impact of these perturbations on the bacterial components of the biocrusts remains poorly understood. We employed multiple long-term field experiments to assess the impacts of chronic physical (foot trampling) and climatic changes (2°C soil warming, altered summer precipitation [wetting], and combined warming and wetting) on biocrust bacterial biomass, composition, and metabolic profile. The biocrust bacterial communities adopted distinct states based on the mechanism of disturbance. Chronic trampling decreased biomass and caused small community compositional changes. Soil warming had little effect on biocrust biomass or composition, while wetting resulted in an increase in the cyanobacterial biomass and altered bacterial composition. Warming combined with wetting dramatically altered bacterial composition and decreased Cyanobacteria abundance. Shotgun metagenomic sequencing identified four functional gene categories that differed in relative abundance among the manipulations, suggesting that climate and land use changes affected soil bacterial functional potential. This study illustrates that different types of biocrust disturbance damage biocrusts in macroscopically similar ways, but they differentially impact the resident soil bacterial communities, and the communities' functional profiles can differ depending on the disturbance type. Therefore, the nature of the perturbation and the microbial response are important considerations for management and restoration of drylands. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Climate change and physical disturbance manipulations result in distinct biological soil crust communities

USGS Publications Warehouse

Steven, Blaire; Kuske, Cheryl R.; Gallegos-Graves, La Verne; Reed, Sasha C.; Belnap, Jayne

2015-01-01

Biological soil crusts (biocrusts) colonize plant interspaces in many drylands and are critical to soil nutrient cycling. Multiple climate change and land use factors have been shown to detrimentally impact biocrusts on a macroscopic (i.e., visual) scale. However, the impact of these perturbations on the bacterial components of the biocrusts remain poorly understood. We employed multiple long-term field experiments to assess the impacts of chronic physical (foot trampling) and climatic changes (2 °C soil warming, altered summer precipitation (wetting), and combined warming and wetting) on biocrust bacterial biomass, composition, and metabolic profile. The biocrust bacterial communities adopted distinct states based on the mechanism of disturbance. Chronic trampling decreased biomass and caused small community compositional change. Soil warming had little effect on biocrust biomass or composition, while wetting resulted in an increase in cyanobacterial biomass and altered bacterial composition. Warming combined with wetting dramatically altered bacterial composition and decreased cyanobacteria abundance. Shotgun metagenomic sequencing identified four functional gene categories that differed in relative abundance among the manipulations, suggesting that climate and land use changes affected soil bacterial functional potential. This study illustrates that different types of biocrust disturbance damage biocrusts in macroscopically similar ways, but they differentially impact the resident soil bacterial communities and the community functional profile can differ depending on the disturbance type. Therefore, the nature of the perturbation and the microbial response are important considerations for management and restoration of drylands.

Variations in flood magnitude-effect relations and the implications for flood risk assessment and river management

NASA Astrophysics Data System (ADS)

Hooke, J. M.

2015-12-01

In spite of major physical impacts from large floods, present river management rarely takes into account the possible dynamics and variation in magnitude-impact relations over time in flood risk mapping and assessment nor incorporates feedback effects of changes into modelling. Using examples from the literature and from field measurements over several decades in two contrasting environments, a semi-arid region and a humid-temperate region, temporal variations in channel response to flood events are evaluated. The evidence demonstrates how flood physical impacts can vary at a location over time. The factors influencing that variation on differing timescales are examined. The analysis indicates the importance of morphological changes and trajectory of adjustment in relation to thresholds, and that trends in force or resistance can take place over various timescales, altering those thresholds. Sediment supply can also change with altered connectivity upstream and changes in state of hillslope-channel coupling. It demonstrates that seasonal timing and sequence of events can affect response, particularly deposition through sediment supply. Duration can also have a significant effect and modify the magnitude relation. Lack of response or deposits in some events can mean that flood frequency using such evidence is underestimated. A framework for assessment of both past and possible future changes is provided which emphasises the uncertainty and the inconstancy of the magnitude-impact relation and highlights the dynamic factors and nature of variability that should be considered in sustainable management of river channels.

Magnetostratigraphy of the impact breccias and post-impact carbonates from borehole Yaxcopoil-1, Chicxulub impact crater, Yucatán, Mexico

NASA Astrophysics Data System (ADS)

Rebolledo-Vieyra, Mario; Urrutia-Fucugauchi, Jaime

2004-06-01

We report the magnetostratigraphy of the sedimentary sequence between the impact breccias and the post-impact carbonate sequence conducted on samples recovered by Yaxcopoil-1 (Yax-1). Samples of impact breccias show reverse polarities that span up to ~56 cm into the postimpact carbonate lithologies. We correlate these breccias to those of PEMEX boreholes Yucatán-6 and Chicxulub-1, from which we tied our magnetostratigraphy to the radiometric age from a melt sample from the Yucatán-6 borehole. Thin section analyses of the carbonate samples showed a significant amount of dark minerals and glass shards that we identified as the magnetic carriers; therefore, we propose that the mechanism of magnetic acquisition within the carbonate rocks for the interval studied is detrital remanent magnetism (DRM). With these samples, we constructed the scale of geomagnetic polarities where we find two polarities within the sequence, a reverse polarity event within the impact breccias and the base of the post-impact carbonate sequence (up to 794.07 m), and a normal polarity event in the last ~20 cm of the interval studied. The polarities recorded in the sequence analyzed are interpreted to span from chron 29r to 29n, and we propose that the reverse polarity event lies within the 29r chron. The magnetostratigraphy of the sequence studied shows that the horizon at 794.11 m deep, interpreted as the K/T boundary, lies within the geomagnetic chron 29r, which contains the K/T boundary.

The impact of past climate change on genetic variation and population connectivity in the Icelandic arctic fox

PubMed Central

Mellows, Andrew; Barnett, Ross; Dalén, Love; Sandoval-Castellanos, Edson; Linderholm, Anna; McGovern, Thomas H.; Church, Mike J.; Larson, Greger

2012-01-01

Previous studies have suggested that the presence of sea ice is an important factor in facilitating migration and determining the degree of genetic isolation among contemporary arctic fox populations. Because the extent of sea ice is dependent upon global temperatures, periods of significant cooling would have had a major impact on fox population connectivity and genetic variation. We tested this hypothesis by extracting and sequencing mitochondrial control region sequences from 17 arctic foxes excavated from two late-ninth-century to twelfth-century AD archaeological sites in northeast Iceland, both of which predate the Little Ice Age (approx. sixteenth to nineteenth century). Despite the fact that five haplotypes have been observed in modern Icelandic foxes, a single haplotype was shared among all of the ancient individuals. Results from simulations within an approximate Bayesian computation framework suggest that the rapid increase in Icelandic arctic fox haplotype diversity can only be explained by sea-ice-mediated fox immigration facilitated by the Little Ice Age. PMID:22977155

The impact of past climate change on genetic variation and population connectivity in the Icelandic arctic fox.

PubMed

Mellows, Andrew; Barnett, Ross; Dalén, Love; Sandoval-Castellanos, Edson; Linderholm, Anna; McGovern, Thomas H; Church, Mike J; Larson, Greger

2012-11-22

Previous studies have suggested that the presence of sea ice is an important factor in facilitating migration and determining the degree of genetic isolation among contemporary arctic fox populations. Because the extent of sea ice is dependent upon global temperatures, periods of significant cooling would have had a major impact on fox population connectivity and genetic variation. We tested this hypothesis by extracting and sequencing mitochondrial control region sequences from 17 arctic foxes excavated from two late-ninth-century to twelfth-century AD archaeological sites in northeast Iceland, both of which predate the Little Ice Age (approx. sixteenth to nineteenth century). Despite the fact that five haplotypes have been observed in modern Icelandic foxes, a single haplotype was shared among all of the ancient individuals. Results from simulations within an approximate Bayesian computation framework suggest that the rapid increase in Icelandic arctic fox haplotype diversity can only be explained by sea-ice-mediated fox immigration facilitated by the Little Ice Age.

River history.

PubMed

Vita-Finzi, Claudio

2012-05-13

During the last half century, advances in geomorphology-abetted by conceptual and technical developments in geophysics, geochemistry, remote sensing, geodesy, computing and ecology-have enhanced the potential value of fluvial history for reconstructing erosional and depositional sequences on the Earth and on Mars and for evaluating climatic and tectonic changes, the impact of fluvial processes on human settlement and health, and the problems faced in managing unstable fluvial systems. This journal is © 2012 The Royal Society

Improving livestock for agriculture - technological progress from random transgenesis to precision genome editing heralds a new era.

PubMed

Laible, Götz; Wei, Jingwei; Wagner, Stefan

2015-01-01

Humans have a long history in shaping the genetic makeup of livestock to optimize production and meet growing human demands for food and other animal products. Until recently, this has only been possible through traditional breeding and selection, which is a painstakingly slow process of accumulating incremental gains over a long period. The development of transgenic livestock technology offers a more direct approach with the possibility for making genetic improvements with greater impact and within a single generation. However, initially the technology was hampered by technical difficulties and limitations, which have now largely been overcome by progressive improvements over the past 30 years. Particularly, the advent of genome editing in combination with homologous recombination has added a new level of efficiency and precision that holds much promise for the genetic improvement of livestock using the increasing knowledge of the phenotypic impact of genetic sequence variants. So far not a single line of transgenic livestock has gained approval for commercialization. The step change to genome-edited livestock with precise sequence changes may accelerate the path to market, provided applications of this new technology for agriculture can deliver, in addition to economic incentives for producers, also compelling benefits for animals, consumers, and the environment. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploring the Impact of Food on the Gut Ecosystem Based on the Combination of Machine Learning and Network Visualization.

PubMed

Shima, Hideaki; Masuda, Shizuka; Date, Yasuhiro; Shino, Amiu; Tsuboi, Yuuri; Kajikawa, Mizuho; Inoue, Yoshihiro; Kanamoto, Taisei; Kikuchi, Jun

2017-12-01

Prebiotics and probiotics strongly impact the gut ecosystem by changing the composition and/or metabolism of the microbiota to improve the health of the host. However, the composition of the microbiota constantly changes due to the intake of daily diet. This shift in the microbiota composition has a considerable impact; however, non-pre/probiotic foods that have a low impact are ignored because of the lack of a highly sensitive evaluation method. We performed comprehensive acquisition of data using existing measurements (nuclear magnetic resonance, next-generation DNA sequencing, and inductively coupled plasma-optical emission spectroscopy) and analyses based on a combination of machine learning and network visualization, which extracted important factors by the Random Forest approach, and applied these factors to a network module. We used two pteridophytes, Pteridium aquilinum and Matteuccia struthiopteris , for the representative daily diet. This novel analytical method could detect the impact of a small but significant shift associated with Matteuccia struthiopteris but not Pteridium aquilinum intake, using the functional network module. In this study, we proposed a novel method that is useful to explore a new valuable food to improve the health of the host as pre/probiotics.

The Impact of Genomics on Public Health Practice: The Case for Change

PubMed Central

Zimmern, R.L.; Khoury, M.J.

2017-01-01

Public health practice will not be able in the 21st century to ignore the impact of genomics, cell and molecular biology. It will need to take into consideration issues that include, among others: the complementary nature of social and biological models of disease, genetic exceptionalism, the readiness of public and patient to respond to genomic information, the relationship between individuals and populations, and concepts of population stratification. Health systems will need to adapt their practice and organisation to include new sequencing technologies, bioinformatic expertise and proper evaluation of genetic and molecular tests. Links with the commercial sector will increase in importance. The impact on developing countries cannot be ignored and will require special attention. PMID:22488453

The fast changing landscape of sequencing technologies and their impact on microbial genome assemblies and annotation.

PubMed

Mavromatis, Konstantinos; Land, Miriam L; Brettin, Thomas S; Quest, Daniel J; Copeland, Alex; Clum, Alicia; Goodwin, Lynne; Woyke, Tanja; Lapidus, Alla; Klenk, Hans Peter; Cottingham, Robert W; Kyrpides, Nikos C

2012-01-01

The emergence of next generation sequencing (NGS) has provided the means for rapid and high throughput sequencing and data generation at low cost, while concomitantly creating a new set of challenges. The number of available assembled microbial genomes continues to grow rapidly and their quality reflects the quality of the sequencing technology used, but also of the analysis software employed for assembly and annotation. In this work, we have explored the quality of the microbial draft genomes across various sequencing technologies. We have compared the draft and finished assemblies of 133 microbial genomes sequenced at the Department of Energy-Joint Genome Institute and finished at the Los Alamos National Laboratory using a variety of combinations of sequencing technologies, reflecting the transition of the institute from Sanger-based sequencing platforms to NGS platforms. The quality of the public assemblies and of the associated gene annotations was evaluated using various metrics. Results obtained with the different sequencing technologies, as well as their effects on downstream processes, were analyzed. Our results demonstrate that the Illumina HiSeq 2000 sequencing system, the primary sequencing technology currently used for de novo genome sequencing and assembly at JGI, has various advantages in terms of total sequence throughput and cost, but it also introduces challenges for the downstream analyses. In all cases assembly results although on average are of high quality, need to be viewed critically and consider sources of errors in them prior to analysis. These data follow the evolution of microbial sequencing and downstream processing at the JGI from draft genome sequences with large gaps corresponding to missing genes of significant biological role to assemblies with multiple small gaps (Illumina) and finally to assemblies that generate almost complete genomes (Illumina+PacBio).

The impact of Last Glacial climate variability in west-European loess revealed by radiocarbon dating of fossil earthworm granules.

PubMed

Moine, Olivier; Antoine, Pierre; Hatté, Christine; Landais, Amaëlle; Mathieu, Jérôme; Prud'homme, Charlotte; Rousseau, Denis-Didier

2017-06-13

The characterization of Last Glacial millennial-timescale warming phases, known as interstadials or Dansgaard-Oeschger events, requires precise chronologies for the study of paleoclimate records. On the European continent, such chronologies are only available for several Last Glacial pollen and rare speleothem archives principally located in the Mediterranean domain. Farther north, in continental lowlands, numerous high-resolution records of loess and paleosols sequences show a consistent environmental response to stadial-interstadial cycles. However, the limited precision and accuracy of luminescence dating methods commonly used in loess deposits preclude exact correlations of paleosol horizons with Greenland interstadials. To overcome this problem, a radiocarbon dating protocol has been developed to date earthworm calcite granules from the reference loess sequence of Nussloch (Germany). Its application yields a consistent radiocarbon chronology of all soil horizons formed between 47 and 20 ka and unambiguously shows the correlation of every Greenland interstadial identified in isotope records with specific soil horizons. Furthermore, eight additional minor soil horizons dated between 27.5 and 21 ka only correlate with minor decreases in Greenland dust records. This dating strategy reveals the high sensitivity of loess paleoenvironments to Northern Hemisphere climate changes. A connection between loess sedimentation rate, Fennoscandian ice sheet dynamics, and sea level changes is proposed. The chronological improvements enabled by the radiocarbon "earthworm clock" thus strongly enhance our understanding of loess records to a better perception of the impact of Last Glacial climate changes on European paleoenvironments.

The impact of Last Glacial climate variability in west-European loess revealed by radiocarbon dating of fossil earthworm granules

PubMed Central

Moine, Olivier; Antoine, Pierre; Hatté, Christine; Landais, Amaëlle; Mathieu, Jérôme; Prud’homme, Charlotte

2017-01-01

The characterization of Last Glacial millennial-timescale warming phases, known as interstadials or Dansgaard–Oeschger events, requires precise chronologies for the study of paleoclimate records. On the European continent, such chronologies are only available for several Last Glacial pollen and rare speleothem archives principally located in the Mediterranean domain. Farther north, in continental lowlands, numerous high-resolution records of loess and paleosols sequences show a consistent environmental response to stadial–interstadial cycles. However, the limited precision and accuracy of luminescence dating methods commonly used in loess deposits preclude exact correlations of paleosol horizons with Greenland interstadials. To overcome this problem, a radiocarbon dating protocol has been developed to date earthworm calcite granules from the reference loess sequence of Nussloch (Germany). Its application yields a consistent radiocarbon chronology of all soil horizons formed between 47 and 20 ka and unambiguously shows the correlation of every Greenland interstadial identified in isotope records with specific soil horizons. Furthermore, eight additional minor soil horizons dated between 27.5 and 21 ka only correlate with minor decreases in Greenland dust records. This dating strategy reveals the high sensitivity of loess paleoenvironments to Northern Hemisphere climate changes. A connection between loess sedimentation rate, Fennoscandian ice sheet dynamics, and sea level changes is proposed. The chronological improvements enabled by the radiocarbon “earthworm clock” thus strongly enhance our understanding of loess records to a better perception of the impact of Last Glacial climate changes on European paleoenvironments. PMID:28559353

Study Sequence Matters for the Inductive Learning of Cognitive Concepts

ERIC Educational Resources Information Center

Sana, Faria; Yan, Veronica X.; Kim, Joseph A.

2017-01-01

The sequence in which problems of different concepts are studied during instruction impacts concept learning. For example, several problems of a given concept can be studied together (blocking) or several problems of different concepts can be studied together (interleaving). In the current study, we demonstrate that the 2 sequences impact concept…

Nanostructure Control of Biologically Inspired Polymers

NASA Astrophysics Data System (ADS)

Rosales, Adrianne Marie

Biological polymers, such as polypeptides, are responsible for many of life's most sophisticated functions due to precisely evolved hierarchical structures. These protein structures are the result of monodisperse sequences of amino acids that fold into well-defined chain shapes and tertiary structures. Recently, there has been much interest in the design of such sequence-specific polymers for materials applications in fields ranging from biotechnology to separations membranes. Non-natural polymers offer the stability and robustness necessary for materials applications; however, our ability to control monomer sequence in non-natural polymers has traditionally operated on a much simpler level. In addition, the relationship between monomer sequence and self-assembly is not well understood for biological molecules, much less synthetic polymers. Thus, there is a need to explore self-assembly phase space with sequence using a model system. Polypeptoids are non-natural, sequence-specific polymers that offer the opportunity to probe the effect of sequence on self-assembly. A variety of monomer interactions have an impact on polymer properties, such as chirality, hydrophobicity, and electrostatic interactions. Thus, a necessary starting point for this project was to investigate monomer sequence effects on the bulk properties of polypeptoid homopolymers. It was found that several polypeptoids have experimentally accessible melting transitions that are dependent on the choice of side chains, and it was shown that this transition is tuned by the incorporation of "defects" or a comonomer. The polypeptoid chain shape is also controlled with the choice of monomer and monomer sequence. By using at least 50% monomers with bulky, chiral side chains, the polypeptoid backbone is sterically twisted into a helix, and as found for the first time in this work, the persistence length is increased. However, this persistence length, which is a measure of the stiffness of the polymer, is small compared to other folded helices, indicating the conformational flexibility of polypeptoid chains. With a firmer understanding of how monomer sequence and composition influence polypeptoid bulk properties, we designed block copolymer systems for self-assembly. Because the governing parameters of block copolymer self-assembly are well understood, this architecture provides a convenient starting point for probing the effect of changing polymer sequence. We found that polystyrene-polypeptoid block copolymers readily self-assemble into hexagonally-packed and lamellar morphologies with long range order, and furthermore, sequence control of the polypeptoid block enables us to tune the strength of segregation (and therefore the order-disorder transition) of the block copolymer. Polypeptoid chain shape also affects self-assembly. In classical synthetic block copolymers, it has typically been difficult to change chain shape without also changing polymer chemistry and therefore other factors affecting self-assembly. The advantage of the polypeptoid system is that it is modular, as the side chain chemistry (and therefore polymer properties) can easily be changed without changing the backbone chemistry. Thus, we have decoupled conformational effects from chemical composition by comparing the self-assembly of block copolymers containing either a helical peptoid block or its racemic, non-helical analog. The increase in the persistence length of the peptoid block due to helicity translates to an increase in the morphological domain spacing. In this work, we further the understanding of the effect of monomer sequence on bulk polypeptoid properties and self-assembly. Our findings pave the way for the rational design of structured synthetic polymers with tunable, sequence-specific properties.

Influence of Stacking Sequence and Notch Angle on the Charpy Impact Behavior of Hybrid Composites

NASA Astrophysics Data System (ADS)

Behnia, S.; Daghigh, V.; Nikbin, K.; Fereidoon, A.; Ghorbani, J.

2016-09-01

The low-velocity impact behavior of hybrid composite laminates was investigated. The epoxy matrix was reinforced with aramid, glass, basalt, and carbon fabrics using the hand lay-up technique. Different stacking sequences and notch angles were and notch angles considered and tested using a Charpy impact testing machine to study the hybridization and notch angle effects on the impact response of the hybrid composites. The energy absorption capability of specimens with different stacking sequences and notch angles is compared and discussed. It is shown that the hybridization can enhance the mechanical performance of composite materials.

Genome Sequencing of Museum Specimens Reveals Rapid Changes in the Genetic Composition of Honey Bees in California

PubMed Central

Ramirez, Santiago R; Dean, Cheryl A; Sciligo, Amber; Tsutsui, Neil D

2018-01-01

Abstract The western honey bee, Apis mellifera, is an enormously influential pollinator in both natural and managed ecosystems. In North America, this species has been introduced numerous times from a variety of different source populations in Europe and Africa. Since then, feral populations have expanded into many different environments across their broad introduced range. Here, we used whole genome sequencing of historical museum specimens and newly collected modern populations from California (USA) to analyze the impact of demography and selection on introduced populations during the past 105 years. We find that populations from both northern and southern California exhibit pronounced genetic changes, but have changed in different ways. In northern populations, honey bees underwent a substantial shift from western European to eastern European ancestry since the 1960s, whereas southern populations are dominated by the introgression of Africanized genomes during the past two decades. Additionally, we identify an isolated island population that has experienced comparatively little change over a large time span. Fine-scale comparison of different populations and time points also revealed SNPs that differ in frequency, highlighting a number of genes that may be important for recent adaptations in these introduced populations. PMID:29346588

Influence of Flow Sequencing Attributed to Climate Change and Climate Variability on the Assessment of Water-dependent Ecosystem Outcomes

NASA Astrophysics Data System (ADS)

Wang, J.; Nathan, R.; Horne, A.

2017-12-01

Traditional approaches to characterize water-dependent ecosystem outcomes in response to flow have been based on time-averaged hydrological indicators, however there is increasing recognition for the need to characterize ecological processes that are highly dependent on the sequencing of flow conditions (i.e. floods and droughts). This study considers the representation of flow regimes when considering assessment of ecological outcomes, and in particular, the need to account for sequencing and variability of flow. We conducted two case studies - one in the largely unregulated Ovens River catchment and one in the highly regulated Murray River catchment (both located in south-eastern Australia) - to explore the importance of flow sequencing to the condition of a typical long-lived ecological asset in Australia, the River Red Gum forests. In the first, the Ovens River case study, the implications of representing climate change using different downscaling methods (annual scaling, monthly scaling, quantile mapping, and weather generator method) on the sequencing of flows and resulting ecological outcomes were considered. In the second, the Murray River catchment, sequencing within a historic drought period was considered by systematically making modest adjustments on an annual basis to the hydrological records. In both cases, the condition of River Red Gum forests was assessed using an ecological model that incorporates transitions between ecological conditions in response to sequences of required flow components. The results of both studies show the importance of considering how hydrological alterations are represented when assessing ecological outcomes. The Ovens case study showed that there is significant variation in the predicted ecological outcomes when different downscaling techniques are applied. Similarly, the analysis in the Murray case study showed that the drought as it historically occurred provided one of the best possible outcomes for River Red Gum forests when compared to other re-arrangements of flow within the same drought. These results have implications for the way we represent climate change impacts and drought risk assessments where ecological outcomes are a key management objective.

Investigation of occult hepatitis B virus infection in anti-hbc positive patients from a liver clinic.

PubMed

Martinez, Maria Carmela; Kok, Chee Choy; Baleriola, Cristina; Robertson, Peter; Rawlinson, William D

2015-01-01

Occult hepatitis B infection (OBI) is manifested by presence of very low levels (<200IU/mL) of Hepatitis B viral DNA (HBV DNA) in the blood and the liver while exhibiting undetectable HBV surface antigen (HBsAg). The molecular mechanisms underlying this occurrence are still not completely understood. This study investigated the prevalence of OBI in a high-risk Australian population and compared the HBV S gene sequences of our cohort with reference sequences. Serum from HBV DNA positive, HBsAg negative, and hepatitis B core antibody (anti-HBc) positive patients (study cohort) were obtained from samples tested at SEALS Serology Laboratory using the Abbott Architect, as part of screening and diagnostic testing. From a total of 228,108 samples reviewed, 1,451 patients were tested for all three OBI markers. Only 10 patients (0.69%) out of the 1,451 patients were found to fit the selection criteria for OBI. Sequence analysis of the HBV S gene from 5 suspected OBI infected patients showed increased sequence variability in the 'a' epitope of the major hydrophilic region compared to reference sequences. In addition, a total of eight consistent nucleotide substitutions resulting in seven amino acid changes were observed, and three patients had truncated S gene sequence. These mutations appeared to be stable and may result in alterations in HBsAg conformation. These may negatively impact the affinity of hepatitis B surface antibody (anti-HBs) and may explain the false negative results in serological HBV diagnosis. These changes may also enable the virus to persist in the liver by evading immune surveillance. Further studies on a bigger cohort are required to determine whether these amino acid variations have been acquired in the process of immune escape and serve as markers of OBI.

Rapid evolutionary change of common bean (Phaseolus vulgaris L) plastome, and the genomic diversification of legume chloroplasts

PubMed Central

Guo, Xianwu; Castillo-Ramírez, Santiago; González, Víctor; Bustos, Patricia; Luís Fernández-Vázquez, José; Santamaría, Rosa Isela; Arellano, Jesús; Cevallos, Miguel A; Dávila, Guillermo

2007-01-01

Background Fabaceae (legumes) is one of the largest families of flowering plants, and some members are important crops. In contrast to what we know about their great diversity or economic importance, our knowledge at the genomic level of chloroplast genomes (cpDNAs or plastomes) for these crops is limited. Results We sequenced the complete genome of the common bean (Phaseolus vulgaris cv. Negro Jamapa) chloroplast. The plastome of P. vulgaris is a 150,285 bp circular molecule. It has gene content similar to that of other legume plastomes, but contains two pseudogenes, rpl33 and rps16. A distinct inversion occurred at the junction points of trnH-GUG/rpl14 and rps19/rps8, as in adzuki bean [1]. These two pseudogenes and the inversion were confirmed in 10 varieties representing the two domestication centers of the bean. Genomic comparative analysis indicated that inversions generally occur in legume plastomes and the magnitude and localization of insertions/deletions (indels) also vary. The analysis of repeat sequences demonstrated that patterns and sequences of tandem repeats had an important impact on sequence diversification between legume plastomes and tandem repeats did not belong to dispersed repeats. Interestingly, P. vulgaris plastome had higher evolutionary rates of change on both genomic and gene levels than G. max, which could be the consequence of pressure from both mutation and natural selection. Conclusion Legume chloroplast genomes are widely diversified in gene content, gene order, indel structure, abundance and localization of repetitive sequences, intracellular sequence exchange and evolutionary rates. The P. vulgaris plastome is a rapidly evolving genome. PMID:17623083

A single bout of high-intensity aerobic exercise facilitates response to paired associative stimulation and promotes sequence-specific implicit motor learning

PubMed Central

Mang, Cameron S.; Snow, Nicholas J.; Campbell, Kristin L.; Ross, Colin J. D.

2014-01-01

The objectives of the present study were to evaluate the impact of a single bout of high-intensity aerobic exercise on 1) long-term potentiation (LTP)-like neuroplasticity via response to paired associative stimulation (PAS) and 2) the temporal and spatial components of sequence-specific implicit motor learning. Additionally, relationships between exercise-induced increases in systemic brain-derived neurotrophic factor (BDNF) and response to PAS and motor learning were evaluated. Sixteen young healthy participants completed six experimental sessions, including the following: 1) rest followed by PAS; 2) aerobic exercise followed by PAS; 3) rest followed by practice of a continuous tracking (CT) task and 4) a no-exercise 24-h retention test; and 5) aerobic exercise followed by CT task practice and 6) a no-exercise 24-h retention test. The CT task included an embedded repeated sequence allowing for evaluation of sequence-specific implicit learning. Slope of motor-evoked potential recruitment curves generated with transcranial magnetic stimulation showed larger increases when PAS was preceded by aerobic exercise (59.8% increase) compared with rest (14.2% increase, P = 0.02). Time lag of CT task performance on the repeated sequence improved under the aerobic exercise condition from early (−100.8 ms) to late practice (−75.2 ms, P < 0.001) and was maintained at retention (−79.2 ms, P = 0.004) but did not change under the rest condition (P > 0.16). Systemic BDNF increased on average by 3.4-fold following aerobic exercise (P = 0.003), but the changes did not relate to neurophysiological or behavioral measures (P > 0.42). These results indicate that a single bout of high-intensity aerobic exercise can prime LTP-like neuroplasticity and promote sequence-specific implicit motor learning. PMID:25257866

Programming in a Robotics Context in the Kindergarten Classroom: The Impact on Sequencing Skills

ERIC Educational Resources Information Center

Kazakoff, Elizabeth; Bers, Marina

2012-01-01

This paper examines the impact of computer programming of robots on sequencing ability in early childhood and the relationship between sequencing skills, class size, and teacher's comfort level and experience with technology. Fifty-eight children participated in the study, 54 of whom were included in data analysis. This study was conducted in two…

Assessing the Impact of Sequencing Practicums for Welding in Agricultural Mechanics

ERIC Educational Resources Information Center

Rose, Malcolm; Pate, Michael L.; Lawver, Rebecca G.; Warnick, Brian K.; Dai, Xin

2015-01-01

This study examined the impact of sequencing practicums for welding on students' ability to perform a 1F (flat position-fillet lap joint) weld on low-carbon steel. Participants were randomly assigned a specific practice sequence of welding for using gas metal arc welding (GMAW) and shielded metal arc welding (SMAW). A total of 71 participants…

Design and Manufacturing of a Novel Shear Thickening Fluid Composite (STFC) with Enhanced out-of-Plane Properties and Damage Suppression

NASA Astrophysics Data System (ADS)

Pinto, F.; Meo, M.

2017-06-01

The ability to absorb a large amount of energy during an impact event without generating critical damages represents a key feature of new generation composite systems. Indeed, the intrinsic layered nature of composite materials allows the embodiment of specific hybrid plies within the stacking sequence that can be exploited to increase impact resistance and damping of the entire structure without dramatic weight increase. This work is based on the development of an impact-resistant hybrid composite obtained by including a thin layer of Non-Newtonian silica based fluid in a carbon fibres reinforced polymer (CFRP) laminate. This hybrid phase is able to respond to an external solicitation by activating an order-disorder transition that thickens the fluid increasing its viscosity, hence dissipating the energy impact without any critical failure. Several Shear Thickening Fluids (STFs) were manufactured by changing the dimensions of the particles that constitute the disperse phase and their concentrations into the continuous phase. The dynamic viscosity of the different STFs was evaluated via rheometric tests, observing both shear thinning and shear thickening effects depending on the concentration of silica particles. The solutions were then embedded as an active layer within the stacking sequence to manufacture the hybrid CFRP laminates with different embedded STFs. Free vibration tests were carried out in order to assess the damping properties of the different laminates, while low velocity impact tests were used to evaluate their impact properties. Results indicate that the presence of the non-Newtonian fluid is able to absorb up to 45 % of the energy during an impact event for impacts at 2.5 m/s depending on the different concentrations and particles dimensions. These results were confirmed via C-Scan analyses to assess the extent of the internal delamination.

Revisiting Caveiro Lake sediment record: the Holocene NAO and AMO impact on Pico Island (Azores archipelago)

NASA Astrophysics Data System (ADS)

Hernandez, A.; Giralt, S.; Raposeiro, P. M.; Gonçalves, V. M.; Pueyo, J. J.; Trigo, R. M.; Bao, R.; Sáez, A.

2017-12-01

Northern Hemisphere climate is partly conditioned by a number of atmospheric and oceanic patterns which occur in the North Atlantic sector. The favourable location of the Azores Archipelago (37°-40° N, 25°-31° W) results in a privileged place to generate high-resolution Holocene climatic proxy data that can contribute to deep our understanding on the evolution of these atmospheric and oceanic patterns. In the frame of three research projects, namely PALEONAO (CGL2010-15767), RAPIDNAO (CGL2013-40608-R) and PALEOMODES (CGL2016-75281-C2), high-resolution proxy-based reconstructions from Azores Archipelago have recently shown a combined impact of atmospheric and oceanic patterns at multiannual and decadal time-scales (Rubio-Inglés et al. 2016; Hernández et al. 2017). However, the long-term evolution coupling/uncoupling of these patterns is not well-determined yet. Here, we present a new high-resolution climate reconstruction based on the Caveiro Lake sedimentary sequence in order to fill this gap. Previously, Björck et al. (2006) studied a section of this sequence (the uppermost 4.6 m covering last 6 Ka cal BP) concluding that changes in the thermohaline circulation and the SST were the main drivers in the long-term precipitation variability, whereas the NAO impact was the main atmospheric driver of short-term precipitation changes. However, they only distinguished the NAO impact for the last 600 years owing to the low resolution of the study for the lower portion of the core. The new studied sequence (8.40 m long, 8.2 Ka cal BP) has been analysed at decadal-to centennial time-scale resolution for X-ray diffraction (XRD), X-ray fluorescence (XRF) core scanning and elemental and isotope geochemistry on bulk organic matter. The statistical multivariate analysis of the data highlights the main drivers triggering the sedimentary infill of the lake would be the NAO and AMO by controlling the lacustrine productivity via nutrients input. This new high-resolution climate reconstruction from Caveiro Lake disentangles the combined influences of the NAO and AMO through the Holocene at decadal-to-centennial time scales. References Björck et al. (2006) - Quat Sci Rev 25, 9-32. Rubio-Inglés et al. (2016) - AGU fall meeting, PP51A­-2287. Hernández et al. (2017) - Glob Planet Change 154, 61-74.

The Baltic Sea: Geophysical and geochemical properties of Holocene sediment sequences as indicators of past environmental variability

NASA Astrophysics Data System (ADS)

Lenz, Conny; Reinholdsson, Maja; Zillén, Lovisa; Conley, Daniel J.; Snowball, Ian

2010-05-01

The Baltic Sea has undergone large environmental changes since the retreat of the Weischselian Ice-sheet. In the Late Glacial Period and the early Holocene these changes were most likely caused by natural environmental changes (i.e. changes in the morphology and depths of the Baltic basin and the sills). In more recent time anthropogenic impacts have become more important as a possible and likely cause for changes. During the whole Holocene period climate variability played an important role. However, the relative importance between humans and nature is largely unknown. Here we present the results of a combined geophysical and geochemical study on selected sediment sequences from the Baltic Sea within the two BONUS (Baltic Organisations Network For Funding Science) funded projects HYPER (HYPoxia mitigation for Baltic Sea Ecosystem Restoration) and Baltic GAS (GAS storage and effects of climate change and eutrophication). The over-all aim of these projects is to understand large-scale Baltic Sea ecosystem responses to environmental, climate and anthropogenic forcing. During two Baltic Sea research cruises in 2009 long sediment cores from 8 different locations were recovered. We present preliminary results from one site (LL19) located in the north central Baltic Proper at 169 m water depth. The Littorina Sea sediment record (i.e. the last c. 8000 years) is characterised by alternating periods of homogenised sediments (indicative of oxic conditions) and laminated sediments (indicative of hypoxic/anoxic conditions). Mineral magnetic properties illustrate clear changes between laminated and non-laminated sections of the core. The concentration of ferrimagnetic minerals, as revealed by initial magnetic susceptibility (χ) and saturation isothermal remanent magnetization (SIRM) is variable. The laminated sections in particular show high concentrations and to reveal the origin of the ferrimagnetic signal additional magnetic properties were measured, specifically the acquisition of rotational remanent magnetization (RRM), frequency dependency of susceptibility (χfd) and magnetic loops. These data show that magnetic assemblage of the laminated sections is dominated by a single-domain magnetic grain size. The elemental composition was measured with a high resolution Itrax XRF-scanner throughout the core. In addition, biogenic silica (BSi) and total organic carbon (TOC) were determined. Distinct changes of elemental contents between the laminated and homogenous sections in the Littorina Sea sediments were identified. A combination of the physical and geochemical properties of the sediment sequences and the construction of geochronologies will provide information about past environmental variability to identify casual relationships to climate and human impact in the Baltic Sea.

Peptide de novo sequencing of mixture tandem mass spectra.

PubMed

Gorshkov, Vladimir; Hotta, Stéphanie Yuki Kolbeck; Verano-Braga, Thiago; Kjeldsen, Frank

2016-09-01

The impact of mixture spectra deconvolution on the performance of four popular de novo sequencing programs was tested using artificially constructed mixture spectra as well as experimental proteomics data. Mixture fragmentation spectra are recognized as a limitation in proteomics because they decrease the identification performance using database search engines. De novo sequencing approaches are expected to be even more sensitive to the reduction in mass spectrum quality resulting from peptide precursor co-isolation and thus prone to false identifications. The deconvolution approach matched complementary b-, y-ions to each precursor peptide mass, which allowed the creation of virtual spectra containing sequence specific fragment ions of each co-isolated peptide. Deconvolution processing resulted in equally efficient identification rates but increased the absolute number of correctly sequenced peptides. The improvement was in the range of 20-35% additional peptide identifications for a HeLa lysate sample. Some correct sequences were identified only using unprocessed spectra; however, the number of these was lower than those where improvement was obtained by mass spectral deconvolution. Tight candidate peptide score distribution and high sensitivity to small changes in the mass spectrum introduced by the employed deconvolution method could explain some of the missing peptide identifications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Al Hoceima earthquake sequence of 1994, 2004 and 2016: Stress transfer and poroelasticity in the Rif and Alboran Sea region

NASA Astrophysics Data System (ADS)

Kariche, J.; Meghraoui, M.; Timoulali, Y.; Cetin, E.; Toussaint, R.

2018-01-01

The 2016 January 25 earthquake (Mw 6.3) follows in sequence from the1994 May 26 earthquake (Mw 6.0) and the 2004 February 24 earthquake (Mw 6.4) in the Rif Mountains and Alboran Sea. The earlier two seismic events which were destructive took place on inland conjugate faults, and the third event occurred on an offshore fault. These earthquake sequences occurred within a period of 22 yr at ˜25 km distance and 11-16-km depth. The three events have similar strike-slip focal mechanism solutions with NNE-SSW trending left-lateral faulting for the 1994 and 2016 events and NW-SE trending right-lateral faulting for the 2004 event. This shallow seismic sequence offers the possibility (i) to model the change in Coulomb Failure Function (ΔCFF with low μ΄ including the pore pressure change) and understand fault-rupture interaction, and (ii) to analyse the effect of pore fluid on the rupture mechanism, and infer the clock-time advance. The variation of static stress change has a direct impact on the main shock, aftershocks and related positive lobes of the 2004 earthquake rupture with a stress change increase of 0.7-1.1 bar. Similarly, the 2004 main shock and aftershocks indicate loading zones with a stress change (>0.25 bar) that includes the 2016 earthquake rupture. The tectonic loading of 19-24 nanostrain yr-1 obtained from the seismicity catalogue of Morocco is comparable to the 5.0 × 1017 N.m yr-1 seismic strain release in the Rif Mountains. The seismic sequence is apparently controlled by the poroelastic properties of the seismogenic layer that depend on the undrained and drained fluid conditions. The short interseismic period between main shocks and higher rate of aftershocks with relatively large magnitudes (4 < Mw < 5.5) implies the pore-fluid physical effect in undrained and drained conditions. The stress-rate ranges between 461 and 582 Pa yr-1 with a ΔCFF of 0.2-1.1 bar. The computed clock-time advance reaches 239 ± 22 yr in agreement with the ˜10 yr delay between main shocks. The calculated static stress change of 0.9-1.3 bar, under pore-fluid stimulus added with well-constrained geodetic and seismic strain rates are critical for any seismic hazard assessment.

The Al Hoceima earthquake sequence of 1994, 2004 and 2016: Stress transfer and poro-elasticity in the Rif and Alboran Sea region

NASA Astrophysics Data System (ADS)

Kariche, Jughurta; Meghraoui, Mustapha; Timoulali, Youssef; Cetin, Esra; Toussaint, Renaud

2017-04-01

The 25 January 2016 earthquake (Mw 6.3) follows in sequence the 26 May 1994 earthquake (Mw 6.0) and the 24 February 2004 earthquake (Mw 6.4) in the Rif Mountains and Alboran Sea. The earlier two seismic events which were destructive took place on inland conjugate faults, and the third event occurred on an offshore fault. These earthquake sequences occurred within a period of 22 years at 25 km distance and 11 - 16-km-depth. The three events have similar strike-slip focal mechanism solutions with NNE-SSW trending left lateral faulting for the 1994 and 2016 events and NW-SE trending right-lateral faulting for the 2004 event. This shallow seismic sequence offers the possibility a) to model the change in Coulomb Failure Function (CFF with μ' = 0.4 including the pore pressure change) and understand fault-rupture interaction, and b) to analyze the effect of pore-fluid on the rupture mechanism, and infer the clock-time advance. The variation of static stress change has a direct impact on the 1994 mainshock, aftershocks and related positive lobes of the 2004 earthquake rupture with a stress change increase of 0.7 - 1.1 bar. Similarly, the 2004 mainshock and aftershocks indicate loading zones with a stress change (> 0.25 bar) that includes the 2016 earthquake rupture. The tectonic loading 19 - 24 nanostrain/yr obtained from the seismicity catalogue of Morocco are comparable to the 5 1017 N.m/yr seismic strain release in the Rif Mountains. The seismic sequence is apparently controlled by the poro-elastic properties of the seismogenic layer that depend on the undrained and drained fluid condition. The short interseismic period between mainshocks and higher rate of aftershocks with relatively large magnitudes (4< Mw <5.5) implies the pore-fluid physical effect in an undrained condition. The stress-rate ranges between 461 - 582 Pa/yr with a CFF of 0.2 - 1.1 bar. The computed clock-time advance reaches 239 ±22 years in agreement with the 10 years delay between mainshocks. The calculated static stress change of 0.9 - 1.3 bar, under pore-fluid stimulus added with well-constrained geodetic and seismic strain rates are critical for any seismic hazard assessment.

Swept Impact Seismic Technique (SIST)

USGS Publications Warehouse

Park, C.B.; Miller, R.D.; Steeples, D.W.; Black, R.A.

1996-01-01

A coded seismic technique is developed that can result in a higher signal-to-noise ratio than a conventional single-pulse method does. The technique is cost-effective and time-efficient and therefore well suited for shallow-reflection surveys where high resolution and cost-effectiveness are critical. A low-power impact source transmits a few to several hundred high-frequency broad-band seismic pulses during several seconds of recording time according to a deterministic coding scheme. The coding scheme consists of a time-encoded impact sequence in which the rate of impact (cycles/s) changes linearly with time providing a broad range of impact rates. Impact times used during the decoding process are recorded on one channel of the seismograph. The coding concept combines the vibroseis swept-frequency and the Mini-Sosie random impact concepts. The swept-frequency concept greatly improves the suppression of correlation noise with much fewer impacts than normally used in the Mini-Sosie technique. The impact concept makes the technique simple and efficient in generating high-resolution seismic data especially in the presence of noise. The transfer function of the impact sequence simulates a low-cut filter with the cutoff frequency the same as the lowest impact rate. This property can be used to attenuate low-frequency ground-roll noise without using an analog low-cut filter or a spatial source (or receiver) array as is necessary with a conventional single-pulse method. Because of the discontinuous coding scheme, the decoding process is accomplished by a "shift-and-stacking" method that is much simpler and quicker than cross-correlation. The simplicity of the coding allows the mechanical design of the source to remain simple. Several different types of mechanical systems could be adapted to generate a linear impact sweep. In addition, the simplicity of the coding also allows the technique to be used with conventional acquisition systems, with only minor modifications.

Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses

PubMed Central

Harvey, William T.; Benton, Donald J.; Gregory, Victoria; Hall, James P. J.; Daniels, Rodney S.; Bedford, Trevor; Haydon, Daniel T.; Hay, Alan J.; McCauley, John W.; Reeve, Richard

2016-01-01

Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens. PMID:27057693

New Technologies for the Identification of Novel Genetic Markers of Disorders of Sex Development (DSD)

PubMed Central

Bashamboo, A.; Ledig, S.; Wieacker, P.; Achermann, J.; McElreavey, K.

2010-01-01

Although the genetic basis of human sexual determination and differentiation has advanced considerably in recent years, the fact remains that in most subjects with disorders of sex development (DSD) the underlying genetic cause is unknown. Where pathogenic mutations have been identified, the phenotype can be highly variable, even within families, suggesting that other genetic variants are influencing the expression of the phenotype. This situation is likely to change, as more powerful and affordable tools become widely available for detailed genetic analyses. Here, we describe recent advances in comparative genomic hybridisation, sequencing by hybridisation and next generation sequencing, and we describe how these technologies will have an impact on our understanding of the genetic causes of DSD. PMID:20820110

Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases

PubMed Central

Schadt, Eric E.; Banerjee, Onureena; Fang, Gang; Feng, Zhixing; Wong, Wing H.; Zhang, Xuegong; Kislyuk, Andrey; Clark, Tyson A.; Luong, Khai; Keren-Paz, Alona; Chess, Andrew; Kumar, Vipin; Chen-Plotkin, Alice; Sondheimer, Neal; Korlach, Jonas; Kasarskis, Andrew

2013-01-01

Current generation DNA sequencing instruments are moving closer to seamlessly sequencing genomes of entire populations as a routine part of scientific investigation. However, while significant inroads have been made identifying small nucleotide variation and structural variations in DNA that impact phenotypes of interest, progress has not been as dramatic regarding epigenetic changes and base-level damage to DNA, largely due to technological limitations in assaying all known and unknown types of modifications at genome scale. Recently, single-molecule real time (SMRT) sequencing has been reported to identify kinetic variation (KV) events that have been demonstrated to reflect epigenetic changes of every known type, providing a path forward for detecting base modifications as a routine part of sequencing. However, to date no statistical framework has been proposed to enhance the power to detect these events while also controlling for false-positive events. By modeling enzyme kinetics in the neighborhood of an arbitrary location in a genomic region of interest as a conditional random field, we provide a statistical framework for incorporating kinetic information at a test position of interest as well as at neighboring sites that help enhance the power to detect KV events. The performance of this and related models is explored, with the best-performing model applied to plasmid DNA isolated from Escherichia coli and mitochondrial DNA isolated from human brain tissue. We highlight widespread kinetic variation events, some of which strongly associate with known modification events, while others represent putative chemically modified sites of unknown types. PMID:23093720

Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases.

PubMed

Schadt, Eric E; Banerjee, Onureena; Fang, Gang; Feng, Zhixing; Wong, Wing H; Zhang, Xuegong; Kislyuk, Andrey; Clark, Tyson A; Luong, Khai; Keren-Paz, Alona; Chess, Andrew; Kumar, Vipin; Chen-Plotkin, Alice; Sondheimer, Neal; Korlach, Jonas; Kasarskis, Andrew

2013-01-01

Current generation DNA sequencing instruments are moving closer to seamlessly sequencing genomes of entire populations as a routine part of scientific investigation. However, while significant inroads have been made identifying small nucleotide variation and structural variations in DNA that impact phenotypes of interest, progress has not been as dramatic regarding epigenetic changes and base-level damage to DNA, largely due to technological limitations in assaying all known and unknown types of modifications at genome scale. Recently, single-molecule real time (SMRT) sequencing has been reported to identify kinetic variation (KV) events that have been demonstrated to reflect epigenetic changes of every known type, providing a path forward for detecting base modifications as a routine part of sequencing. However, to date no statistical framework has been proposed to enhance the power to detect these events while also controlling for false-positive events. By modeling enzyme kinetics in the neighborhood of an arbitrary location in a genomic region of interest as a conditional random field, we provide a statistical framework for incorporating kinetic information at a test position of interest as well as at neighboring sites that help enhance the power to detect KV events. The performance of this and related models is explored, with the best-performing model applied to plasmid DNA isolated from Escherichia coli and mitochondrial DNA isolated from human brain tissue. We highlight widespread kinetic variation events, some of which strongly associate with known modification events, while others represent putative chemically modified sites of unknown types.

An Exploratory Analysis of Game Telemetry from a Pediatric mHealth Intervention.

PubMed

Padman, Rema; Gupta, Disha; Sri Prakash, Bhargav; Krishnan, Chelladurai; Panchatcharam, K

2017-01-01

Pediatric obesity is a growing epidemic, with unhealthy eating habits and poor physical activity being major contributors. While video and mobile games have been shown to have a positive impact on behavior change in children, the mechanisms underlying game play that impact outcomes of interest are poorly understood. This research aims to examine the impact of a novel mobile gaming app on the design of behavioral interventions by learning from the rich and unique game telemetry generated from a randomized controlled trial of the app use by school children. In this exploratory analysis, we extract a partial dataset to build and analyze chronological sequences of game plays to understand key patterns in the game mechanics that players utilize as they navigate the game, and possible implications of the results.

HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences

PubMed Central

Wymant, Chris; Colijn, Caroline; Danaviah, Siva; Essex, Max; Frost, Simon; Gall, Astrid; Gaseitsiwe, Simani; Grabowski, Mary K.; Gray, Ronald; Guindon, Stephane; von Haeseler, Arndt; Kaleebu, Pontiano; Kendall, Michelle; Kozlov, Alexey; Manasa, Justen; Minh, Bui Quang; Moyo, Sikhulile; Novitsky, Vlad; Nsubuga, Rebecca; Pillay, Sureshnee; Quinn, Thomas C.; Serwadda, David; Ssemwanga, Deogratius; Stamatakis, Alexandros; Trifinopoulos, Jana; Wawer, Maria; Brown, Andy Leigh; de Oliveira, Tulio; Kellam, Paul; Pillay, Deenan; Fraser, Christophe

2017-01-01

Abstract To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the “Phylogenetics and Networks for Generalised HIV Epidemics in Africa” consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n = 2,833; MRC/UVRI Uganda, n = 701; Mochudi Prevention Project, n = 359; Africa Health Research Institute Resistance Cohort, n = 92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3′ end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences (NGS) has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected. PMID:28540766

HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

PubMed

Ratmann, Oliver; Wymant, Chris; Colijn, Caroline; Danaviah, Siva; Essex, M; Frost, Simon D W; Gall, Astrid; Gaiseitsiwe, Simani; Grabowski, Mary; Gray, Ronald; Guindon, Stephane; von Haeseler, Arndt; Kaleebu, Pontiano; Kendall, Michelle; Kozlov, Alexey; Manasa, Justen; Minh, Bui Quang; Moyo, Sikhulile; Novitsky, Vladimir; Nsubuga, Rebecca; Pillay, Sureshnee; Quinn, Thomas C; Serwadda, David; Ssemwanga, Deogratius; Stamatakis, Alexandros; Trifinopoulos, Jana; Wawer, Maria; Leigh Brown, Andrew; de Oliveira, Tulio; Kellam, Paul; Pillay, Deenan; Fraser, Christophe

2017-05-25

To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3' end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.

Trends and driving mechanism of land-use change in metropolitan areas of Pearl River Delta

NASA Astrophysics Data System (ADS)

Chen, Feng-gui; Zhang, Hong-ou; Wang, Juan; Wu, Qi-tao

2008-10-01

Taking Pearl River Delta for an example this study focuses on the trends and the driving mechanism of land-use changes in metropolises, in order to achieve the fundamental objectives of LUCC study increasing the awareness on dynamics of global land-use and land-cover changes, and improving the ability of forecasting LUCC. By analyzing the land-use change in Pearl River Delta from 1996 to 2006, it is found that the differences among internal space are notable. By establishing time-sequence-curve with SPSS software, it is shown that trends of land-use change are very clear. With factor analysis on land-use change, the study summarizes four factors of driving mechanism, including factors of economic development level, regional industrial structure, demographic and agricultural structure adjustment, which impact land change in Pearl River Delta to a different extent.

Impact of Land Use Change to the Soil Erosion Estimation for Cultural Landscapes: Case Study of Paphos Disrict in Cyprus

NASA Astrophysics Data System (ADS)

Cuca, B.; Agapiou, A.

2017-05-01

In 2006 UNESCO report has identified soil loss as one of the main threats of climate change with possible impact to natural and cultural heritage. The study illustrated in this paper shows the results from geomatic perspective, applying an interdisciplinary approach undertaken in order to identify major natural hazards affecting cultural landscapes and archaeological heritage in rural areas in Cyprus. In particular, Earth Observation (EO) and ground-based methods were identified and applied for mapping, monitoring and estimation of the possible soil loss caused by soil erosion. Special attention was given to the land use/land cover factor (C) and its impact on the overall estimation of the soil-loss. Cover factor represents the effect of soil-disturbing activities, plants, crop sequence and productivity level, soil cover and subsurface bio-mass on soil erosion. Urban areas have a definite role in retarding the recharge process, leading to increased runoff and soil loss in the broader area. On the other hand, natural vegetation plays a predominant role in reducing water erosion. The land use change was estimated based on the difference of the NDVI value between Landsat 5 TM and Sentinel-2 data for the period between 1980s' until today. Cover factor was then estimated for both periods and significant land use changes were further examined in areas of significant cultural and natural landscape value. The results were then compared in order to study the impact of land use change on the soil erosion and hence on the soil loss rate in the selected areas.

The epigenomic landscape of African rainforest hunter-gatherers and farmers.

PubMed

Fagny, Maud; Patin, Etienne; MacIsaac, Julia L; Rotival, Maxime; Flutre, Timothée; Jones, Meaghan J; Siddle, Katherine J; Quach, Hélène; Harmant, Christine; McEwen, Lisa M; Froment, Alain; Heyer, Evelyne; Gessain, Antoine; Betsem, Edouard; Mouguiama-Daouda, Patrick; Hombert, Jean-Marie; Perry, George H; Barreiro, Luis B; Kobor, Michael S; Quintana-Murci, Lluis

2015-11-30

The genetic history of African populations is increasingly well documented, yet their patterns of epigenomic variation remain uncharacterized. Moreover, the relative impacts of DNA sequence variation and temporal changes in lifestyle and habitat on the human epigenome remain unknown. Here we generate genome-wide genotype and DNA methylation profiles for 362 rainforest hunter-gatherers and sedentary farmers. We find that the current habitat and historical lifestyle of a population have similarly critical impacts on the methylome, but the biological functions affected strongly differ. Specifically, methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas that associated with historical lifestyle affects developmental processes. Furthermore, methylation variation--particularly that correlated with historical lifestyle--shows strong associations with nearby genetic variants that, moreover, are enriched in signals of natural selection. Our work provides new insight into the genetic and environmental factors affecting the epigenomic landscape of human populations over time.

Marks of Change in Sequences

NASA Astrophysics Data System (ADS)

Jürgensen, H.

2011-12-01

Given a sequence of events, how does one recognize that a change has occurred? We explore potential definitions of the concept of change in a sequence and propose that words in relativized solid codes might serve as indicators of change.

The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions

PubMed Central

Kwong, Waldan K.; McFrederick, Quinn; Anderson, Kirk E.; Barribeau, Seth Michael; Chandler, James Angus; Cornman, R. Scott; Dainat, Jacques; Doublet, Vincent; Emery, Olivier; Evans, Jay D.; Farinelli, Laurent; Flenniken, Michelle L.; Granberg, Fredrik; Grasis, Juris A.; Gauthier, Laurent; Hayer, Juliette; Koch, Hauke; Kocher, Sarah; Martinson, Vincent G.; Moran, Nancy; Munoz-Torres, Monica; Newton, Irene; Paxton, Robert J.; Powell, Eli; Sadd, Ben M.; Schmid-Hempel, Paul; Schmid-Hempel, Regula; Schwarz, Ryan S.; vanEngelsdorp, Dennis

2016-01-01

ABSTRACT As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee microbiome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health. PMID:27118586

The bee microbiome: Impact on bee health and model for evolution and ecology of host-microbe interactions

USGS Publications Warehouse

Engel, Philipp; Kwong, Waldan K.; McFrederick, Quinn; Anderson, Kirk E.; Barribeau, Seth Michael; Chandler, James Angus; Cornman, Robert S.; Dainat, Jacques; de Miranda, Joachim R.; Doublet, Vincent; Emery, Olivier; Evans, Jay D.; Farinelli, Laurent; Flenniken, Michelle L.; Granberg, Fredrik; Grasis, Juris A.; Gauthier, Laurent; Hayer, Juliette; Koch, Hauke; Kocher, Sarah; Martinson, Vincent G.; Moran, Nancy; Munoz-Torres, Monica; Newton, Irene; Paxton, Robert J.; Powell, Eli; Sadd, Ben M.; Schmid-Hempel, Paul; Schmid-Hempel, Regula; Song, Se Jin; Schwarz, Ryan S.; vanEngelsdorp, Dennis; Dainat, Benjamin

2016-01-01

As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee microbiome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health.

The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions.

PubMed

Engel, Philipp; Kwong, Waldan K; McFrederick, Quinn; Anderson, Kirk E; Barribeau, Seth Michael; Chandler, James Angus; Cornman, R Scott; Dainat, Jacques; de Miranda, Joachim R; Doublet, Vincent; Emery, Olivier; Evans, Jay D; Farinelli, Laurent; Flenniken, Michelle L; Granberg, Fredrik; Grasis, Juris A; Gauthier, Laurent; Hayer, Juliette; Koch, Hauke; Kocher, Sarah; Martinson, Vincent G; Moran, Nancy; Munoz-Torres, Monica; Newton, Irene; Paxton, Robert J; Powell, Eli; Sadd, Ben M; Schmid-Hempel, Paul; Schmid-Hempel, Regula; Song, Se Jin; Schwarz, Ryan S; vanEngelsdorp, Dennis; Dainat, Benjamin

2016-04-26

As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee microbiome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health. Copyright © 2016 Engel et al.

Composition of methane-oxidizing bacterial communities as a function of nutrient loading in the Florida everglades.

PubMed

Chauhan, Ashvini; Pathak, Ashish; Ogram, Andrew

2012-10-01

Agricultural runoff of phosphorus (P) in the northern Florida Everglades has resulted in several ecosystem level changes, including shifts in the microbial ecology of carbon cycling, with significantly higher methane being produced in the nutrient-enriched soils. Little is, however, known of the structure and activities of methane-oxidizing bacteria (MOB) in these environments. To address this, 0 to 10 cm plant-associated soil cores were collected from nutrient-impacted (F1), transition (F4), and unimpacted (U3) areas, sectioned in 2-cm increments, and methane oxidation rates were measured. F1 soils consumed approximately two-fold higher methane than U3 soils; additionally, most probable numbers of methanotrophs were 4-log higher in F1 than U3 soils. Metabolically active MOB containing pmoA sequences were characterized by stable-isotope probing using 10 % (v/v) (13)CH(4). pmoA sequences, encoding the alpha subunit of methane monooxygenase and related to type I methanotrophs, were identified from both impacted and unimpacted soils. Additionally, impacted soils also harbored type II methanotrophs, which have been shown to exhibit preferences for high methane concentrations. Additionally, across all soils, novel pmoA-type sequences were also detected, indicating presence of MOB specific to the Everglades. Multivariate statistical analyses confirmed that eutrophic soils consisted of metabolically distinct MOB community that is likely driven by nutrient enrichment. This study enhances our understanding on the biological fate of methane being produced in productive wetland soils of the Florida Everglades and how nutrient-enrichment affects the composition of methanotroph bacterial communities.

Alteration of Microbial Communities Colonizing Leaf Litter in a Temperate Woodland Stream by Growth of Trees under Conditions of Elevated Atmospheric CO2 ▿

PubMed Central

Kelly, John J.; Bansal, Amit; Winkelman, Jonathan; Janus, Lori R.; Hell, Shannon; Wencel, Marie; Belt, Patricia; Kuehn, Kevin A.; Rier, Steven T.; Tuchman, Nancy C.

2010-01-01

Elevated atmospheric CO2 can cause increased carbon fixation and altered foliar chemical composition in a variety of plants, which has the potential to impact forested headwater streams because they are detritus-based ecosystems that rely on leaf litter as their primary source of organic carbon. Fungi and bacteria play key roles in the entry of terrestrial carbon into aquatic food webs, as they decompose leaf litter and serve as a source of nutrition for invertebrate consumers. This study tested the hypothesis that changes in leaf chemistry caused by elevated atmospheric CO2 would result in changes in the size and composition of microbial communities colonizing leaves in a woodland stream. Three tree species, Populus tremuloides, Salix alba, and Acer saccharum, were grown under ambient (360 ppm) or elevated (720 ppm) CO2, and their leaves were incubated in a woodland stream. Elevated-CO2 treatment resulted in significant increases in the phenolic and tannin contents and C/N ratios of leaves. Microbial effects, which occurred only for P. tremuloides leaves, included decreased fungal biomass and decreased bacterial counts. Analysis of fungal and bacterial communities on P. tremuloides leaves via terminal restriction fragment length polymorphism (T-RFLP) and clone library sequencing revealed that fungal community composition was mostly unchanged by the elevated-CO2 treatment, whereas bacterial communities showed a significant shift in composition and a significant increase in diversity. Specific changes in bacterial communities included increased numbers of alphaproteobacterial and cytophaga-flavobacter-bacteroides (CFB) group sequences and decreased numbers of betaproteobacterial and firmicutes sequences, as well as a pronounced decrease in overall Gram-positive bacterial sequences. PMID:20543045

Comparison of complete genome sequences of dog rabies viruses isolated from China and Mexico reveals key amino acid changes that may be associated with virus replication and virulence.

PubMed

Yu, Fulai; Zhang, Guoqing; Zhong, Xiangfu; Han, Na; Song, Yunfeng; Zhao, Ling; Cui, Min; Rayner, Simon; Fu, Zhen F

2014-07-01

Rabies is a global problem, but its impact and prevalence vary across different regions. In some areas, such as parts of Africa and Asia, the virus is prevalent in the domestic dog population, leading to epidemic waves and large numbers of human fatalities. In other regions, such as the Americas, the virus predominates in wildlife and bat populations, with sporadic spillover into domestic animals. In this work, we attempted to investigate whether these distinct environments led to selective pressures that result in measurable changes within the genome at the amino acid level. To this end, we collected and sequenced the full genome of two isolates from divergent environments. The first isolate (DRV-AH08) was from China, where the virus is present in the dog population and the country is experiencing a serious epidemic. The second isolate (DRV-Mexico) was taken from Mexico, where the virus is present in both wildlife and domestic dog populations, but at low levels as a consequence of an effective vaccination program. We then combined and compared these with other full genome sequences to identify distinct amino acid changes that might be associated with environment. Phylogenetic analysis identified strain DRV-AH08 as belonging to the China-I lineage, which has emerged to become the dominant lineage in the current epidemic. The Mexico strain was placed in the D11 Mexico lineage, associated with the West USA-Mexico border clade. Amino acid sequence analysis identified only 17 amino acid differences in the N, G and L proteins. These differences may be associated with virus replication and virulence-for example, the short incubation period observed in the current epidemic in China.

Alteration of microbial communities colonizing leaf litter in a temperate woodland stream by growth of trees under conditions of elevated atmospheric CO2.

PubMed

Kelly, John J; Bansal, Amit; Winkelman, Jonathan; Janus, Lori R; Hell, Shannon; Wencel, Marie; Belt, Patricia; Kuehn, Kevin A; Rier, Steven T; Tuchman, Nancy C

2010-08-01

Elevated atmospheric CO(2) can cause increased carbon fixation and altered foliar chemical composition in a variety of plants, which has the potential to impact forested headwater streams because they are detritus-based ecosystems that rely on leaf litter as their primary source of organic carbon. Fungi and bacteria play key roles in the entry of terrestrial carbon into aquatic food webs, as they decompose leaf litter and serve as a source of nutrition for invertebrate consumers. This study tested the hypothesis that changes in leaf chemistry caused by elevated atmospheric CO(2) would result in changes in the size and composition of microbial communities colonizing leaves in a woodland stream. Three tree species, Populus tremuloides, Salix alba, and Acer saccharum, were grown under ambient (360 ppm) or elevated (720 ppm) CO(2), and their leaves were incubated in a woodland stream. Elevated-CO(2) treatment resulted in significant increases in the phenolic and tannin contents and C/N ratios of leaves. Microbial effects, which occurred only for P. tremuloides leaves, included decreased fungal biomass and decreased bacterial counts. Analysis of fungal and bacterial communities on P. tremuloides leaves via terminal restriction fragment length polymorphism (T-RFLP) and clone library sequencing revealed that fungal community composition was mostly unchanged by the elevated-CO(2) treatment, whereas bacterial communities showed a significant shift in composition and a significant increase in diversity. Specific changes in bacterial communities included increased numbers of alphaproteobacterial and cytophaga-flavobacter-bacteroides (CFB) group sequences and decreased numbers of betaproteobacterial and firmicutes sequences, as well as a pronounced decrease in overall gram-positive bacterial sequences.

Comparative multibody dynamics analysis of falls from playground climbing frames.

PubMed

Forero Rueda, M A; Gilchrist, M D

2009-10-30

This paper shows the utility of multibody dynamics in evaluating changes in injury related parameters of the head and lower limbs of children following falls from playground climbing frames. A particular fall case was used as a starting point to analyze the influence of surface properties, posture of the body at impact, and intermediate collisions against the climbing frame before impacting the ground. Simulations were made using the 6-year-old pedestrian MADYMO rigid body model and scaled head contact characteristics. Energy absorbing surfaces were shown to reduce injury severity parameters by up to 30-80% of those of rigid surfaces, depending on impact posture and surface. Collisions against components of a climbing frame during a fall can increase injury severity of the final impact of the head with the ground by more than 90%. Negligible changes are associated with lower limb injury risks when different surfacing materials are used. Computer reconstructions of actual falls that are intended to quantify the severity of physical injuries rely on accurate knowledge of initial conditions prior to falling, intermediate kinematics of the fall and the orientation of the body when it impacts against the ground. Multibody modelling proved to be a valuable tool to analyze the quality of eyewitness information and analyze the relative injury risk associated with changes in components influencing fall injuries from playground climbing frames. Such simulations can also support forensic investigations by evaluating alternative hypotheses for the sequence of kinematic motion of falls which result in known injuries.

Satellite DNA in Plants: More than Just Rubbish.

PubMed

Garrido-Ramos, Manuel A

2015-01-01

For decades, satellite DNAs have been the hidden part of genomes. Initially considered as junk DNA, there is currently an increasing appreciation of the functional significance of satellite DNA repeats and of their sequences. Satellite DNA families accumulate in the heterochromatin in different parts of the eukaryotic chromosomes, mainly in pericentromeric and subtelomeric regions, but they also span the functional centromere. Tandem repeat sequences may spread from subtelomeric to interstitial loci, leading to the formation of chromosome-specific loci or to the accumulation in equilocal sites in different chromosomes. They also appear as the main components of the heterochromatin in the sex-specific region of sex chromosomes. Satellite DNA, required for chromosome organization, also plays a role in pairing and segregation. Some satellite repeats are transcribed and can participate in the formation and maintenance of heterochromatin structure and in the modulation of gene expression. In addition to the identification of the different satellite DNA families, their characteristics and location, we are interested in determining their impact on the genomes, by identifying the mechanisms leading to their appearance and amplification as well as in understanding how they change over time, the factors affecting these changes, and the influence exerted by the evolutionary history of the organisms. On the other hand, satellite DNA sequences are rapidly evolving sequences that may cause reproductive barriers between organisms and promote speciation. The accumulation of experimental data collected in recent years and the emergence of new approaches based on next-generation sequencing and high-throughput genome analysis are opening new perspectives that are changing our understanding of satellite DNA. This review examines recent data to provide a timely update on the overall information gathered about this part of the genome, focusing on the advances in the knowledge of its origin, its evolution, and its potential functional roles. © 2015 S. Karger AG, Basel.

Nursing Student Perceptions Regarding Simulation Experience Sequencing.

PubMed

Woda, Aimee A; Gruenke, Theresa; Alt-Gehrman, Penny; Hansen, Jamie

2016-09-01

The use of simulated learning experiences (SLEs) have increased within nursing curricula with positive learning outcomes for nursing students. The purpose of this study is to explore nursing students' perceptions of their clinical decision making (CDM) related to the block sequencing of different patient care experiences, SLEs versus hospital-based learning experiences (HLEs). A qualitative descriptive design used open-ended survey questions to generate information about the block sequencing of SLEs and its impact on nursing students' perceived CDM. Three themes emerged from the data: Preexperience Anxiety, Real-Time Decision Making, and Increased Patient Care Experiences. Nursing students identified that having SLEs prior to HLEs provided several benefits. Even when students preferred SLEs prior to HLEs, the sequence did not impact their CDM. This suggests that alternating block sequencing can be used without impacting the students' perceptions of their ability to make decisions. [J Nurs Educ. 2016;55(9):528-532.]. Copyright 2016, SLACK Incorporated.

De Novo Centromere Formation and Centromeric Sequence Expansion in Wheat and its Wide Hybrids.

PubMed

Guo, Xiang; Su, Handong; Shi, Qinghua; Fu, Shulan; Wang, Jing; Zhang, Xiangqi; Hu, Zanmin; Han, Fangpu

2016-04-01

Centromeres typically contain tandem repeat sequences, but centromere function does not necessarily depend on these sequences. We identified functional centromeres with significant quantitative changes in the centromeric retrotransposons of wheat (CRW) contents in wheat aneuploids (Triticum aestivum) and the offspring of wheat wide hybrids. The CRW signals were strongly reduced or essentially lost in some wheat ditelosomic lines and in the addition lines from the wide hybrids. The total loss of the CRW sequences but the presence of CENH3 in these lines suggests that the centromeres were formed de novo. In wheat and its wide hybrids, which carry large complex genomes or no sequenced genome, we performed CENH3-ChIP-dot-blot methods alone or in combination with CENH3-ChIP-seq and identified the ectopic genomic sequences present at the new centromeres. In adcdition, the transcription of the identified DNA sequences was remarkably increased at the new centromere, suggesting that the transcription of the corresponding sequences may be associated with de novo centromere formation. Stable alien chromosomes with two and three regions containing CRW sequences induced by centromere breakage were observed in the wheat-Th. elongatum hybrid derivatives, but only one was a functional centromere. In wheat-rye (Secale cereale) hybrids, the rye centromere-specific sequences spread along the chromosome arms and may have caused centromere expansion. Frequent and significant quantitative alterations in the centromere sequence via chromosomal rearrangement have been systematically described in wheat wide hybridizations, which may affect the retention or loss of the alien chromosomes in the hybrids. Thus, the centromere behavior in wide crosses likely has an important impact on the generation of biodiversity, which ultimately has implications for speciation.

De Novo Centromere Formation and Centromeric Sequence Expansion in Wheat and its Wide Hybrids

PubMed Central

Fu, Shulan; Wang, Jing; Zhang, Xiangqi; Hu, Zanmin; Han, Fangpu

2016-01-01

Centromeres typically contain tandem repeat sequences, but centromere function does not necessarily depend on these sequences. We identified functional centromeres with significant quantitative changes in the centromeric retrotransposons of wheat (CRW) contents in wheat aneuploids (Triticum aestivum) and the offspring of wheat wide hybrids. The CRW signals were strongly reduced or essentially lost in some wheat ditelosomic lines and in the addition lines from the wide hybrids. The total loss of the CRW sequences but the presence of CENH3 in these lines suggests that the centromeres were formed de novo. In wheat and its wide hybrids, which carry large complex genomes or no sequenced genome, we performed CENH3-ChIP-dot-blot methods alone or in combination with CENH3-ChIP-seq and identified the ectopic genomic sequences present at the new centromeres. In adcdition, the transcription of the identified DNA sequences was remarkably increased at the new centromere, suggesting that the transcription of the corresponding sequences may be associated with de novo centromere formation. Stable alien chromosomes with two and three regions containing CRW sequences induced by centromere breakage were observed in the wheat-Th. elongatum hybrid derivatives, but only one was a functional centromere. In wheat-rye (Secale cereale) hybrids, the rye centromere-specific sequences spread along the chromosome arms and may have caused centromere expansion. Frequent and significant quantitative alterations in the centromere sequence via chromosomal rearrangement have been systematically described in wheat wide hybridizations, which may affect the retention or loss of the alien chromosomes in the hybrids. Thus, the centromere behavior in wide crosses likely has an important impact on the generation of biodiversity, which ultimately has implications for speciation. PMID:27110907

Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach

PubMed Central

Holmes, Ben; Jung, Seung Ho; Lu, Jing; Wagner, Jessica A.; Rubbi, Liudmilla; Pellegrini, Matteo

2016-01-01

Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied. PMID:28119786

Experimental Climate Change Modifies Degradative Succession in Boreal Peatland Fungal Communities.

PubMed

Asemaninejad, Asma; Thorn, R Greg; Lindo, Zoë

2017-04-01

Peatlands play an important role in global climate change through sequestration of atmospheric CO 2 . Climate-driven changes in the structure of fungal communities in boreal peatlands that favor saprotrophic fungi can substantially impact carbon dynamics and nutrient cycling in these crucial ecosystems. In a mesocosm study using a full factorial design, 100 intact peat monoliths, complete with living Sphagnum and above-ground vascular vegetation, were subjected to three climate change variables (increased temperature, reduced water table, and elevated CO 2 concentrations). Peat litterbags were placed in mesocosms, and fungal communities in litterbags were monitored over 12 months to assess the impacts of climate change variables on peat-inhabiting fungi. Changes in fungal richness, diversity, and community composition were assessed using Illumina MiSeq sequencing of ribosomal DNA (rDNA). While general fungal richness reduced under warming conditions, Ascomycota exhibited higher diversity under increased temperature treatments over the course of the experiment. Both increased temperature and lowered water table position drove shifts in fungal community composition with a strong positive effect on endophytic and mycorrhizal fungi (including one operational taxonomic unit (OTU) tentatively identified as Barrenia panicia) and different groups of saprotrophs identified as Mortierella, Galerina, and Mycena. These shifts were observed during a predicted degradative succession in the decomposer community as different carbon substrates became available. Since fungi play a central role in peatland communities, increased abundances of saprotrophic fungi under warming conditions, at the expense of reduced fungal richness overall, may increase decomposition rates under future climate scenarios and could potentially aggravate the impacts of climate change.

Activity of genes with functions in human Williams-Beuren Syndrome are impacted by mobile element insertions in the gray wolf genome.

PubMed

vonHoldt, Bridgett M; Ji, Sarah S; Aardema, Matthew L; Stahler, Daniel; Udell, Monique A R; Sinsheimer, Janet S

2018-06-01

In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions in dogs and Yellowstone wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of mobile element insertions (MEIs), suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that mobile element insertions impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation.

Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly

PubMed Central

Schneider, Valerie A.; Graves-Lindsay, Tina; Howe, Kerstin; Bouk, Nathan; Chen, Hsiu-Chuan; Kitts, Paul A.; Murphy, Terence D.; Pruitt, Kim D.; Thibaud-Nissen, Françoise; Albracht, Derek; Fulton, Robert S.; Kremitzki, Milinn; Magrini, Vincent; Markovic, Chris; McGrath, Sean; Steinberg, Karyn Meltz; Auger, Kate; Chow, William; Collins, Joanna; Harden, Glenn; Hubbard, Timothy; Pelan, Sarah; Simpson, Jared T.; Threadgold, Glen; Torrance, James; Wood, Jonathan M.; Clarke, Laura; Koren, Sergey; Boitano, Matthew; Peluso, Paul; Li, Heng; Chin, Chen-Shan; Phillippy, Adam M.; Durbin, Richard; Wilson, Richard K.; Flicek, Paul; Eichler, Evan E.; Church, Deanna M.

2017-01-01

The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions, and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that although the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health. PMID:28396521

“Maxillary lateral incisor partial anodontia sequence”: a clinical entity with epigenetic origin

PubMed Central

Consolaro, Alberto; Cardoso, Maurício Almeida; Consolaro, Renata Bianco

2017-01-01

ABSTRACT The relationship between maxillary lateral incisor anodontia and the palatal displacement of unerupted maxillary canines cannot be considered as a multiple tooth abnormality with defined genetic etiology in order to be regarded as a “syndrome”. Neither were the involved genes identified and located in the human genome, nor was it presumed on which chromosome the responsible gene would be located. The palatal maxillary canine displacement in cases of partial anodontia of the maxillary lateral incisor is potentially associated with environmental changes caused by its absence in its place of formation and eruption, which would characterize an epigenetic etiology. The lack of the maxillary lateral incisor in the canine region means removing one of the reference guides for the eruptive trajectory of the maxillary canine, which would therefore, not erupt and /or impact on the palate. Consequently, and in sequence, it would lead to malocclusion, maxillary atresia, transposition, prolonged retention of the deciduous canine and resorption in the neighboring teeth. Thus, we can say that we are dealing with a set of anomalies and multiple sequential changes known as sequential development anomalies or, simply, sequence. Once the epigenetics and sequential condition is accepted for this clinical picture, it could be called “Maxillary Lateral Incisor Partial Anodontia Sequence.” PMID:29364376

The impact of targeting repetitive BamHI-W sequences on the sensitivity and precision of EBV DNA quantification.

PubMed

Sanosyan, Armen; Fayd'herbe de Maudave, Alexis; Bollore, Karine; Zimmermann, Valérie; Foulongne, Vincent; Van de Perre, Philippe; Tuaillon, Edouard

2017-01-01

Viral load monitoring and early Epstein-Barr virus (EBV) DNA detection are essential in routine laboratory testing, especially in preemptive management of Post-transplant Lymphoproliferative Disorder. Targeting the repetitive BamHI-W sequence was shown to increase the sensitivity of EBV DNA quantification, but the variability of BamHI-W reiterations was suggested to be a source of quantification bias. We aimed to assess the extent of variability associated with BamHI-W PCR and its impact on the sensitivity of EBV DNA quantification using the 1st WHO international standard, EBV strains and clinical samples. Repetitive BamHI-W- and LMP2 single- sequences were amplified by in-house qPCRs and BXLF-1 sequence by a commercial assay (EBV R-gene™, BioMerieux). Linearity and limits of detection of in-house methods were assessed. The impact of repeated versus single target sequences on EBV DNA quantification precision was tested on B95.8 and Raji cell lines, possessing 11 and 7 copies of the BamHI-W sequence, respectively, and on clinical samples. BamHI-W qPCR demonstrated a lower limit of detection compared to LMP2 qPCR (2.33 log10 versus 3.08 log10 IU/mL; P = 0.0002). BamHI-W qPCR underestimated the EBV DNA load on Raji strain which contained fewer BamHI-W copies than the WHO standard derived from the B95.8 EBV strain (mean bias: - 0.21 log10; 95% CI, -0.54 to 0.12). Comparison of BamHI-W qPCR versus LMP2 and BXLF-1 qPCR showed an acceptable variability between EBV DNA levels in clinical samples with the mean bias being within 0.5 log10 IU/mL EBV DNA, whereas a better quantitative concordance was observed between LMP2 and BXLF-1 assays. Targeting BamHI-W resulted to a higher sensitivity compared to LMP2 but the variable reiterations of BamHI-W segment are associated with higher quantification variability. BamHI-W can be considered for clinical and therapeutic monitoring to detect an early EBV DNA and a dynamic change in viral load.

The impact of targeting repetitive BamHI-W sequences on the sensitivity and precision of EBV DNA quantification

PubMed Central

Fayd’herbe de Maudave, Alexis; Bollore, Karine; Zimmermann, Valérie; Foulongne, Vincent; Van de Perre, Philippe; Tuaillon, Edouard

2017-01-01

Background Viral load monitoring and early Epstein-Barr virus (EBV) DNA detection are essential in routine laboratory testing, especially in preemptive management of Post-transplant Lymphoproliferative Disorder. Targeting the repetitive BamHI-W sequence was shown to increase the sensitivity of EBV DNA quantification, but the variability of BamHI-W reiterations was suggested to be a source of quantification bias. We aimed to assess the extent of variability associated with BamHI-W PCR and its impact on the sensitivity of EBV DNA quantification using the 1st WHO international standard, EBV strains and clinical samples. Methods Repetitive BamHI-W- and LMP2 single- sequences were amplified by in-house qPCRs and BXLF-1 sequence by a commercial assay (EBV R-gene™, BioMerieux). Linearity and limits of detection of in-house methods were assessed. The impact of repeated versus single target sequences on EBV DNA quantification precision was tested on B95.8 and Raji cell lines, possessing 11 and 7 copies of the BamHI-W sequence, respectively, and on clinical samples. Results BamHI-W qPCR demonstrated a lower limit of detection compared to LMP2 qPCR (2.33 log10 versus 3.08 log10 IU/mL; P = 0.0002). BamHI-W qPCR underestimated the EBV DNA load on Raji strain which contained fewer BamHI-W copies than the WHO standard derived from the B95.8 EBV strain (mean bias: - 0.21 log10; 95% CI, -0.54 to 0.12). Comparison of BamHI-W qPCR versus LMP2 and BXLF-1 qPCR showed an acceptable variability between EBV DNA levels in clinical samples with the mean bias being within 0.5 log10 IU/mL EBV DNA, whereas a better quantitative concordance was observed between LMP2 and BXLF-1 assays. Conclusions Targeting BamHI-W resulted to a higher sensitivity compared to LMP2 but the variable reiterations of BamHI-W segment are associated with higher quantification variability. BamHI-W can be considered for clinical and therapeutic monitoring to detect an early EBV DNA and a dynamic change in viral load. PMID:28850597

Applications of nanotechnology, next generation sequencing and microarrays in biomedical research.

PubMed

Elingaramil, Sauli; Li, Xiaolong; He, Nongyue

2013-07-01

Next-generation sequencing technologies, microarrays and advances in bio nanotechnology have had an enormous impact on research within a short time frame. This impact appears certain to increase further as many biomedical institutions are now acquiring these prevailing new technologies. Beyond conventional sampling of genome content, wide-ranging applications are rapidly evolving for next-generation sequencing, microarrays and nanotechnology. To date, these technologies have been applied in a variety of contexts, including whole-genome sequencing, targeted re sequencing and discovery of transcription factor binding sites, noncoding RNA expression profiling and molecular diagnostics. This paper thus discusses current applications of nanotechnology, next-generation sequencing technologies and microarrays in biomedical research and highlights the transforming potential these technologies offer.

Genome Sequencing of Museum Specimens Reveals Rapid Changes in the Genetic Composition of Honey Bees in California.

PubMed

Cridland, Julie M; Ramirez, Santiago R; Dean, Cheryl A; Sciligo, Amber; Tsutsui, Neil D

2018-02-01

The western honey bee, Apis mellifera, is an enormously influential pollinator in both natural and managed ecosystems. In North America, this species has been introduced numerous times from a variety of different source populations in Europe and Africa. Since then, feral populations have expanded into many different environments across their broad introduced range. Here, we used whole genome sequencing of historical museum specimens and newly collected modern populations from California (USA) to analyze the impact of demography and selection on introduced populations during the past 105 years. We find that populations from both northern and southern California exhibit pronounced genetic changes, but have changed in different ways. In northern populations, honey bees underwent a substantial shift from western European to eastern European ancestry since the 1960s, whereas southern populations are dominated by the introgression of Africanized genomes during the past two decades. Additionally, we identify an isolated island population that has experienced comparatively little change over a large time span. Fine-scale comparison of different populations and time points also revealed SNPs that differ in frequency, highlighting a number of genes that may be important for recent adaptations in these introduced populations. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Heritable heading time variation in wheat lines with the same number of Ppd-B1 gene copies.

PubMed

Ivaničová, Zuzana; Valárik, Miroslav; Pánková, Kateřina; Trávníčková, Martina; Doležel, Jaroslav; Šafář, Jan; Milec, Zbyněk

2017-01-01

The ability of plants to identify an optimal flowering time is critical for ensuring the production of viable seeds. The main environmental factors that influence the flowering time include the ambient temperature and day length. In wheat, the ability to assess the day length is controlled by photoperiod (Ppd) genes. Due to its allohexaploid nature, bread wheat carries the following three Ppd-1 genes: Ppd-A1, Ppd-B1 and Ppd-D1. While photoperiod (in)sensitivity controlled by Ppd-A1 and Ppd-D1 is mainly determined by sequence changes in the promoter region, the impact of the Ppd-B1 alleles on the heading time has been linked to changes in the copy numbers (and possibly their methylation status) and sequence changes in the promoter region. Here, we report that plants with the same number of Ppd-B1 copies may have different heading times. Differences were observed among F7 lines derived from crossing two spring hexaploid wheat varieties. Several lines carrying three copies of Ppd-B1 headed 16 days later than other plants in the population with the same number of gene copies. This effect was associated with changes in the gene expression level and methylation of the Ppd-B1 gene.

Heritable heading time variation in wheat lines with the same number of Ppd-B1 gene copies

PubMed Central

Ivaničová, Zuzana; Valárik, Miroslav; Pánková, Kateřina; Trávníčková, Martina; Doležel, Jaroslav; Šafář, Jan

2017-01-01

The ability of plants to identify an optimal flowering time is critical for ensuring the production of viable seeds. The main environmental factors that influence the flowering time include the ambient temperature and day length. In wheat, the ability to assess the day length is controlled by photoperiod (Ppd) genes. Due to its allohexaploid nature, bread wheat carries the following three Ppd-1 genes: Ppd-A1, Ppd-B1 and Ppd-D1. While photoperiod (in)sensitivity controlled by Ppd-A1 and Ppd-D1 is mainly determined by sequence changes in the promoter region, the impact of the Ppd-B1 alleles on the heading time has been linked to changes in the copy numbers (and possibly their methylation status) and sequence changes in the promoter region. Here, we report that plants with the same number of Ppd-B1 copies may have different heading times. Differences were observed among F7 lines derived from crossing two spring hexaploid wheat varieties. Several lines carrying three copies of Ppd-B1 headed 16 days later than other plants in the population with the same number of gene copies. This effect was associated with changes in the gene expression level and methylation of the Ppd-B1 gene. PMID:28846721

Effect of Temporal Pattern of Radiation in Intensity Modulated Radiotherapy on Cell Cycle Progression and Apoptosis of ACHN Renal Cell Carcinoma Cell Line.

PubMed

Khorramizadeh, Maryam; Saberi, Alihossein; Tahmasebi-Birgani, Mohammadjavad; Shokrani, Parvaneh; Amouhedari, Alireza

The existence of a hypersensitive radiation response to doses below 1 Gy is well established for many normal and tumor cell lines. The aim of this study was to ascertain the impact of temporal pattern modeling IMRT on survival, cell cycle and apoptosis of human RCC cell line ACHN, so as to provide radiobiological basis for optimizing IMRT plans for this disease. The ACHN renal cell carcinoma cell line was used in this study. Impact of the triangle, V, small-large or large-small temporal patterns in the presence and absence of threshold dose of hyper-radiosensitivity at the beginning of patterns were studied using soft agarclonogenic assays. Cell cycle and apoptosis analysis were performed after irradiation with the temporal patterns. For triangle and small-large dose sequences, survival fraction was significantly reduced after irradiation with or without threshold dose of hyper-radiosensitivity at the beginning of the patterns. In all of the dose patterns, cell cycle distributions and the percentage of apoptotic cells at 24 h after irradiation with or without priming dose of hyper-radiosensitivity showed no significant difference. However, apoptotic cells were increased when beams with the smallest dose applied at the beginning of dose pattern like triangle and small-large dose sequence. These data show that the biologic effects of single fraction may differ in clinical settings depending on the size and sequence of the partial fractions. Doses at the beginning but not at the end of sequences may change cytotoxicity effects of radiation.

Early transcriptional changes in the reef-building coral Acropora aspera in response to thermal and nutrient stress.

PubMed

Rosic, Nedeljka; Kaniewska, Paulina; Chan, Chon-Kit Kenneth; Ling, Edmund Yew Siang; Edwards, David; Dove, Sophie; Hoegh-Guldberg, Ove

2014-12-02

Changes to the environment as a result of human activities can result in a range of impacts on reef building corals that include coral bleaching (reduced concentrations of algal symbionts), decreased coral growth and calcification, and increased incidence of diseases and mortality. Understanding how elevated temperatures and nutrient concentration affect early transcriptional changes in corals and their algal endosymbionts is critically important for evaluating the responses of coral reefs to global changes happening in the environment. Here, we investigated the expression of genes in colonies of the reef-building coral Acropora aspera exposed to short-term sub-lethal levels of thermal (+6°C) and nutrient stress (ammonium-enrichment: 20 μM). The RNA-Seq data provided hundreds of differentially expressed genes (DEGs) corresponding to various stress regimes, with 115 up- and 78 down-regulated genes common to all stress regimes. A list of DEGs included up-regulated coral genes like cytochrome c oxidase and NADH-ubiquinone oxidoreductase and up-regulated photosynthetic genes of algal origin, whereas coral GFP-like fluorescent chromoprotein and sodium/potassium-transporting ATPase showed reduced transcript levels. Taxonomic analyses of the coral holobiont disclosed the dominant presence of transcripts from coral (~70%) and Symbiodinium (~10-12%), as well as ~15-20% of unknown sequences which lacked sequence identity to known genes. Gene ontology analyses revealed enriched pathways, which led to changes in the dynamics of protein networks affecting growth, cellular processes, and energy requirement. In corals with preserved symbiont physiological performance (based on Fv/Fm, photo-pigment and symbiont density), transcriptomic changes and DEGs provided important insight into early stages of the stress response in the coral holobiont. Although there were no signs of coral bleaching after exposure to short-term thermal and nutrient stress conditions, we managed to detect oxidative stress and apoptotic changes on a molecular level and provide a list of prospective stress biomarkers for both partners in symbiosis. Consequently, our findings are important for understanding and anticipating impacts of anthropogenic global climate change on coral reefs.

Carnivore-specific SINEs (Can-SINEs): distribution, evolution, and genomic impact.

PubMed

Walters-Conte, Kathryn B; Johnson, Diana L E; Allard, Marc W; Pecon-Slattery, Jill

2011-01-01

Short interspersed nuclear elements (SINEs) are a type of class 1 transposable element (retrotransposon) with features that allow investigators to resolve evolutionary relationships between populations and species while providing insight into genome composition and function. Characterization of a Carnivora-specific SINE family, Can-SINEs, has, has aided comparative genomic studies by providing rare genomic changes, and neutral sequence variants often needed to resolve difficult evolutionary questions. In addition, Can-SINEs constitute a significant source of functional diversity with Carnivora. Publication of the whole-genome sequence of domestic dog, domestic cat, and giant panda serves as a valuable resource in comparative genomic inferences gleaned from Can-SINEs. In anticipation of forthcoming studies bolstered by new genomic data, this review describes the discovery and characterization of Can-SINE motifs as well as describes composition, distribution, and effect on genome function. As the contribution of noncoding sequences to genomic diversity becomes more apparent, SINEs and other transposable elements will play an increasingly large role in mammalian comparative genomics.

Carnivore-Specific SINEs (Can-SINEs): Distribution, Evolution, and Genomic Impact

PubMed Central

Johnson, Diana L.E.; Allard, Marc W.; Pecon-Slattery, Jill

2011-01-01

Short interspersed nuclear elements (SINEs) are a type of class 1 transposable element (retrotransposon) with features that allow investigators to resolve evolutionary relationships between populations and species while providing insight into genome composition and function. Characterization of a Carnivora-specific SINE family, Can-SINEs, has, has aided comparative genomic studies by providing rare genomic changes, and neutral sequence variants often needed to resolve difficult evolutionary questions. In addition, Can-SINEs constitute a significant source of functional diversity with Carnivora. Publication of the whole-genome sequence of domestic dog, domestic cat, and giant panda serves as a valuable resource in comparative genomic inferences gleaned from Can-SINEs. In anticipation of forthcoming studies bolstered by new genomic data, this review describes the discovery and characterization of Can-SINE motifs as well as describes composition, distribution, and effect on genome function. As the contribution of noncoding sequences to genomic diversity becomes more apparent, SINEs and other transposable elements will play an increasingly large role in mammalian comparative genomics. PMID:21846743

Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone

PubMed Central

Park, Daniel J.; Dudas, Gytis; Wohl, Shirlee; Goba, Augustine; Whitmer, Shannon L.M.; Andersen, Kristian G.; Sealfon, Rachel S.; Ladner, Jason T.; Kugelman, Jeffrey R.; Matranga, Christian B.; Winnicki, Sarah M.; Qu, James; Gire, Stephen K.; Gladden-Young, Adrianne; Jalloh, Simbirie; Nosamiefan, Dolo; Yozwiak, Nathan L.; Moses, Lina M.; Jiang, Pan-Pan; Lin, Aaron E.; Schaffner, Stephen F.; Bird, Brian; Towner, Jonathan; Mamoh, Mambu; Gbakie, Michael; Kanneh, Lansana; Kargbo, David; Massally, James L.B.; Kamara, Fatima K.; Konuwa, Edwin; Sellu, Josephine; Jalloh, Abdul A.; Mustapha, Ibrahim; Foday, Momoh; Yillah, Mohamed; Erickson, Bobbie R.; Sealy, Tara; Blau, Dianna; Paddock, Christopher; Brault, Aaron; Amman, Brian; Basile, Jane; Bearden, Scott; Belser, Jessica; Bergeron, Eric; Campbell, Shelley; Chakrabarti, Ayan; Dodd, Kimberly; Flint, Mike; Gibbons, Aridth; Goodman, Christin; Klena, John; McMullan, Laura; Morgan, Laura; Russell, Brandy; Salzer, Johanna; Sanchez, Angela; Wang, David; Jungreis, Irwin; Tomkins-Tinch, Christopher; Kislyuk, Andrey; Lin, Michael F.; Chapman, Sinead; MacInnis, Bronwyn; Matthews, Ashley; Bochicchio, James; Hensley, Lisa E.; Kuhn, Jens H.; Nusbaum, Chad; Schieffelin, John S.; Birren, Bruce W.; Forget, Marc; Nichol, Stuart T.; Palacios, Gustavo F.; Ndiaye, Daouda; Happi, Christian; Gevao, Sahr M.; Vandi, Mohamed A.; Kargbo, Brima; Holmes, Edward C.; Bedford, Trevor; Gnirke, Andreas; Ströher, Ute; Rambaut, Andrew; Garry, Robert F.; Sabeti, Pardis C.

2015-01-01

Summary The 2013–2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. PMID:26091036

Enhanced nitrogen removal with spent mushroom compost in a sequencing batch reactor.

PubMed

Yang, Yunlong; Tao, Xin; Lin, Ershu; Hu, Kaihui

2017-11-01

In order to remove nitrogen effectively from the wastewater with a low C/N ratio, the feasibility of using spent mushroom compost (SMC) hydrolysates as carbon sources for denitrification was investigated in a sequencing batch reactor (SBR). With SMCs supplement, the SBR performance was improved obviously within the 180days of operation. The total nitrogen removal was promoted from 46.9% to 81-89.4%, and no negative impact induced by different SMCs on the SBR system was observed. The abundance of functional genes including amoA, nirS/K, norB and nosZ in the active sludge was quantified by qPCR, and most of them elevated after SMC was fed. 16S rRNA gene high-throughput sequencing showed that the significant change in microbial community not only promoted pollutants removal but also benefited the stability of the reactor. Therefore, SMC could be an extremely promising carbon source used for nitrogen removal due to its cost-effective and efficient characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Global Statistical Response of the Outer Radiation Belt During Geomagnetic Storms

NASA Astrophysics Data System (ADS)

Murphy, K. R.; Watt, C. E. J.; Mann, I. R.; Jonathan Rae, I.; Sibeck, D. G.; Boyd, A. J.; Forsyth, C. F.; Turner, D. L.; Claudepierre, S. G.; Baker, D. N.; Spence, H. E.; Reeves, G. D.; Blake, J. B.; Fennell, J.

2018-05-01

Using the total radiation belt electron content calculated from Van Allen Probe phase space density, the time-dependent and global response of the outer radiation belt during storms is statistically studied. Using phase space density reduces the impacts of adiabatic changes in the main phase, allowing a separation of adiabatic and nonadiabatic effects and revealing a clear modality and repeatable sequence of events in storm time radiation belt electron dynamics. This sequence exhibits an important first adiabatic invariant (μ)-dependent behavior in the seed (150 MeV/G), relativistic (1,000 MeV/G), and ultrarelativistic (4,000 MeV/G) populations. The outer radiation belt statistically shows an initial phase dominated by loss followed by a second phase of rapid acceleration, while the seed population shows little loss and immediate enhancement. The time sequence of the transition to the acceleration is also strongly μ dependent and occurs at low μ first, appearing to be repeatable from storm to storm.

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

Daling, P.M.; Marler, J.E.; Vo, T.V.

This study evaluates the values (benefits) and impacts (costs) associated with potential resolutions to Generic Issue 143, ``Availability of HVAC and Chilled Water Systems.`` The study identifies vulnerabilities related to failures of HVAC, chilled water, and room cooling systems; develops estimates of room heatup rates and safety-related equipment vulnerabilities following losses of HVAC/room cooler systems; develops estimates of the core damage frequencies and public risks associated with failures of these systems; develops three proposed resolution strategies to this generic issue; and performs a value/impact analysis of the proposed resolutions. Existing probabilistic risk assessments for four representative plants, including one plantmore » from each vendor, form the basis for the core damage frequency and public risk calculations. Both internal and external events were considered. It was concluded that all three proposed resolution strategies exceed the $1,000/person-rem cost-effectiveness ratio. Additional evaluations were performed to develop ``generic`` insights on potential design-related and configuration-related vulnerabilities and potential high-frequency ({approximately}1E-04/RY) accident sequences that involve failures of HVAC/room cooling functions. It was concluded that, although high-frequency accident sequences may exist at some plants, these high-frequency sequences are plant-specific in nature or have been resolved through hardware and/or operational changes. The plant-specific Individual Plant Examinations are an effective vehicle for identification and resolution of these plant-specific anomalies and hardware configurations.« less

Modic Type 1 Changes: Detection Performance of Fat-Suppressed Fluid-Sensitive MRI Sequences.

PubMed

Finkenstaedt, Tim; Del Grande, Filippo; Bolog, Nicolae; Ulrich, Nils; Tok, Sina; Kolokythas, Orpheus; Steurer, Johann; Andreisek, Gustav; Winklhofer, Sebastian

2018-02-01

 To assess the performance of fat-suppressed fluid-sensitive MRI sequences compared to T1-weighted (T1w) / T2w sequences for the detection of Modic 1 end-plate changes on lumbar spine MRI.  Sagittal T1w, T2w, and fat-suppressed fluid-sensitive MRI images of 100 consecutive patients (consequently 500 vertebral segments; 52 female, mean age 74 ± 7.4 years; 48 male, mean age 71 ± 6.3 years) were retrospectively evaluated. We recorded the presence (yes/no) and extension (i. e., Likert-scale of height, volume, and end-plate extension) of Modic I changes in T1w/T2w sequences and compared the results to fat-suppressed fluid-sensitive sequences (McNemar/Wilcoxon-signed-rank test).  Fat-suppressed fluid-sensitive sequences revealed significantly more Modic I changes compared to T1w/T2w sequences (156 vs. 93 segments, respectively; p < 0.001). The extension of Modic I changes in fat-suppressed fluid-sensitive sequences was significantly larger compared to T1w/T2w sequences (height: 2.53 ± 0.82 vs. 2.27 ± 0.79, volume: 2.35 ± 0.76 vs. 2.1 ± 0.65, end-plate: 2.46 ± 0.76 vs. 2.19 ± 0.81), (p < 0.05). Modic I changes that were only visible in fat-suppressed fluid-sensitive sequences but not in T1w/T2w sequences were significantly smaller compared to Modic I changes that were also visible in T1w/T2w sequences (p < 0.05).  In conclusion, fat-suppressed fluid-sensitive MRI sequences revealed significantly more Modic I end-plate changes and demonstrated a greater extent compared to standard T1w/T2w imaging.   · When the Modic classification was defined in 1988, T2w sequences were heavily T2-weighted and thus virtually fat-suppressed.. · Nowadays, the bright fat signal in T2w images masks edema-like changes.. · The conventional definition of Modic I changes is not fully applicable anymore.. · Fat-suppressed fluid-sensitive MRI sequences revealed more/greater extent of Modic I changes.. · Finkenstaedt T, Del Grande F, Bolog N et al. Modic Type 1 Changes: Detection Performance of Fat-Suppressed Fluid-Sensitive MRI Sequences. Fortschr Röntgenstr 2018; 190: 152 - 160. © Georg Thieme Verlag KG Stuttgart · New York.

Investigation of the protein osteocalcin of Camelops hesternus: Sequence, structure and phylogenetic implications

NASA Astrophysics Data System (ADS)

Humpula, James F.; Ostrom, Peggy H.; Gandhi, Hasand; Strahler, John R.; Walker, Angela K.; Stafford, Thomas W.; Smith, James J.; Voorhies, Michael R.; George Corner, R.; Andrews, Phillip C.

2007-12-01

Ancient DNA sequences offer an extraordinary opportunity to unravel the evolutionary history of ancient organisms. Protein sequences offer another reservoir of genetic information that has recently become tractable through the application of mass spectrometric techniques. The extent to which ancient protein sequences resolve phylogenetic relationships, however, has not been explored. We determined the osteocalcin amino acid sequence from the bone of an extinct Camelid (21 ka, Camelops hesternus) excavated from Isleta Cave, New Mexico and three bones of extant camelids: bactrian camel ( Camelus bactrianus); dromedary camel ( Camelus dromedarius) and guanaco ( Llama guanacoe) for a diagenetic and phylogenetic assessment. There was no difference in sequence among the four taxa. Structural attributes observed in both modern and ancient osteocalcin include a post-translation modification, Hyp 9, deamidation of Gln 35 and Gln 39, and oxidation of Met 36. Carbamylation of the N-terminus in ancient osteocalcin may result in blockage and explain previous difficulties in sequencing ancient proteins via Edman degradation. A phylogenetic analysis using osteocalcin sequences of 25 vertebrate taxa was conducted to explore osteocalcin protein evolution and the utility of osteocalcin sequences for delineating phylogenetic relationships. The maximum likelihood tree closely reflected generally recognized taxonomic relationships. For example, maximum likelihood analysis recovered rodents, birds and, within hominins, the Homo-Pan-Gorilla trichotomy. Within Artiodactyla, character state analysis showed that a substitution of Pro 4 for His 4 defines the Capra-Ovis clade within Artiodactyla. Homoplasy in our analysis indicated that osteocalcin evolution is not a perfect indicator of species evolution. Limited sequence availability prevented assigning functional significance to sequence changes. Our preliminary analysis of osteocalcin evolution represents an initial step towards a complete character analysis aimed at determining the evolutionary history of this functionally significant protein. We emphasize that ancient protein sequencing and phylogenetic analyses using amino acid sequences must pay close attention to post-translational modifications, amino acid substitutions due to diagenetic alteration and the impacts of isobaric amino acids on mass shifts and sequence alignments.

Sequence alterations in RX in patients with microphthalmia, anophthalmia, and coloboma

PubMed Central

London, Nikolas J.S.; Kessler, Patricia; Williams, Bryan; Pauer, Gayle J.; Hagstrom, Stephanie A.

2009-01-01

Purpose Microphthalmia, anophthalmia, and coloboma are ocular malformations with a significant genetic component. Rx is a homeobox gene expressed early in the developing retina and is important in retinal cell fate specification as well as stem cell proliferation. We screened a group of 24 patients with microphthalmia, coloboma, and/or anophthalmia for RX mutations. Methods We used standard PCR and automated sequencing techniques to amplify and sequence each of the three RX exons. Patients’ charts were reviewed for clinical information. The pathologic impact of the identified sequence variant was analyzed by computational methods using PolyPhen and PMut algorithms. Results In addition to the polymorphisms we identified a single patient with coloboma having a heterozygous nucleotide change (g.197G>C) in the first exon that results in a missense mutation of arginine to threonine at amino acid position 66 (R66T). In silico analysis predicted R66T to be a deleterious mutation. Conclusions Sequence variations in RX are uncommon in patients with congenital ocular malformations, but may play a role in disease pathogenesis. We observed a missense mutation in RX in a patient with a small, typical chorioretinal coloboma, and postulate that the mutation is responsible for the patient’s phenotype. PMID:19158959

PERFORMANCE OF A HIGH-VELOCITY PROPELLANT GUN FOR CONTROLLED IMPACTS

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

Graham, R.A.; Ingram, G.E.; Ingram, W.D.

1961-11-01

Greatly enhanced extractions (synergism) for di, tri, and tetravalent metals were reported for the system M(sup n+/ HTTA/S/diluent where HTTA is thenolytrifluoracetone and S varies from the Highly polar tri-octyl phosphine oxide to the weakly basic triphenyl phosphate. The extracted speenes the partition coefficients of thc metal ion vary over several powers of ten, sometimes by a factor much greater than that obtained by the synergic effect itself. Thc citect. oa the extraction, of so-called inert diluents such as cyclohexane, hexane, carbon tetrachloride, benzene, and chloroform was studied under various conditions. In all cases the distribution ratio decreases as themore » diluent ns changed from cyclobexane in the above sequence, chloroform giving the lowest partition coefficient. This order is in the same sequence as the water solubility in the pure diluent and the diluent effect on metal extraction ns probably connected through the diluent water content with tbe permanent or induced diluent dipole. (auth) The performance of an extensively modified U. S. Army 40-mm gun for producing controlled impacts is described. Various projectile velocities in the range of 200 fps to 3200 fps were achieved by varying the amount of a fastburning propellant. The desired velocity may be varied in small increments. lmpact occurs while the projectile is being guided by the bore of the gun, thus facilitating precise alignment between the impacting surface of the projectile and the target specimen. Evacuating the barrel between the projectile and target eliminates undesired air cushioning to insure a step function impact. Projectile velocity measurements are made just prior to impact. (auth)« less

Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic

PubMed Central

Carlson, Jonathan M.; Chan, Benjamin; Chopera, Denis R.; Brumme, Chanson J.; Markle, Tristan J.; Martin, Eric; Shahid, Aniqa; Anmole, Gursev; Mwimanzi, Philip; Nassab, Pauline; Penney, Kali A.; Rahman, Manal A.; Milloy, M.-J.; Schechter, Martin T.; Markowitz, Martin; Carrington, Mary; Walker, Bruce D.; Wagner, Theresa; Buchbinder, Susan; Fuchs, Jonathan; Koblin, Beryl; Mayer, Kenneth H.; Harrigan, P. Richard; Brockman, Mark A.; Poon, Art F. Y.; Brumme, Zabrina L.

2014-01-01

HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979–1989) and 382 modern (2000–2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a “consensus-like” founder virus, the median “background” frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were “pre-adapted” to the average host HLA profile was only ∼2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins. PMID:24762668

Analysis of a severe head injury in World Cup alpine skiing.

PubMed

Yamazaki, Junya; Gilgien, Matthias; Kleiven, Svein; McIntosh, Andrew S; Nachbauer, Werner; Müller, Erich; Bere, Tone; Bahr, Roald; Krosshaug, Tron

2015-06-01

Traumatic brain injury (TBI) is the leading cause of death in alpine skiing. It has been found that helmet use can reduce the incidence of head injuries between 15% and 60%. However, knowledge on optimal helmet performance criteria in World Cup alpine skiing is currently limited owing to the lack of biomechanical data from real crash situations. This study aimed to estimate impact velocities in a severe TBI case in World Cup alpine skiing. Video sequences from a TBI case in World Cup alpine skiing were analyzed using a model-based image matching technique. Video sequences from four camera views were obtained in full high-definition (1080p) format. A three-dimensional model of the course was built based on accurate measurements of piste landmarks and matched to the background video footage using the animation software Poser 4. A trunk-neck-head model was used for tracking the skier's trajectory. Immediately before head impact, the downward velocity component was estimated to be 8 m·s⁻¹. After impact, the upward velocity was 3 m·s⁻¹, whereas the velocity parallel to the slope surface was reduced from 33 m·s⁻¹ to 22 m·s⁻¹. The frontal plane angular velocity of the head changed from 80 rad·s⁻¹ left tilt immediately before impact to 20 rad·s⁻¹ right tilt immediately after impact. A unique combination of high-definition video footage and accurate measurements of landmarks in the slope made possible a high-quality analysis of head impact velocity in a severe TBI case. The estimates can provide crucial information on how to prevent TBI through helmet performance criteria and design.

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues

PubMed Central

Zhang, Sharon; Ratliff, Eric P.; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W.; Achal, Madhulika; Mauntz, Ruth E.; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A.; Macias, Andrew M.; Daugherty, Daniel; Harris, Greg L.; Edwards, Robert A.; Finley, Kim D.

2018-01-01

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system. PMID:29642630

Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

PubMed

Zhang, Sharon; Ratliff, Eric P; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W; Achal, Madhulika; Mauntz, Ruth E; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A; Macias, Andrew M; Daugherty, Daniel; Harris, Greg L; Edwards, Robert A; Finley, Kim D

2018-04-10

The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

PubMed

Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

2016-01-01

The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

Application of a stochastic weather generator to assess climate change impacts in a semi-arid climate: The Upper Indus Basin

NASA Astrophysics Data System (ADS)

Forsythe, N.; Fowler, H. J.; Blenkinsop, S.; Burton, A.; Kilsby, C. G.; Archer, D. R.; Harpham, C.; Hashmi, M. Z.

2014-09-01

Assessing local climate change impacts requires downscaling from Global Climate Model simulations. Here, a stochastic rainfall model (RainSim) combined with a rainfall conditioned weather generator (CRU WG) have been successfully applied in a semi-arid mountain climate, for part of the Upper Indus Basin (UIB), for point stations at a daily time-step to explore climate change impacts. Validation of the simulated time-series against observations (1961-1990) demonstrated the models' skill in reproducing climatological means of core variables with monthly RMSE of <2.0 mm for precipitation and ⩽0.4 °C for mean temperature and daily temperature range. This level of performance is impressive given complexity of climate processes operating in this mountainous context at the boundary between monsoonal and mid-latitude (westerly) weather systems. Of equal importance the model captures well the observed interannual variability as quantified by the first and last decile of 30-year climatic periods. Differences between a control (1961-1990) and future (2071-2100) regional climate model (RCM) time-slice experiment were then used to provide change factors which could be applied within the rainfall and weather models to produce perturbed ‘future' weather time-series. These project year-round increases in precipitation (maximum seasonal mean change:+27%, annual mean change: +18%) with increased intensity in the wettest months (February, March, April) and year-round increases in mean temperature (annual mean +4.8 °C). Climatic constraints on the productivity of natural resource-dependent systems were also assessed using relevant indices from the European Climate Assessment (ECA) and indicate potential future risk to water resources and local agriculture. However, the uniformity of projected temperature increases is in stark contrast to recent seasonally asymmetrical trends in observations, so an alternative scenario of extrapolated trends was also explored. We conclude that interannual variability in climate will continue to have the dominant impact on water resources management whichever trajectory is followed. This demonstrates the need for sophisticated downscaling methods which can evaluate changes in variability and sequencing of events to explore climate change impacts in this region.

Tools for enhancing motivation in teaching climate change and impacts for students in forest- and environmental engineering

NASA Astrophysics Data System (ADS)

Gálos, Borbála

2017-04-01

Climate change is observed to have severe impacts on forest ecosystems. Ongoing research projects are dealing with the complex analysis of the causes of the health status decline and mortality of the vulnerable tree species. In the Carpathian Basin, recurrent long lasting drought periods and heatwaves of the last decades initiated the sequence of abiotic and biotic impacts in the beech and oak forests. Threatening extreme events are very likely to occur more frequent under changing climate conditions until the end of the 21st century. Therefore adaptation strategies and renewed regulations of the tree species selection are necessary. Learning material of forest education needs to be continuously updated with the new aspects and results of recent research and forest management planning. Therefore ideas and tools have been developed for teaching climate change impacts for students in forest- and environmental engineering. Using examples from world sport championships (e.g. losers and winners of climate change) these tools are applied to communicate the basic research questions in an easily understandable way as well as to motivate students and raise their awareness for the complex processes of forest - climate interactions. By the application of the developed examples for motivation, the key competences and learning outcomes can be the following: • students get an insight into the observed and projected tendencies of climate extremes; • they get an impression on the complexity of the climate change related damage chains; • they will be able to identify the climatic drivers of forest decline and mortality; • with the skill of critical thinking they will be able to evaluate the ecological role of forests that are already affected and that could be affected by the consequences of changing climate conditions; • they recognize the importance and urgency of the appropriate decisions in forestry and nature conservation. Keywords: climate change impacts, forest education, teaching tools for motivation The research is supported by the ÚNKP-16-4-3 New National Excellence Program of the Ministry of Human Capacities.

Effects of Organic Amendments on Microbiota Associated with the Culex nigripalpus Mosquito Vector of the Saint Louis Encephalitis and West Nile Viruses.

PubMed

Duguma, Dagne; Hall, Michael W; Smartt, Chelsea T; Neufeld, Josh D

2017-01-01

Pollution from nutrients in aquatic habitats has been linked to increases in disease vectors, including mosquitoes and other pestiferous insects. One possibility is that changes in mosquito microbiomes are impacted by nutrient enrichments and that these changes affect various traits, including larval development, susceptibility to larval control agents, and susceptibility of the adult mosquitoes to pathogens. We tested this hypothesis using field mesocosms supplemented with low- and high-organic-nutrient regimens and then sampled microbial communities associated with the naturally colonizing Culex nigripalpus mosquito vector. By high-throughput sequencing of 16S rRNA gene sequences, we found no significant differences in overall microbial communities associated with sampled mosquitoes, despite detecting discernible differences in environmental variables, including pH, dissolved oxygen, and nutrient amendments. Nevertheless, indicator species analysis revealed that members of the Clostridiales were significantly associated with mosquitoes that originated from high-nutrient enrichments. In contrast, members of the Burkholderiales were associated with mosquitoes from the low-nutrient enrichment. High bacterial variability associated with the life stages of the C. nigripalpus was largely unaffected by levels of nutrient enrichments that impacted larval microbial resources, including bacteria, ciliates, and flagellates in the larval environments. IMPORTANCE Mosquito microbiota provide important physiological and ecological attributes to mosquitoes, including an impact on their susceptibility to pathogens, fitness, and sensitivity to mosquito control agents. Culex nigripalpus mosquito populations transmit various pathogens, including the Saint Louis and West Nile viruses, and proliferate in nutrient-rich environments, such as in wastewater treatment wetlands. Our study examined whether increases in nutrients within larval mosquito developmental habitats impact microbial communities associated with C. nigripalpus mosquitoes. We characterized the effects of organic enrichments on microbiomes associated with C. nigripalpus mosquitoes and identified potential bacterial microbiota that will be further investigated for whether they alter mosquito life history traits and for their potential role in the development of microbial-based control strategies.

Investigating the impacts of DNA binding mode and sequence on thermodynamic quantities and water exchange values for two small molecule drugs.

PubMed

Kenney, Rachael M; Buxton, Katherine E; Glazier, Samantha

2016-09-01

Doxorubicin and nogalamycin are antitumor antibiotics that interact with DNA via intercalation and threading mechanisms, respectively. Because the importance of water, particularly its impact on entropy changes, has been established in other biological processes, we investigated the role of water in these two drug-DNA binding events. We used the osmotic stress method to calculate the number of water molecules exchanged (Δnwater), and isothermal titration calorimetry to measure Kbinding, ΔH, and ΔS for two synthetic DNAs, poly(dA·dT) and poly(dG·dC), and calf thymus DNA (CT DNA). For nogalamycin, Δnwater<0 for CT DNA and poly(dG·dC). For doxorubicin, Δnwater>0 for CT DNA and Δnwater<0 for poly(dG·dC). For poly(dA·dT), Δnwater~0 with both drugs. Net enthalpy changes were always negative, but net entropy changes depended on the drug. The effect of water exchange on the overall sign of entropy change appears to be smaller than other contributions. Copyright © 2016 Elsevier B.V. All rights reserved.

Cation exchange in a temporally fluctuating thin freshwater lens on top of saline groundwater

NASA Astrophysics Data System (ADS)

Eeman, S.; De Louw, P. G. B.; Van der Zee, S. E. A. T. M.

2017-01-01

In coastal-zone fields with a high groundwater level and sufficient rainfall, freshwater lenses are formed on top of saline or brackish groundwater. The fresh and the saline water meet at shallow depth, where a transition zone is found. This study investigates the mixing zone that is characterized by this salinity change, as well as by cation exchange processes, and which is forced by seepage and by rainfall which varies as a function of time. The processes are first investigated for a one-dimensional (1D) stream tube perpendicular to the interface concerning salt and major cation composition changes. The complex sequence of changes is explained with basic cation exchange theory. It is also possible to show that the sequence of changes is maintained when a two-dimensional field is considered where the upward saline seepage flows to drains. This illustrates that for cation exchange, the horizontal component (dominant for flow of water) has a small impact on the chemical changes in the vertical direction. The flow's horizontal orientation, parallel to the interface, leads to changes in concentration that are insignificant compared with those that are found perpendicular to the interface, and are accounted for in the 1D flow tube. Near the drains, differences with the 1D considerations are visible, especially in the longer term, exceeding 100 years. The simulations are compared with field data from the Netherlands which reveal similar patterns.

High-throughput interpretation of gene structure changes in human and nonhuman resequencing data, using ACE

PubMed Central

Majoros, William H.; Campbell, Michael S.; Holt, Carson; DeNardo, Erin K.; Ware, Doreen; Allen, Andrew S.; Yandell, Mark; Reddy, Timothy E.

2017-01-01

Abstract Motivation: The accurate interpretation of genetic variants is critical for characterizing genotype–phenotype associations. Because the effects of genetic variants can depend strongly on their local genomic context, accurate genome annotations are essential. Furthermore, as some variants have the potential to disrupt or alter gene structure, variant interpretation efforts stand to gain from the use of individualized annotations that account for differences in gene structure between individuals or strains. Results: We describe a suite of software tools for identifying possible functional changes in gene structure that may result from sequence variants. ACE (‘Assessing Changes to Exons’) converts phased genotype calls to a collection of explicit haplotype sequences, maps transcript annotations onto them, detects gene-structure changes and their possible repercussions, and identifies several classes of possible loss of function. Novel transcripts predicted by ACE are commonly supported by spliced RNA-seq reads, and can be used to improve read alignment and transcript quantification when an individual-specific genome sequence is available. Using publicly available RNA-seq data, we show that ACE predictions confirm earlier results regarding the quantitative effects of nonsense-mediated decay, and we show that predicted loss-of-function events are highly concordant with patterns of intolerance to mutations across the human population. ACE can be readily applied to diverse species including animals and plants, making it a broadly useful tool for use in eukaryotic population-based resequencing projects, particularly for assessing the joint impact of all variants at a locus. Availability and Implementation: ACE is written in open-source C ++ and Perl and is available from geneprediction.org/ACE Contact: myandell@genetics.utah.edu or tim.reddy@duke.edu Supplementary information: Supplementary information is available at Bioinformatics online. PMID:28011790

High-throughput interpretation of gene structure changes in human and nonhuman resequencing data, using ACE.

PubMed

Majoros, William H; Campbell, Michael S; Holt, Carson; DeNardo, Erin K; Ware, Doreen; Allen, Andrew S; Yandell, Mark; Reddy, Timothy E

2017-05-15

The accurate interpretation of genetic variants is critical for characterizing genotype-phenotype associations. Because the effects of genetic variants can depend strongly on their local genomic context, accurate genome annotations are essential. Furthermore, as some variants have the potential to disrupt or alter gene structure, variant interpretation efforts stand to gain from the use of individualized annotations that account for differences in gene structure between individuals or strains. We describe a suite of software tools for identifying possible functional changes in gene structure that may result from sequence variants. ACE ('Assessing Changes to Exons') converts phased genotype calls to a collection of explicit haplotype sequences, maps transcript annotations onto them, detects gene-structure changes and their possible repercussions, and identifies several classes of possible loss of function. Novel transcripts predicted by ACE are commonly supported by spliced RNA-seq reads, and can be used to improve read alignment and transcript quantification when an individual-specific genome sequence is available. Using publicly available RNA-seq data, we show that ACE predictions confirm earlier results regarding the quantitative effects of nonsense-mediated decay, and we show that predicted loss-of-function events are highly concordant with patterns of intolerance to mutations across the human population. ACE can be readily applied to diverse species including animals and plants, making it a broadly useful tool for use in eukaryotic population-based resequencing projects, particularly for assessing the joint impact of all variants at a locus. ACE is written in open-source C ++ and Perl and is available from geneprediction.org/ACE. myandell@genetics.utah.edu or tim.reddy@duke.edu. Supplementary information is available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Biodiversity of air-borne microorganisms at Halley Station, Antarctica.

PubMed

Pearce, David A; Hughes, K A; Lachlan-Cope, T; Harangozo, S A; Jones, A E

2010-03-01

A study of air-borne microbial biodiversity over an isolated scientific research station on an ice-shelf in continental Antarctica was undertaken to establish the potential source of microbial colonists. The study aimed to assess: (1) whether microorganisms were likely to have a local (research station) or distant (marine or terrestrial) origin, (2) the effect of changes in sea ice extent on microbial biodiversity and (3) the potential human impact on the environment. Air samples were taken above Halley Research Station during the austral summer and austral winter over a 2-week period. Overall, a low microbial biodiversity was detected, which included many sequence replicates. No significant patterns were detected in the aerial biodiversity between the austral summer and the austral winter. In common with other environmental studies, particularly in the polar regions, many of the sequences obtained were from as yet uncultivated organisms. Very few marine sequences were detected irrespective of the distance to open water, and around one-third of sequences detected were similar to those identified in human studies, though both of these might reflect prevailing wind conditions. The detected aerial microorganisms were markedly different from those obtained in earlier studies over the Antarctic Peninsula in the maritime Antarctic.

New in protein structure and function annotation: hotspots, single nucleotide polymorphisms and the 'Deep Web'.

PubMed

Bromberg, Yana; Yachdav, Guy; Ofran, Yanay; Schneider, Reinhard; Rost, Burkhard

2009-05-01

The rapidly increasing quantity of protein sequence data continues to widen the gap between available sequences and annotations. Comparative modeling suggests some aspects of the 3D structures of approximately half of all known proteins; homology- and network-based inferences annotate some aspect of function for a similar fraction of the proteome. For most known protein sequences, however, there is detailed knowledge about neither their function nor their structure. Comprehensive efforts towards the expert curation of sequence annotations have failed to meet the demand of the rapidly increasing number of available sequences. Only the automated prediction of protein function in the absence of homology can close the gap between available sequences and annotations in the foreseeable future. This review focuses on two novel methods for automated annotation, and briefly presents an outlook on how modern web software may revolutionize the field of protein sequence annotation. First, predictions of protein binding sites and functional hotspots, and the evolution of these into the most successful type of prediction of protein function from sequence will be discussed. Second, a new tool, comprehensive in silico mutagenesis, which contributes important novel predictions of function and at the same time prepares for the onset of the next sequencing revolution, will be described. While these two new sub-fields of protein prediction represent the breakthroughs that have been achieved methodologically, it will then be argued that a different development might further change the way biomedical researchers benefit from annotations: modern web software can connect the worldwide web in any browser with the 'Deep Web' (ie, proprietary data resources). The availability of this direct connection, and the resulting access to a wealth of data, may impact drug discovery and development more than any existing method that contributes to protein annotation.

Dissociable effects of practice variability on learning motor and timing skills.

PubMed

Caramiaux, Baptiste; Bevilacqua, Frédéric; Wanderley, Marcelo M; Palmer, Caroline

2018-01-01

Motor skill acquisition inherently depends on the way one practices the motor task. The amount of motor task variability during practice has been shown to foster transfer of the learned skill to other similar motor tasks. In addition, variability in a learning schedule, in which a task and its variations are interweaved during practice, has been shown to help the transfer of learning in motor skill acquisition. However, there is little evidence on how motor task variations and variability schedules during practice act on the acquisition of complex motor skills such as music performance, in which a performer learns both the right movements (motor skill) and the right time to perform them (timing skill). This study investigated the impact of rate (tempo) variability and the schedule of tempo change during practice on timing and motor skill acquisition. Complete novices, with no musical training, practiced a simple musical sequence on a piano keyboard at different rates. Each novice was assigned to one of four learning conditions designed to manipulate the amount of tempo variability across trials (large or small tempo set) and the schedule of tempo change (randomized or non-randomized order) during practice. At test, the novices performed the same musical sequence at a familiar tempo and at novel tempi (testing tempo transfer), as well as two novel (but related) sequences at a familiar tempo (testing spatial transfer). We found that practice conditions had little effect on learning and transfer performance of timing skill. Interestingly, practice conditions influenced motor skill learning (reduction of movement variability): lower temporal variability during practice facilitated transfer to new tempi and new sequences; non-randomized learning schedule improved transfer to new tempi and new sequences. Tempo (rate) and the sequence difficulty (spatial manipulation) affected performance variability in both timing and movement. These findings suggest that there is a dissociable effect of practice variability on learning complex skills that involve both motor and timing constraints.

Can genomics deliver climate-change ready crops?

PubMed

Varshney, Rajeev K; Singh, Vikas K; Kumar, Arvind; Powell, Wayne; Sorrells, Mark E

2018-04-20

Development of climate resilient crops with accelerating genetic gains in crops will require integration of different disciplines/technologies, to see the impact in the farmer's field. In this review, we summarize how we are utilizing our germplasm collections to identify superior alleles/haplotypes through NGS based sequencing approaches and how genomics-enabled technologies together with precise phenotyping are being used in crop breeding. Pre-breeding and genomics-assisted breeding approaches are contributing to the more efficient development of climate-resilient crops. It is anticipated that the integration of several disciplines/technologies will result in the delivery of climate change ready crops in less time. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The green impact: bacterioplankton response toward a phytoplankton spring bloom in the southern North Sea assessed by comparative metagenomic and metatranscriptomic approaches

PubMed Central

Wemheuer, Bernd; Wemheuer, Franziska; Hollensteiner, Jacqueline; Meyer, Frauke-Dorothee; Voget, Sonja; Daniel, Rolf

2015-01-01

Phytoplankton blooms exhibit a severe impact on bacterioplankton communities as they change nutrient availabilities and other environmental factors. In the current study, the response of a bacterioplankton community to a Phaeocystis globosa spring bloom was investigated in the southern North Sea. For this purpose, water samples were taken inside and reference samples outside of an algal spring bloom. Structural changes of the bacterioplankton community were assessed by amplicon-based analysis of 16S rRNA genes and transcripts generated from environmental DNA and RNA, respectively. Several marine groups responded to bloom presence. The abundance of the Roseobacter RCA cluster and the SAR92 clade significantly increased in bloom presence in the total and active fraction of the bacterial community. Functional changes were investigated by direct sequencing of environmental DNA and mRNA. The corresponding datasets comprised more than 500 million sequences across all samples. Metatranscriptomic data sets were mapped on representative genomes of abundant marine groups present in the samples and on assembled metagenomic and metatranscriptomic datasets. Differences in gene expression profiles between non-bloom and bloom samples were recorded. The genome-wide gene expression level of Planktomarina temperata, an abundant member of the Roseobacter RCA cluster, was higher inside the bloom. Genes that were differently expressed included transposases, which showed increased expression levels inside the bloom. This might contribute to the adaptation of this organism toward environmental stresses through genome reorganization. In addition, several genes affiliated to the SAR92 clade were significantly upregulated inside the bloom including genes encoding for proteins involved in isoleucine and leucine incorporation. Obtained results provide novel insights into compositional and functional variations of marine bacterioplankton communities as response to a phytoplankton bloom. PMID:26322028

Synthetic drought event sets: thousands of meteorological drought events for risk-based management under present and future conditions

NASA Astrophysics Data System (ADS)

Guillod, Benoit P.; Massey, Neil; Otto, Friederike E. L.; Allen, Myles R.; Jones, Richard; Hall, Jim W.

2016-04-01

Droughts and related water scarcity can have large impacts on societies and consist of interactions between a number of natural and human factors. Meteorological conditions are usually the first natural trigger of droughts, and climate change is expected to impact these and thereby the frequency and intensity of the events. However, extreme events such as droughts are, by definition, rare, and accurately quantifying the risk related to such events is therefore difficult. The MaRIUS project (Managing the Risks, Impacts and Uncertainties of drought and water Scarcity) aims at quantifying the risks associated with droughts in the UK under present and future conditions. To do so, a large number of drought events, from climate model simulations downscaled at 25km over Europe, are being fed into hydrological models of various complexity and used for the estimation of drought risk associated with human and natural systems, including impacts on the economy, industry, agriculture, terrestrial and aquatic ecosystems, and socio-cultural aspects. Here, we present the hydro-meteorological drought event set that has been produced by weather@home [1] for MaRIUS. Using idle processor time on volunteers' computers around the world, we have run a very large number (10'000s) of Global Climate Model (GCM) simulations, downscaled at 25km over Europe by a nested Regional Climate Model (RCM). Simulations include the past 100 years as well as two future horizons (2030s and 2080s), and provide a large number of sequences of spatio-temporally consistent weather, which are consistent with the boundary forcing such as the ocean, greenhouse gases and solar forcing. The drought event set for use in impact studies is constructed by extracting sequences of dry conditions from these model runs, leading to several thousand drought events. In addition to describing methodological and validation aspects of the synthetic drought event sets, we provide insights into drought risk in the UK, its meteorological drivers, and how it can be expected to change in the future. Finally, we assess the applicability of this methodology to other regions. [1] Massey, N. et al., 2014, Q. J. R. Meteorol. Soc.

The impact of visual sequencing of graphic symbols on the sentence construction output of children who have acquired language.

PubMed

Alant, Erna; du Plooy, Amelia; Dada, Shakila

2007-01-01

Although the sequence of graphic or pictorial symbols displayed on a communication board can have an impact on the language output of children, very little research has been conducted to describe this. Research in this area is particularly relevant for prioritising the importance of specific visual and graphic features in providing more effective and user-friendly access to communication boards. This study is concerned with understanding the impact ofspecific sequences of graphic symbol input on the graphic and spoken output of children who have acquired language. Forty participants were divided into two comparable groups. Each group was exposed to graphic symbol input with a certain word order sequence. The structure of input was either in typical English word order sequence Subject- Verb-Object (SVO) or in the word order sequence of Subject-Object-Verb (SOV). Both input groups had to answer six questions by using graphic output as well as speech. The findings indicated that there are significant differences in the PCS graphic output patterns of children who are exposed to graphic input in the SOV and SVO sequences. Furthermore, the output produced in the graphic mode differed considerably to the output produced in the spoken mode. Clinical implications of these findings are discussed

Impact of future climate change on wheat production in relation to plant-available water capacity in a semiaridenvironment

NASA Astrophysics Data System (ADS)

Yang, Yanmin; Liu, De Li; Anwar, Muhuddin Rajin; Zuo, Heping; Yang, Yonghui

2014-02-01

Conceptions encompassing climate change are irreversible rise of atmospheric carbon dioxide (CO2) concentration, increased temperature, and changes in rainfall both in spatial- and temporal-scales worldwide. This will have a major impact on wheat production, particularly if crops are frequently exposed to a sequence, frequency, and intensity of specific weather events like high temperature during growth period. However, the process of wheat response to climate change is complex and compounded by interactions among atmospheric CO2 concentration, climate variables, soil, nutrition, and agronomic management. In this study, we use the Agricultural Production Systems sIMulator (APSIM)-wheat model, driven by statistically downscaled climate projections of 18 global circulation models (GCMs) under the 2007 Intergovernmental Panel on Climate Change (IPCC) Special Report on Emission Scenarios (SRES) A2 CO2 emission scenario to examine impact on future wheat yields across key wheat growing regions considering different soil types in New South Wales (NSW) of Australia. The response of wheat yield, yield components, and phenology vary across sites and soil types, but yield is closely related to plant available water capacity (PAWC). Results show a decreasing yield trend during the period of 2021-2040 compared to the baseline period of 1961-1990. Across different wheat-growing regions in NSW, grain yield difference in the future period (2021-2040) over the baseline (1961-1990) varies from +3.4 to -14.7 %, and in most sites, grain number is decreased, while grain size is increased in future climate. Reduction of wheat yield is mainly due to shorter growth duration, where average flowering and maturing time are advanced by an average of 11 and 12 days, respectively. In general, larger negative impacts of climate change are exhibited in those sites with higher PAWC. Current wheat cultivars with shorter growing season properties are viable in the future climate, but breading for early sowing wheat varieties with longer growing duration will be a desirable adaptation strategy for mitigating the impact of changing climate on wheat yield.

Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly.

PubMed

Schneider, Valerie A; Graves-Lindsay, Tina; Howe, Kerstin; Bouk, Nathan; Chen, Hsiu-Chuan; Kitts, Paul A; Murphy, Terence D; Pruitt, Kim D; Thibaud-Nissen, Françoise; Albracht, Derek; Fulton, Robert S; Kremitzki, Milinn; Magrini, Vincent; Markovic, Chris; McGrath, Sean; Steinberg, Karyn Meltz; Auger, Kate; Chow, William; Collins, Joanna; Harden, Glenn; Hubbard, Timothy; Pelan, Sarah; Simpson, Jared T; Threadgold, Glen; Torrance, James; Wood, Jonathan M; Clarke, Laura; Koren, Sergey; Boitano, Matthew; Peluso, Paul; Li, Heng; Chin, Chen-Shan; Phillippy, Adam M; Durbin, Richard; Wilson, Richard K; Flicek, Paul; Eichler, Evan E; Church, Deanna M

2017-05-01

The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions, and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that although the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health. © 2017 Schneider et al.; Published by Cold Spring Harbor Laboratory Press.

Adaptive evolution in the Arabidopsis MADS-box gene family inferred from its complete resolved phylogeny

PubMed Central

Martínez-Castilla, León Patricio; Alvarez-Buylla, Elena R.

2003-01-01

Gene duplication is a substrate of evolution. However, the relative importance of positive selection versus relaxation of constraints in the functional divergence of gene copies is still under debate. Plant MADS-box genes encode transcriptional regulators key in various aspects of development and have undergone extensive duplications to form a large family. We recovered 104 MADS sequences from the Arabidopsis genome. Bayesian phylogenetic trees recover type II lineage as a monophyletic group and resolve a branching sequence of monophyletic groups within this lineage. The type I lineage is comprised of several divergent groups. However, contrasting gene structure and patterns of chromosomal distribution between type I and II sequences suggest that they had different evolutionary histories and support the placement of the root of the gene family between these two groups. Site-specific and site-branch analyses of positive Darwinian selection (PDS) suggest that different selection regimes could have affected the evolution of these lineages. We found evidence for PDS along the branch leading to flowering time genes that have a direct impact on plant fitness. Sites with high probabilities of having been under PDS were found in the MADS and K domains, suggesting that these played important roles in the acquisition of novel functions during MADS-box diversification. Detected sites are targets for further experimental analyses. We argue that adaptive changes in MADS-domain protein sequences have been important for their functional divergence, suggesting that changes within coding regions of transcriptional regulators have influenced phenotypic evolution of plants. PMID:14597714

Structure of Infaunal Communities on the Beaufort Sea Shelf and Slope: Insights from Morphological and Environmental DNA Sequencing Approaches

NASA Astrophysics Data System (ADS)

Hardy, S. M.; Bik, H.; Walker, A.; Sharma, J.; Blanchard, A.

2016-02-01

Rapid change is occurring in the Arctic concurrently with increased human activity, yet our knowledge of the structure and function of high-Arctic sediment communities is still rudimentary. The Beaufort Sea is particularly poorly sampled, and largely unexplored at slope depths, providing little information with which to assess the impacts of petroleum exploration activities now beginning in this area. We are investigating diversity and community structure of meio- and macrobenthic infauna on the continental shelf and slope of the Beaufort Sea across a range of depths (50 to 1000 m) using traditional taxonomic and environmental DNA sequencing approaches, and comparing results to additional sites in the adjacent NE Chukchi Sea petroleum lease-sale area. The Beaufort slope is topographically complex and characterized by an east-west gradient in benthic habitat characteristics, with heavy input of terrestrial organic matter particularly in the region of the Mackenzie River delta. Warmer, saltier subsurface Atlantic water masses impact benthic communities at mid-slope depths, likely influencing turnover in community structure observed with depth. Food resources are variable across the region, with very high sediment chlorophyll concentrations at 350 m depth in some areas. Differences in nematode assemblages were detected across the Beaufort Sea shelf/slope, across depths within the Beaufort Sea, and between the Beaufort and adjacent NE Chukchi Sea. These differences were apparent in both morphological and environmental sequencing data. Macrofaunal communities showed variable community structure among transects, with high abundance and high dominance in polychaete assemblages coincident with the chlorophyll maximum. Sequencing data also revealed an abundance of protists in sediments which have been mostly ignored in studies of ecosystem dynamics in this region, and may represent an important component of the food web.

Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

PubMed

Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

2017-02-01

There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut-brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198-206; http://dx.doi.org/10.1289/EHP202.

Deep Impact Sequence Planning Using Multi-Mission Adaptable Planning Tools With Integrated Spacecraft Models

NASA Technical Reports Server (NTRS)

Wissler, Steven S.; Maldague, Pierre; Rocca, Jennifer; Seybold, Calina

2006-01-01

The Deep Impact mission was ambitious and challenging. JPL's well proven, easily adaptable multi-mission sequence planning tools combined with integrated spacecraft subsystem models enabled a small operations team to develop, validate, and execute extremely complex sequence-based activities within very short development times. This paper focuses on the core planning tool used in the mission, APGEN. It shows how the multi-mission design and adaptability of APGEN made it possible to model spacecraft subsystems as well as ground assets throughout the lifecycle of the Deep Impact project, starting with models of initial, high-level mission objectives, and culminating in detailed predictions of spacecraft behavior during mission-critical activities.

Response and recovery lessons from the 2010-2011 earthquake sequence in Canterbury, New Zealand

USGS Publications Warehouse

Pierepiekarz, Mark; Johnston, David; Berryman, Kelvin; Hare, John; Gomberg, Joan S.; Williams, Robert A.; Weaver, Craig S.

2014-01-01

The impacts and opportunities that result when low-probability moderate earthquakes strike an urban area similar to many throughout the US were vividly conveyed in a one-day workshop in which social and Earth scientists, public officials, engineers, and an emergency manager shared their experiences of the earthquake sequence that struck the city of Christchurch and surrounding Canterbury region of New Zealand in 2010-2011. Without question, the earthquake sequence has had unprecedented impacts in all spheres on New Zealand society, locally to nationally--10% of the country's population was directly impacted and losses total 8-10% of their GDP. The following paragraphs present a few lessons from Christchurch.

Stage Separation Failure: Model Based Diagnostics and Prognostics

NASA Technical Reports Server (NTRS)

Luchinsky, Dmitry; Hafiychuk, Vasyl; Kulikov, Igor; Smelyanskiy, Vadim; Patterson-Hine, Ann; Hanson, John; Hill, Ashley

2010-01-01

Safety of the next-generation space flight vehicles requires development of an in-flight Failure Detection and Prognostic (FD&P) system. Development of such system is challenging task that involves analysis of many hard hitting engineering problems across the board. In this paper we report progress in the development of FD&P for the re-contact fault between upper stage nozzle and the inter-stage caused by the first stage and upper stage separation failure. A high-fidelity models and analytical estimations are applied to analyze the following sequence of events: (i) structural dynamics of the nozzle extension during the impact; (ii) structural stability of the deformed nozzle in the presence of the pressure and temperature loads induced by the hot gas flow during engine start up; and (iii) the fault induced thrust changes in the steady burning regime. The diagnostic is based on the measurements of the impact torque. The prognostic is based on the analysis of the correlation between the actuator signal and fault-induced changes in the nozzle structural stability and thrust.

Identifying and mitigating batch effects in whole genome sequencing data.

PubMed

Tom, Jennifer A; Reeder, Jens; Forrest, William F; Graham, Robert R; Hunkapiller, Julie; Behrens, Timothy W; Bhangale, Tushar R

2017-07-24

Large sample sets of whole genome sequencing with deep coverage are being generated, however assembling datasets from different sources inevitably introduces batch effects. These batch effects are not well understood and can be due to changes in the sequencing protocol or bioinformatics tools used to process the data. No systematic algorithms or heuristics exist to detect and filter batch effects or remove associations impacted by batch effects in whole genome sequencing data. We describe key quality metrics, provide a freely available software package to compute them, and demonstrate that identification of batch effects is aided by principal components analysis of these metrics. To mitigate batch effects, we developed new site-specific filters that identified and removed variants that falsely associated with the phenotype due to batch effect. These include filtering based on: a haplotype based genotype correction, a differential genotype quality test, and removing sites with missing genotype rate greater than 30% after setting genotypes with quality scores less than 20 to missing. This method removed 96.1% of unconfirmed genome-wide significant SNP associations and 97.6% of unconfirmed genome-wide significant indel associations. We performed analyses to demonstrate that: 1) These filters impacted variants known to be disease associated as 2 out of 16 confirmed associations in an AMD candidate SNP analysis were filtered, representing a reduction in power of 12.5%, 2) In the absence of batch effects, these filters removed only a small proportion of variants across the genome (type I error rate of 3%), and 3) in an independent dataset, the method removed 90.2% of unconfirmed genome-wide SNP associations and 89.8% of unconfirmed genome-wide indel associations. Researchers currently do not have effective tools to identify and mitigate batch effects in whole genome sequencing data. We developed and validated methods and filters to address this deficiency.

Impact of Soil Texture on Soil Ciliate Communities

NASA Astrophysics Data System (ADS)

Chau, J. F.; Brown, S.; Habtom, E.; Brinson, F.; Epps, M.; Scott, R.

2014-12-01

Soil water content and connectivity strongly influence microbial activities in soil, controlling access to nutrients and electron acceptors, and mediating interactions between microbes within and between trophic levels. These interactions occur at or below the pore scale, and are influenced by soil texture and structure, which determine the microscale architecture of soil pores. Soil protozoa are relatively understudied, especially given the strong control they exert on bacterial communities through predation. Here, ciliate communities in soils of contrasting textures were investigated. Two ciliate-specific primer sets targeting the 18S rRNA gene were used to amplify DNA extracted from eight soil samples collected from Sumter National Forest in western South Carolina. Primer sets 121F-384F-1147R (semi-nested) and 315F-959R were used to amplify soil ciliate DNA via polymerase chain reaction (PCR), and the resulting PCR products were analyzed by gel electrophoresis to obtain quantity and band size. Approximately two hundred ciliate 18S rRNA sequences were obtained were obtained from each of two contrasting soils. Sequences were aligned against the NCBI GenBank database for identification, and the taxonomic classification of best-matched sequences was determined. The ultimate goal of the work is to quantify changes in the ciliate community under short-timescale changes in hydrologic conditions for varying soil textures, elucidating dynamic responses to desiccation stress in major soil ciliate taxa.

Processing of musical syntax tonic versus subdominant: an event-related potential study.

PubMed

Poulin-Charronnat, Bénédicte; Bigand, Emmanuel; Koelsch, Stefan

2006-09-01

The present study investigates the effect of a change in syntactic-like musical function on event-related brain potentials (ERPs). Eight-chord piano sequences were presented to musically expert and novice listeners. Instructed to watch a movie and to ignore the musical sequences, the participants had to react when a chord was played with a different instrument than the piano. Participants were not informed that the relevant manipulation was the musical function of the last chord (target) of the sequences. The target chord acted either as a syntactically stable tonic chord (i.e., a C major chord in the key of C major) or as a less syntactically stable subdominant chord (i.e., a C major chord in the key of G major). The critical aspect of the results related to the impact such a manipulation had on the ERPs. An N5-like frontal negative component was found to be larger for subdominant than for tonic chords and attained significance only in musically expert listeners. These findings suggest that the subdominant chord is more difficult to integrate with the previous context than the tonic chord (as indexing by the observed N5) and that the processing of a small change in musical function occurs in an automatic way in musically expert listeners. The present results are discussed in relation to previous studies investigating harmonic violations with ERPs.

Impacts on Water Management and Crop Production of Regional Cropping System Adaptation to Climate Change

NASA Astrophysics Data System (ADS)

Zhong, H.; Sun, L.; Tian, Z.; Liang, Z.; Fischer, G.

2014-12-01

China is one of the most populous and fast developing countries, also faces a great pressure on grain production and food security. Multi-cropping system is widely applied in China to fully utilize agro-climatic resources and increase land productivity. As the heat resource keep improving under climate warming, multi-cropping system will also shifting northward, and benefit crop production. But water shortage in North China Plain will constrain the adoption of new multi-cropping system. Effectiveness of multi-cropping system adaptation to climate change will greatly depend on future hydrological change and agriculture water management. So it is necessary to quantitatively express the water demand of different multi-cropping systems under climate change. In this paper, we proposed an integrated climate-cropping system-crops adaptation framework, and specifically focused on: 1) precipitation and hydrological change under future climate change in China; 2) the best multi-cropping system and correspondent crop rotation sequence, and water demand under future agro-climatic resources; 3) attainable crop production with water constraint; and 4) future water management. In order to obtain climate projection and precipitation distribution, global climate change scenario from HADCAM3 is downscaled with regional climate model (PRECIS), historical climate data (1960-1990) was interpolated from more than 700 meteorological observation stations. The regional Agro-ecological Zone (AEZ) model is applied to simulate the best multi-cropping system and crop rotation sequence under projected climate change scenario. Finally, we use the site process-based DSSAT model to estimate attainable crop production and the water deficiency. Our findings indicate that annual land productivity may increase and China can gain benefit from climate change if multi-cropping system would be adopted. This study provides a macro-scale view of agriculture adaptation, and gives suggestions to national agriculture adaptation strategy decisions.

Genomic information as a behavioral health intervention: can it work?

PubMed Central

Bloss, Cinnamon S; Madlensky, Lisa; Schork, Nicholas J; Topol, Eric J

2011-01-01

Individuals can now obtain their personal genomic information via direct-to-consumer genetic testing, but what, if any, impact will this have on their lifestyle and health? A recent longitudinal cohort study of individuals who underwent consumer genome scanning found minimal impacts of testing on risk-reducing lifestyle behaviors, such as diet and exercise. These results raise an important question: is personal genomic information likely to beneficially impact public health through motivation of lifestyle behavioral change? In this article, we review the literature on lifestyle behavioral change in response to genetic testing for common disease susceptibility variants. We find that only a few studies have been carried out, and that those that have been done have yielded little evidence to suggest that the mere provision of genetic information alone results in widespread changes in lifestyle health behaviors. We suggest that further study of this issue is needed, in particular studies that examine response to multiplex testing for multiple genetic markers and conditions. This will be critical as we anticipate the wide availability of whole-genome sequencing and more comprehensive phenotyping of individuals. We also note that while simple communication of genomic information and disease susceptibility may be sufficient to catalyze lifestyle changes in some highly motivated groups of individuals, for others, additional strategies may be required to prompt changes, including more sophisticated means of risk communication (e.g., in the context of social norm feedback) either alone or in combination with other promising interventions (e.g., real-time wireless health monitoring devices). PMID:22199991

Permafrost Meta-Omics and Climate Change

NASA Astrophysics Data System (ADS)

Mackelprang, Rachel; Saleska, Scott R.; Jacobsen, Carsten Suhr; Jansson, Janet K.; Taş, Neslihan

2016-06-01

Permanently frozen soil, or permafrost, covers a large portion of the Earth's terrestrial surface and represents a unique environment for cold-adapted microorganisms. As permafrost thaws, previously protected organic matter becomes available for microbial degradation. Microbes that decompose soil carbon produce carbon dioxide and other greenhouse gases, contributing substantially to climate change. Next-generation sequencing and other -omics technologies offer opportunities to discover the mechanisms by which microbial communities regulate the loss of carbon and the emission of greenhouse gases from thawing permafrost regions. Analysis of nucleic acids and proteins taken directly from permafrost-associated soils has provided new insights into microbial communities and their functions in Arctic environments that are increasingly impacted by climate change. In this article we review current information from various molecular -omics studies on permafrost microbial ecology and explore the relevance of these insights to our current understanding of the dynamics of permafrost loss due to climate change.

A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans

PubMed Central

Koch, Evan; Novembre, John

2017-01-01

When mutations have small effects on fitness, population size plays an important role in determining the amount and nature of deleterious genetic variation. The extent to which recent population size changes have impacted deleterious variation in humans has been a question of considerable interest and debate. An emerging consensus is that the Out-of-Africa bottleneck and subsequent growth events have been too short to cause meaningful differences in genetic load between populations; though changes in the number and average frequencies of deleterious variants have taken place. To provide more support for this view and to offer additional insight into the divergent evolution of deleterious variation across populations, we numerically solve time-inhomogeneous diffusion equations and study the temporal dynamics of the frequency spectra in models of population size change for modern humans. We observe how the response to demographic change differs by the strength of selection, and we then assess whether similar patterns are observed in exome sequence data from 33,370 and 5203 individuals of non-Finnish European and West African ancestry, respectively. Our theoretical results highlight how even simple summaries of the frequency spectrum can have complex responses to demographic change. These results support the finding that some apparent discrepancies between previous results have been driven by the behaviors of the precise summaries of deleterious variation. Further, our empirical results make clear the difficulty of inferring slight differences in frequency spectra using recent next-generation sequence data. PMID:28159863

Advances in sarcoma diagnostics and treatment

PubMed Central

Dancsok, Amanda R; Asleh-Aburaya, Karama; Nielsen, Torsten O

2017-01-01

The heterogeneity of sarcomas with regard to molecular genesis, histology, clinical characteristics, and response to treatment makes management of these rare yet diverse neoplasms particularly challenging. This review encompasses recent developments in sarcoma diagnostics and treatment, including cytotoxic, targeted, epigenetic, and immune therapy agents. In the past year, groups internationally explored the impact of adding mandatory molecular testing to histological diagnosis, reporting some changes in diagnosis and/or management; however, the impact on outcomes could not be adequately assessed. Transcriptome sequencing techniques have brought forward new diagnostic tools for identifying fusions and/or characterizing unclassified entities. Next-generation sequencing and advanced molecular techniques were also applied to identify potential targets for directed and epigenetic therapy, where preclinical studies reported results for agents active within the receptor tyrosine kinase, mTOR, Notch, Wnt, Hedgehog, Hsp90, and MDM2 signaling networks. At the level of clinical practice, modest developments were seen for some sarcoma subtypes in conventional chemotherapy and in therapies targeting the pathways activated by various receptor tyrosine kinases. In the burgeoning field of immune therapy, sarcoma work is in its infancy; however, elaborate protocols for immune stimulation are being explored, and checkpoint blockade agents advance from preclinical models to clinical studies. PMID:27732970

Evidence from central Mexico supporting the Younger Dryas extraterrestrial impact hypothesis

USGS Publications Warehouse

Israde-Alcántara, Isabel; Bischoff, James L.; Domínguez-Vázquez, Gabriela; Li, Hong-Chun; DeCarli, Paul S.; Bunch, Ted E.; Wittke, James H.; Weaver, James C.; Firestone, Richard B.; West, Allen; Kennett, James P.; Mercer, Chris; Xie, Sujing; Richman, Eric K.; Kinzie, Charles R.; Wolbach, Wendy S.

2012-01-01

We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon-rich, lacustrine layer, containing nanodiamonds, microspherules, and other unusual materials that date to the early Younger Dryas and are interpreted to result from an extraterrestrial impact. These proxies were found in a 27-m-long core as part of an interdisciplinary effort to extract a paleoclimate record back through the previous interglacial. Our attention focused early on an anomalous, 10-cm-thick, carbon-rich layer at a depth of 2.8 m that dates to 12.9 ka and coincides with a suite of anomalous coeval environmental and biotic changes independently recognized in other regional lake sequences. Collectively, these changes have produced the most distinctive boundary layer in the late Quaternary record. This layer contains a diverse, abundant assemblage of impact-related markers, including nanodiamonds, carbon spherules, and magnetic spherules with rapid melting/quenching textures, all reaching synchronous peaks immediately beneath a layer containing the largest peak of charcoal in the core. Analyses by multiple methods demonstrate the presence of three allotropes of nanodiamond: n-diamond, i-carbon, and hexagonal nanodiamond (lonsdaleite), in order of estimated relative abundance. This nanodiamond-rich layer is consistent with the Younger Dryas boundary layer found at numerous sites across North America, Greenland, and Western Europe. We have examined multiple hypotheses to account for these observations and find the evidence cannot be explained by any known terrestrial mechanism. It is, however, consistent with the Younger Dryas boundary impact hypothesis postulating a major extraterrestrial impact involving multiple airburst(s) and and/or ground impact(s) at 12.9 ka.

Evidence from Central Mexico supporting the Younger Dryas extraterrestrial impact hypothesis

USGS Publications Warehouse

Israde-Alcántaraa, Isabel; Bischoff, James L.; Domínguez-Vázquez, Gabriela; Li, Hong-Chun; DeCarli, Paul S.; Bunch, Ted E.; Wittke, James H.; Weaver, James C.; Firestone, Richard B.; West, Allen; Kennett, James P.; Mercer, Chris; Xie, Sujing; Richman, Eric K.; Kinzie, Charles R.; Wolbach, Wendy S.; Stanley, Steven M.

2012-01-01

We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon-rich, lacustrine layer, containing nanodiamonds, microspherules, and other unusual materials that date to the early Younger Dryas and are interpreted to result from an extraterrestrial impact. These proxies were found in a 27-m-long core as part of an interdisciplinary effort to extract a paleoclimate record back through the previous interglacial. Our attention focused early on an anomalous, 10-cm-thick, carbon-rich layer at a depth of 2.8 m that dates to 12.9 ka and coincides with a suite of anomalous coeval environmental and biotic changes independently recognized in other regional lake sequences. Collectively, these changes have produced the most distinctive boundary layer in the late Quaternary record. This layer contains a diverse, abundant assemblage of impact-related markers, including nanodiamonds, carbon spherules, and magnetic spherules with rapid melting/quenching textures, all reaching synchronous peaks immediately beneath a layer containing the largest peak of charcoal in the core. Analyses by multiple methods demonstrate the presence of three allotropes of nanodiamond: n-diamond, i-carbon, and hexagonal nanodiamond (lonsdaleite), in order of estimated relative abundance. This nanodiamond-rich layer is consistent with the Younger Dryas boundary layer found at numerous sites across North America, Greenland, and Western Europe. We have examined multiple hypotheses to account for these observations and find the evidence cannot be explained by any known terrestrial mechanism. It is, however, consistent with the Younger Dryas boundary impact hypothesis postulating a major extraterrestrial impact involving multiple airburst(s) and and/or ground impact(s) at 12.9 ka.

Atmospheric conditions and weather regimes associated with extreme winter dry spells over the Mediterranean basin

NASA Astrophysics Data System (ADS)

Raymond, Florian; Ullmann, Albin; Camberlin, Pierre; Oueslati, Boutheina; Drobinski, Philippe

2018-06-01

Very long dry spell events occurring during winter are natural hazards to which the Mediterranean region is extremely vulnerable, because they can lead numerous impacts for environment and society. Four dry spell patterns have been identified in a previous work. Identifying the main associated atmospheric conditions controlling the dry spell patterns is key to better understand their dynamics and their evolution in a changing climate. Except for the Levant region, the dry spells are generally associated with anticyclonic blocking conditions located about 1000 km to the Northwest of the affected area. These anticyclonic conditions are favourable to dry spell occurrence as they are associated with subsidence of cold and dry air coming from boreal latitudes which bring low amount of water vapour and non saturated air masses, leading to clear sky and absence of precipitation. These extreme dry spells are also partly related to the classical four Euro-Atlantic weather regimes are: the two phases of the North Atlantic Oscillation, the Scandinavian "blocking" or "East-Atlantic", and the "Atlantic ridge". Only the The "East-Atlantic", "Atlantic ridge" and the positive phase of the North Atlantic Oscillation are frequently associated with extremes dry spells over the Mediterranean basin but they do not impact the four dry spell patterns equally. Finally long sequences of those weather regimes are more favourable to extreme dry spells than short sequences. These long sequences are associated with the favourable prolonged and reinforced anticyclonic conditions

Intrinsic diffusion sensitivity of the balanced steady-state free precession (bSSFP) imaging sequence.

PubMed

Bär, Sébastien; Weigel, Matthias; von Elverfeldt, Dominik; Hennig, Jürgen; Leupold, Jochen

2015-11-01

The purpose of this work was to analyze the intrinsic diffusion sensitivity of the balanced steady-state free precession (bSSFP) imaging sequence, meaning the observation of diffusion-induced attenuation of the bSSFP steady-state signal due to the imaging gradients. Although these diffusion effects are usually neglected for most clinical gradient systems, such strong gradient systems are employed for high resolution imaging of small animals or MR Microscopy. The impact on the bSSFP signal of the imaging gradients characterized by their b-values was analyzed with simulations and experiments at a 7T animal scanner using a gradient system with maximum gradient amplitude of approx. 700 mT/m. It was found that the readout gradients have a stronger impact on the attenuation than the phase encoding gradients. Also, as the PE gradients are varying with each repetition interval, the diffusion effects induce strong modulations of the bSSFP signal over the sequence repetition cycles depending on the phase encoding gradient table. It is shown that a signal gain can be obtained through a change of flip angle as a new optimal flip angle maximizing the signal can be defined. The dependency of the diffusion effects on relaxation times and b-values were explored with simulations. The attenuation increases with T2. In conclusion, diffusion attenuation of the bSSFP signal becomes significant for high resolution imaging voxel size (roughly < 100 μm) of long T2 substances. Copyright © 2015 John Wiley & Sons, Ltd.

Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing.

PubMed

Kauffman, Tia L; Wilfond, Benjamin S; Jarvik, Gail P; Leo, Michael C; Lynch, Frances L; Reiss, Jacob A; Richards, C Sue; McMullen, Carmit; Nickerson, Deborah; Dorschner, Michael O; Goddard, Katrina A B

2017-02-01

Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy. All results are placed into the medical record for use by healthcare providers. Through quantitative and qualitative measures, including baseline and post result disclosure surveys, post result disclosure interviews, 1-2year follow-up interviews, and team journaling, we are obtaining data about the clinical and personal utility of genomic carrier screening in this population. Key outcomes include the number of reportable carrier and additional findings, and the comparative cost, utilization, and psychosocial impacts of usual care vs. genomic carrier screening. As the study progresses, we will compare the costs of genome sequencing and usual care as well as the cost of screening, pattern of use of genetic or mental health counseling services, number of outpatient visits, and total healthcare costs. This project includes novel investigation into human reactions and responses from would-be parents who are learning information that could both affect a future pregnancy and their own health. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Impact processes, permafrost dynamics, and climate and environmental variability in the terrestrial Arctic as inferred from the unique 3.6 Myr record of Lake El'gygytgyn, Far East Russia - A review

NASA Astrophysics Data System (ADS)

Wennrich, Volker; Andreev, Andrei A.; Tarasov, Pavel E.; Fedorov, Grigory; Zhao, Wenwei; Gebhardt, Catalina A.; Meyer-Jacob, Carsten; Snyder, Jeffrey A.; Nowaczyk, Norbert R.; Schwamborn, Georg; Chapligin, Bernhard; Anderson, Patricia M.; Lozhkin, Anatoly V.; Minyuk, Pavel S.; Koeberl, Christian; Melles, Martin

2016-09-01

Lake El'gygytgyn in Far East Russia is a 3.6 Myr old impact crater lake. Located in an area that has never been affected by Cenozoic glaciations nor desiccation, the unique sediment record of the lake represents the longest continuous sediment archive of the terrestrial Arctic. The surrounding crater is the only impact structure on Earth developed in mostly acid volcanic rocks. Recent studies on the impactite, permafrost, and sediment sequences recovered within the framework of the ICDP "El'gygytgyn Drilling Project" and multiple pre-site surveys yielded new insight into the bedrock origin and cratering processes as well as permafrost dynamics and the climate and environmental history of the terrestrial Arctic back to the mid-Pliocene. Results from the impact rock section recovered during the deep drilling clearly confirm the impact genesis of the El'gygytgyn crater, but indicate an only very reduced fallback impactite sequence without larger coherent melt bodies. Isotope and element data of impact melt samples indicate a F-type asteroid of mixed composition or an ordinary chondrite as the likely impactor. The impact event caused a long-lasting hydrothermal activity in the crater that is assumed to have persisted for c. 300 kyr. Geochemical and microbial analyses of the permafrost core indicate a subaquatic formation of the lower part during lake-level highstand, but a subaerial genesis of the upper part after a lake-level drop after the Allerød. The isotope signal and ion compositions of ground ice is overprinted by several thaw-freeze cycles due to variations in the talik underneath the lake. Modeling results suggest a modern permafrost thickness in the crater of c. 340 m, and further confirm a pervasive character of the talik below Lake El'gygytgyn. The lake sediment sequences shed new leight into the Pliocene and Pleistocene climate and environmental evolution of the Arctic. During the mid-Pliocene, significantly warmer and wetter climatic conditions in western Beringia than today enabled dense boreal forests to grow around Lake El'gygytgyn and, in combination with a higher nutrient flux into the lake, promoted primary production. The exceptional warmth during the mid-Pliocene is in accordance with other marine and terrestrial records from the Arctic and indicates a period of enhanced "Arctic amplification". The favourable conditions during the mid-Pliocene were repeatedly interrupted by climate deteriorations, e.g., during Marine Isotope Stage (MIS) M2, when pollen data and sediment proxies indicate a major cooling and the onset of local permafrost around the lake. A gradual vegetation change after c. 3.0 Ma points to the onset of a long-term cooling trend during the Late Pliocene that culminated in major temperature drops, first during MIS G6, and later during MIS 104. These cold events coincide with the onset of an intensified Northern Hemisphere (NH) glaciation and the largest extent of the Cordilleran Ice Sheet, respectively. After the Pliocene/Pleistocene transition, local vegetation and primary production in Lake El'gygtygyn experienced a major change from relatively uniform conditions to a high-amplitude glacial-to-interglacial cyclicity that fluctuated on a dominant 41 kyr obliquity band, but changed to a 100 kyr eccentricity dominance during the Middle Pleistocene transition (MPT) at c. 1.2-0.6 Ma. Periods of exceptional warming in the Pleistocene record of Lake El'gygytgyn with dense boreal forests around and peaks of primary production in the lake are assigned to so-called "super-interglacial" periods. The occurrence of these super-interglacials well corresponds to collapses of the West Antarctic Ice Sheet (WAIS) recorded in ice-free periods in the ANDRILL core, which suggests strong intrahemispheric teleconnections presumably driven by changes in the thermocline ocean circulation.

Impact of Maternal Diet on the Epigenome during In Utero Life and the Developmental Programming of Diseases in Childhood and Adulthood

PubMed Central

Lee, Ho-Sun

2015-01-01

Exposure to environmental factors in early life can influence developmental processes and long-term health in humans. Early life nutrition and maternal diet are well-known examples of conditions shown to influence the risk of developing metabolic diseases, including type 2 diabetes mellitus and cardiovascular diseases, in adulthood. It is increasingly accepted that environmental compounds, including nutrients, can produce changes in the genome activity that, in spite of not altering the DNA sequence, can produce important, stable and, in some instances, transgenerational alterations in the phenotype. Epigenetics refers to changes in gene function that cannot be explained by changes in the DNA sequence, with DNA methylation patterns/histone modifications that can make important contributions to epigenetic memory. The epigenome can be considered as an interface between the genome and the environment that is central to the generation of phenotypes and their stability throughout the life course. To better understand the role of maternal health and nutrition in the initiation and progression of diseases in childhood and adulthood, it is necessary to identify the physiological and/or pathological roles of specific nutrients on the epigenome and how dietary interventions in utero and early life could modulate disease risk through epigenomic alteration. PMID:26593940

Impact Damage and Strain Rate Effects for Toughened Epoxy Composite Structures

NASA Technical Reports Server (NTRS)

Chamis, Christos C.; Minnetyan, Levon

2006-01-01

Structural integrity of composite systems under dynamic impact loading is investigated herein. The GENOA virtual testing software environment is used to implement the effects of dynamic loading on fracture progression and damage tolerance. Combinations of graphite and glass fibers with a toughened epoxy matrix are investigated. The effect of a ceramic coating for the absorption of impact energy is also included. Impact and post impact simulations include verification and prediction of (1) Load and Impact Energy, (2) Impact Damage Size, (3) Maximum Impact Peak Load, (4) Residual Strength, (5) Maximum Displacement, (6) Contribution of Failure Modes to Failure Mechanisms, (7) Prediction of Impact Load Versus Time, and (8) Damage, and Fracture Pattern. A computer model is utilized for the assessment of structural response, progressive fracture, and defect/damage tolerance characteristics. Results show the damage progression sequence and the changes in the structural response characteristics due to dynamic impact. The fundamental premise of computational simulation is that the complete evaluation of composite fracture requires an assessment of ply and subply level damage/fracture processes as the structure is subjected to loads. Simulation results for the graphite/epoxy composite were compared with the impact and tension failure test data, correlation and verification was obtained that included: (1) impact energy, (2) damage size, (3) maximum impact peak load, (4) residual strength, (5) maximum displacement, and (6) failure mechanisms of the composite structure.

Evolution of poor reporting and inadequate methods over time in 20 920 randomised controlled trials included in Cochrane reviews: research on research study.

PubMed

Dechartres, Agnes; Trinquart, Ludovic; Atal, Ignacio; Moher, David; Dickersin, Kay; Boutron, Isabelle; Perrodeau, Elodie; Altman, Douglas G; Ravaud, Philippe

2017-06-08

Objective  To examine how poor reporting and inadequate methods for key methodological features in randomised controlled trials (RCTs) have changed over the past three decades. Design  Mapping of trials included in Cochrane reviews. Data sources  Data from RCTs included in all Cochrane reviews published between March 2011 and September 2014 reporting an evaluation of the Cochrane risk of bias items: sequence generation, allocation concealment, blinding, and incomplete outcome data. Data extraction  For each RCT, we extracted consensus on risk of bias made by the review authors and identified the primary reference to extract publication year and journal. We matched journal names with Journal Citation Reports to get 2014 impact factors. Main outcomes measures  We considered the proportions of trials rated by review authors at unclear and high risk of bias as surrogates for poor reporting and inadequate methods, respectively. Results  We analysed 20 920 RCTs (from 2001 reviews) published in 3136 journals. The proportion of trials with unclear risk of bias was 48.7% for sequence generation and 57.5% for allocation concealment; the proportion of those with high risk of bias was 4.0% and 7.2%, respectively. For blinding and incomplete outcome data, 30.6% and 24.7% of trials were at unclear risk and 33.1% and 17.1% were at high risk, respectively. Higher journal impact factor was associated with a lower proportion of trials at unclear or high risk of bias. The proportion of trials at unclear risk of bias decreased over time, especially for sequence generation, which fell from 69.1% in 1986-1990 to 31.2% in 2011-14 and for allocation concealment (70.1% to 44.6%). After excluding trials at unclear risk of bias, use of inadequate methods also decreased over time: from 14.8% to 4.6% for sequence generation and from 32.7% to 11.6% for allocation concealment. Conclusions  Poor reporting and inadequate methods have decreased over time, especially for sequence generation and allocation concealment. But more could be done, especially in lower impact factor journals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Large-scale changes in community composition: determining land use and climate change signals.

PubMed

Kampichler, Christian; van Turnhout, Chris A M; Devictor, Vincent; van der Jeugd, Henk P

2012-01-01

Human land use and climate change are regarded as the main driving forces of present-day and future species extinction. They may potentially lead to a profound reorganisation of the composition and structure of natural communities throughout the world. However, studies that explicitly investigate both forms of impact--land use and climate change--are uncommon. Here, we quantify community change of Dutch breeding bird communities over the past 25 years using time lag analysis. We evaluate the chronological sequence of the community temperature index (CTI) which reflects community response to temperature increase (increasing CTI indicates an increase in relative abundance of more southerly species), and the temporal trend of the community specialisation index (CSI) which reflects community response to land use change (declining CSI indicates an increase of generalist species). We show that the breeding bird fauna underwent distinct directional change accompanied by significant changes both in CTI and CSI which suggests a causal connection between climate and land use change and bird community change. The assemblages of particular breeding habitats neither changed at the same speed and nor were they equally affected by climate versus land use changes. In the rapidly changing farmland community, CTI and CSI both declined slightly. In contrast, CTI increased in the more slowly changing forest and heath communities, while CSI remained stable. Coastal assemblages experienced both an increase in CTI and a decline in CSI. Wetland birds experienced the fastest community change of all breeding habitat assemblages but neither CTI nor CSI showed a significant trend. Overall, our results suggest that the interaction between climate and land use changes differs between habitats, and that comparing trends in CSI and CTI may be useful in tracking the impact of each determinant.

Sequence and facies architecture of the upper Blackhawk Formation and the Lower Castlegate Sandstone (Upper Cretaceous), Book Cliffs, Utah, USA

NASA Astrophysics Data System (ADS)

Yoshida, S.

2000-11-01

High-frequency stratigraphic sequences that comprise the Desert Member of the Blackhawk Formation, the Lower Castlegate Sandstone, and the Buck Tongue in the Green River area of Utah display changes in sequence architecture from marine deposits to marginal marine deposits to an entirely nonmarine section. Facies and sequence architecture differ above and below the regionally extensive Castlegate sequence boundary, which separates two low-frequency (106-year cyclicity) sequences. Below this surface, high-frequency sequences are identified and interpreted as comprising the highstand systems tract of the low-frequency Blackhawk sequence. Each high-frequency sequence has a local incised valley system on top of the wave-dominated delta, and coastal plain to shallow marine deposits are preserved. Above the Castlegate sequence boundary, in contrast, a regionally extensive sheet sandstone of fluvial to estuarine origin with laterally continuous internal erosional surfaces occurs. These deposits above the Castlegate sequence boundary are interpreted as the late lowstand to early transgressive systems tracts of the low-frequency Castlegate sequence. The base-level changes that generated both the low- and high-frequency sequences are attributed to crustal response to fluctuations in compressive intraplate stress on two different time scales. The low-frequency stratigraphic sequences are attributed to changes in the long-term regional subsidence rate and regional tilting of foreland basin fill. High-frequency sequences probably reflect the response of anisotropic basement to tectonism. Sequence architecture changes rapidly across the faulted margin of the underlying Paleozoic Paradox Basin. The high-frequency sequences are deeply eroded and stack above the Paradox Basin, but display less relief and become conformable updip. These features indicate that the area above the Paradox Basin was more prone to vertical structural movements during formation of the Blackhawk-Lower Castlegate succession.

Network Design in Close-Range Photogrammetry with Short Baseline Images

NASA Astrophysics Data System (ADS)

Barazzetti, L.

2017-08-01

The avaibility of automated software for image-based 3D modelling has changed the way people acquire images for photogrammetric applications. Short baseline images are required to match image points with SIFT-like algorithms, obtaining more images than those necessary for "old fashioned" photogrammetric projects based on manual measurements. This paper describes some considerations on network design for short baseline image sequences, especially on precision and reliability of bundle adjustment. Simulated results reveal that the large number of 3D points used for image orientation has very limited impact on network precision.

Molecular Epidemiology and Genomics of Group A Streptococcus

PubMed Central

Bessen, Debra E.; McShan, W. Michael; Nguyen, Scott V.; Shetty, Amol; Agrawal, Sonia; Tettelin, Hervé

2014-01-01

Streptococcus pyogenes (group A streptococcus; GAS) is a strict human pathogen with a very high prevalence worldwide. This review highlights the genetic organization of the species and the important ecological considerations that impact its evolution. Recent advances are presented on the topics of molecular epidemiology, population biology, molecular basis for genetic change, genome structure and genetic flux, phylogenomics and closely related streptococcal species, and the long- and short-term evolution of GAS. The application of whole genome sequence data to addressing key biological questions is discussed. PMID:25460818

Computationally mapping sequence space to understand evolutionary protein engineering.

PubMed

Armstrong, Kathryn A; Tidor, Bruce

2008-01-01

Evolutionary protein engineering has been dramatically successful, producing a wide variety of new proteins with altered stability, binding affinity, and enzymatic activity. However, the success of such procedures is often unreliable, and the impact of the choice of protein, engineering goal, and evolutionary procedure is not well understood. We have created a framework for understanding aspects of the protein engineering process by computationally mapping regions of feasible sequence space for three small proteins using structure-based design protocols. We then tested the ability of different evolutionary search strategies to explore these sequence spaces. The results point to a non-intuitive relationship between the error-prone PCR mutation rate and the number of rounds of replication. The evolutionary relationships among feasible sequences reveal hub-like sequences that serve as particularly fruitful starting sequences for evolutionary search. Moreover, genetic recombination procedures were examined, and tradeoffs relating sequence diversity and search efficiency were identified. This framework allows us to consider the impact of protein structure on the allowed sequence space and therefore on the challenges that each protein presents to error-prone PCR and genetic recombination procedures.

The origins and impact of primate segmental duplications.

PubMed

Marques-Bonet, Tomas; Girirajan, Santhosh; Eichler, Evan E

2009-10-01

Duplicated sequences are substrates for the emergence of new genes and are an important source of genetic instability associated with rare and common diseases. Analyses of primate genomes have shown an increase in the proportion of interspersed segmental duplications (SDs) within the genomes of humans and great apes. This contrasts with other mammalian genomes that seem to have their recently duplicated sequences organized in a tandem configuration. In this review, we focus on the mechanistic origin and impact of this difference with respect to evolution, genetic diversity and primate phenotype. Although many genomes will be sequenced in the future, resolution of this aspect of genomic architecture still requires high quality sequences and detailed analyses.

Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation

PubMed Central

Collins, Anne L.; Greenfield, Venuz Y.; Bye, Jeffrey K.; Linker, Kay E.; Wang, Alice S.; Wassum, Kate M.

2016-01-01

Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well-trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation. PMID:26869075

Identification of optimum sequencing depth especially for de novo genome assembly of small genomes using next generation sequencing data.

PubMed

Desai, Aarti; Marwah, Veer Singh; Yadav, Akshay; Jha, Vineet; Dhaygude, Kishor; Bangar, Ujwala; Kulkarni, Vivek; Jere, Abhay

2013-01-01

Next Generation Sequencing (NGS) is a disruptive technology that has found widespread acceptance in the life sciences research community. The high throughput and low cost of sequencing has encouraged researchers to undertake ambitious genomic projects, especially in de novo genome sequencing. Currently, NGS systems generate sequence data as short reads and de novo genome assembly using these short reads is computationally very intensive. Due to lower cost of sequencing and higher throughput, NGS systems now provide the ability to sequence genomes at high depth. However, currently no report is available highlighting the impact of high sequence depth on genome assembly using real data sets and multiple assembly algorithms. Recently, some studies have evaluated the impact of sequence coverage, error rate and average read length on genome assembly using multiple assembly algorithms, however, these evaluations were performed using simulated datasets. One limitation of using simulated datasets is that variables such as error rates, read length and coverage which are known to impact genome assembly are carefully controlled. Hence, this study was undertaken to identify the minimum depth of sequencing required for de novo assembly for different sized genomes using graph based assembly algorithms and real datasets. Illumina reads for E.coli (4.6 MB) S.kudriavzevii (11.18 MB) and C.elegans (100 MB) were assembled using SOAPdenovo, Velvet, ABySS, Meraculous and IDBA-UD. Our analysis shows that 50X is the optimum read depth for assembling these genomes using all assemblers except Meraculous which requires 100X read depth. Moreover, our analysis shows that de novo assembly from 50X read data requires only 6-40 GB RAM depending on the genome size and assembly algorithm used. We believe that this information can be extremely valuable for researchers in designing experiments and multiplexing which will enable optimum utilization of sequencing as well as analysis resources.

Immunoglobulin heavy variable (IGHV) genes and alleles: new entities, new names and implications for research and prognostication in chronic lymphocytic leukaemia.

PubMed

Xochelli, Aliki; Agathangelidis, Andreas; Kavakiotis, Ioannis; Minga, Evangelia; Sutton, Lesley Ann; Baliakas, Panagiotis; Chouvarda, Ioanna; Giudicelli, Véronique; Vlahavas, Ioannis; Maglaveras, Nikos; Bonello, Lisa; Trentin, Livio; Tedeschi, Alessandra; Panagiotidis, Panagiotis; Geisler, Christian; Langerak, Anton W; Pospisilova, Sarka; Jelinek, Diane F; Oscier, David; Chiorazzi, Nicholas; Darzentas, Nikos; Davi, Fred; Ghia, Paolo; Rosenquist, Richard; Hadzidimitriou, Anastasia; Belessi, Chrysoula; Lefranc, Marie-Paule; Stamatopoulos, Kostas

2015-01-01

Νext generation sequencing studies in Homo sapiens have identified novel immunoglobulin heavy variable (IGHV) genes and alleles necessitating changes in the international ImMunoGeneTics information system (IMGT) GENE-DB and reference directories of IMGT/V-QUEST. In chronic lymphocytic leukaemia (CLL), the somatic hypermutation (SHM) status of the clonotypic rearranged IGHV gene is strongly associated with patient outcome. Correct determination of this parameter strictly depends on the comparison of the nucleotide sequence of the clonotypic rearranged IGHV gene with that of the closest germline counterpart. Consequently, changes in the reference directories could, in principle, affect the correct interpretation of the IGHV mutational status in CLL. To this end, we analyzed 8066 productive IG heavy chain (IGH) rearrangement sequences from our consortium both before and after the latest update of the IMGT/V-QUEST reference directory. Differences were identified in 405 cases (5 % of the cohort). In 291/405 sequences (71.9 %), changes concerned only the IGHV gene or allele name, whereas a change in the percent germline identity (%GI) was noted in 114/405 (28.1 %) sequences; in 50/114 (43.8 %) sequences, changes in the %GI led to a change in the mutational set. In conclusion, recent changes in the IMGT reference directories affected the interpretation of SHM in a sizeable number of IGH rearrangement sequences from CLL patients. This indicates that both physicians and researchers should consider a re-evaluation of IG sequence data, especially for those IGH rearrangement sequences that, up to date, have a GI close to 98 %, where caution is warranted.

Genome sequence of Stachybotrys chartarum Strain 51-11

EPA Science Inventory

Stachybotrys chartarum strain 51-11 genome was sequenced by shotgun sequencing utilizing Illumina Hiseq 2000 and PacBio long read technology. Since Stachybotrys chartarum has been implicated in health impacts within water-damaged buildings, any information extracted from the geno...

The impact of environment change on culture evolution in east Ancient Silk Road.

NASA Astrophysics Data System (ADS)

Dong, G.; Liu, F.; Li, G.; Zhang, D. D.; Lee, H. F.; Chen, F.

2017-12-01

Ancient Silk Road played an important role in culture communication between west and east parts of the Eurasia during Bronze Age and historical period. Tens of archaic civilizations rise and fall in east parts of the Ancient Silk Road, climate change is attributed as one of the most important driving forces, while the process and mechanism for the impact of environmental change on culture evolution in the area has not been well-understood. Here we report new paleoclimate data based on multi-proxy analysis from two well-dated aeolian deposit sequences in the Hexi Corridor and Qaidam basin, where locate at the throat position of the Ancient Silk Road. Comparing with high-resolution tree rings from Qilian Mountain nearby, and archaeological evidence and historical documents, we proposed that two desertification events occurred in west Hexi Corridor between 3400-3100 BP and post 1450 AD, which induced two cultural discontinuity in that area. Climate was dry between 3400-2900 BP and wet between 2900-2000 BP in lowlands of east Qaidam basin, mismatching with the development of Nuomuhong Bronze culture in the area during 3400-2450 BP. We propose culture evolution in east Ancient Silk Road was mainly influenced by precipitation change of highlands in mountain areas,which was further influenced by large-scale vapor transport.

Contrasting population histories of the deep-sea demersal fish, Lycodes matsubarai, in the Sea of Japan and the Sea of Okhotsk.

PubMed

Sakuma, Kay; Ueda, Yuji; Hamatsu, Tomonori; Kojima, Shigeaki

2014-06-01

Recent studies have revealed the impact of the drastic climate change during the last glacial period on coastal marine and anadromous species in the marginal seas of the northwestern Pacific Ocean; however, its influence on deep-sea species remains poorly understood. To compare the effects of the last glacial period on populations from the Sea of Japan and the Sea of Okhotsk, we examined the mitochondrial control region and cytochrome b gene sequences of Lycodes matsubarai, a deepsea demersal fish that inhabits these two seas. Our results showed clear genetic differentiation of populations between the two seas. The populations may have diverged during the last glacial period, probably as a result of vicariance due to the drastic sea level change. The population in the Sea of Okhotsk was larger than that in the Sea of Japan, but suddenly decreased after the last glacial period. However, the Sea of Japan population expanded after the last glacial period, coincident with high levels of oxygenation in deep-sea areas. These results elucidate regional-scale impacts of climate change on deep-sea organisms.

Practice-based learning for improvement: the pursuit of clinical excellence.

PubMed

Staker, L V

2000-10-01

Physicians often seem to be paralyzed waiting for a health plan, a health maintenance organization, or an integrated health care system to bring about change or improvement in health care. But small changes in individual practices (microsystems) can have a profound impact on outcomes in an organization (microsystem). With simple graphical measurement tools, physicians can teach patients to measure and empower themselves to learn to improve both their health and their health care. At the same time, physicians can learn a great deal from their patient population data. When these measurement tools and a well-known and widely accepted method for clinical practice improvement called rapid cycle testing were used in a population of patients with diabetes, the average fasting blood sugar changed from 187 to 110 and the average hemoglobin A1c from 10.5 to 7.2. This article shows that measurement using specification charts and control charts in patient care can have a profound impact on patients, physicians, and organizations. Understanding these principles and using time-sequence measurement with graphical data feedback, physicians can engage in practice-based learning and can participate in improvement in the microsystems over which they have control.

Disturbance History,Spatial Variability, and Patterns of Biodiversity

NASA Astrophysics Data System (ADS)

Bendix, J.; Wiley, J. J.; Commons, M.

2012-12-01

The intermediate disturbance hypothesis predicts that species diversity will be maximized in environments experiencing intermediate intensity disturbance, after an intermediate timespan. Because many landscapes comprise mosaics with complex disturbance histories, the theory implies that each patch in those mosaics should have a distinct level of diversity reflecting combined impact of the magnitude of disturbance and the time since it occurred. We modeled the changing patterns of species richness across a landscape experiencing varied scenarios of simulated disturbance. Model outputs show that individual landscape patches have highly variable species richness through time, with the details reflecting the timing, intensity and sequence of their disturbance history. When the results are mapped across the landscape, the resulting temporal and spatial complexity illustrates both the contingent nature of diversity and the danger of generalizing about the impacts of disturbance.

DNA isolation protocol effects on nuclear DNA analysis by microarrays, droplet digital PCR, and whole genome sequencing, and on mitochondrial DNA copy number estimation.

PubMed

Nacheva, Elizabeth; Mokretar, Katya; Soenmez, Aynur; Pittman, Alan M; Grace, Colin; Valli, Roberto; Ejaz, Ayesha; Vattathil, Selina; Maserati, Emanuela; Houlden, Henry; Taanman, Jan-Willem; Schapira, Anthony H; Proukakis, Christos

2017-01-01

Potential bias introduced during DNA isolation is inadequately explored, although it could have significant impact on downstream analysis. To investigate this in human brain, we isolated DNA from cerebellum and frontal cortex using spin columns under different conditions, and salting-out. We first analysed DNA using array CGH, which revealed a striking wave pattern suggesting primarily GC-rich cerebellar losses, even against matched frontal cortex DNA, with a similar pattern on a SNP array. The aCGH changes varied with the isolation protocol. Droplet digital PCR of two genes also showed protocol-dependent losses. Whole genome sequencing showed GC-dependent variation in coverage with spin column isolation from cerebellum. We also extracted and sequenced DNA from substantia nigra using salting-out and phenol / chloroform. The mtDNA copy number, assessed by reads mapping to the mitochondrial genome, was higher in substantia nigra when using phenol / chloroform. We thus provide evidence for significant method-dependent bias in DNA isolation from human brain, as reported in rat tissues. This may contribute to array "waves", and could affect copy number determination, particularly if mosaicism is being sought, and sequencing coverage. Variations in isolation protocol may also affect apparent mtDNA abundance.

DNA isolation protocol effects on nuclear DNA analysis by microarrays, droplet digital PCR, and whole genome sequencing, and on mitochondrial DNA copy number estimation

PubMed Central

Nacheva, Elizabeth; Mokretar, Katya; Soenmez, Aynur; Pittman, Alan M.; Grace, Colin; Valli, Roberto; Ejaz, Ayesha; Vattathil, Selina; Maserati, Emanuela; Houlden, Henry; Taanman, Jan-Willem; Schapira, Anthony H.

2017-01-01

Potential bias introduced during DNA isolation is inadequately explored, although it could have significant impact on downstream analysis. To investigate this in human brain, we isolated DNA from cerebellum and frontal cortex using spin columns under different conditions, and salting-out. We first analysed DNA using array CGH, which revealed a striking wave pattern suggesting primarily GC-rich cerebellar losses, even against matched frontal cortex DNA, with a similar pattern on a SNP array. The aCGH changes varied with the isolation protocol. Droplet digital PCR of two genes also showed protocol-dependent losses. Whole genome sequencing showed GC-dependent variation in coverage with spin column isolation from cerebellum. We also extracted and sequenced DNA from substantia nigra using salting-out and phenol / chloroform. The mtDNA copy number, assessed by reads mapping to the mitochondrial genome, was higher in substantia nigra when using phenol / chloroform. We thus provide evidence for significant method-dependent bias in DNA isolation from human brain, as reported in rat tissues. This may contribute to array “waves”, and could affect copy number determination, particularly if mosaicism is being sought, and sequencing coverage. Variations in isolation protocol may also affect apparent mtDNA abundance. PMID:28683077

Deep COI sequencing of standardized benthic samples unveils overlooked diversity of Jordanian coral reefs in the northern Red Sea.

PubMed

Al-Rshaidat, Mamoon M D; Snider, Allison; Rosebraugh, Sydney; Devine, Amanda M; Devine, Thomas D; Plaisance, Laetitia; Knowlton, Nancy; Leray, Matthieu

2016-09-01

High-throughput sequencing (HTS) of DNA barcodes (metabarcoding), particularly when combined with standardized sampling protocols, is one of the most promising approaches for censusing overlooked cryptic invertebrate communities. We present biodiversity estimates based on sequencing of the cytochrome c oxidase subunit 1 (COI) gene for coral reefs of the Gulf of Aqaba, a semi-enclosed system in the northern Red Sea. Samples were obtained from standardized sampling devices (Autonomous Reef Monitoring Structures (ARMS)) deployed for 18 months. DNA barcoding of non-sessile specimens >2 mm revealed 83 OTUs in six phyla, of which only 25% matched a reference sequence in public databases. Metabarcoding of the 2 mm - 500 μm and sessile bulk fractions revealed 1197 OTUs in 15 animal phyla, of which only 4.9% matched reference barcodes. These results highlight the scarcity of COI data for cryptobenthic organisms of the Red Sea. Compared with data obtained using similar methods, our results suggest that Gulf of Aqaba reefs are less diverse than two Pacific coral reefs but much more diverse than an Atlantic oyster reef at a similar latitude. The standardized approaches used here show promise for establishing baseline data on biodiversity, monitoring the impacts of environmental change, and quantifying patterns of diversity at regional and global scales.

Recent "omics" advances in Helicobacter pylori.

PubMed

Berthenet, Elvire; Sheppard, Sam; Vale, Filipa F

2016-09-01

The development of high-throughput whole genome sequencing (WGS) technologies is changing the face of microbiology, facilitating the comparison of large numbers of genomes from different lineages of a same organism. Our aim was to review the main advances on Helicobacter pylori "omics" and to understand how this is improving our knowledge of the biology, diversity and pathogenesis of H. pylori. Since the first H. pylori isolate was sequenced in 1997, 510 genomes have been deposited in the NCBI archive, providing a basis for improved understanding of the epidemiology and evolution of this important pathogen. This review focuses on works published between April 2015 and March 2016. Helicobacter "omics" is already making an impact and is a growing research field. Ultimately these advances will be translated into a routine clinical laboratory setting in order to improve public health. © 2016 John Wiley & Sons Ltd.

Salient Features of Endonuclease Platforms for Therapeutic Genome Editing.

PubMed

Certo, Michael T; Morgan, Richard A

2016-03-01

Emerging gene-editing technologies are nearing a revolutionary phase in genetic medicine: precisely modifying or repairing causal genetic defects. This may include any number of DNA sequence manipulations, such as knocking out a deleterious gene, introducing a particular mutation, or directly repairing a defective sequence by site-specific recombination. All of these edits can currently be achieved via programmable rare-cutting endonucleases to create targeted DNA breaks that can engage and exploit endogenous DNA repair pathways to impart site-specific genetic changes. Over the past decade, several distinct technologies for introducing site-specific DNA breaks have been developed, yet the different biological origins of these gene-editing technologies bring along inherent differences in parameters that impact clinical implementation. This review aims to provide an accessible overview of the various endonuclease-based gene-editing platforms, highlighting the strengths and weakness of each with respect to therapeutic applications.

Salient Features of Endonuclease Platforms for Therapeutic Genome Editing

PubMed Central

Certo, Michael T; Morgan, Richard A

2016-01-01

Emerging gene-editing technologies are nearing a revolutionary phase in genetic medicine: precisely modifying or repairing causal genetic defects. This may include any number of DNA sequence manipulations, such as knocking out a deleterious gene, introducing a particular mutation, or directly repairing a defective sequence by site-specific recombination. All of these edits can currently be achieved via programmable rare-cutting endonucleases to create targeted DNA breaks that can engage and exploit endogenous DNA repair pathways to impart site-specific genetic changes. Over the past decade, several distinct technologies for introducing site-specific DNA breaks have been developed, yet the different biological origins of these gene-editing technologies bring along inherent differences in parameters that impact clinical implementation. This review aims to provide an accessible overview of the various endonuclease-based gene-editing platforms, highlighting the strengths and weakness of each with respect to therapeutic applications. PMID:26796671

Sheep genome functional annotation reveals proximal regulatory elements contributed to the evolution of modern breeds.

PubMed

Naval-Sanchez, Marina; Nguyen, Quan; McWilliam, Sean; Porto-Neto, Laercio R; Tellam, Ross; Vuocolo, Tony; Reverter, Antonio; Perez-Enciso, Miguel; Brauning, Rudiger; Clarke, Shannon; McCulloch, Alan; Zamani, Wahid; Naderi, Saeid; Rezaei, Hamid Reza; Pompanon, Francois; Taberlet, Pierre; Worley, Kim C; Gibbs, Richard A; Muzny, Donna M; Jhangiani, Shalini N; Cockett, Noelle; Daetwyler, Hans; Kijas, James

2018-02-28

Domestication fundamentally reshaped animal morphology, physiology and behaviour, offering the opportunity to investigate the molecular processes driving evolutionary change. Here we assess sheep domestication and artificial selection by comparing genome sequence from 43 modern breeds (Ovis aries) and their Asian mouflon ancestor (O. orientalis) to identify selection sweeps. Next, we provide a comparative functional annotation of the sheep genome, validated using experimental ChIP-Seq of sheep tissue. Using these annotations, we evaluate the impact of selection and domestication on regulatory sequences and find that sweeps are significantly enriched for protein coding genes, proximal regulatory elements of genes and genome features associated with active transcription. Finally, we find individual sites displaying strong allele frequency divergence are enriched for the same regulatory features. Our data demonstrate that remodelling of gene expression is likely to have been one of the evolutionary forces that drove phenotypic diversification of this common livestock species.

Genome Sequence of Stachybotrys chartarum Strain 51-11

PubMed Central

Kim, Jean; Levy, Josh

2015-01-01

The Stachybotrys chartarum strain 51-11 genome was sequenced by shotgun sequencing utilizing Illumina HiSeq 2000 and PacBio technologies. Since S. chartarum has been implicated as having health impacts within water-damaged buildings, any information extracted from the genomic sequence data relating to toxins or the metabolism of the fungus might be useful. PMID:26430036

Full genome sequence of Rocio virus reveal substantial variations from the prototype Rocio virus SPH 34675 sequence.

PubMed

Setoh, Yin Xiang; Amarilla, Alberto A; Peng, Nias Y; Slonchak, Andrii; Periasamy, Parthiban; Figueiredo, Luiz T M; Aquino, Victor H; Khromykh, Alexander A

2018-01-01

Rocio virus (ROCV) is an arbovirus belonging to the genus Flavivirus, family Flaviviridae. We present an updated sequence of ROCV strain SPH 34675 (GenBank: AY632542.4), the only available full genome sequence prior to this study. Using next-generation sequencing of the entire genome, we reveal substantial sequence variation from the prototype sequence, with 30 nucleotide differences amounting to 14 amino acid changes, as well as significant changes to predicted 3'UTR RNA structures. Our results present an updated and corrected sequence of a potential emerging human-virulent flavivirus uniquely indigenous to Brazil (GenBank: MF461639).

The Decoupling of Marriage and Parenthood? Trends in the Timing of Marital First Births, 1945–2002

PubMed Central

Hayford, Sarah R.; Guzzo, Karen Benjamin; Smock, Pamela J.

2014-01-01

Family formation changed dramatically over the twentieth century in the United States. The impact of these changes on childbearing has primarily been studied in terms of nonmarital fertility. However, changes in family formation behavior also have implications for fertility within marriage. We use data from ten fertility surveys to describe changes in the timing of marital childbearing from the 1940s through the 21st century for non-Hispanic white and non-Hispanic black women. Based on harmonized data from the Integrated Fertility Survey Series, our results suggest increasing divergence in fertility timing for white women. A growing proportion of marriages begin with a premarital conception; at the same time, an increasing proportion of white women are postponing fertility within marriage. For black women, marital fertility is increasingly postponed beyond the early years of marriage. Evaluating the sequencing of marriage and parenthood over time is critical to understanding the changing meaning of marriage. PMID:24791019

Ebolavirus is evolving but not changing: No evidence for functional change in EBOV from 1976 to the 2014 outbreak.

PubMed

Olabode, Abayomi S; Jiang, Xiaowei; Robertson, David L; Lovell, Simon C

2015-08-01

The 2014 epidemic of Ebola virus disease (EVD) has had a devastating impact in West Africa. Sequencing of ebolavirus (EBOV) from infected individuals has revealed extensive genetic variation, leading to speculation that the virus may be adapting to humans, accounting for the scale of the 2014 outbreak. We computationally analyze the variation associated with all EVD outbreaks, and find none of the amino acid replacements lead to identifiable functional changes. These changes have minimal effect on protein structure, being neither stabilizing nor destabilizing, are not found in regions of the proteins associated with known functions and tend to cluster in poorly constrained regions of proteins, specifically intrinsically disordered regions. We find no evidence that the difference between the current and previous outbreaks is due to evolutionary changes associated with transmission to humans. Instead, epidemiological factors are likely to be responsible for the unprecedented spread of EVD. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

What is a melody? On the relationship between pitch and brightness of timbre.

PubMed

Cousineau, Marion; Carcagno, Samuele; Demany, Laurent; Pressnitzer, Daniel

2013-01-01

Previous studies showed that the perceptual processing of sound sequences is more efficient when the sounds vary in pitch than when they vary in loudness. We show here that sequences of sounds varying in brightness of timbre are processed with the same efficiency as pitch sequences. The sounds used consisted of two simultaneous pure tones one octave apart, and the listeners' task was to make same/different judgments on pairs of sequences varying in length (one, two, or four sounds). In one condition, brightness of timbre was varied within the sequences by changing the relative level of the two pure tones. In other conditions, pitch was varied by changing fundamental frequency, or loudness was varied by changing the overall level. In all conditions, only two possible sounds could be used in a given sequence, and these two sounds were equally discriminable. When sequence length increased from one to four, discrimination performance decreased substantially for loudness sequences, but to a smaller extent for brightness sequences and pitch sequences. In the latter two conditions, sequence length had a similar effect on performance. These results suggest that the processes dedicated to pitch and brightness analysis, when probed with a sequence-discrimination task, share unexpected similarities.

Genomic sequencing and the impact of molecular diagnosis on patient care.

PubMed

Solomon, Benjamin D

2015-02-01

Evolving sequencing technologies allow more accurate, efficient and affordable genomic analysis. As a result, these technologies are increasingly available, especially to provide molecular diagnoses for patients with suspected genetic disorders. However, there are many challenges to using genomic sequencing to benefit patients, including concerns that there is insufficient evidence that identifying an underlying molecular explanation may positively impact a patient's healthcare. This concern has many repercussions, including funding and/or (in some countries and healthcare systems) insurance reimbursement for genomic sequencing. To investigate this concern, all monogenic disorders were analyzed based on the impact of achieving molecular diagnosis. Of the 2,849 individual genes in which germline mutations cause disorders (not including contiguous gene syndromes or what may be categorized as susceptibility alleles), our analyses showed a specific, available intervention related to at least one affected organ system for 1,419 (49.8%) genes. In 95.6% of these genes, the intervention(s) would be recommended during the pediatric time frame.

Through Increasing "Information Literacy" Capital and Habitus (Agency): The Complementary Impact on Composition Skills When Appropriately Sequenced

ERIC Educational Resources Information Center

Karas, Timothy

2017-01-01

Through a case study approach of a cohort of community college students at a single community college, the impact on success rates in composition courses was analyzed based on the sequence of completing an information literacy course. Two student cohorts were sampled based on completing an information literacy course prior to, or concurrently with…

How Changes in Anti-SD Sequences Would Affect SD Sequences in Escherichia coli and Bacillus subtilis.

PubMed

Abolbaghaei, Akram; Silke, Jordan R; Xia, Xuhua

2017-05-05

The 3' end of the small ribosomal RNAs (ssu rRNA) in bacteria is directly involved in the selection and binding of mRNA transcripts during translation initiation via well-documented interactions between a Shine-Dalgarno (SD) sequence located upstream of the initiation codon and an anti-SD (aSD) sequence at the 3' end of the ssu rRNA. Consequently, the 3' end of ssu rRNA (3'TAIL) is strongly conserved among bacterial species because a change in the region may impact the translation of many protein-coding genes. Escherichia coli and Bacillus subtilis differ in their 3' ends of ssu rRNA, being GAUC ACCUCCUUA 3' in E. coli and GAUC ACCUCCUU UCU3' or GAUC ACCUCCUU UCUA3' in B. subtilis Such differences in 3'TAIL lead to species-specific SDs (designated SD Ec for E. coli and SD Bs for B. subtilis ) that can form strong and well-positioned SD/aSD pairing in one species but not in the other. Selection mediated by the species-specific 3'TAIL is expected to favor SD Bs against SD Ec in B. subtilis , but favor SD Ec against SD Bs in E. coli Among well-positioned SDs, SD Ec is used more in E. coli than in B. subtilis , and SD Bs more in B. subtilis than in E. coli Highly expressed genes and genes of high translation efficiency tend to have longer SDs than lowly expressed genes and genes with low translation efficiency in both species, but more so in B. subtilis than in E. coli Both species overuse SDs matching the bolded part of the 3'TAIL shown above. The 3'TAIL difference contributes to the host specificity of phages. Copyright © 2017 Abolbaghaei et al.

Developmental changes in using verbal self-cueing in task-switching situations: the impact of task practice and task-sequencing demands.

PubMed

Kray, Jutta; Gaspard, Hanna; Karbach, Julia; Blaye, Agnès

2013-01-01

In this study we examined whether developmental changes in using verbal self-cueing for task-goal maintenance are dependent on the amount of task practice and task-sequencing demands. To measure task-goal maintenance we applied a switching paradigm in which children either performed only task A or B in single-task blocks or switched between them on every second trial in mixed-task blocks. Task-goal maintenance was determined by comparing the performance between both blocks (mixing costs). The influence of verbal self-cueing was measured by instructing children to either name the next task aloud or not to verbalize during task preparation. Task-sequencing demands were varied between groups whereas one group received spatial task cues to support keeping track of the task sequence, while the other group did not. We also varied by the amount of prior practice in task switching while one group of participants practiced task switching first, before performing the task naming in addition, and the other group did it vice versa. Results of our study investigating younger (8-10 years) and older children (11-13 years) revealed no age differences in beneficial effects of verbal self-cueing. In line with previous findings, children showed reduced mixing costs under task-naming instructions and under conditions of low task-sequence demands (with the presence of spatial task cues). Our results also indicated that these benefits were only obtained for those groups of children that first received practice in task switching alone with no additional verbalization instruction. These findings suggest that internal task-cueing strategies can be efficiently used in children but only if they received prior practice in the underlying task so that demands on keeping and coordinating various instructions are reduced. Moreover, children benefitted from spatial task cues for better task-goal maintenance only if no verbal task-cueing strategy was introduced first.

Role of different β-turns in β-hairpin conformation and stability studied by optical spectroscopy.

PubMed

Wu, Ling; McElheny, Dan; Setnicka, Vladimír; Hilario, Jovencio; Keiderling, Timothy A

2012-01-01

Model β-hairpin peptides based on variations in the turn sequence of Cochran's tryptophan zipper peptide, SWTWENGKWTWK, were studied using electronic circular dichroism (ECD), fluorescence, and infrared (IR) spectroscopies. The trpzip2 Asn-Gly turn sequence was substituted with Thr-Gly, Aib-Gly, (D)Pro-Gly, and Gly-Asn (trpzip1) to study the impact of turn stability on β-hairpin formation. Stability and conformational changes of these hairpins were monitored by thermodynamic analyses of the temperature variation of both FTIR (amide I') and ECD spectral intensities. These changes were fit to a two-state model which yielded different T(m) values, representing the folding/unfolding process, for hairpins with different β-turns. Different β-turns show systematic contributions to hairpin structure formation, and their inclusion in hairpin design can modify the folding pathways. Aib-Gly or (D)Pro-Gly sequences stabilize the turn resulting in residual Trp-Trp interaction at high temperatures, but at the same time the β-structure (cross strand H-bonds) can become less stable due to constraints of the turn, as seen for (D)Pro-Gly. The structure of the Aib-Gly turn containing hairpin was determined by NMR and was shown to be like trpzip2 (Asn-Gly turn) as regards turn and strand geometries, but to differ from trpzip1 (Gly-Asn turn). The Munoz and Eaton statistical mechanically derived multistate model, tested as an alternate point of view, represented contributions from H-bonds and hydrophobic interactions as well as conformational change as interdependent. Use of different spectral methods that vary in dependence on these physical interactions along with the structural variations provided insight to the complex folding pathways of these small, well-folded peptides. Copyright © 2011 Wiley Periodicals, Inc.

Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics.

PubMed

Yu, Meng; Jia, Hongmei; Zhou, Chao; Yang, Yong; Zhao, Yang; Yang, Maohua; Zou, Zhongmei

2017-05-10

As a prevalent, life-threatening and highly recurrent psychiatric illness, depression is characterized by a wide range of pathological changes; however, its etiology remains incompletely understood. Accumulating evidence supports that gut microbiota affects not only gastrointestinal physiology but also central nervous system (CNS) function and behavior through the microbiota-gut-brain axis. To assess the impact of gut microbiota on fecal metabolic phenotype in depressive conditions, an integrated approach of 16S rRNA gene sequencing combined with ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) based metabolomics was performed in chronic variable stress (CVS)-induced depression rat model. Interestingly, depression led to significant gut microbiota changes, at the phylum and genus levels in rats treated with CVS compared to controls. The relative abundances of the bacterial genera Marvinbryantia, Corynebacterium, Psychrobacter, Christensenella, Lactobacillus, Peptostreptococcaceae incertae sedis, Anaerovorax, Clostridiales incertae sedis and Coprococcus were significantly decreased, whereas Candidatus Arthromitus and Oscillibacter were markedly increased in model rats compared with normal controls. Meanwhile, distinct changes in fecal metabolic phenotype of depressive rats were also found, including lower levels of amino acids, and fatty acids, and higher amounts of bile acids, hypoxanthine and stercobilins. Moreover, there were substantial associations of perturbed gut microbiota genera with the altered fecal metabolites, especially compounds involved in the metabolism of tryptophan and bile acids. These results showed that the gut microbiota was altered in association with fecal metabolism in depressive conditions. These findings suggest that the 16S rRNA gene sequencing and LC-MS based metabolomics approach can be further applied to assess pathogenesis of depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Microbial diversity in the floral nectar of Linaria vulgaris along an urbanization gradient.

PubMed

Bartlewicz, Jacek; Lievens, Bart; Honnay, Olivier; Jacquemyn, Hans

2016-03-30

Microbes are common inhabitants of floral nectar and are capable of influencing plant-pollinator interactions. All studies so far investigated microbial communities in floral nectar in plant populations that were located in natural environments, but nothing is known about these communities in nectar of plants inhabiting urban environments. However, at least some microbes are vectored into floral nectar by pollinators, and because urbanization can have a profound impact on pollinator communities and plant-pollinator interactions, it can be expected that it affects nectar microbes as well. To test this hypothesis, we related microbial diversity in floral nectar to the degree of urbanization in the late-flowering plant Linaria vulgaris. Floral nectar was collected from twenty populations along an urbanization gradient and culturable bacteria and yeasts were isolated and identified by partially sequencing the genes coding for small and large ribosome subunits, respectively. A total of seven yeast and 13 bacterial operational taxonomic units (OTUs) were found at 3 and 1% sequence dissimilarity cut-offs, respectively. In agreement with previous studies, Metschnikowia reukaufii and M. gruessi were the main yeast constituents of nectar yeast communities, whereas Acinetobacter nectaris and Rosenbergiella epipactidis were the most frequently found bacterial species. Microbial incidence was high and did not change along the investigated urbanization gradient. However, microbial communities showed a nested subset structure, indicating that species-poor communities were a subset of species-rich communities. The level of urbanization was putatively identified as an important driver of nestedness, suggesting that environmental changes related to urbanization may impact microbial communities in floral nectar of plants growing in urban environments.

Shifts of tundra bacterial and archaeal communities along a permafrost thaw gradient in Alaska.

PubMed

Deng, Jie; Gu, Yunfu; Zhang, Jin; Xue, Kai; Qin, Yujia; Yuan, Mengting; Yin, Huaqun; He, Zhili; Wu, Liyou; Schuur, Edward A G; Tiedje, James M; Zhou, Jizhong

2015-01-01

Understanding the response of permafrost microbial communities to climate warming is crucial for evaluating ecosystem feedbacks to global change. This study investigated soil bacterial and archaeal communities by Illumina MiSeq sequencing of 16S rRNA gene amplicons across a permafrost thaw gradient at different depths in Alaska with thaw progression for over three decades. Over 4.6 million passing 16S rRNA gene sequences were obtained from a total of 97 samples, corresponding to 61 known classes and 470 genera. Soil depth and the associated soil physical-chemical properties had predominant impacts on the diversity and composition of the microbial communities. Both richness and evenness of the microbial communities decreased with soil depth. Acidobacteria, Verrucomicrobia, Alpha- and Gamma-Proteobacteria dominated the microbial communities in the upper horizon, whereas abundances of Bacteroidetes, Delta-Proteobacteria and Firmicutes increased towards deeper soils. Effects of thaw progression were absent in microbial communities in the near-surface organic soil, probably due to greater temperature variation. Thaw progression decreased the abundances of the majority of the associated taxa in the lower organic soil, but increased the abundances of those in the mineral soil, including groups potentially involved in recalcitrant C degradation (Actinomycetales, Chitinophaga, etc.). The changes in microbial communities may be related to altered soil C sources by thaw progression. Collectively, this study revealed different impacts of thaw in the organic and mineral horizons and suggests the importance of studying both the upper and deeper soils while evaluating microbial responses to permafrost thaw. © 2014 John Wiley & Sons Ltd.

The Sudbury impact layer in the paleoproterozoiciron ranges of northern Michigan, USA

USGS Publications Warehouse

Cannon, W.F.; Schulz, K.J.; Horton, J. Wright; King, David A.

2010-01-01

A layer of breccia that contains fragments of impact ejecta has been found at 10 sites in the Paleoproterozoic iron ranges of northern Michigan, in the Lake Superior region of the United States. Radiometric age constraints from events predating and postdating deposition of the breccia are ca. 1875 Ma and 1830 Ma. The major bolide impact that occurred at 1850 Ma at Sudbury, Ontario, 500–700 km east of these sites, is the likely causative event. The Michigan sites described here, along with previously described sites in Minnesota and Ontario, define an extensive ejecta-bearing deposit throughout the Paleoproterozoic iron ranges of the Lake Superior region that we refer to as the Sudbury impact layer. The layer at the sites in Michigan exhibits a range of thicknesses, lithologic characters, and sedimentary settings. The diversity of rock types and internal stratigraphic details of the layer imply that several different processes of transport and deposition are represented, but the detailed investigations needed to document them are incomplete. Many of the sites had been described and interpreted previously as products of common terrestrial processes, but the presence of relict shock-induced planar deformation features in quartz indicates that the breccia layer is in fact the product of an extraterrestrial impact. At most localities, this layer also contains relict fragments of altered devitrified glass and/or accretionary lapilli. One immediate use of the impact layer is as an ultraprecise time line that ties together the well-known stratigraphic sequences of the various geographically separated iron ranges, the correlation of which has remained controversial for many decades. The Sudbury impact layer most commonly lies at a horizon that records a significant change in the character of sediments across the region. The impact layer marks the end of a major period of banded iron formation deposition that was succeeded by deposition of fine clastic rocks, commonly black shales. The impact may have produced regional, if not global, changes in the environment that resulted in this widespread synchronous change in sedimentation style.

Digital Sequences and a Time Reversal-Based Impact Region Imaging and Localization Method

PubMed Central

Qiu, Lei; Yuan, Shenfang; Mei, Hanfei; Qian, Weifeng

2013-01-01

To reduce time and cost of damage inspection, on-line impact monitoring of aircraft composite structures is needed. A digital monitor based on an array of piezoelectric transducers (PZTs) is developed to record the impact region of impacts on-line. It is small in size, lightweight and has low power consumption, but there are two problems with the impact alarm region localization method of the digital monitor at the current stage. The first one is that the accuracy rate of the impact alarm region localization is low, especially on complex composite structures. The second problem is that the area of impact alarm region is large when a large scale structure is monitored and the number of PZTs is limited which increases the time and cost of damage inspections. To solve the two problems, an impact alarm region imaging and localization method based on digital sequences and time reversal is proposed. In this method, the frequency band of impact response signals is estimated based on the digital sequences first. Then, characteristic signals of impact response signals are constructed by sinusoidal modulation signals. Finally, the phase synthesis time reversal impact imaging method is adopted to obtain the impact region image. Depending on the image, an error ellipse is generated to give out the final impact alarm region. A validation experiment is implemented on a complex composite wing box of a real aircraft. The validation results show that the accuracy rate of impact alarm region localization is approximately 100%. The area of impact alarm region can be reduced and the number of PZTs needed to cover the same impact monitoring region is reduced by more than a half. PMID:24084123

Sequencing of intraductal biopsies is feasible and potentially impacts clinical management of patients with indeterminate biliary stricture and cholangiocarcinoma.

PubMed

Bankov, Katrin; Döring, Claudia; Schneider, Markus; Hartmann, Sylvia; Winkelmann, Ria; Albert, Joerg G; Bechstein, Wolf Otto; Zeuzem, Stefan; Hansmann, Martin Leo; Peveling-Oberhag, Jan; Walter, Dirk

2018-04-30

Definite diagnosis and therapeutic management of cholangiocarcinoma (CCA) remains a challenge. The aim of the current study was to investigate feasibility and potential impact on clinical management of targeted sequencing of intraductal biopsies. Intraductal biopsies with suspicious findings from 16 patients with CCA in later clinical course were analyzed with targeted sequencing including tumor and control benign tissue (n = 55 samples). A CCA-specific sequencing panel containing 41 genes was designed and a dual strand targeted enrichment was applied. Sequencing was successfully performed for all samples. In total, 79 mutations were identified and a mean of 1.7 mutations per tumor sample (range 0-4) as well as 2.3 per biopsy (0-6) were detected and potentially therapeutically relevant genes were identified in 6/16 cases. In 14/18 (78%) biopsies with dysplasia or inconclusive findings at least one mutation was detected. The majority of mutations were found in both surgical specimen and biopsy (68%), while 28% were only present in biopsies in contrast to 4% being only present in the surgical tumor specimen. Targeted sequencing from intraductal biopsies is feasible and potentially improves the diagnostic yield. A profound genetic heterogeneity in biliary dysplasia needs to be considered in clinical management and warrants further investigation. The current study is the first to demonstrate the feasibility of sequencing of intraductal biopsies which holds the potential to impact diagnostic and therapeutical management of patients with biliary dysplasia and neoplasia.

Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.

PubMed

Briggs, C E; Rucinski, D; Rosenfeld, P J; Hirose, T; Berson, E L; Dryja, T P

2001-09-01

To determine the spectrum of ABCR mutations associated with Stargardt macular degeneration and cone-rod degeneration (CRD). One hundred eighteen unrelated patients with recessive Stargardt macular degeneration and eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single-strand conformation polymorphism analysis. Variants were characterized by direct genomic sequencing. Segregation analysis was performed on the families of 20 patients in whom at least two or more likely pathogenic sequence changes were identified. The authors found 77 sequence changes likely to be pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one deletion of a consensus glycosylation site (also novel). Fifty-two patients with Stargardt macular degeneration (44% of those screened) and five with CRD each had two of these sequence changes or were homozygous for one of them. Segregation analyses in the families of 19 of these patients were informative and revealed that the index cases and all available affected siblings were compound heterozygotes or homozygotes. The authors found one instance of an apparently de novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients with Stargardt disease and one with CRD had only one likely pathogenic sequence change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no identified sequence changes. This report of 42 novel mutations brings the growing number of identified likely pathogenic sequence changes in ABCR to approximately 250.

Genome Sequence of Stachybotrys chartarum Strain 51-11.

PubMed

Betancourt, Doris A; Dean, Timothy R; Kim, Jean; Levy, Josh

2015-10-01

The Stachybotrys chartarum strain 51-11 genome was sequenced by shotgun sequencing utilizing Illumina HiSeq 2000 and PacBio technologies. Since S. chartarum has been implicated as having health impacts within water-damaged buildings, any information extracted from the genomic sequence data relating to toxins or the metabolism of the fungus might be useful. Copyright © 2015 Betancourt et al.

A fluvial record of the mid-Holocene rapid climatic changes in the middle Rhone valley (Espeluche-Lalo, France) and of their impact on Late Mesolithic and Early Neolithic societies

NASA Astrophysics Data System (ADS)

Berger, Jean-François; Delhon, Claire; Magnin, Frédéric; Bonté, Sandrine; Peyric, Dominique; Thiébault, Stéphanie; Guilbert, Raphaele; Beeching, Alain

2016-03-01

This multi-proxy study of a small floodplain in the Rhone catchment area, at the northern edge of the Mediterranean morphoclimatic system, provides valuable information concerning the impact of mid-Holocene climate variability (8.5-7.0 ka) and the effects of two rapid climatic changes (8.2 and 7.7/7.1 ka) on an alluvial plain, its basin and the first farming societies of the Rhone valley. Around 7.7/7.1 ka, the combined effects of (1) a strong rate of change in insolation and (2) variations in solar activity amplified marine and atmospheric circulation in the north-west Atlantic (Bond event 5b), which imply continental hydrological, soil and vegetation changes in the small catchment area. For this period, strong fluctuations in the plant cover ratio have been identified, related to a regime of sustained and regular fires, as well as abundant erosion of the hill slopes and frequent fluvial metamorphoses which led to braiding of the watercourse in this floodplain. There are few data available to evaluate the impact of natural events on prehistoric communities. This continental archive offers clear multi-proxy data for discussion of these aspects, having 4 cultural layers interbedded in the fluvial sequence (1 Late Mesolithic, 3 Cardial/Epicardial). Earlier data indicate the difficulty in recognizing such cultural features in the low alluvial plains of southern France during the Mesolithic/Early Neolithic transition, which should lead to caution when developing settlement models for this period.

Identification of the bacteria scavenging atmospheric CO and evaluation of the impact of land-use change on their distribution and activity

NASA Astrophysics Data System (ADS)

Constant, P.; Quiza, L.; Lalonde, I.

2013-12-01

Soil bacteria scavenging carbon monoxide (CO) are responsible for the biological sink of atmospheric CO. These bacteria mitigate an important fraction of the global emissions of CO from natural and anthropogenic sources. This ubiquitous soil ecosystem service is of critical importance since CO indirectly regulates the atmospheric lifetime of methane - the second most powerful greenhouse gas. So far, only few carboxydovore bacteria were shown to oxidize atmospheric CO. The CO-dehydrogenase (CODH) is the enzyme catalyzing the CO oxidation reaction in these bacteria. The enzyme is a dimer of heterotrimers encoded by the genes coxS, coxM and coxL. CoxL is the large subunit of the CODH. Phylogenetic analyzes revealed that coxL gene sequences encompass two main clusters: BMS and OMP groups but the version conferring a high affinity for CO and the ability to scavenge atmospheric CO is unknown. The objective of this investigation was to relate the diversity of coxL gene sequences with CO soil uptake activity and soil physicochemical properties. For this purpose, we collected soil samples in three neighbouring sites encompassing different land-use types: an undisturbed deciduous forest, a maize field and a larch monoculture. We analyzed (i) coxL diversity in the three environments, using a new coxL PCR detection assay targeting both OMP and BMS groups, (ii) CO oxidation activity using a gas chromatography assay and, (iii) soil physicochemical properties. Our results demonstrate that land-use change exerts a significant impact on coxL diversity as well as CO oxidation activity, with significant loss of the potential CO soil uptake activity following the conversion of native forest to maize or larch plantation. Most of the coxL gene sequences retrieved from the soil samples were not affiliated to sequences derived from microbial genome databases, impairing a taxonomic identification of the potential CO-oxidizing bacteria detected in soil. Canonical ordination analysis allowed us to identify coxL sequences belonging to potential high affinity CO-oxidizing bacteria, in addition to recognise environmental factors influencing their distribution and CO soil uptake activity. The activity increased with total carbon and nitrogen in soil and was inversely correlated to water content, pH, potassium and phosphorus. Candidates belonging to OMP group were identified as potential high affinity CO oxidizing bacteria. These bacteria were enriched in the laboratory and tested for their CO uptake activity. Work is currently in progress to assess the abundance and the CO uptake activity of these microorganisms in soil. Taken together, these results will be implemented into molecular models aimed at predicting CO uptake activity in soil. These models will be utilized to predict the response of the biological sink of CO to global change, while determining how land management practices could protect this important ecosystem service.

Evidence from central Mexico supporting the Younger Dryas extraterrestrial impact hypothesis.

PubMed

Israde-Alcántara, Isabel; Bischoff, James L; Domínguez-Vázquez, Gabriela; Li, Hong-Chun; DeCarli, Paul S; Bunch, Ted E; Wittke, James H; Weaver, James C; Firestone, Richard B; West, Allen; Kennett, James P; Mercer, Chris; Xie, Sujing; Richman, Eric K; Kinzie, Charles R; Wolbach, Wendy S

2012-03-27

We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon-rich, lacustrine layer, containing nanodiamonds, microspherules, and other unusual materials that date to the early Younger Dryas and are interpreted to result from an extraterrestrial impact. These proxies were found in a 27-m-long core as part of an interdisciplinary effort to extract a paleoclimate record back through the previous interglacial. Our attention focused early on an anomalous, 10-cm-thick, carbon-rich layer at a depth of 2.8 m that dates to 12.9 ka and coincides with a suite of anomalous coeval environmental and biotic changes independently recognized in other regional lake sequences. Collectively, these changes have produced the most distinctive boundary layer in the late Quaternary record. This layer contains a diverse, abundant assemblage of impact-related markers, including nanodiamonds, carbon spherules, and magnetic spherules with rapid melting/quenching textures, all reaching synchronous peaks immediately beneath a layer containing the largest peak of charcoal in the core. Analyses by multiple methods demonstrate the presence of three allotropes of nanodiamond: n-diamond, i-carbon, and hexagonal nanodiamond (lonsdaleite), in order of estimated relative abundance. This nanodiamond-rich layer is consistent with the Younger Dryas boundary layer found at numerous sites across North America, Greenland, and Western Europe. We have examined multiple hypotheses to account for these observations and find the evidence cannot be explained by any known terrestrial mechanism. It is, however, consistent with the Younger Dryas boundary impact hypothesis postulating a major extraterrestrial impact involving multiple airburst(s) and and/or ground impact(s) at 12.9 ka.

Stable Patterns of CENH3 Occupancy Through Maize Lineages Containing Genetically Similar Centromeres

PubMed Central

Gent, Jonathan I.; Wang, Kai; Jiang, Jiming; Dawe, R. Kelly

2015-01-01

While the approximate chromosomal position of centromeres has been identified in many species, little is known about the dynamics and diversity of centromere positions within species. Multiple lines of evidence indicate that DNA sequence has little or no impact in specifying centromeres in maize and in most multicellular organisms. Given that epigenetically defined boundaries are expected to be dynamic, we hypothesized that centromere positions would change rapidly over time, which would result in a diversity of centromere positions in isolated populations. To test this hypothesis, we used CENP-A/cenH3 (CENH3 in maize) chromatin immunoprecipitation to define centromeres in breeding pedigrees that included the B73 inbred as a common parent. While we found a diversity of CENH3 profiles for centromeres with divergent sequences that were not inherited from B73, the CENH3 profiles from centromeres that were inherited from B73 were indistinguishable from each other. We propose that specific genetic elements in centromeric regions favor or inhibit CENH3 accumulation, leading to reproducible patterns of CENH3 occupancy. These data also indicate that dramatic shifts in centromere position normally originate from accumulated or large-scale genetic changes rather than from epigenetic positional drift. PMID:26063660

Microbial compositional changes in broiler chicken cecal contents from birds challenged with different Salmonella vaccine candidate strains.

PubMed

Park, Si Hong; Kim, Sun Ae; Rubinelli, Peter M; Roto, Stephanie M; Ricke, Steven C

2017-05-31

Previously, we constructed and characterized the vaccine efficacy of Salmonella Typhimurium mutant strains in poultry with either inducible mviN expression (P BAD -mviN) or methionine auxotrophy (ΔΔmetRmetD). The aim of the present study was to assess potential impact of these Salmonella vaccine strains on the cecal microbiota using a next generation sequencing (NGS). The cecal microbial community obtained from unvaccinated (group 1) and vaccinated chickens (group 2, vaccinated with P BAD -mviN; group 3, vaccinated with wild type; group 4, vaccinated with ΔΔmetRmetD) were subjected to microbiome sequencing analysis with an Illumina MiSeq platform. The NGS microbiome analysis of chicken ceca revealed considerable changes in microbial composition in the presence of the different vaccine strains and exhibited detectable patterns of distinctive clustering among the respective groups (the R value of unweighted PCoA plot was 0.68). The present study indicates that different S. Typhimurium vaccine strains can differentially influence the microbiota of the ceca in terms of presence but not in the relative abundance of microbiota. Copyright © 2017 Elsevier Ltd. All rights reserved.

Short-term Influence of Two Types of Drilling Fluids on Wastewater Treatment Rate and Eukaryotic Organisms of Activated Sludge in Sequencing Batch Reactors.

PubMed

Babko, Roman; Jaromin-Gleń, Katarzyna; Łagód, Grzegorz; Danko, Yaroslav; Kuzmina, Tatiana; Pawłowska, Małgorzata; Pawłowski, Artur

2017-07-01

This work presents the results of studies on the impact of spent drilling fluids cotreated with municipal wastewater on the rate of the wastewater treatment process and the structure of the community of eukaryotic organisms inhabiting an activated sludge. The studies were conducted under laboratory conditions in sequencing batch reactors. The effect of added polymer-potassium drilling fluid (DF1) and polymer drilling fluid (DF2) at dosages of 1 and 3% of wastewater volume on the rate of removal of total suspended solids, turbidity, chemical oxygen demand, and the content of total and ammonium nitrogen were analyzed, taking into account the values of these parameters measured at the end of each operating cycle. In addition to the impacts on the aforementioned physicochemical indices, the influence of drilling fluid on the biomass of various groups of eukaryotes in activated sludge was analyzed. The impact of the drilling fluid was highly dependent on its type and dosage. A noticeable slowdown in the rate of the wastewater treatment process and a negative effect on the organisms were observed after the addition of DF2. This effect intensified after an increase in fluid dose. However, no statistically significant negative changes were observed after the introduction of DF1. Conversely, the removal rate of some of the analyzed pollutant increased. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Cortical Thickness Changes Correlate with Cognition Changes after Cognitive Training: Evidence from a Chinese Community Study

PubMed Central

Jiang, Lijuan; Cao, Xinyi; Li, Ting; Tang, Yingying; Li, Wei; Wang, Jijun; Chan, Raymond C.; Li, Chunbo

2016-01-01

The aim of this study was to investigate whether changes in cortical thickness correlated with cognitive function changes in healthy older adults after receiving cognitive training interventions. Moreover, it also aimed to examine the differential impacts of a multi-domain and a single-domain cognitive training interventions. Longitudinal magnetic resonance imaging (MRI) scanning was performed on participants 65–75 years of age using the Siemens 3.0 T Trio Tim with the Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequence. The cortical thickness was determined using FreeSurfer Software. Cognitive functioning was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were significant group × time interaction effects on the left supramarginal, the left frontal pole cortical regions; and a marginal significant group × time interaction effects on visuospatial/constructional and delayed memory scores. In a multi-domain cognitive training group, a number of cortical region changes were significantly positively correlated with changes in attention, delayed memory, and the total score, but significantly negatively correlated with changes in immediate memory and language scores. In the single-domain cognitive training group, some cortical region changes were significantly positively associated with changes in immediate memory, delayed memory, and the total score, while they were significantly negatively associated with changes in visuospatial/constructional, language, and attention scores. Overall, multi-domain cognitive training offered more advantages in visuospatial/constructional, attention, and delayed memory abilities, while single-domain cognitive training benefited immediate memory ability more effectively. These findings suggest that healthy older adults benefit more from the multi-domain cognitive training than single-domain cognitive training. Cognitive training has impacted on cortical thickness changes in healthy elderly. PMID:27252649

Early anthropogenic impact on Western Central African rainforests 2,600 y ago

NASA Astrophysics Data System (ADS)

Garcin, Yannick; Deschamps, Pierre; Ménot, Guillemette; de Saulieu, Geoffroy; Schefuß, Enno; Sebag, David; Dupont, Lydie M.; Oslisly, Richard; Brademann, Brian; Mbusnum, Kevin G.; Onana, Jean-Michel; Ako, Andrew A.; Epp, Laura S.; Tjallingii, Rik; Strecker, Manfred R.; Brauer, Achim; Sachse, Dirk

2018-03-01

A potential human footprint on Western Central African rainforests before the Common Era has become the focus of an ongoing controversy. Between 3,000 y ago and 2,000 y ago, regional pollen sequences indicate a replacement of mature rainforests by a forest–savannah mosaic including pioneer trees. Although some studies suggested an anthropogenic influence on this forest fragmentation, current interpretations based on pollen data attribute the ‘‘rainforest crisis’’ to climate change toward a drier, more seasonal climate. A rigorous test of this hypothesis, however, requires climate proxies independent of vegetation changes. Here we resolve this controversy through a continuous 10,500-y record of both vegetation and hydrological changes from Lake Barombi in Southwest Cameroon based on changes in carbon and hydrogen isotope compositions of plant waxes. δ13C-inferred vegetation changes confirm a prominent and abrupt appearance of C4 plants in the Lake Barombi catchment, at 2,600 calendar years before AD 1950 (cal y BP), followed by an equally sudden return to rainforest vegetation at 2,020 cal y BP. δD values from the same plant wax compounds, however, show no simultaneous hydrological change. Based on the combination of these data with a comprehensive regional archaeological database we provide evidence that humans triggered the rainforest fragmentation 2,600 y ago. Our findings suggest that technological developments, including agricultural practices and iron metallurgy, possibly related to the large-scale Bantu expansion, significantly impacted the ecosystems before the Common Era.

Early anthropogenic impact on Western Central African rainforests 2,600 y ago.

PubMed

Garcin, Yannick; Deschamps, Pierre; Ménot, Guillemette; de Saulieu, Geoffroy; Schefuß, Enno; Sebag, David; Dupont, Lydie M; Oslisly, Richard; Brademann, Brian; Mbusnum, Kevin G; Onana, Jean-Michel; Ako, Andrew A; Epp, Laura S; Tjallingii, Rik; Strecker, Manfred R; Brauer, Achim; Sachse, Dirk

2018-03-27

A potential human footprint on Western Central African rainforests before the Common Era has become the focus of an ongoing controversy. Between 3,000 y ago and 2,000 y ago, regional pollen sequences indicate a replacement of mature rainforests by a forest-savannah mosaic including pioneer trees. Although some studies suggested an anthropogenic influence on this forest fragmentation, current interpretations based on pollen data attribute the ''rainforest crisis'' to climate change toward a drier, more seasonal climate. A rigorous test of this hypothesis, however, requires climate proxies independent of vegetation changes. Here we resolve this controversy through a continuous 10,500-y record of both vegetation and hydrological changes from Lake Barombi in Southwest Cameroon based on changes in carbon and hydrogen isotope compositions of plant waxes. [Formula: see text] 13 C-inferred vegetation changes confirm a prominent and abrupt appearance of C 4 plants in the Lake Barombi catchment, at 2,600 calendar years before AD 1950 (cal y BP), followed by an equally sudden return to rainforest vegetation at 2,020 cal y BP. [Formula: see text]D values from the same plant wax compounds, however, show no simultaneous hydrological change. Based on the combination of these data with a comprehensive regional archaeological database we provide evidence that humans triggered the rainforest fragmentation 2,600 y ago. Our findings suggest that technological developments, including agricultural practices and iron metallurgy, possibly related to the large-scale Bantu expansion, significantly impacted the ecosystems before the Common Era.

Mutations that Cause Human Disease: A Computational/Experimental Approach

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

Beernink, P; Barsky, D; Pesavento, B

International genome sequencing projects have produced billions of nucleotides (letters) of DNA sequence data, including the complete genome sequences of 74 organisms. These genome sequences have created many new scientific opportunities, including the ability to identify sequence variations among individuals within a species. These genetic differences, which are known as single nucleotide polymorphisms (SNPs), are particularly important in understanding the genetic basis for disease susceptibility. Since the report of the complete human genome sequence, over two million human SNPs have been identified, including a large-scale comparison of an entire chromosome from twenty individuals. Of the protein coding SNPs (cSNPs), approximatelymore » half leads to a single amino acid change in the encoded protein (non-synonymous coding SNPs). Most of these changes are functionally silent, while the remainder negatively impact the protein and sometimes cause human disease. To date, over 550 SNPs have been found to cause single locus (monogenic) diseases and many others have been associated with polygenic diseases. SNPs have been linked to specific human diseases, including late-onset Parkinson disease, autism, rheumatoid arthritis and cancer. The ability to predict accurately the effects of these SNPs on protein function would represent a major advance toward understanding these diseases. To date several attempts have been made toward predicting the effects of such mutations. The most successful of these is a computational approach called ''Sorting Intolerant From Tolerant'' (SIFT). This method uses sequence conservation among many similar proteins to predict which residues in a protein are functionally important. However, this method suffers from several limitations. First, a query sequence must have a sufficient number of relatives to infer sequence conservation. Second, this method does not make use of or provide any information on protein structure, which can be used to understand how an amino acid change affects the protein. The experimental methods that provide the most detailed structural information on proteins are X-ray crystallography and NMR spectroscopy. However, these methods are labor intensive and currently cannot be carried out on a genomic scale. Nonetheless, Structural Genomics projects are being pursued by more than a dozen groups and consortia worldwide and as a result the number of experimentally determined structures is rising exponentially. Based on the expectation that protein structures will continue to be determined at an ever-increasing rate, reliable structure prediction schemes will become increasingly valuable, leading to information on protein function and disease for many different proteins. Given known genetic variability and experimentally determined protein structures, can we accurately predict the effects of single amino acid substitutions? An objective assessment of this question would involve comparing predicted and experimentally determined structures, which thus far has not been rigorously performed. The completed research leveraged existing expertise at LLNL in computational and structural biology, as well as significant computing resources, to address this question.« less

Robust sensorimotor representation to physical interaction changes in humanoid motion learning.

PubMed

Shimizu, Toshihiko; Saegusa, Ryo; Ikemoto, Shuhei; Ishiguro, Hiroshi; Metta, Giorgio

2015-05-01

This paper proposes a learning from demonstration system based on a motion feature, called phase transfer sequence. The system aims to synthesize the knowledge on humanoid whole body motions learned during teacher-supported interactions, and apply this knowledge during different physical interactions between a robot and its surroundings. The phase transfer sequence represents the temporal order of the changing points in multiple time sequences. It encodes the dynamical aspects of the sequences so as to absorb the gaps in timing and amplitude derived from interaction changes. The phase transfer sequence was evaluated in reinforcement learning of sitting-up and walking motions conducted by a real humanoid robot and compatible simulator. In both tasks, the robotic motions were less dependent on physical interactions when learned by the proposed feature than by conventional similarity measurements. Phase transfer sequence also enhanced the convergence speed of motion learning. Our proposed feature is original primarily because it absorbs the gaps caused by changes of the originally acquired physical interactions, thereby enhancing the learning speed in subsequent interactions.

What is a melody? On the relationship between pitch and brightness of timbre

PubMed Central

Cousineau, Marion; Carcagno, Samuele; Demany, Laurent; Pressnitzer, Daniel

2014-01-01

Previous studies showed that the perceptual processing of sound sequences is more efficient when the sounds vary in pitch than when they vary in loudness. We show here that sequences of sounds varying in brightness of timbre are processed with the same efficiency as pitch sequences. The sounds used consisted of two simultaneous pure tones one octave apart, and the listeners’ task was to make same/different judgments on pairs of sequences varying in length (one, two, or four sounds). In one condition, brightness of timbre was varied within the sequences by changing the relative level of the two pure tones. In other conditions, pitch was varied by changing fundamental frequency, or loudness was varied by changing the overall level. In all conditions, only two possible sounds could be used in a given sequence, and these two sounds were equally discriminable. When sequence length increased from one to four, discrimination performance decreased substantially for loudness sequences, but to a smaller extent for brightness sequences and pitch sequences. In the latter two conditions, sequence length had a similar effect on performance. These results suggest that the processes dedicated to pitch and brightness analysis, when probed with a sequence-discrimination task, share unexpected similarities. PMID:24478638

The environmental impacts on the star formation main sequence: An Hα study of the newly discovered rich cluster at z = 1.52

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

Koyama, Yusei; Kodama, Tadayuki; Tadaki, Ken-ichi

2014-07-01

We report the discovery of a strong over-density of galaxies in the field of a radio galaxy at z = 1.52 (4C 65.22) based on our broadband and narrow-band (Hα) photometry with the Subaru Telescope. We find that Hα emitters are located in the outskirts of the density peak (cluster core) dominated by passive red-sequence galaxies. This resembles the situation in lower-redshift clusters, suggesting that the newly discovered structure is a well-evolved rich galaxy cluster at z = 1.5. Our data suggest that the color-density and stellar mass-density relations are already in place at z ∼ 1.5, mostly driven bymore » the passive red massive galaxies residing within r{sub c} ≲ 200 kpc from the cluster core. These environmental trends almost disappear when we consider only star-forming (SF) galaxies. We do not find SFR-density or SSFR-density relations amongst SF galaxies, and the location of the SF main sequence does not significantly change with environment. Nevertheless, we find a tentative hint that star-bursting galaxies (up-scattered objects from the main sequence) are preferentially located in a small group at ∼1 Mpc away from the main body of the cluster. We also argue that the scatter of the SF main sequence could be dependent on the distance to the nearest neighboring galaxy.« less

A comparison of honey bee-collected pollen from working agricultural lands using light microscopy and ITS metabarcoding

USGS Publications Warehouse

Smart, Matthew; Cornman, Robert S.; Iwanowicz, Deborah; McDermott-Kubeczko, Margaret; Pettis, Jeff S; Spivak, Marla S; Otto, Clint R.

2017-01-01

Taxonomic identification of pollen has historically been accomplished via light microscopy but requires specialized knowledge and reference collections, particularly when identification to lower taxonomic levels is necessary. Recently, next-generation sequencing technology has been used as a cost-effective alternative for identifying bee-collected pollen; however, this novel approach has not been tested on a spatially or temporally robust number of pollen samples. Here, we compare pollen identification results derived from light microscopy and DNA sequencing techniques with samples collected from honey bee colonies embedded within a gradient of intensive agricultural landscapes in the Northern Great Plains throughout the 2010–2011 growing seasons. We demonstrate that at all taxonomic levels, DNA sequencing was able to discern a greater number of taxa, and was particularly useful for the identification of infrequently detected species. Importantly, substantial phenological overlap did occur for commonly detected taxa using either technique, suggesting that DNA sequencing is an appropriate, and enhancing, substitutive technique for accurately capturing the breadth of bee-collected species of pollen present across agricultural landscapes. We also show that honey bees located in high and low intensity agricultural settings forage on dissimilar plants, though with overlap of the most abundantly collected pollen taxa. We highlight practical applications of utilizing sequencing technology, including addressing ecological issues surrounding land use, climate change, importance of taxa relative to abundance, and evaluating the impact of conservation program habitat enhancement efforts.

Potential concerns with analytical Methods Used for the detection of Batrachochytrium salamandrivorans from archived DNA of amphibian swab samples, Oregon, USA

USGS Publications Warehouse

Iwanowicz, Deborah; Olson, Deanna H.; Adams, Michael J.; Adams, Cynthia; Anderson, Chauncey; Blaustein, Andrew R; Densmore, Christine L.; Figiel, Chester; Schill, William B.; Chestnut, Tara

2017-01-01

Taxonomic identification of pollen has historically been accomplished via light microscopy but requires specialized knowledge and reference collections, particularly when identification to lower taxonomic levels is necessary. Recently, next-generation sequencing technology has been used as a cost-effective alternative for identifying bee-collected pollen; however, this novel approach has not been tested on a spatially or temporally robust number of pollen samples. Here, we compare pollen identification results derived from light microscopy and DNA sequencing techniques with samples collected from honey bee colonies embedded within a gradient of intensive agricultural landscapes in the Northern Great Plains throughout the 2010–2011 growing seasons. We demonstrate that at all taxonomic levels, DNA sequencing was able to discern a greater number of taxa, and was particularly useful for the identification of infrequently detected species. Importantly, substantial phenological overlap did occur for commonly detected taxa using either technique, suggesting that DNA sequencing is an appropriate, and enhancing, substitutive technique for accurately capturing the breadth of bee-collected species of pollen present across agricultural landscapes. We also show that honey bees located in high and low intensity agricultural settings forage on dissimilar plants, though with overlap of the most abundantly collected pollen taxa. We highlight practical applications of utilizing sequencing technology, including addressing ecological issues surrounding land use, climate change, importance of taxa relative to abundance, and evaluating the impact of conservation program habitat enhancement efforts.

Similar genomic proportions of copy number variation within gray wolves and modern dog breeds inferred from whole genome sequencing.

PubMed

Serres-Armero, Aitor; Povolotskaya, Inna S; Quilez, Javier; Ramirez, Oscar; Santpere, Gabriel; Kuderna, Lukas F K; Hernandez-Rodriguez, Jessica; Fernandez-Callejo, Marcos; Gomez-Sanchez, Daniel; Freedman, Adam H; Fan, Zhenxin; Novembre, John; Navarro, Arcadi; Boyko, Adam; Wayne, Robert; Vilà, Carles; Lorente-Galdos, Belen; Marques-Bonet, Tomas

2017-12-19

Whole genome re-sequencing data from dogs and wolves are now commonly used to study how natural and artificial selection have shaped the patterns of genetic diversity. Single nucleotide polymorphisms, microsatellites and variants in mitochondrial DNA have been interrogated for links to specific phenotypes or signals of domestication. However, copy number variation (CNV), despite its increasingly recognized importance as a contributor to phenotypic diversity, has not been extensively explored in canids. Here, we develop a new accurate probabilistic framework to create fine-scale genomic maps of segmental duplications (SDs), compare patterns of CNV across groups and investigate their role in the evolution of the domestic dog by using information from 34 canine genomes. Our analyses show that duplicated regions are enriched in genes and hence likely possess functional importance. We identify 86 loci with large CNV differences between dogs and wolves, enriched in genes responsible for sensory perception, immune response, metabolic processes, etc. In striking contrast to the observed loss of nucleotide diversity in domestic dogs following the population bottlenecks that occurred during domestication and breed creation, we find a similar proportion of CNV loci in dogs and wolves, suggesting that other dynamics are acting to particularly select for CNVs with potentially functional impacts. This work is the first comparison of genome wide CNV patterns in domestic and wild canids using whole-genome sequencing data and our findings contribute to study the impact of novel kinds of genetic changes on the evolution of the domestic dog.

The Value of DNA Sequencing - TCGA

Cancer.gov

DNA sequencing: what it tells us about DNA changes in cancer, how looking across many tumors will help to identify meaningful changes and potential drug targets, and how genomics is changing the way we think about cancer.

The All-Asteroids Lab Course: Kepler's Laws, Collisions, And Authentic Undergraduate Research

NASA Astrophysics Data System (ADS)

Puckett, Andrew W.; Rector, T. A.

2010-01-01

We have developed a 12-week undergraduate laboratory sequence based entirely on asteroids and the hazards they pose. This curriculum has been designed primarily for use in an introductory Solar System Astronomy course, but it can be broken into smaller segments for a variety of course scenarios and educational goals. The course begins with a four-lab sequence based on our new online Java applet OrbitMaster, (adapted from AstroArts’ OrbitViewer under the GNU General Public License). OrbitMaster allows the user to alter an asteroid's orbital parameters and monitor its position and speed relative to both Sun and Earth. It also detects close approaches and collisions with Earth, and calculates revised speeds due to Earth's gravity. Students are able to confirm Kepler's laws, examine orbital properties that produce impacts, discover the kinetic energy-crater size relationship, understand the regional/global consequences of impacts, and experiment with deflection strategies. A three-lab sequence follows that examines the orbit-refinement and changing impact odds of 2007 WD5, which briefly had a 4% chance of hitting Mars in 2008. These labs introduce software that allows students to make astrometric measurements, fit orbital parameters, and predict future positions and uncertainties. They then use these tools in a four-lab research project to improve their own asteroids’ orbits, using images from the SDSS and WIYN 0.9-meter telescopes. Their work culminates in a presentation to their peers and submission of their astrometric measurements to the Minor Planet Center for publication. This effort is part of our NSF CCLI grant to develop Research Based Science Education (RBSE) curricula for non-majors. We have designed six projects that allow students to learn science by actually doing science. These projects are now being tested at six institutions around the country, and will eventually be distributed to a national audience.

Early to mid-Holocene spatiotemporal vegetation changes and tsunami impact in a paradigmatic coastal transitional system (Doñana National Park, southwestern Europe)

NASA Astrophysics Data System (ADS)

Manzano, Saúl; Carrión, José S.; López-Merino, Lourdes; Ochando, Juan; Munuera, Manuel; Fernández, Santiago; González-Sampériz, Penélope

2018-02-01

The southern European Doñana wetlands host a highly biodiverse landscape mosaic of complex transitional ecosystems. It is one of the largest protected natural sites in Europe, nowadays endangered by intensive agricultural practices, and more recently tourism and human-induced fires. Its present-day spatial heterogeneity has been deeply investigated for the last three decades. However, a long-term perspective has not been applied systematically to this unique landscape. In this new study, a palaeoecological approach was selected in order to unravel patterns of landscape dynamism comparing dry upland and aquatic ecosystems. A 709 cm-long sediment core was retrieved and a multi-proxy approach applied (palynological, microcharcoal, grain size, magnetic susceptibility, loss-on-ignition and multivariate statistical analyses). Pollen signatures show how sensitive aquatic wetland vegetation was to environmental changes while terrestrial vegetation was stable at millennial scale. The impact of several high energy events punctuates the Early and Middle Holocene sequence, two of which relate to the local tsunami record ( 6.6 and 9.1 cal. kyr BP). Contrasting impacts of these two events in the aquatic and upland ecosystems show the importance of landscape configuration and the contingent history as key elements for coastal protection.

Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses.

PubMed

Lagator, Mato; Colegrave, Nick; Neve, Paul

2014-11-07

In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Laboratory Sequence in Computational Methods for Introductory Chemistry

NASA Astrophysics Data System (ADS)

Cody, Jason A.; Wiser, Dawn C.

2003-07-01

A four-exercise laboratory sequence for introductory chemistry integrating hands-on, student-centered experience with computer modeling has been designed and implemented. The progression builds from exploration of molecular shapes to intermolecular forces and the impact of those forces on chemical separations made with gas chromatography and distillation. The sequence ends with an exploration of molecular orbitals. The students use the computers as a tool; they build the molecules, submit the calculations, and interpret the results. Because of the construction of the sequence and its placement spanning the semester break, good laboratory notebook practices are reinforced and the continuity of course content and methods between semesters is emphasized. The inclusion of these techniques in the first year of chemistry has had a positive impact on student perceptions and student learning.

Daily thanatomicrobiome changes in soil as an approach of postmortem interval estimation: An ecological perspective.

PubMed

Adserias-Garriga, Joe; Hernández, Marta; Quijada, Narciso M; Rodríguez Lázaro, David; Steadman, Dawnie; Garcia-Gil, Jesús

2017-09-01

Understanding human decomposition is critical for its use in postmortem interval (PMI) estimation, having a significant impact on forensic investigations. In recognition of the need to establish the scientific basis for PMI estimation, several studies on decomposition have been carried out in the last years. The aims of the present study were: (i) to identify soil microbiota communities involved in human decomposition through high-throughput sequencing (HTS) of DNA sequences from the different bacteria, (ii) to monitor quantitatively and qualitatively the decay of such signature species, and (iii) to describe succesional changes in bacterial populations from the early putrefaction state until skeletonization. Three donated individuals to the University of Tennessee FAC were studied. Soil samples around the body were taken from the placement of the donor until advanced decay/dry remains stage. Bacterial DNA extracts were obtained from the samples, HTS techniques were applied and bioinformatic data analysis was performed. The three cadavers showed similar overall successional changes. At the beginning of the decomposition process the soil microbiome consisted of diverse indigenous soil bacterial communities. As decomposition advanced, Firmicutes community abundance increased in the soil during the bloat stage. The growth curve of Firmicutes from human remains can be used to estimate time since death during Tennessee summer conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Protocol optimization of sacroiliac joint MR Imaging at 3 Tesla: Impact of coil design and motion resistant sequences on image quality.

PubMed

Gondim Teixeira, P A; Bravetti, M; Hossu, G; Lecocq, S; Petit, D; Loeuille, D; Blum, A

2017-12-01

To evaluate the impact of coil design and motion-resistant sequences on the quality of sacroiliac magnetic resonance imaging (MRI) examination in patients with spondyloarthropathy. One hundred and twenty-one patients with suspected sacroiliitis and referred for MRI of the sacroiliac joints were retrospectively evaluated with MRI at 3-Tesla. There were 78 women and 43 men with a mean age of 36.7±11.5 (SD) years (range: 15.8-78.4 years). Conventional and motion-resistant fat-saturated fast-spin echo T2-weighted sequences were performed with two different coils. Image quality was subjectively evaluated by two independent readers (R1 and R2) using a four-point scale. Confidence in the identification of bone marrow edema pattern (BMEP) was also evaluated subjectively using a three-point scale. Phased array body coil yielded improved image quality compared to surface coil (14.1 to 30.4% for R1 and 14.6 to 25.7% for R2; P<0.0001). The impact of the sequence type on quality was also statistically significant (P=0.0046). BMEP was identified in 40 patients and best inter-reader agreement was obtained using the combination of phased-array body coil with motion-resistant T2-weighted sequence (kappa 0.990). The smallest number of indeterminate BMEP zones was seen on MRI set acquired with the phased-array body coil and motion-resistant T2-weighted sequence. Phased array body coil and motion-resistant T2-weighted sequences perform better than surface coil and conventional T2-weighted sequences for the evaluation of sacroiliac joints, increasing confidence in the identification of BMEP. Copyright © 2017 Editions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Military Health Care Dilemmas and Genetic Discrimination: A Family's Experience with Whole Exome Sequencing.

PubMed

Helm, Benjamin M; Langley, Katherine; Spangler, Brooke B; Schrier Vergano, Samantha A

2015-01-01

Whole-exome sequencing (WES) has increased our ability to analyze large parts of the human genome, bringing with it a plethora of ethical, legal, and social implications. A topic dominating discussion of WES is identification of "secondary findings" (SFs), defined as the identification of risk in an asymptomatic individual unrelated to the indication for the test. SFs can have considerable psychosocial impact on patients and families, and patients with an SF may have concerns regarding genomic privacy and genetic discrimination. The Genetic Information Nondiscrimination Act of 2008 (GINA) currently excludes protections for members of the military. This may cause concern in military members and families regarding genetic discrimination when considering genetic testing. In this report, we discuss a case involving a patient and family in which a secondary finding was discovered by WES. The family members have careers in the U.S. military, and a risk-predisposing condition could negatively affect employment. While beneficial medical management changes were made, the information placed exceptional stress on the family, who were forced to navigate career-sensitive "extra-medical" issues, to consider the impacts of uncovering risk-predisposition, and to manage the privacy of their genetic information. We highlight how information obtained from WES may collide with these issues and emphasize the importance of genetic counseling for anyone undergoing WES.

Sasquatch: predicting the impact of regulatory SNPs on transcription factor binding from cell- and tissue-specific DNase footprints

PubMed Central

Suciu, Maria C.; Telenius, Jelena

2017-01-01

In the era of genome-wide association studies (GWAS) and personalized medicine, predicting the impact of single nucleotide polymorphisms (SNPs) in regulatory elements is an important goal. Current approaches to determine the potential of regulatory SNPs depend on inadequate knowledge of cell-specific DNA binding motifs. Here, we present Sasquatch, a new computational approach that uses DNase footprint data to estimate and visualize the effects of noncoding variants on transcription factor binding. Sasquatch performs a comprehensive k-mer-based analysis of DNase footprints to determine any k-mer's potential for protein binding in a specific cell type and how this may be changed by sequence variants. Therefore, Sasquatch uses an unbiased approach, independent of known transcription factor binding sites and motifs. Sasquatch only requires a single DNase-seq data set per cell type, from any genotype, and produces consistent predictions from data generated by different experimental procedures and at different sequence depths. Here we demonstrate the effectiveness of Sasquatch using previously validated functional SNPs and benchmark its performance against existing approaches. Sasquatch is available as a versatile webtool incorporating publicly available data, including the human ENCODE collection. Thus, Sasquatch provides a powerful tool and repository for prioritizing likely regulatory SNPs in the noncoding genome. PMID:28904015

Impact of predator dormancy on prey-predator dynamics

NASA Astrophysics Data System (ADS)

Freire, Joana G.; Gallas, Marcia R.; Gallas, Jason A. C.

2018-05-01

The impact of predator dormancy on the population dynamics of phytoplankton-zooplankton in freshwater ecosystems is investigated using a simple model including dormancy, a strategy to avoid extinction. In addition to recently reported chaos-mediated mixed-mode oscillations, as the carrying capacity grows, we find surprisingly wide phases of nonchaos-mediated mixed-mode oscillations to be present well before the onset of chaos in the system. Nonchaos-mediated cascades display spike-adding sequences, while chaos-mediated cascades show spike-doubling. A host of braided periodic phases with exotic shapes is found embedded in a region of control parameters dominated by chaotic oscillations. We describe the organization of these complicated phases and show how they are interconnected and how their complexity unfolds as control parameters change. The novel nonchaos-mediated phases are found to be large and stable, even for low carrying capacity.

Behaviour Centred Design: towards an applied science of behaviour change.

PubMed

Aunger, Robert; Curtis, Valerie

2016-12-01

Behaviour change has become a hot topic. We describe a new approach, Behaviour Centred Design (BCD), which encompasses a theory of change, a suite of behavioural determinants and a programme design process. The theory of change is generic, assuming that successful interventions must create a cascade of effects via environments, through brains, to behaviour and hence to the desired impact, such as improved health. Changes in behaviour are viewed as the consequence of a reinforcement learning process involving the targeting of evolved motives and changes to behaviour settings, and are produced by three types of behavioural control mechanism (automatic, motivated and executive). The implications are that interventions must create surprise, revalue behaviour and disrupt performance in target behaviour settings. We then describe a sequence of five steps required to design an intervention to change specific behaviours: Assess, Build, Create, Deliver and Evaluate. The BCD approach has been shown to change hygiene, nutrition and exercise-related behaviours and has the advantages of being applicable to product, service or institutional design, as well as being able to incorporate future developments in behaviour science. We therefore argue that BCD can become the foundation for an applied science of behaviour change.

Behaviour Centred Design: towards an applied science of behaviour change

PubMed Central

Aunger, Robert; Curtis, Valerie

2016-01-01

ABSTRACT Behaviour change has become a hot topic. We describe a new approach, Behaviour Centred Design (BCD), which encompasses a theory of change, a suite of behavioural determinants and a programme design process. The theory of change is generic, assuming that successful interventions must create a cascade of effects via environments, through brains, to behaviour and hence to the desired impact, such as improved health. Changes in behaviour are viewed as the consequence of a reinforcement learning process involving the targeting of evolved motives and changes to behaviour settings, and are produced by three types of behavioural control mechanism (automatic, motivated and executive). The implications are that interventions must create surprise, revalue behaviour and disrupt performance in target behaviour settings. We then describe a sequence of five steps required to design an intervention to change specific behaviours: Assess, Build, Create, Deliver and Evaluate. The BCD approach has been shown to change hygiene, nutrition and exercise-related behaviours and has the advantages of being applicable to product, service or institutional design, as well as being able to incorporate future developments in behaviour science. We therefore argue that BCD can become the foundation for an applied science of behaviour change. PMID:27535821

Surface water areas significantly impacted 2014 dengue outbreaks in Guangzhou, China

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

Tian, Huaiyu; Huang, Shanqian

Dengue transmission in urban areas is strongly influenced by a range of biological and environmental factors, yet the key drivers still need further exploration. To better understand mechanisms of environment–mosquito–urban dengue transmission, we propose an empirical model parameterized and cross-validated from a unique dataset including viral gene sequences, vector dynamics and human dengue cases in Guangzhou, China, together with a 36-year urban environmental change maps investigated by spatiotemporal satellite image fusion. The dengue epidemics in Guangzhou are highly episodic and were not associated with annual rainfall over time. Our results indicate that urban environmental changes, especially variations in surface areamore » covered by water in urban areas, can substantially alter the virus population and dengue transmission. The recent severe dengue outbreaks in Guangzhou may be due to the surge in an artificial lake construction, which could increase infection force between vector (mainly Aedes albopictus) and host when urban water area significantly increased. Impacts of urban environmental change on dengue dynamics may not have been thoroughly investigated in the past studies and more work needs to be done to better understand the consequences of urbanization processes in our changing world. - Highlights: • Urban dengue outbreak is associated with water area in Guangzhou, 1978–2014. • Surface water area can alter population size of dengue virus in urban area. • Urban dengue outbreak is not associated with annual rainfall in Guangzhou. • Spatiotemporal satellite image fusion can investigate urban environmental change. • Urban environmental change could induce virus, vector, and dengue epidemic change.« less

The effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on protein-protein interactions.

PubMed

Yates, Christopher M; Sternberg, Michael J E

2013-11-01

Non-synonymous single nucleotide polymorphisms (nsSNPs) are single base changes leading to a change to the amino acid sequence of the encoded protein. Many of these variants are associated with disease, so nsSNPs have been well studied, with studies looking at the effects of nsSNPs on individual proteins, for example, on stability and enzyme active sites. In recent years, the impact of nsSNPs upon protein-protein interactions has also been investigated, giving a greater insight into the mechanisms by which nsSNPs can lead to disease. In this review, we summarize these studies, looking at the various mechanisms by which nsSNPs can affect protein-protein interactions. We focus on structural changes that can impair interaction, changes to disorder, gain of interaction, and post-translational modifications before looking at some examples of nsSNPs at human-pathogen protein-protein interfaces and the analysis of nsSNPs from a network perspective. © 2013.

Sequence editing by Apolipoprotein B RNA-editing catalytic component-B and epidemiological surveillance of transmitted HIV-1 drug resistance

PubMed Central

Gifford, Robert J.; Rhee, Soo-Yon; Eriksson, Nicolas; Liu, Tommy F.; Kiuchi, Mark; Das, Amar K.; Shafer, Robert W.

2008-01-01

Design Promiscuous guanine (G) to adenine (A) substitutions catalysed by apolipoprotein B RNA-editing catalytic component (APOBEC) enzymes are observed in a proportion of HIV-1 sequences in vivo and can introduce artifacts into some genetic analyses. The potential impact of undetected lethal editing on genotypic estimation of transmitted drug resistance was assessed. Methods Classifiers of lethal, APOBEC-mediated editing were developed by analysis of lentiviral pol gene sequence variation and evaluated using control sets of HIV-1 sequences. The potential impact of sequence editing on genotypic estimation of drug resistance was assessed in sets of sequences obtained from 77 studies of 25 or more therapy-naive individuals, using mixture modelling approaches to determine the maximum likelihood classification of sequences as lethally edited as opposed to viable. Results Analysis of 6437 protease and reverse transcriptase sequences from therapy-naive individuals using a novel classifier of lethal, APOBEC3G-mediated sequence editing, the polypeptide-like 3G (APOBEC3G)-mediated defectives (A3GD) index’, detected lethal editing in association with spurious ‘transmitted drug resistance’ in nearly 3% of proviral sequences obtained from whole blood and 0.2% of samples obtained from plasma. Conclusion Screening for lethally edited sequences in datasets containing a proportion of proviral DNA, such as those likely to be obtained for epidemiological surveillance of transmitted drug resistance in the developing world, can eliminate rare but potentially significant errors in genotypic estimation of transmitted drug resistance. PMID:18356601

The value of new genome references.

PubMed

Worley, Kim C; Richards, Stephen; Rogers, Jeffrey

2017-09-15

Genomic information has become a ubiquitous and almost essential aspect of biological research. Over the last 10-15 years, the cost of generating sequence data from DNA or RNA samples has dramatically declined and our ability to interpret those data increased just as remarkably. Although it is still possible for biologists to conduct interesting and valuable research on species for which genomic data are not available, the impact of having access to a high quality whole genome reference assembly for a given species is nothing short of transformational. Research on a species for which we have no DNA or RNA sequence data is restricted in fundamental ways. In contrast, even access to an initial draft quality genome (see below for definitions) opens a wide range of opportunities that are simply not available without that reference genome assembly. Although a complete discussion of the impact of genome sequencing and assembly is beyond the scope of this short paper, the goal of this review is to summarize the most common and highest impact contributions that whole genome sequencing and assembly has had on comparative and evolutionary biology. Copyright © 2016. Published by Elsevier Inc.

Foliar fungi of Betula pendula: impact of tree species mixtures and assessment methods

PubMed Central

Nguyen, Diem; Boberg, Johanna; Cleary, Michelle; Bruelheide, Helge; Hönig, Lydia; Koricheva, Julia; Stenlid, Jan

2017-01-01

Foliar fungi of silver birch (Betula pendula) in an experimental Finnish forest were investigated across a gradient of tree species richness using molecular high-throughput sequencing and visual macroscopic assessment. We hypothesized that the molecular approach detects more fungal taxa than visual assessment, and that there is a relationship among the most common fungal taxa detected by both techniques. Furthermore, we hypothesized that the fungal community composition, diversity, and distribution patterns are affected by changes in tree diversity. Sequencing revealed greater diversity of fungi on birch leaves than the visual assessment method. One species showed a linear relationship between the methods. Species-specific variation in fungal community composition could be partially explained by tree diversity, though overall fungal diversity was not affected by tree diversity. Analysis of specific fungal taxa indicated tree diversity effects at the local neighbourhood scale, where the proportion of birch among neighbouring trees varied, but not at the plot scale. In conclusion, both methods may be used to determine tree diversity effects on the foliar fungal community. However, high-throughput sequencing provided higher resolution of the fungal community, while the visual macroscopic assessment detected functionally active fungal species. PMID:28150710

BeerDeCoded: the open beer metagenome project.

PubMed

Sobel, Jonathan; Henry, Luc; Rotman, Nicolas; Rando, Gianpaolo

2017-01-01

Next generation sequencing has radically changed research in the life sciences, in both academic and corporate laboratories. The potential impact is tremendous, yet a majority of citizens have little or no understanding of the technological and ethical aspects of this widespread adoption. We designed BeerDeCoded as a pretext to discuss the societal issues related to genomic and metagenomic data with fellow citizens, while advancing scientific knowledge of the most popular beverage of all. In the spirit of citizen science, sample collection and DNA extraction were carried out with the participation of non-scientists in the community laboratory of Hackuarium, a not-for-profit organisation that supports unconventional research and promotes the public understanding of science. The dataset presented herein contains the targeted metagenomic profile of 39 bottled beers from 5 countries, based on internal transcribed spacer (ITS) sequencing of fungal species. A preliminary analysis reveals the presence of a large diversity of wild yeast species in commercial brews. With this project, we demonstrate that coupling simple laboratory procedures that can be carried out in a non-professional environment with state-of-the-art sequencing technologies and targeted metagenomic analyses, can lead to the detection and identification of the microbial content in bottled beer.

Protocol matters: which methylome are you actually studying?

PubMed Central

Robinson, Mark D; Statham, Aaron L; Speed, Terence P; Clark, Susan J

2011-01-01

The field of epigenetics is now capitalizing on the vast number of emerging technologies, largely based on second-generation sequencing, which interrogate DNA methylation status and histone modifications genome-wide. However, getting an exhaustive and unbiased view of a methylome at a reasonable cost is proving to be a significant challenge. In this article, we take a closer look at the impact of the DNA sequence and bias effects introduced to datasets by genome-wide DNA methylation technologies and where possible, explore the bioinformatics tools that deconvolve them. There remains much to be learned about the performance of genome-wide technologies, the data we mine from these assays and how it reflects the actual biology. While there are several methods to interrogate the DNA methylation status genome-wide, our opinion is that no single technique suitably covers the minimum criteria of high coverage and, high resolution at a reasonable cost. In fact, the fraction of the methylome that is studied currently depends entirely on the inherent biases of the protocol employed. There is promise for this to change, as the third generation of sequencing technologies is expected to again ‘revolutionize’ the way that we study genomes and epigenomes. PMID:21566704

BeerDeCoded: the open beer metagenome project

PubMed Central

Sobel, Jonathan; Henry, Luc; Rotman, Nicolas; Rando, Gianpaolo

2017-01-01

Next generation sequencing has radically changed research in the life sciences, in both academic and corporate laboratories. The potential impact is tremendous, yet a majority of citizens have little or no understanding of the technological and ethical aspects of this widespread adoption. We designed BeerDeCoded as a pretext to discuss the societal issues related to genomic and metagenomic data with fellow citizens, while advancing scientific knowledge of the most popular beverage of all. In the spirit of citizen science, sample collection and DNA extraction were carried out with the participation of non-scientists in the community laboratory of Hackuarium, a not-for-profit organisation that supports unconventional research and promotes the public understanding of science. The dataset presented herein contains the targeted metagenomic profile of 39 bottled beers from 5 countries, based on internal transcribed spacer (ITS) sequencing of fungal species. A preliminary analysis reveals the presence of a large diversity of wild yeast species in commercial brews. With this project, we demonstrate that coupling simple laboratory procedures that can be carried out in a non-professional environment with state-of-the-art sequencing technologies and targeted metagenomic analyses, can lead to the detection and identification of the microbial content in bottled beer. PMID:29123645

Trends in structural coverage of the protein universe and the impact of the Protein Structure Initiative

PubMed Central

Khafizov, Kamil; Madrid-Aliste, Carlos; Almo, Steven C.; Fiser, Andras

2014-01-01

The exponential growth of protein sequence data provides an ever-expanding body of unannotated and misannotated proteins. The National Institutes of Health-supported Protein Structure Initiative and related worldwide structural genomics efforts facilitate functional annotation of proteins through structural characterization. Recently there have been profound changes in the taxonomic composition of sequence databases, which are effectively redefining the scope and contribution of these large-scale structure-based efforts. The faster-growing bacterial genomic entries have overtaken the eukaryotic entries over the last 5 y, but also have become more redundant. Despite the enormous increase in the number of sequences, the overall structural coverage of proteins—including proteins for which reliable homology models can be generated—on the residue level has increased from 30% to 40% over the last 10 y. Structural genomics efforts contributed ∼50% of this new structural coverage, despite determining only ∼10% of all new structures. Based on current trends, it is expected that ∼55% structural coverage (the level required for significant functional insight) will be achieved within 15 y, whereas without structural genomics efforts, realizing this goal will take approximately twice as long. PMID:24567391

Trends in structural coverage of the protein universe and the impact of the Protein Structure Initiative.

PubMed

Khafizov, Kamil; Madrid-Aliste, Carlos; Almo, Steven C; Fiser, Andras

2014-03-11

The exponential growth of protein sequence data provides an ever-expanding body of unannotated and misannotated proteins. The National Institutes of Health-supported Protein Structure Initiative and related worldwide structural genomics efforts facilitate functional annotation of proteins through structural characterization. Recently there have been profound changes in the taxonomic composition of sequence databases, which are effectively redefining the scope and contribution of these large-scale structure-based efforts. The faster-growing bacterial genomic entries have overtaken the eukaryotic entries over the last 5 y, but also have become more redundant. Despite the enormous increase in the number of sequences, the overall structural coverage of proteins--including proteins for which reliable homology models can be generated--on the residue level has increased from 30% to 40% over the last 10 y. Structural genomics efforts contributed ∼50% of this new structural coverage, despite determining only ∼10% of all new structures. Based on current trends, it is expected that ∼55% structural coverage (the level required for significant functional insight) will be achieved within 15 y, whereas without structural genomics efforts, realizing this goal will take approximately twice as long.

Climate change underlies global demographic, genetic, and cultural transitions in pre-Columbian southern Peru.

PubMed

Fehren-Schmitz, Lars; Haak, Wolfgang; Mächtle, Bertil; Masch, Florian; Llamas, Bastien; Cagigao, Elsa Tomasto; Sossna, Volker; Schittek, Karsten; Isla Cuadrado, Johny; Eitel, Bernhard; Reindel, Markus

2014-07-01

Several archaeological studies in the Central Andes have pointed at the temporal coincidence of climatic fluctuations (both long- and short-term) and episodes of cultural transition and changes of socioeconomic structures throughout the pre-Columbian period. Although most scholars explain the connection between environmental and cultural changes by the impact of climatic alterations on the capacities of the ecosystems inhabited by pre-Columbian cultures, direct evidence for assumed demographic consequences is missing so far. In this study, we address directly the impact of climatic changes on the spatial population dynamics of the Central Andes. We use a large dataset of pre-Columbian mitochondrial DNA sequences from the northern Rio Grande de Nasca drainage (RGND) in southern Peru, dating from ∼840 BC to 1450 AD. Alternative demographic scenarios are tested using Bayesian serial coalescent simulations in an approximate Bayesian computational framework. Our results indicate migrations from the lower coastal valleys of southern Peru into the Andean highlands coincident with increasing climate variability at the end of the Nasca culture at ∼640 AD. We also find support for a back-migration from the highlands to the coast coincident with droughts in the southeastern Andean highlands and improvement of climatic conditions on the coast after the decline of the Wari and Tiwanaku empires (∼1200 AD), leading to a genetic homogenization in the RGND and probably southern Peru as a whole.

Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients.

PubMed

Medina, Daniel A; Pedreros, Juan P; Turiel, Dannae; Quezada, Nicolas; Pimentel, Fernando; Escalona, Alex; Garrido, Daniel

2017-01-01

Bariatric surgery is highly successful in improving health compared to conventional dietary treatments. It has been suggested that the gut microbiota is a relevant factor in weight loss after bariatric surgery. Considering that bariatric procedures cause different rearrangements of the digestive tract, they probably have different effects on the gut microbiota. In this study, we compared the impact of medical treatment, sleeve gastrectomy and Roux-en-Y gastric bypass on the gut microbiota from obese subjects. Anthropometric and clinical parameters were registered before, 6 and 12 months after treatment. Fecal samples were collected and microbiota composition was studied before and six months post treatment using 16S rRNA gene sequencing and qPCR. In comparison to dietary treatment, changes in intestinal microbiota were more pronounced in patients subjected to surgery, observing a bloom in Proteobacteria . Interestingly, Bacteroidetes abundance was largely different after six months of each surgical procedure. Furthermore, changes in weight and BMI, or glucose metabolism, correlated positively with changes in these two phyla in these surgical procedures. These results indicate that distinct surgical procedures alter the gut microbiota differently, and changes in gut microbiota might contribute to health improvement. This study contributes to our understanding of the impact of weight loss surgery on the gut microbiota, and could be used to replicate this effect using targeted therapies.

Climate change underlies global demographic, genetic, and cultural transitions in pre-Columbian southern Peru

PubMed Central

Fehren-Schmitz, Lars; Haak, Wolfgang; Mächtle, Bertil; Masch, Florian; Llamas, Bastien; Tomasto Cagigao, Elsa; Sossna, Volker; Schittek, Karsten; Isla Cuadrado, Johny; Eitel, Bernhard; Reindel, Markus

2014-01-01

Several archaeological studies in the Central Andes have pointed at the temporal coincidence of climatic fluctuations (both long- and short-term) and episodes of cultural transition and changes of socioeconomic structures throughout the pre-Columbian period. Although most scholars explain the connection between environmental and cultural changes by the impact of climatic alterations on the capacities of the ecosystems inhabited by pre-Columbian cultures, direct evidence for assumed demographic consequences is missing so far. In this study, we address directly the impact of climatic changes on the spatial population dynamics of the Central Andes. We use a large dataset of pre-Columbian mitochondrial DNA sequences from the northern Rio Grande de Nasca drainage (RGND) in southern Peru, dating from ∼840 BC to 1450 AD. Alternative demographic scenarios are tested using Bayesian serial coalescent simulations in an approximate Bayesian computational framework. Our results indicate migrations from the lower coastal valleys of southern Peru into the Andean highlands coincident with increasing climate variability at the end of the Nasca culture at ∼640 AD. We also find support for a back-migration from the highlands to the coast coincident with droughts in the southeastern Andean highlands and improvement of climatic conditions on the coast after the decline of the Wari and Tiwanaku empires (∼1200 AD), leading to a genetic homogenization in the RGND and probably southern Peru as a whole. PMID:24979787

Rate of Change in Lake Level and its Impact on Reservoir-triggered Seismicity

NASA Astrophysics Data System (ADS)

Simpson, D. W.

2017-12-01

With recent interest in increased seismicity related to fluid injection, it is useful to review cases of reservoir-triggered earthquakes to explore common characteristics and seek ways to mitigate the influence of anthropogenic impacts. Three reservoirs - Koyna, India; Nurek, Tajikistan; and Aswan, Egypt - are well-documented cases of triggered earthquakes with recorded time series of seismicity and water levels that extend for more than 30 years. The geological setting, regional tectonics and modes of reservoir utilization, along with the characteristics of the reservoir-seismicity interaction, are distinctly different in each of these three cases. Similarities and differences between these three cases point to regional and local geological and hydrological structures and the rate of changes in reservoir water level as important factors controlling the presence and timing of triggered seismicity. In a manner similar to the way in which the rate of fluid injection influences injection-related seismicity, the rate of change in reservoir water level is a significant factor in determining whether or not reservoir-triggered seismicity occurs. The high rate of annual water level rise may be important in sustaining the exceptionally long sequence of earthquakes at Koyna. In addition to the rate of filling being a determining factor in whether or not earthquakes are triggered, changes in the rate of filling may influence the time of occurrence of individual earthquakes.

Effective normalization for copy number variation detection from whole genome sequencing.

PubMed

Janevski, Angel; Varadan, Vinay; Kamalakaran, Sitharthan; Banerjee, Nilanjana; Dimitrova, Nevenka

2012-01-01

Whole genome sequencing enables a high resolution view of the human genome and provides unique insights into genome structure at an unprecedented scale. There have been a number of tools to infer copy number variation in the genome. These tools, while validated, also include a number of parameters that are configurable to genome data being analyzed. These algorithms allow for normalization to account for individual and population-specific effects on individual genome CNV estimates but the impact of these changes on the estimated CNVs is not well characterized. We evaluate in detail the effect of normalization methodologies in two CNV algorithms FREEC and CNV-seq using whole genome sequencing data from 8 individuals spanning four populations. We apply FREEC and CNV-seq to a sequencing data set consisting of 8 genomes. We use multiple configurations corresponding to different read-count normalization methodologies in FREEC, and statistically characterize the concordance of the CNV calls between FREEC configurations and the analogous output from CNV-seq. The normalization methodologies evaluated in FREEC are: GC content, mappability and control genome. We further stratify the concordance analysis within genic, non-genic, and a collection of validated variant regions. The GC content normalization methodology generates the highest number of altered copy number regions. Both mappability and control genome normalization reduce the total number and length of copy number regions. Mappability normalization yields Jaccard indices in the 0.07 - 0.3 range, whereas using a control genome normalization yields Jaccard index values around 0.4 with normalization based on GC content. The most critical impact of using mappability as a normalization factor is substantial reduction of deletion CNV calls. The output of another method based on control genome normalization, CNV-seq, resulted in comparable CNV call profiles, and substantial agreement in variable gene and CNV region calls. Choice of read-count normalization methodology has a substantial effect on CNV calls and the use of genomic mappability or an appropriately chosen control genome can optimize the output of CNV analysis.

Soil Metabolome and Metabolic Fate: Microbial Insights into Freshwater Tidal Wetland Redox Biogeochemistry

NASA Astrophysics Data System (ADS)

Roy Chowdhury, T.; Bramer, L.; Hoyt, D. W.; Kim, Y. M.; Metz, T. O.; McCue, L. A.; Jansson, J.; Bailey, V. L.

2017-12-01

Earth System Models predict climate extremes that will impact regional and global hydrology. Aquatic-terrestrial transition zones like wetlands will experience the immediate consequence of climate change as shifts in the magnitude and dynamics of hydrologic flow. Such fluctuating hydrology can alter the structure and function of the soil microbial populations that in turn will alter the nature and rate of biogeochemical transformations and significantly impact the carbon balance of the ecosystem. We tested the impacts of shifting hydrology on the soil microbiome and the role of antecedent moisture condition on redox active microbial processes in soils sampled from a tidal freshwater wetland system in the lower Columbia River, WA, USA. Our objectives were to characterize changes in the soil microbial community composition in response to soil moisture legacy effects, and to elucidate relationships between community response, geochemical signatures and metabolite profiles in this soil. The 16S rRNA gene sequencing showed significant decreases in bacterial abundance capable of anaerobic metabolism in response to drying, but quickly recovered to the antecedent moisture condition, as observed by redox processes. Metabolomics and biogeochemical process rates generated evidence for moisture-driven redox conditions as principal controls on the community and metabolic function. Fluctuating redox conditions altered terminal electron acceptor and donor availability and recovery strengths of these pools in soil such that a disproportionate release of carbon dioxide stemmed from alternative anaerobic degradation processes like sulfate and iron reduction in compared to methanogenesis. Our results show that anoxic conditions impact microbial communities in both permanently and temporarily saturated conditions and that rapid change in hydrology can increase substrate availability for both aerobic and anaerobic decomposition processes, including methanogenesis.

Temporal Dynamics in Auditory Perceptual Learning: Impact of Sequencing and Incidental Learning

ERIC Educational Resources Information Center

Church, Barbara A.; Mercado, Eduardo, III; Wisniewski, Matthew G.; Liu, Estella H.

2013-01-01

Training can improve perceptual sensitivities. We examined whether the temporal dynamics and the incidental versus intentional nature of training are important. Within the context of a birdsong rate discrimination task, we examined whether the sequencing of pretesting exposure to the stimuli mattered. Easy-to-hard (progressive) sequencing of…

IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples

PubMed Central

Hintzsche, Jennifer; Kim, Jihye; Yadav, Vinod; Amato, Carol; Robinson, Steven E; Seelenfreund, Eric; Shellman, Yiqun; Wisell, Joshua; Applegate, Allison; McCarter, Martin; Box, Neil; Tentler, John; De, Subhajyoti

2016-01-01

Objective Currently, there is a disconnect between finding a patient’s relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics. Methods and materials The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR mutations. We also used IMPACT to analyze melanoma patient tumor samples before treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor treatment. Results IMPACT Food and Drug Administration (FDA) correctly identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis pipeline predicts these somatic variants to actionable therapeutics. We observed the clonal dynamic in the tumor samples after various treatments. We showed that IMPACT not only helped in successful prioritization of clinically relevant variants but also linked these variations to possible targeted therapies. Conclusion IMPACT provides a new bioinformatics strategy to delineate candidate somatic variants and actionable therapies. This approach can be applied to other patient tumor samples to discover effective drug targets for personalized medicine. IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT. PMID:27026619

IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples.

PubMed

Hintzsche, Jennifer; Kim, Jihye; Yadav, Vinod; Amato, Carol; Robinson, Steven E; Seelenfreund, Eric; Shellman, Yiqun; Wisell, Joshua; Applegate, Allison; McCarter, Martin; Box, Neil; Tentler, John; De, Subhajyoti; Robinson, William A; Tan, Aik Choon

2016-07-01

Currently, there is a disconnect between finding a patient's relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics. The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR mutations. We also used IMPACT to analyze melanoma patient tumor samples before treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor treatment. IMPACT Food and Drug Administration (FDA) correctly identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis pipeline predicts these somatic variants to actionable therapeutics. We observed the clonal dynamic in the tumor samples after various treatments. We showed that IMPACT not only helped in successful prioritization of clinically relevant variants but also linked these variations to possible targeted therapies. IMPACT provides a new bioinformatics strategy to delineate candidate somatic variants and actionable therapies. This approach can be applied to other patient tumor samples to discover effective drug targets for personalized medicine.IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Molecular Diagnosis of Long-QT syndrome at 10 Days of Life by Rapid Whole Genome Sequencing

PubMed Central

Priest, James R.; Ceresnak, Scott R.; Dewey, Frederick E.; Malloy-Walton, Lindsey E.; Dunn, Kyla; Grove, Megan E.; Perez, Marco V.; Maeda, Katsuhide; Dubin, Anne M.; Ashley, Euan A.

2014-01-01

Background The advent of clinical next generation sequencing is rapidly changing the landscape of rare disease medicine. Molecular diagnosis of long QT syndrome (LQTS) can impact clinical management, including risk stratification and selection of pharmacotherapy based on the type of ion channel affected, but results from current gene panel testing requires 4 to 16 weeks before return to clinicians. Objective A term female infant presented with 2:1 atrioventricular block and ventricular arrhythmias consistent with perinatal LQTS, requiring aggressive treatment including epicardial pacemaker, and cardioverter-defibrillator implantation and sympathectomy on day of life two. We sought to provide a rapid molecular diagnosis for optimization of treatment strategies. Methods We performed CLIA-certified rapid whole genome sequencing (WGS) with a speed-optimized bioinformatics platform to achieve molecular diagnosis at 10 days of life. Results We detected a known pathogenic variant in KCNH2 that was demonstrated to be paternally inherited by followup genotyping. The unbiased assessment of the entire catalog of human genes provided by whole genome sequencing revealed a maternally inherited variant of unknown significance in a novel gene. Conclusions Rapid clinical WGS provides faster and more comprehensive diagnostic information by 10 days of life than standard gene-panel testing. In selected clinical scenarios such as perinatal LQTS, rapid WGS may be able to provide more timely and clinically actionable information than a standard commercial test. PMID:24973560

Accurate identification of RNA editing sites from primitive sequence with deep neural networks.

PubMed

Ouyang, Zhangyi; Liu, Feng; Zhao, Chenghui; Ren, Chao; An, Gaole; Mei, Chuan; Bo, Xiaochen; Shu, Wenjie

2018-04-16

RNA editing is a post-transcriptional RNA sequence alteration. Current methods have identified editing sites and facilitated research but require sufficient genomic annotations and prior-knowledge-based filtering steps, resulting in a cumbersome, time-consuming identification process. Moreover, these methods have limited generalizability and applicability in species with insufficient genomic annotations or in conditions of limited prior knowledge. We developed DeepRed, a deep learning-based method that identifies RNA editing from primitive RNA sequences without prior-knowledge-based filtering steps or genomic annotations. DeepRed achieved 98.1% and 97.9% area under the curve (AUC) in training and test sets, respectively. We further validated DeepRed using experimentally verified U87 cell RNA-seq data, achieving 97.9% positive predictive value (PPV). We demonstrated that DeepRed offers better prediction accuracy and computational efficiency than current methods with large-scale, mass RNA-seq data. We used DeepRed to assess the impact of multiple factors on editing identification with RNA-seq data from the Association of Biomolecular Resource Facilities and Sequencing Quality Control projects. We explored developmental RNA editing pattern changes during human early embryogenesis and evolutionary patterns in Drosophila species and the primate lineage using DeepRed. Our work illustrates DeepRed's state-of-the-art performance; it may decipher the hidden principles behind RNA editing, making editing detection convenient and effective.

Extremely low genetic diversity across mangrove taxa reflects past sea level changes and hints at poor future responses.

PubMed

Guo, Zixiao; Li, Xinnian; He, Ziwen; Yang, Yuchen; Wang, Wenqing; Zhong, Cairong; Greenberg, Anthony J; Wu, Chung-I; Duke, Norman C; Shi, Suhua

2018-04-01

The projected increases in sea levels are expected to affect coastal ecosystems. Tropical communities, anchored by mangrove trees and having experienced frequent past sea level changes, appear to be vibrant at present. However, any optimism about the resilience of these ecosystems is premature because the impact of past climate events may not be reflected in the current abundance. To assess the impact of historical sea level changes, we conducted an extensive genetic diversity survey on the Indo-Malayan coast, a hotspot with a large global mangrove distribution. A survey of 26 populations in six species reveals extremely low genome-wide nucleotide diversity and hence very small effective population sizes (N e ) in all populations. Whole-genome sequencing of three mangrove species further shows the decline in N e to be strongly associated with the speed of past changes in sea level. We also used a recent series of flooding events in Yalong Bay, southern China, to test the robustness of mangroves to sea level changes in relation to their genetic diversity. The events resulted in the death of half of the mangrove trees in this area. Significantly, less genetically diverse mangrove species suffered much greater destruction. The dieback was accompanied by a drastic reduction in local invertebrate biodiversity. We thus predict that tropical coastal communities will be seriously endangered as the global sea level rises. Well-planned coastal development near mangrove forests will be essential to avert this crisis. © 2017 John Wiley & Sons Ltd.

Exposure to low pH induces molecular level changes in the marine worm, Platynereis dumerilii.

PubMed

Wäge, Janine; Lerebours, Adelaide; Hardege, Jörg D; Rotchell, Jeanette M

2016-02-01

Fossil fuel emissions and changes in net land use lead to an increase in atmospheric CO2 concentration and a subsequent decrease of ocean pH. Noticeable effects on organisms' calcification rate, shell structure and energy metabolism have been reported in the literature. To date, little is known about the molecular mechanisms altered under low pH exposure, especially in non-calcifying organisms. We used a suppression subtractive hybridisation (SSH) approach to characterise differentially expressed genes isolated from Platynereis dumerilii, a non-calcifying marine polychaeta species, kept at normal and low pH conditions. Several gene sequences have been identified as differentially regulated. These are involved in processes previously considered as indicators of environment change, such as energy metabolism (NADH dehydrogenase, 2-oxoglutarate dehydrogenase, cytochrome c oxidase and ATP synthase subunit F), while others are involved in cytoskeleton function (paramyosin and calponin) and immune defence (fucolectin-1 and paneth cell-specific alpha-defensin) processes. This is the first study of differential gene expression in a non-calcifying, marine polychaete exposed to low pH seawater conditions and suggests that mechanisms of impact may include additional pathways not previously identified as impacted by low pH in other species. Copyright © 2015 Elsevier Inc. All rights reserved.

A not-so-big crisis: re-reading Silurian conodont diversity in a sequence-stratigraphic framework

NASA Astrophysics Data System (ADS)

Jarochowska, Emilia; Munnecke, Axel

2016-04-01

Conodonts are extensively used in Ordovician through Triassic biostratigraphy and fossil-based geochemistry. However, their distribution in rock successions is commonly taken at face value, without taking into account their diverse and poorly understood ecology. Multielement taxonomy, ontogenetic and environmental variability, difficulties in extraction, and relative rarity all contribute to the general lack of quantitative studies on conodont stratigraphic distribution and temporal turnover. With respect to Silurian conodonts, the concept of recurrent conodont extinction events - the so called Ireviken, Mulde and Lau events - has become a standard in the stratigraphic literature. The concept has been proposed based on qualitative observations of local extirpations of open-marine pelagic or nekto-benthic taxa and temporary dominance of shallow-water species in the Silurian succession of the Swedish island of Gotland. These changes coincided with positive carbon isotope excursions, abrupt facies shifts, "blooms" of benthic fauna, and changes in reef communities, which have all been combined into a general view of Silurian bio-geochemical events. This view posits a deterministic, reproducible pattern in Silurian conodont diversity, attributed to recurrent ecological or geochemical conditions. The growing body of sequence-stratigraphic interpretations across these events in Gotland and other sections worldwide indicate that in all cases the Silurian "events" are associated with rapid global regressions. This suggests that faunal changes such as the dominance of shallow-water, low-diversity conodont fauna and the increase of benthic invertebrate diversity and abundance represent predictable consequences of the variation in the completeness of the rock record and preservation potential of different environments. Our studies in Poland and Ukraine indicate that the magnitude of change in the taxonomic composition of conodont assemblages across the middle Silurian global regression and the hypothesized Mulde Event is proportional to the associated facies shift. Quantitative data on facies distribution of individual conodont species combined with sequence stratigraphic architecture provides a testable model for the impact of sea-level changes on perceived conodont diversity in a section or basin. This approach highlights the need for quantitative data on conodont distribution in their environmental context, their integration into conodont-based stratigraphy and geochemistry, and for the regular use of Occam's razor to interpretations of paleobiodiversity.

Analysis of selected genes associated with cardiomyopathy by next-generation sequencing.

PubMed

Szabadosova, Viktoria; Boronova, Iveta; Ferenc, Peter; Tothova, Iveta; Bernasovska, Jarmila; Zigova, Michaela; Kmec, Jan; Bernasovsky, Ivan

2018-02-01

As the leading cause of congestive heart failure, cardiomyopathy represents a heterogenous group of heart muscle disorders. Despite considerable progress being made in the genetic diagnosis of cardiomyopathy by detection of the mutations in the most prevalent cardiomyopathy genes, the cause remains unsolved in many patients. High-throughput mutation screening in the disease genes for cardiomyopathy is now possible because of using target enrichment followed by next-generation sequencing. The aim of the study was to analyze a panel of genes associated with dilated or hypertrophic cardiomyopathy based on previously published results in order to identify the subjects at risk. The method of next-generation sequencing by IlluminaHiSeq 2500 platform was used to detect sequence variants in 16 individuals diagnosed with dilated or hypertrophic cardiomyopathy. Detected variants were filtered and the functional impact of amino acid changes was predicted by computational programs. DNA samples of the 16 patients were analyzed by whole exome sequencing. We identified six nonsynonymous variants that were shown to be pathogenic in all used prediction softwares: rs3744998 (EPG5), rs11551768 (MGME1), rs148374985 (MURC), rs78461695 (PLEC), rs17158558 (RET) and rs2295190 (SYNE1). Two of the analyzed sequence variants had minor allele frequency (MAF)<0.01: rs148374985 (MURC), rs34580776 (MYBPC3). Our data support the potential role of the detected variants in pathogenesis of dilated or hypertrophic cardiomyopathy; however, the possibility that these variants might not be true disease-causing variants but are susceptibility alleles that require additional mutations or injury to cause the clinical phenotype of disease must be considered. © 2017 Wiley Periodicals, Inc.

Modulation of Aneuploidy in Leishmania donovani during Adaptation to Different In Vitro and In Vivo Environments and Its Impact on Gene Expression.

PubMed

Dumetz, F; Imamura, H; Sanders, M; Seblova, V; Myskova, J; Pescher, P; Vanaerschot, M; Meehan, C J; Cuypers, B; De Muylder, G; Späth, G F; Bussotti, G; Vermeesch, J R; Berriman, M; Cotton, J A; Volf, P; Dujardin, J C; Domagalska, M A

2017-05-23

Aneuploidy is usually deleterious in multicellular organisms but appears to be tolerated and potentially beneficial in unicellular organisms, including pathogens. Leishmania , a major protozoan parasite, is emerging as a new model for aneuploidy, since in vitro -cultivated strains are highly aneuploid, with interstrain diversity and intrastrain mosaicism. The alternation of two life stages in different environments (extracellular promastigotes and intracellular amastigotes) offers a unique opportunity to study the impact of environment on aneuploidy and gene expression. We sequenced the whole genomes and transcriptomes of Leishmania donovani strains throughout their adaptation to in vivo conditions mimicking natural vertebrate and invertebrate host environments. The nucleotide sequences were almost unchanged within a strain, in contrast to highly variable aneuploidy. Although high in promastigotes in vitro , aneuploidy dropped significantly in hamster amastigotes, in a progressive and strain-specific manner, accompanied by the emergence of new polysomies. After a passage through a sand fly, smaller yet consistent karyotype changes were detected. Changes in chromosome copy numbers were correlated with the corresponding transcript levels, but additional aneuploidy-independent regulation of gene expression was observed. This affected stage-specific gene expression, downregulation of the entire chromosome 31, and upregulation of gene arrays on chromosomes 5 and 8. Aneuploidy changes in Leishmania are probably adaptive and exploited to modulate the dosage and expression of specific genes; they are well tolerated, but additional mechanisms may exist to regulate the transcript levels of other genes located on aneuploid chromosomes. Our model should allow studies of the impact of aneuploidy on molecular adaptations and cellular fitness. IMPORTANCE Aneuploidy is usually detrimental in multicellular organisms, but in several microorganisms, it can be tolerated and even beneficial. Leishmania -a protozoan parasite that kills more than 30,000 people each year-is emerging as a new model for aneuploidy studies, as unexpectedly high levels of aneuploidy are found in clinical isolates. Leishmania lacks classical regulation of transcription at initiation through promoters, so aneuploidy could represent a major adaptive strategy of this parasite to modulate gene dosage in response to stressful environments. For the first time, we document the dynamics of aneuploidy throughout the life cycle of the parasite, in vitro and in vivo We show its adaptive impact on transcription and its interaction with regulation. Besides offering a new model for aneuploidy studies, we show that further genomic studies should be done directly in clinical samples without parasite isolation and that adequate methods should be developed for this. Copyright © 2017 Dumetz et al.

Insights from 20 years of bacterial genome sequencing

DOE PAGES

Land, Miriam L.; Hauser, Loren; Jun, Se-Ran; ...

2015-02-27

Since the first two complete bacterial genome sequences were published in 1995, the science of bacteria has dramatically changed. Using third-generation DNA sequencing, it is possible to completely sequence a bacterial genome in a few hours and identify some types of methylation sites along the genome as well. Sequencing of bacterial genome sequences is now a standard procedure, and the information from tens of thousands of bacterial genomes has had a major impact on our views of the bacterial world. In this review, we explore a series of questions to highlight some insights that comparative genomics has produced. To date,more » there are genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. However, the distribution is quite skewed towards a few phyla that contain model organisms. But the breadth is continuing to improve, with projects dedicated to filling in less characterized taxonomic groups. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system provides bacteria with immunity against viruses, which outnumber bacteria by tenfold. How fast can we go? Second-generation sequencing has produced a large number of draft genomes (close to 90 % of bacterial genomes in GenBank are currently not complete); third-generation sequencing can potentially produce a finished genome in a few hours, and at the same time provide methlylation sites along the entire chromosome. The diversity of bacterial communities is extensive as is evident from the genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. Genome sequencing can help in classifying an organism, and in the case where multiple genomes of the same species are available, it is possible to calculate the pan- and core genomes; comparison of more than 2000 Escherichia coli genomes finds an E. coli core genome of about 3100 gene families and a total of about 89,000 different gene families. Why do we care about bacterial genome sequencing? There are many practical applications, such as genome-scale metabolic modeling, biosurveillance, bioforensics, and infectious disease epidemiology. In the near future, high-throughput sequencing of patient metagenomic samples could revolutionize medicine in terms of speed and accuracy of finding pathogens and knowing how to treat them.« less

Insights from 20 years of bacterial genome sequencing

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

Land, Miriam L.; Hauser, Loren; Jun, Se-Ran

Since the first two complete bacterial genome sequences were published in 1995, the science of bacteria has dramatically changed. Using third-generation DNA sequencing, it is possible to completely sequence a bacterial genome in a few hours and identify some types of methylation sites along the genome as well. Sequencing of bacterial genome sequences is now a standard procedure, and the information from tens of thousands of bacterial genomes has had a major impact on our views of the bacterial world. In this review, we explore a series of questions to highlight some insights that comparative genomics has produced. To date,more » there are genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. However, the distribution is quite skewed towards a few phyla that contain model organisms. But the breadth is continuing to improve, with projects dedicated to filling in less characterized taxonomic groups. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system provides bacteria with immunity against viruses, which outnumber bacteria by tenfold. How fast can we go? Second-generation sequencing has produced a large number of draft genomes (close to 90 % of bacterial genomes in GenBank are currently not complete); third-generation sequencing can potentially produce a finished genome in a few hours, and at the same time provide methlylation sites along the entire chromosome. The diversity of bacterial communities is extensive as is evident from the genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. Genome sequencing can help in classifying an organism, and in the case where multiple genomes of the same species are available, it is possible to calculate the pan- and core genomes; comparison of more than 2000 Escherichia coli genomes finds an E. coli core genome of about 3100 gene families and a total of about 89,000 different gene families. Why do we care about bacterial genome sequencing? There are many practical applications, such as genome-scale metabolic modeling, biosurveillance, bioforensics, and infectious disease epidemiology. In the near future, high-throughput sequencing of patient metagenomic samples could revolutionize medicine in terms of speed and accuracy of finding pathogens and knowing how to treat them.« less

The influence of lay-up and thickness on composite impact damage and compression strength

NASA Technical Reports Server (NTRS)

Guynn, E. G.; Obrien, T. K.

1985-01-01

The effects of composite stacking sequence, thickness, and percentage of zero-degree plies on the size, shape, and distribution of delamination through the laminate thickness and on residual compression strength following impact were studied. Graphite/epoxy laminates were impacted with an 0.5 inch diameter aluminum sphere at a specific low or high velocity. Impact damage was measured nondestructively by ultrasonic C-scans and X-radiography and destructively by the deply technique, and compression strength tests were performed. It was found that differences in compression failure strain due to stacking sequence were small, while laminates with very low percentages of zero-degree plies had similar failure loads but higher failure strains than laminates with higher percentages of zero-degree plies. Failure strain did not correlate with planar impact damage area, and delaminations in impact regions were associated with matrix cracking.

Late Neogene sedimentary facies and sequences in the Pannonian Basin, Hungary

USGS Publications Warehouse

Juhasz, E.; Phillips, L.; Muller, P.; Ricketts, B.; Toth-Makk, A.; Lantos, M.; Kovacs, L.O.

1999-01-01

This paper is part of the special publication No.156, The Mediterranean basins: Tertiary extension within the Alpine Orogen. (eds B.Durand, L. Jolivet, F.Horvath and M.Seranne). Detailed sedimentological, facies and numerical cycle analysis, combined with magnetostratigraphy, have been made in a number of boreholes in the Pannonian Basin, in order to study the causes of relative water-level changes and the history of the basin subsidence. Subsidence and infilling of the Pannonian Basin, which was an isolated lake at that time occurred mainly during the Late Miocene and Pliocene. The subsidence history was remarkably different in the individual sub-basins: early thermal subsidence was interrupted in the southern part of the basin, while high sedimentation rate and continuous subsidence was detected in the northeastern sub-basin. Three regional unconformities were detected in the Late Neogene Pannonian Basin fill, which represent 0.5 and 7.5 Ma time spans corresponding to single and composite unconformities. Consequently two main sequences build up the Late Neogene Pannonian Basin fill: a Late Miocene and a Pliocene one. Within the Late Miocene sequence there are smaller sedimentary cycles most probably corresponding to climatically driven relative lake-level changes in the Milankovitch frequency band. Considering the periods, the estimated values for precession and eccentricity in this study (19 and 370 ka) are close to the usually cited ones. In the case of obliquity the calculated period (71 ka) slightly deviates from the generally accepted number. Based on the relative amplitudes of oscillations, precession (sixth order) and obliquity (fifth order) cycles had the most significant impact on the sedimentation. Eccentricity caused cycles (fourth order) are poorly detectable in the sediments. The longer term (third order) cycles had very slight influence on the sedimentation pattern. Progradation, recorded in the Late Miocene sequence, correlates poorly in time within the basin. The dominant controls of this process probably were changes of basin subsidence rate and the very high sedimentation rate. The slow, upward trend of silt and sand bed thickness as well as that of the grain size also reflects the local progradation.

Use of ancient sedimentary DNA as a novel conservation tool for high-altitude tropical biodiversity.

PubMed

Boessenkool, Sanne; McGlynn, Gayle; Epp, Laura S; Taylor, David; Pimentel, Manuel; Gizaw, Abel; Nemomissa, Sileshi; Brochmann, Christian; Popp, Magnus

2014-04-01

Conservation of biodiversity may in the future increasingly depend upon the availability of scientific information to set suitable restoration targets. In traditional paleoecology, sediment-based pollen provides a means to define preanthropogenic impact conditions, but problems in establishing the exact provenance and ecologically meaningful levels of taxonomic resolution of the evidence are limiting. We explored the extent to which the use of sedimentary ancient DNA (sedaDNA) may complement pollen data in reconstructing past alpine environments in the tropics. We constructed a record of afro-alpine plants retrieved from DNA preserved in sediment cores from 2 volcanic crater sites in the Albertine Rift, eastern Africa. The record extended well beyond the onset of substantial anthropogenic effects on tropical mountains. To ensure high-quality taxonomic inference from the sedaDNA sequences, we built an extensive DNA reference library covering the majority of the afro-alpine flora, by sequencing DNA from taxonomically verified specimens. Comparisons with pollen records from the same sediment cores showed that plant diversity recovered with sedaDNA improved vegetation reconstructions based on pollen records by revealing both additional taxa and providing increased taxonomic resolution. Furthermore, combining the 2 measures assisted in distinguishing vegetation change at different geographic scales; sedaDNA almost exclusively reflects local vegetation, whereas pollen can potentially originate from a wide area that in highlands in particular can span several ecozones. Our results suggest that sedaDNA may provide information on restoration targets and the nature and magnitude of human-induced environmental changes, including in high conservation priority, biodiversity hotspots, where understanding of preanthropogenic impact (or reference) conditions is highly limited. © 2013 Society for Conservation Biology.

The impact of persistent bacterial bronchitis on the pulmonary microbiome of children

PubMed Central

Bingle, Lynne; Cookson, William O. C. M.; Everard, Mark L.; Moffatt, Miriam F.

2017-01-01

Introduction Persistent bacterial bronchitis (PBB) is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of PBB. Blind, protected brushings were obtained from 20 healthy controls and 24 children with PBB, with an additional directed sample obtained from PBB patients. DNA was extracted, quantified using a 16S rRNA gene quantitative PCR assay prior to microbial community analysis by 16S rRNA gene sequencing. Results No significant difference in bacterial diversity or community composition (R2 = 0.01, P = 0.36) was observed between paired blind and non-blind brushes, showing that blind brushings are a valid means of accessing the airway microbiota. This has important implications for collecting lower respiratory samples from healthy children. A significant decrease in bacterial diversity (P < 0.001) and change in community composition (R2 = 0.08, P = 0.004) was observed among controls, in comparison with patients. Bacterial communities within patients with PBB were dominated by Proteobacteria, and indicator species analysis showed that Haemophilus and Neisseria were significantly associated with the patient group. In 15 (52.9%) cases the dominant organism by sequencing was not identified by standard routine clinical culture. Conclusion The bacteria present in the lungs of patients with PBB were less diverse in terms of richness and evenness. The results validate the clinical diagnosis, and suggest that more attention to bacterial communities in children with chronic cough may lead to more rapid recognition of this condition with earlier treatment and reduction in disease burden. PMID:29281698

Species-Specific Exon Loss in Human Transcriptomes

PubMed Central

Wang, Jinkai; Lu, Zhi-xiang; Tokheim, Collin J.; Miller, Sara E.; Xing, Yi

2015-01-01

Changes in exon–intron structures and splicing patterns represent an important mechanism for the evolution of gene functions and species-specific regulatory networks. Although exon creation is widespread during primate and human evolution and has been studied extensively, much less is known about the scope and potential impact of human-specific exon loss events. Historically, transcriptome data and exon annotations are significantly biased toward humans over nonhuman primates. This ascertainment bias makes it challenging to discover human-specific exon loss events. We carried out a transcriptome-wide search of human-specific exon loss events, by taking advantage of RNA sequencing (RNA-seq) as a powerful and unbiased tool for exon discovery and annotation. Using RNA-seq data of humans, chimpanzees, and other primates, we reconstructed and compared transcript structures across the primate phylogeny. We discovered 33 candidate human-specific exon loss events, among which six exons passed stringent experimental filters for the complete loss of splicing activities in diverse human tissues. These events may result from human-specific deletion of genomic DNA, or small-scale sequence changes that inactivated splicing signals. The impact of human-specific exon loss events is predominantly regulatory. Three of the six events occurred in the 5′ untranslated region (5′-UTR) and affected cis-regulatory elements of mRNA translation. In SLC7A6, a gene encoding an amino acid transporter, luciferase reporter assays suggested that both a human-specific exon loss event and an independent human-specific single nucleotide substitution in the 5′-UTR increased mRNA translational efficiency. Our study provides novel insights into the molecular mechanisms and evolutionary consequences of exon loss during human evolution. PMID:25398629

Thousands of Viral Populations Recovered from Peatland Soil Metagenomes Reveal Viral Impacts on Carbon Cycling in Thawing Permafrost

NASA Astrophysics Data System (ADS)

Emerson, J. B.; Brum, J. R.; Roux, S.; Bolduc, B.; Woodcroft, B. J.; Singleton, C. M.; Boyd, J. A.; Hodgkins, S. B.; Wilson, R.; Trubl, G. G.; Jang, H. B.; Crill, P. M.; Chanton, J.; Saleska, S. R.; Rich, V. I.; Tyson, G. W.; Sullivan, M. B.

2016-12-01

Methane and carbon dioxide emissions, which are under significant microbial control, provide positive feedbacks to climate change in thawing permafrost peatlands. Although viruses in marine systems have been shown to impact microbial ecology and biogeochemical cycling through host cell lysis, horizontal gene transfer, and auxiliary metabolic gene expression, viral ecology in permafrost and other soils remains virtually unstudied due to methodological challenges. Here, we identified viral sequences in 208 assembled bulk soil metagenomes derived from a permafrost thaw gradient in Stordalen Mire, northern Sweden, from 2010-2012. 2,048 viral populations were recovered, which genome- and network-based classification revealed to be largely novel, increasing known viral genera globally by 40%. Ecologically, viral communities differed significantly across the thaw gradient and by soil depth. Co-occurring microbial community composition, soil moisture, and pH were predictors of viral community composition, indicative of biological and biogeochemical feedbacks as permafrost thaws. Host prediction—achieved through clustered regularly interspaced short palindromic repeats (CRISPRs), tetranucleotide frequency patterns, and other sequence similarities to binned microbial population genomes—was able to link 38% of the viral populations to a microbial host. 5% of the implicated hosts were archaea, predominantly methanogens and ammonia-oxidizing Nitrososphaera, 45% were Acidobacteria or Verrucomicrobia (mostly predicted heterotrophic complex carbon degraders), and 21% were Proteobacteria, including methane oxidizers. Recovered viral genome fragments also contained auxiliary metabolic genes involved in carbon and nitrogen cycling. Together, these data reveal multiple levels of previously unknown viral contributions to biogeochemical cycling, including to carbon gas emissions, in peatland soils undergoing and contributing to climate change. This work represents a significant step towards understanding viral roles in microbially-mediated biogeochemical cycling in soil.

Geomorphic and habitat response to a large-dam removal in a Mediterranean river

NASA Astrophysics Data System (ADS)

Harrison, L.; East, A. E.; Smith, D. P.; Bond, R.; Logan, J. B.; Nicol, C.; Williams, T.; Boughton, D. A.; Chow, K.

2017-12-01

The presence of large dams has fundamentally altered physical and biological processes in riverine ecosystems, and dam removal is becoming more common as a river restoration strategy. We used a before-after-control-impact study design to investigate the geomorphic and habitat response to removal of 32-m-high San Clemente Dam on the Carmel River, CA. The project represents the first major dam removal in a Mediterranean river and is also unique among large dam removals in that most reservoir sediment was sequestered in place. We found that in the first year post-removal, a sediment pulse migrated 3.5 km downstream, filling pools and the interstitial pore spaces of gravels with sand. These sedimentary and topographic changes initially reduced the overall quality of steelhead (O. mykiss) spawning and rearing habitat in impacted reaches. Over the second winter after dam removal, a sequence of high flows flushed large volumes of sand from pools and mobilized the river bed throughout much of the active channel. The floods substantially altered fluvial evolution in the upper part of the reservoir, promoting new avulsion and the subsequent delivery of gravel and large wood to below dam reaches. These geomorphic processes increased the availability of spawning-sized gravel and enhanced channel complexity in reaches within several km of the former dam, which should improve habitat for multiple life stages of steelhead. Results indicate that when most reservoir sediment remains impounded, high flows become more important drivers of geomorphic and habitat change than dam removal alone. In such cases, the rates at which biophysical processes are reestablished will depend largely on post-dam removal flow sequencing and the upstream supply of sediment and large wood.

Changes in spinal reflex excitability associated with motor sequence learning.

PubMed

Lungu, Ovidiu; Frigon, Alain; Piché, Mathieu; Rainville, Pierre; Rossignol, Serge; Doyon, Julien

2010-05-01

There is ample evidence that motor sequence learning is mediated by changes in brain activity. Yet the question of whether this form of learning elicits changes detectable at the spinal cord level has not been addressed. To date, studies in humans have revealed that spinal reflex activity may be altered during the acquisition of various motor skills, but a link between motor sequence learning and changes in spinal excitability has not been demonstrated. To address this issue, we studied the modulation of H-reflex amplitude evoked in the flexor carpi radialis muscle of 14 healthy individuals between blocks of movements that involved the implicit acquisition of a sequence versus other movements that did not require learning. Each participant performed the task in three conditions: "sequence"-externally triggered, repeating and sequential movements, "random"-similar movements, but performed in an arbitrary order, and "simple"- involving alternating movements in a left-right or up-down direction only. When controlling for background muscular activity, H-reflex amplitude was significantly more reduced in the sequence (43.8 +/- 1.47%. mean +/- SE) compared with the random (38.2 +/- 1.60%) and simple (31.5 +/- 1.82%) conditions, while the M-response was not different across conditions. Furthermore, H-reflex changes were observed from the beginning of the learning process up to when subjects reached asymptotic performance on the motor task. Changes also persisted for >60 s after motor activity ceased. Such findings suggest that the excitability in some spinal reflex circuits is altered during the implicit learning process of a new motor sequence.

Weeds in a Changing Climate: Vulnerabilities, Consequences, and Implications for Future Weed Management

PubMed Central

Ramesh, Kulasekaran; Matloob, Amar; Aslam, Farhena; Florentine, Singarayer K.; Chauhan, Bhagirath S.

2017-01-01

Whilst it is agreed that climate change will impact on the long-term interactions between crops and weeds, the results of this impact are far from clear. We suggest that a thorough understanding of weed dominance and weed interactions, depending on crop and weed ecosystems and crop sequences in the ecosystem, will be the key determining factor for successful weed management. Indeed, we claim that recent changes observed throughout the world within the weed spectrum in different cropping systems which were ostensibly related to climate change, warrant a deeper examination of weed vulnerabilities before a full understanding is reached. For example, the uncontrolled establishment of weeds in crops leads to a mixed population, in terms of C3 and C4 pathways, and this poses a considerable level of complexity for weed management. There is a need to include all possible combinations of crops and weeds while studying the impact of climate change on crop-weed competitive interactions, since, from a weed management perspective, C4 weeds would flourish in the increased temperature scenario and pose serious yield penalties. This is particularly alarming as a majority of the most competitive weeds are C4 plants. Although CO2 is considered as a main contributing factor for climate change, a few Australian studies have also predicted differing responses of weed species due to shifts in rainfall patterns. Reduced water availability, due to recurrent and unforeseen droughts, would alter the competitive balance between crops and some weed species, intensifying the crop-weed competition pressure. Although it is recognized that the weed pressure associated with climate change is a significant threat to crop production, either through increased temperatures, rainfall shift, and elevated CO2 levels, the current knowledge of this effect is very sparse. A few models that have attempted to predict these interactions are discussed in this paper, since these models could play an integral role in developing future management programs for future weed threats. This review has presented a comprehensive discussion of the recent research in this area, and has identified key deficiencies which need further research in crop-weed eco-systems to formulate suitable control measures before the real impacts of climate change set in. PMID:28243245

Divergent Relationships between Fecal Microbiota and Metabolome following Distinct Antibiotic-Induced Disruptions.

PubMed

Choo, Jocelyn M; Kanno, Tokuwa; Zain, Nur Masirah Mohd; Leong, Lex E X; Abell, Guy C J; Keeble, Julie E; Bruce, Kenneth D; Mason, A James; Rogers, Geraint B

2017-01-01

The intestinal microbiome plays an essential role in regulating many aspects of host physiology, and its disruption through antibiotic exposure has been implicated in the development of a range of serious pathologies. The complex metabolic relationships that exist between members of the intestinal microbiota and the potential redundancy in functional pathways mean that an integrative analysis of changes in both structure and function are needed to understand the impact of antibiotic exposure. We used a combination of next-generation sequencing and nuclear magnetic resonance (NMR) metabolomics to characterize the effects of two clinically important antibiotic treatments, ciprofloxacin and vancomycin-imipenem, on the intestinal microbiomes of female C57BL/6 mice. This assessment was performed longitudinally and encompassed both antibiotic challenge and subsequent microbiome reestablishment. Both antibiotic treatments significantly altered the microbiota and metabolite compositions of fecal pellets during challenge and recovery. Spearman's correlation analysis of microbiota and NMR data revealed that, while some metabolites could be correlated with individual operational taxonomic units (OTUs), frequently multiple OTUs were associated with a significant change in a given metabolite. Furthermore, one metabolite, arginine, can be associated with increases/decreases in different sets of OTUs under differing conditions. Taken together, these findings indicate that reliance on shifts in one data set alone will generate an incomplete picture of the functional effect of antibiotic intervention. A full mechanistic understanding will require knowledge of the baseline microbiota composition, combined with both a comparison and an integration of microbiota, metabolomics, and phenotypic data. IMPORTANCE Despite the fundamental importance of antibiotic therapies to human health, their functional impact on the intestinal microbiome and its subsequent ability to recover are poorly understood. Much research in this area has focused on changes in microbiota composition, despite the interdependency and overlapping functions of many members of the microbial community. These relationships make prediction of the functional impact of microbiota-level changes difficult, while analyses based on the metabolome alone provide relatively little insight into the taxon-level changes that underpin changes in metabolite levels. Here, we used combined microbiota and metabolome profiling to characterize changes associated with clinically important antibiotic combinations with distinct effects on the gut. Correlation analysis of changes in the metabolome and microbiota indicate that a combined approach will be essential for a mechanistic understanding of the functional impact of distinct antibiotic classes.

Weeds in a Changing Climate: Vulnerabilities, Consequences, and Implications for Future Weed Management.

PubMed

Ramesh, Kulasekaran; Matloob, Amar; Aslam, Farhena; Florentine, Singarayer K; Chauhan, Bhagirath S

2017-01-01

Whilst it is agreed that climate change will impact on the long-term interactions between crops and weeds, the results of this impact are far from clear. We suggest that a thorough understanding of weed dominance and weed interactions, depending on crop and weed ecosystems and crop sequences in the ecosystem, will be the key determining factor for successful weed management. Indeed, we claim that recent changes observed throughout the world within the weed spectrum in different cropping systems which were ostensibly related to climate change, warrant a deeper examination of weed vulnerabilities before a full understanding is reached. For example, the uncontrolled establishment of weeds in crops leads to a mixed population, in terms of C 3 and C 4 pathways, and this poses a considerable level of complexity for weed management. There is a need to include all possible combinations of crops and weeds while studying the impact of climate change on crop-weed competitive interactions, since, from a weed management perspective, C 4 weeds would flourish in the increased temperature scenario and pose serious yield penalties. This is particularly alarming as a majority of the most competitive weeds are C 4 plants. Although CO 2 is considered as a main contributing factor for climate change, a few Australian studies have also predicted differing responses of weed species due to shifts in rainfall patterns. Reduced water availability, due to recurrent and unforeseen droughts, would alter the competitive balance between crops and some weed species, intensifying the crop-weed competition pressure. Although it is recognized that the weed pressure associated with climate change is a significant threat to crop production, either through increased temperatures, rainfall shift, and elevated CO 2 levels, the current knowledge of this effect is very sparse. A few models that have attempted to predict these interactions are discussed in this paper, since these models could play an integral role in developing future management programs for future weed threats. This review has presented a comprehensive discussion of the recent research in this area, and has identified key deficiencies which need further research in crop-weed eco-systems to formulate suitable control measures before the real impacts of climate change set in.

The Cretaceous-Tertiary boundary interval in Badlands National Park, South Dakota

USGS Publications Warehouse

Stoffer, Philip W.; Messina, Paula; Chamberlain, John A.; Terry, Dennis O.

2001-01-01

A marine K-T boundary interval has been identified throughout the Badlands National Park region of South Dakota. Data from marine sediments suggest that deposits from two asteroid impacts (one close, one far away) may be preserved in the Badlands. These impact-generated deposits may represent late Maestrichtian events or possibly the terminal K-T event. Interpretation is supported by paleontological correlation, sequence stratigraphy, magnetostratigraphy, and strontium isotope geochronology. This research is founded on nearly a decade of NPS approved field work in Badlands National Park and a foundation of previously published data and interpretations. The K-T boundary occurs within or near the base of a stratigraphic interval referred to as the "Interior Zone." We interpret the stratigraphy of the Interior Zone as a series of distinct, recognizable lithologic members and units from oldest to youngest, an upper weathered interval of the Elk Butte Member of the Pierre Shale (early late Maestrichtian), a complete (albeit condensed) interval of Fox Hill Formation, a pedogenically altered K-T Boundary "Disturbed Zone," and a generally unresolved sequence of marine to marginal marine units ranging in age from possibly latest Maestrichtian to late Paleocene (the "Yellow Mounds"), that underlie a basal red clay unit (the late Eocene overbank channel facies of the Chamberlain Pass Formation at the base of the White River Group). Within this sequence is a series of unconformities that all display some degree of subaerial weathering and erosion. The dating of marine fossils above and below these unconformities are in line with generally accepted global sea-level changes recognized for the late Campanian through early Eocene. Within the greater framework of regional geology, these findings support that the Western Interior Seaway and subsequent Cannonball Seaway were dependently linked to the changing base-level controlled by sea-level of the global ocean through the Gulf of Mexico and possibly the Arctic Ocean. The variation of facies preserved in Late Cretaceous strata in the Badlands National Park area were in part controlled by local or regional tectonic blocks that were either rising or sinking contemporaneous with deposition.

WONOEP appraisal: new genetic approaches to study epilepsy

PubMed Central

Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

2014-01-01

Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non-coding RNAs involved in modifying gene expression following seizures. In addition, genetically-based bioluminescent reporters are providing new opportunities to assess neuronal activity and neurotransmitter levels both in vitro and in vivo in the context of epilepsy. Finally, genetically rederived neurons generated from patient iPS cells and genetically-modified zebrafish have become high-throughput means to investigate disease mechanisms and potential new therapies. Significance Genetics has considerably changed the field of epilepsy research and is paving the way for better diagnosis and therapies for patients with epilepsy. PMID:24965021

The effect of repetitive subconcussive collisions on brain integrity in collegiate football players over a single football season: A multi-modal neuroimaging study.

PubMed

Slobounov, Semyon M; Walter, Alexa; Breiter, Hans C; Zhu, David C; Bai, Xiaoxiao; Bream, Tim; Seidenberg, Peter; Mao, Xianglun; Johnson, Brian; Talavage, Thomas M

2017-01-01

The cumulative effect of repetitive subconcussive collisions on the structural and functional integrity of the brain remains largely unknown. Athletes in collision sports, like football, experience a large number of impacts across a single season of play. The majority of these impacts, however, are generally overlooked, and their long-term consequences remain poorly understood. This study sought to examine the effects of repetitive collisions across a single competitive season in NCAA Football Bowl Subdivision athletes using advanced neuroimaging approaches. Players were evaluated before and after the season using multiple MRI sequences, including T 1 -weighted imaging, diffusion tensor imaging (DTI), arterial spin labeling (ASL), resting-state functional MRI (rs-fMRI), and susceptibility weighted imaging (SWI). While no significant differences were found between pre- and post-season for DTI metrics or cortical volumes, seed-based analysis of rs-fMRI revealed significant ( p  < 0.05) changes in functional connections to right isthmus of the cingulate cortex (ICC), left ICC, and left hippocampus. ASL data revealed significant ( p  < 0.05) increases in global cerebral blood flow (CBF), with a specific regional increase in right postcentral gyrus. SWI data revealed that 44% of the players exhibited outlier rates ( p  < 0.05) of regional decreases in SWI signal. Of key interest, athletes in whom changes in rs-fMRI, CBF and SWI were observed were more likely to have experienced high G impacts on a daily basis. These findings are indicative of potential pathophysiological changes in brain integrity arising from only a single season of participation in the NCAA Football Bowl Subdivision, even in the absence of clinical symptoms or a diagnosis of concussion. Whether these changes reflect compensatory adaptation to cumulative head impacts or more lasting alteration of brain integrity remains to be further explored.

Adapting crop rotations to climate change in regional impact modelling assessments.

PubMed

Teixeira, Edmar I; de Ruiter, John; Ausseil, Anne-Gaelle; Daigneault, Adam; Johnstone, Paul; Holmes, Allister; Tait, Andrew; Ewert, Frank

2018-03-01

The environmental and economic sustainability of future cropping systems depends on adaptation to climate change. Adaptation studies commonly rely on agricultural systems models to integrate multiple components of production systems such as crops, weather, soil and farmers' management decisions. Previous adaptation studies have mostly focused on isolated monocultures. However, in many agricultural regions worldwide, multi-crop rotations better represent local production systems. It is unclear how adaptation interventions influence crops grown in sequences. We develop a catchment-scale assessment to investigate the effects of tactical adaptations (choice of genotype and sowing date) on yield and underlying crop-soil factors of rotations. Based on locally surveyed data, a silage-maize followed by catch-crop-wheat rotation was simulated with the APSIM model for the RCP 8.5 emission scenario, two time periods (1985-2004 and 2080-2100) and six climate models across the Kaituna catchment in New Zealand. Results showed that direction and magnitude of climate change impacts, and the response to adaptation, varied spatially and were affected by rotation carryover effects due to agronomical (e.g. timing of sowing and harvesting) and soil (e.g. residual nitrogen, N) aspects. For example, by adapting maize to early-sowing dates under a warmer climate, there was an advance in catch crop establishment which enhanced residual soil N uptake. This dynamics, however, differed with local environment and choice of short- or long-cycle maize genotypes. Adaptation was insufficient to neutralize rotation yield losses in lowlands but consistently enhanced yield gains in highlands, where other constraints limited arable cropping. The positive responses to adaptation were mainly due to increases in solar radiation interception across the entire growth season. These results provide deeper insights on the dynamics of climate change impacts for crop rotation systems. Such knowledge can be used to develop improved regional impact assessments for situations where multi-crop rotations better represent predominant agricultural systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Professional development that works: Impacting elementary science teachers' learning and practice during the implementation of an inquiry-oriented science curriculum

NASA Astrophysics Data System (ADS)

Schlang, Jodi A.

One of the most important factors for developing science literacy for all students is teacher knowledge of science content and pedagogy. This study was designed to evaluate the impact of professional development on teacher learning, changes in teacher behavior, and student learning. The goal was to develop a deeper understanding of how the Elementary Science Teaching and Learning (ESTL) program affected teacher learning and changed teacher behavior in the classroom. This study also provided insight into the effect of the ESTL program on student learning during the first year of the professional development. This mixed method case study was used to examine the link between participation in the ESTL program, teacher learning, changes in teacher classroom behavior, and student learning. Qualitative observations and videotaped sessions provided rich description of the professional development and implementation of inquiry-oriented strategies in participant's classrooms. Artifacts and interviews provided evidence of teacher learning and changes in teacher behaviors. Quantitative data included self-report survey data examining changes in teacher behavior and the measurement of student learning used both science district assessment scores and CSAP writing scores. Key findings include: (1) teacher learning was reported in the areas of questioning and scope and sequence of the curriculum occurred; (2) statistically significant changes teacher behavior were reported and were noted in teacher interviews; (3) participation in the ESTL program did not positively impact student learning; (4) unanticipated findings include the role of camaraderie in professional development and the role of additional training in teacher's confidence in both their own teaching and in helping others; and, (5) teacher's perceptions identified the role of inquiry-based science curriculum as providing the rich experiences necessary for improved student writing. Overall participation in the ESTL program increased the implementation of inquiry-oriented strategies and it strengthened teacher inquiry-based science teaching in the classroom even though no increases were found in student test scores.

Impact of a low severity fire on soil organic carbon and nitrogen characteristics in Japanese cedar soil Yamagata Prefecture, Japan

NASA Astrophysics Data System (ADS)

Seidel, Felix

2017-04-01

Slash and burn practices are widely used around the globe with different degrees of success which are mostly related to the impact of fire on the soil properties. In Japan slash and burn practises, known as Yakihata, have a long history and are still used in Yamagata Prefecture today. The purpose of this study was to determine the impact of a low severity controlled fire on Japanese cedar (Cryptomeria japonica) forest soil (Cambisol) which is the dominant species among plantations in Japan. We measured organic carbon and nitrogen content as well as changes in carbon (δ13C) and nitrogen (δ15N) stable isotope composition in a steep west facing slope under heavy precipitation ( 2600 mm/a) and heavy snowfall ( 3-4 m/a). The results show that Ctotal and Ntotal values as well as the isotopes ratios of C and N change with decreasing elevation in the forest as well as in the burned site being consistent with leaching and erosion. The accumulation of Ctotal and Ntotal at the bottom of the slopes was remarkably higher at the slash and burned site than in the control forest site. After slash and burn δ15N isotopes in the slope in general became significantly lighter than in the control forest while the δ13C did not show any significant difference between the two sites except at the bottom of the slopes where δ13C was heavier in the forest. The reason for these changes in nitrogen and carbon isotopes appears to be related to the physical changes in soil horizon sequence of the original forest soil layer. Keywords: high precipitation, Japanese cedar forest soil, low severity fire, stable isotopes, steep slopes

Analysis of simian immunodeficiency virus sequence variation in tissues of rhesus macaques with simian AIDS.

PubMed Central

Kodama, T; Mori, K; Kawahara, T; Ringler, D J; Desrosiers, R C

1993-01-01

One rhesus macaque displayed severe encephalomyelitis and another displayed severe enterocolitis following infection with molecularly cloned simian immunodeficiency virus (SIV) strain SIVmac239. Little or no free anti-SIV antibody developed in these two macaques, and they died relatively quickly (4 to 6 months) after infection. Manifestation of the tissue-specific disease in these macaques was associated with the emergence of variants with high replicative capacity for macrophages and primary infection of tissue macrophages. The nature of sequence variation in the central region (vif, vpr, and vpx), the env gene, and the nef long terminal repeat (LTR) region in brain, colon, and other tissues was examined to see whether specific genetic changes were associated with SIV replication in brain or gut. Sequence analysis revealed strong conservation of the intergenic central region, nef, and the LTR. However, analysis of env sequences in these two macaques and one other revealed significant, interesting patterns of sequence variation. (i) Changes in env that were found previously to contribute to the replicative ability of SIVmac for macrophages in culture were present in the tissues of these animals. (ii) The greatest variability was located in the regions between V1 and V2 and from "V3" through C3 in gp120, which are different in location from the variable regions observed previously in animals with strong antibody responses and long-term persistent infection. (iii) The predominant sequence change of D-->N at position 385 in C3 is most surprising, since this change in both SIV and human immunodeficiency virus type 1 has been associated with dramatically diminished affinity for CD4 and replication in vitro. (iv) The nature of sequence changes at some positions (146, 178, 345, 385, and "V3") suggests that viral replication in brain and gut may be facilitated by specific sequence changes in env in addition to those that impart a general ability to replicate well in macrophages. These results demonstrate that complex selective pressures, including immune responses and varying cell and tissue specificity, can influence the nature of sequence changes in env. Images PMID:8411355

Application of a time-dependent coalescence process for inferring the history of population size changes from DNA sequence data.

PubMed

Polanski, A; Kimmel, M; Chakraborty, R

1998-05-12

Distribution of pairwise differences of nucleotides from data on a sample of DNA sequences from a given segment of the genome has been used in the past to draw inferences about the past history of population size changes. However, all earlier methods assume a given model of population size changes (such as sudden expansion), parameters of which (e.g., time and amplitude of expansion) are fitted to the observed distributions of nucleotide differences among pairwise comparisons of all DNA sequences in the sample. Our theory indicates that for any time-dependent population size, N(tau) (in which time tau is counted backward from present), a time-dependent coalescence process yields the distribution, p(tau), of the time of coalescence between two DNA sequences randomly drawn from the population. Prediction of p(tau) and N(tau) requires the use of a reverse Laplace transform known to be unstable. Nevertheless, simulated data obtained from three models of monotone population change (stepwise, exponential, and logistic) indicate that the pattern of a past population size change leaves its signature on the pattern of DNA polymorphism. Application of the theory to the published mtDNA sequences indicates that the current mtDNA sequence variation is not inconsistent with a logistic growth of the human population.

Adolescence and changing family relations in the Central Canadian Arctic.

PubMed

Condon, R G

1990-04-01

This paper reports on a ten-year longitudinal study of adolescent development and socialization conducted in the Copper Inuit community of Holman. This research has documented how demographic, social, and economic changes have dramatically altered the patterning and sequencing of traditional Inuit life stages, thus giving rise to a prolonged adolescent life stage which was non-existent in the precontact period. At the same time, Inuit family relations have undergone drastic changes as a result of population increase, population concentration, access to government housing, introduction of formal schooling, and the availability of social subsides. Today, the Copper Inuit family has lost its focus as the primary agent of socialization and learning, and many young Inuit now spend most of their time within the context of a greatly expanded peer group which has gradually acquired the values and aspirations of the southern adolescent sub-culture. This paper will discuss the impact of these changing attitudes upon parent-child relations as well as the social adjustment problems experienced by young Inuit as they strive to find a place in the North's changing social landscape.

Environmental conditions and geomorphologic changes during the Middle-Upper Paleolithic in the southern Iberian Peninsula

NASA Astrophysics Data System (ADS)

Jiménez-Espejo, Francisco J.; Rodríguez-Vidal, Joaquín; Finlayson, Clive; Martínez-Ruiz, Francisca; Carrión, José S.; García-Alix, Antonio; Paytan, Adina; Giles Pacheco, Francisco; Fa, Darren A.; Finlayson, Geraldine; Cortés-Sánchez, Miguel; Rodrigo Gámiz, Marta; González-Donoso, José M.; Linares, M. Dolores; Cáceres, Luis M.; Fernández, Santiago; Iijima, Koichi; Martínez Aguirre, Aranzazu

2013-01-01

This study utilizes geomorphology, marine sediment data, environmental reconstructions and the Gorham's Cave occupational record during the Middle to Upper Paleolithic transition to illustrate the impacts of climate changes on human population dynamics in the Western Mediterranean. Geomorphologic evolution has been dated and appears to be driven primarily by coastal dune systems, sea-level changes and seismo-tectonic evolution. Continental and marine records are well correlated and used to interpret the Gorham's Cave sequence. Specific focus is given to the three hiatus sections found in Gorham's Cave during Heinrich periods 4, 3 and 2. These time intervals are compared with a wide range of regional geomorphologic, climatic, paleoseismic, faunal and archeological records. Our data compilations indicate that climatic and local geomorphologic changes explain the Homo sapiens spp. occupational hiatuses during Heinrich periods 4 and 3. The last hiatus corresponds to the replacement of Homo neanderthalensis by H. sapiens. Records of dated cave openings, slope breccias and stalactite falls suggest that marked geomorphologic changes, seismic activity and ecological perturbations occurred during the period when Homo replacement took place.

Geomorphic Complexity of Sequential Fire and Floods in Mountain Watersheds

NASA Astrophysics Data System (ADS)

Brogan, D. J.; Nelson, P. A.; MacDonald, L. H.; Morgan, J. A.

2017-12-01

Fires and floods are important drivers of fluvial geomorphic changes. While each has been studied independently, there have been almost no situations where the hydrologic and geomorphic effects of fires and extreme floods could be compared at the watershed scale. Following the 2012 High Park fire in montane northcentral Colorado we began intensively monitoring channel changes in two 15 km2 watersheds (Skin Gulch and Hill Gulch) burned primarily at moderate to high severity. Summer thunderstorms resulted in extensive hillslope erosion and deposition in the valley bottoms, and subsequent incision through these deposits occurred due to spring snowmelt and elevated baseflows. The complex response associated with this state change from unburned to burned can be completely disrupted and overwhelmed by the larger changes resulting from extreme floods. Fifteen months after burning, both watersheds experienced an extreme flood resulting from a long-duration rainstorm; however, the geomorphic changes resulting from this flood differed markedly between the two watersheds. In Skin Gulch, sustained high flows from the September 2013 flood excavated nearly all of the accumulated sediment, expanded the active channel, and either scoured to bedrock or armored the bed with coarser substrate. Geomorphic changes in Hill Gulch due to the September 2013 flood, however, were small. The disparity between watersheds is likely the legacy of the catastrophic 1976 Big Thompson flood, which scoured out much of the previously accumulated sediment in Hill Gulch but did not appreciably impact Skin Gulch. These different sequences of disturbances indicate that fires in the Rocky Mountains often generate significant and dynamic geomorphic changes over sub-decadal timescales, while extreme floods can result in much longer lasting geomorphic changes. Our results allow us to compare the geomorphic sensitivity for different sequences of fire and floods, and propose a new conceptual model to explain the complicated interactions between the effects of fires and floods on the landscape.

Exploring the Impacts of Anthropogenic Disturbance on Seawater and Sediment Microbial Communities in Korean Coastal Waters Using Metagenomics Analysis

PubMed Central

Won, Nam-Il; Kim, Ki-Hwan; Kang, Ji Hyoun; Park, Sang Rul; Lee, Hyuk Je

2017-01-01

The coastal ecosystems are considered as one of the most dynamic and vulnerable environments under various anthropogenic developments and the effects of climate change. Variations in the composition and diversity of microbial communities may be a good indicator for determining whether the marine ecosystems are affected by complex forcing stressors. DNA sequence-based metagenomics has recently emerged as a promising tool for analyzing the structure and diversity of microbial communities based on environmental DNA (eDNA). However, few studies have so far been performed using this approach to assess the impacts of human activities on the microbial communities in marine systems. In this study, using metagenomic DNA sequencing (16S ribosomal RNA gene), we analyzed and compared seawater and sediment communities between sand mining and control (natural) sites in southern coastal waters of Korea to assess whether anthropogenic activities have significantly affected the microbial communities. The sand mining sites harbored considerably lower levels of microbial diversities in the surface seawater community during spring compared with control sites. Moreover, the sand mining areas had distinct microbial taxonomic group compositions, particularly during spring season. The microbial groups detected solely in the sediment load/dredging areas (e.g., Marinobacter, Alcanivorax, Novosphingobium) are known to be involved in degradation of toxic chemicals such as hydrocarbon, oil, and aromatic compounds, and they also contain potential pathogens. This study highlights the versatility of metagenomics in monitoring and diagnosing the impacts of human disturbance on the environmental health of marine ecosystems from eDNA. PMID:28134828

Exploring the Impacts of Anthropogenic Disturbance on Seawater and Sediment Microbial Communities in Korean Coastal Waters Using Metagenomics Analysis.

PubMed

Won, Nam-Il; Kim, Ki-Hwan; Kang, Ji Hyoun; Park, Sang Rul; Lee, Hyuk Je

2017-01-27

The coastal ecosystems are considered as one of the most dynamic and vulnerable environments under various anthropogenic developments and the effects of climate change. Variations in the composition and diversity of microbial communities may be a good indicator for determining whether the marine ecosystems are affected by complex forcing stressors. DNA sequence-based metagenomics has recently emerged as a promising tool for analyzing the structure and diversity of microbial communities based on environmental DNA (eDNA). However, few studies have so far been performed using this approach to assess the impacts of human activities on the microbial communities in marine systems. In this study, using metagenomic DNA sequencing (16S ribosomal RNA gene), we analyzed and compared seawater and sediment communities between sand mining and control (natural) sites in southern coastal waters of Korea to assess whether anthropogenic activities have significantly affected the microbial communities. The sand mining sites harbored considerably lower levels of microbial diversities in the surface seawater community during spring compared with control sites. Moreover, the sand mining areas had distinct microbial taxonomic group compositions, particularly during spring season. The microbial groups detected solely in the sediment load/dredging areas (e.g., Marinobacter, Alcanivorax, Novosphingobium) are known to be involved in degradation of toxic chemicals such as hydrocarbon, oil, and aromatic compounds, and they also contain potential pathogens. This study highlights the versatility of metagenomics in monitoring and diagnosing the impacts of human disturbance on the environmental health of marine ecosystems from eDNA.

Integration of mechanical, structural and electrical imaging to understand response to cardiac resynchronization therapy.

PubMed

Silva, Etelvino; Bijnens, Bart; Berruezo, Antonio; Mont, Lluis; Doltra, Adelina; Andreu, David; Brugada, Josep; Sitges, Marta

2014-10-01

There is extensive controversy exists on whether cardiac resynchronization therapy corrects electrical or mechanical asynchrony. The aim of this study was to determine if there is a correlation between electrical and mechanical sequences and if myocardial scar has any relevant impact. Six patients with normal left ventricular function and 12 patients with left ventricular dysfunction and left bundle branch block, treated with cardiac resynchronization therapy, were studied. Real-time three-dimensional echocardiography and electroanatomical mapping were performed in all patients and, where applicable, before and after therapy. Magnetic resonance was performed for evaluation of myocardial scar. Images were postprocessed and mechanical and electrical activation sequences were defined and time differences between the first and last ventricular segment to be activated were determined. Response to therapy was defined as a reduction in left ventricular end-systolic volume ≥ 15% after 12 months of follow-up. Good correlation between electrical and mechanical timings was found in patients with normal left ventricular function (r(2) = 0.88; P = .005) but not in those with left ventricular dysfunction (r(2) = 0.02; P = not significant). After therapy, both timings and sequences were modified and improved, except in those with myocardial scar. Despite a close electromechanical relationship in normal left ventricular function, there is no significant correlation in patients with dysfunction. Although resynchronization therapy improves this correlation, the changes in electrical activation may not yield similar changes in left ventricular mechanics particularly depending on the underlying myocardial substrate. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Targeted Sequencing of Venom Genes from Cone Snail Genomes Improves Understanding of Conotoxin Molecular Evolution

PubMed Central

Mahardika, Gusti N

2018-01-01

Abstract To expand our capacity to discover venom sequences from the genomes of venomous organisms, we applied targeted sequencing techniques to selectively recover venom gene superfamilies and nontoxin loci from the genomes of 32 cone snail species (family, Conidae), a diverse group of marine gastropods that capture their prey using a cocktail of neurotoxic peptides (conotoxins). We were able to successfully recover conotoxin gene superfamilies across all species with high confidence (> 100× coverage) and used these data to provide new insights into conotoxin evolution. First, we found that conotoxin gene superfamilies are composed of one to six exons and are typically short in length (mean = ∼85 bp). Second, we expanded our understanding of the following genetic features of conotoxin evolution: 1) positive selection, where exons coding the mature toxin region were often three times more divergent than their adjacent noncoding regions, 2) expression regulation, with comparisons to transcriptome data showing that cone snails only express a fraction of the genes available in their genome (24–63%), and 3) extensive gene turnover, where Conidae species varied from 120 to 859 conotoxin gene copies. Finally, using comparative phylogenetic methods, we found that while diet specificity did not predict patterns of conotoxin evolution, dietary breadth was positively correlated with total conotoxin gene diversity. Overall, the targeted sequencing technique demonstrated here has the potential to radically increase the pace at which venom gene families are sequenced and studied, reshaping our ability to understand the impact of genetic changes on ecologically relevant phenotypes and subsequent diversification. PMID:29514313

The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia.

PubMed

Holter-Chakrabarty, Jennifer L; Pierson, Namali; Zhang, Mei-Jie; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud D; Artz, Andrew S; Baron, Frédéric; Bredeson, Christopher N; Dvorak, Christopher C; Epstein, Robert B; Lazarus, Hillard M; Olsson, Richard F; Selby, George B; Williams, Kirsten M; Cooke, Kenneth R; Pasquini, Marcelo C; McCarthy, Philip L

2015-07-01

Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A Comparison of Honey Bee-Collected Pollen From Working Agricultural Lands Using Light Microscopy and ITS Metabarcoding.

PubMed

Smart, M D; Cornman, R S; Iwanowicz, D D; McDermott-Kubeczko, M; Pettis, J S; Spivak, M S; Otto, C R V

2017-02-01

Taxonomic identification of pollen has historically been accomplished via light microscopy but requires specialized knowledge and reference collections, particularly when identification to lower taxonomic levels is necessary. Recently, next-generation sequencing technology has been used as a cost-effective alternative for identifying bee-collected pollen; however, this novel approach has not been tested on a spatially or temporally robust number of pollen samples. Here, we compare pollen identification results derived from light microscopy and DNA sequencing techniques with samples collected from honey bee colonies embedded within a gradient of intensive agricultural landscapes in the Northern Great Plains throughout the 2010-2011 growing seasons. We demonstrate that at all taxonomic levels, DNA sequencing was able to discern a greater number of taxa, and was particularly useful for the identification of infrequently detected species. Importantly, substantial phenological overlap did occur for commonly detected taxa using either technique, suggesting that DNA sequencing is an appropriate, and enhancing, substitutive technique for accurately capturing the breadth of bee-collected species of pollen present across agricultural landscapes. We also show that honey bees located in high and low intensity agricultural settings forage on dissimilar plants, though with overlap of the most abundantly collected pollen taxa. We highlight practical applications of utilizing sequencing technology, including addressing ecological issues surrounding land use, climate change, importance of taxa relative to abundance, and evaluating the impact of conservation program habitat enhancement efforts. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

High-resolution seismic sequence stratigraphy and history of relative sea level changes since the Late Miocene, northern continental margin, South China Sea

NASA Astrophysics Data System (ADS)

Zhong, G.; Wang, L.

2013-12-01

The northern South China Sea (SCS) margin is suggested as one of the ideal sites for documenting the late Cenozoic sea level changes for its characteristics of rapid sedimentation and relatively stable structural subsidence since the Late Miocene. In this study, high-resolution seismic profiles acquired by the Guangzhou Marine Geological Survey, calibrated by well control from the ODP sites 1146 and 1148, were utilized to construct a time-significant sequence stratigraphic framework, from which the history of relative sea level changes since the Late Miocene on the northern SCS margin was derived. Our study area is situated in the middle segment of the margin, between the Hainan Island to the west and the Dongsha Islands to the east. This region is to a certain degree far away from the active structural zones and is suggested as the most stable region in the margin. Totally 4000 km seismic profiles were used, which controls an area of about 6×104 km2. The seismic data have a vertical resolution of 5 to 15 m for the Upper Miocene to Quaternary interval. Three regional seismic sequence boundaries were identified. They subdivide the Late Miocene to Quaternary into three mega-sequences, which correspond to the Quaternary, Pliocene and Late Miocene, respectively by tying to well control. The Late Miocene mega-sequence, including 13 component sequences, is characterized with a basal incised canyon-developed interval overlain by three sets of progradational sequences formed in deep-water slope environments. The Pliocene mega-sequence consists of four sets of progradational sequences. Each sequence set contains one to three component sequences. At least 7 component sequences can be identified. The Quaternary mega-sequence consists of five sets of progradational sequences, in which the lower two constitute a retrogressive sequence set and the upper three a progradational sequence set. At least 9 component sequences can be recognized. Most of the component sequences within the Pliocene and Quaternary mega-sequences occur adjacent to modern shelf margin, and therefore were interpreted as shelf-marginal progradational deltaic sequences. A relative sea level curve since the Late Miocene was compiled by integrating the shift trajectory of onlap points, the stacking pattern of component sequences, and the chronostratigraphic diagrams. The curve contains about 29 cycles of relative sea level changes, showing a much higher resolution than the previous results in the region. These cycles constitute three large relative sea level rise and fall cycles. General trend of sea level variations is rising since the Late Miocene, which is opposite to the global sea level changes and is in accordance with the previous regional researches. This deviation is ascribed to the combined effects of very rapid regional subsidence and relative deficiency of sediment supply. This research was funded by the National Natural Science Foundation of China (Grant Nos. 91028003 and 41076020).

Repetitive DNA loci and their modulation by the non-canonical nucleic acid structures R-loops and G-quadruplexes

PubMed Central

Hall, Amanda C.; Ostrowski, Lauren A.; Mekhail, Karim

2017-01-01

ABSTRACT Cells have evolved intricate mechanisms to maintain genome stability despite allowing mutational changes to drive evolutionary adaptation. Repetitive DNA sequences, which represent the bulk of most genomes, are a major threat to genome stability often driving chromosome rearrangements and disease. The major source of repetitive DNA sequences and thus the most vulnerable constituents of the genome are the rDNA (rDNA) repeats, telomeres, and transposable elements. Maintaining the stability of these loci is critical to overall cellular fitness and lifespan. Therefore, cells have evolved mechanisms to regulate rDNA copy number, telomere length and transposon activity, as well as DNA repair at these loci. In addition, non-canonical structure-forming DNA motifs can also modulate the function of these repetitive DNA loci by impacting their transcription, replication, and stability. Here, we discuss key mechanisms that maintain rDNA repeats, telomeres, and transposons in yeast and human before highlighting emerging roles for non-canonical DNA structures at these repetitive loci. PMID:28406751

Human genomics projects and precision medicine.

PubMed

Carrasco-Ramiro, F; Peiró-Pastor, R; Aguado, B

2017-09-01

The completion of the Human Genome Project (HGP) in 2001 opened the floodgates to a deeper understanding of medicine. There are dozens of HGP-like projects which involve from a few tens to several million genomes currently in progress, which vary from having specialized goals or a more general approach. However, data generation, storage, management and analysis in public and private cloud computing platforms have raised concerns about privacy and security. The knowledge gained from further research has changed the field of genomics and is now slowly permeating into clinical medicine. The new precision (personalized) medicine, where genome sequencing and data analysis are essential components, allows tailored diagnosis and treatment according to the information from the patient's own genome and specific environmental factors. P4 (predictive, preventive, personalized and participatory) medicine is introducing new concepts, challenges and opportunities. This review summarizes current sequencing technologies, concentrates on ongoing human genomics projects, and provides some examples in which precision medicine has already demonstrated clinical impact in diagnosis and/or treatment.

Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation.

PubMed

Gellert, Pascal; Segal, Corrinne V; Gao, Qiong; López-Knowles, Elena; Martin, Lesley-Ann; Dodson, Andrew; Li, Tiandao; Miller, Christopher A; Lu, Charles; Mardis, Elaine R; Gillman, Alexa; Morden, James; Graf, Manuela; Sidhu, Kally; Evans, Abigail; Shere, Michael; Holcombe, Christopher; McIntosh, Stuart A; Bundred, Nigel; Skene, Anthony; Maxwell, William; Robertson, John; Bliss, Judith M; Smith, Ian; Dowsett, Mitch

2016-11-09

Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.

Two novel mutations in the GAN gene causing giant axonal neuropathy.

PubMed

Normendez-Martínez, Monica Irad; Monterde-Cruz, Lucero; Martínez, Roberto; Marquez-Harper, Magdalena; Esquitin-Garduño, Nayelli; Valdes-Flores, Margarita; Casas-Avila, Leonora; de Leon-Suarez, Valeria Ponce; Romero-Díaz, Viktor Javier; Hidalgo-Bravo, Alberto

2018-06-06

Giant axonal neuropathy (GAN) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. This disorder presents motor and sensitive symptoms with an onset in early childhood. Progressive neurodegeneration makes the patients wheelchair dependent by the end of the second decade of life. Affected individuals do not survive beyond the third decade of life. Molecular analysis has identified mutations in the gene GAN in patients with this disorder. This gene produces a protein called gigaxonin which is presumably involved in protein degradation via the ubiquitin-proteasome system. However, the underlying molecular mechanism is not clearly understood yet. Here we present the first patient from Mexico with clinical data suggesting GAN. Sequencing of the GAN gene was carried out. Changes in the nucleotide sequence were investigated for their possible impact on protein function and structure using the publicly available prediction tools PolyPhen-2 and PANTHER. The patient is a compound heterozygous carrying two novel mutations in the GAN gene. The sequence analysis revealed two missense mutations in the Kelch repeats domain. In one allele, a C>T transition was found in exon 9 at the nucleotide position 55393 (g.55393C>T). In the other allele, a transversion G>T in exon 11 at the nucleotide position 67471 (g.67471G>T) was observed. Both of the bioinformatic tools predicted that these amino acid substitutions would have a negative impact on gigaxonin's function. This work provides useful information for health professionals and expands the spectrum of disease-causing mutations in the GAN gene and it is the first documented case in Mexican population.

Evolution and virulence contributions of the autotransporter proteins YapJ and YapK of Yersinia pestis CO92 and their homologs in Y. pseudotuberculosis IP32953.

PubMed

Lenz, Jonathan D; Temple, Brenda R S; Miller, Virginia L

2012-10-01

Yersinia pestis, the causative agent of plague, evolved from the gastrointestinal pathogen Yersinia pseudotuberculosis. Both species have numerous type Va autotransporters, most of which appear to be highly conserved. In Y. pestis CO92, the autotransporter genes yapK and yapJ share a high level of sequence identity. By comparing yapK and yapJ to three homologous genes in Y. pseudotuberculosis IP32953 (YPTB0365, YPTB3285, and YPTB3286), we show that yapK is conserved in Y. pseudotuberculosis, while yapJ is unique to Y. pestis. All of these autotransporters exhibit >96% identity in the C terminus of the protein and identities ranging from 58 to 72% in their N termini. By extending this analysis to include homologous sequences from numerous Y. pestis and Y. pseudotuberculosis strains, we determined that these autotransporters cluster into a YapK (YPTB3285) class and a YapJ (YPTB3286) class. The YPTB3286-like gene of most Y. pestis strains appears to be inactivated, perhaps in favor of maintaining yapJ. Since autotransporters are important for virulence in many bacterial pathogens, including Y. pestis, any change in autotransporter content should be considered for its impact on virulence. Using established mouse models of Y. pestis infection, we demonstrated that despite the high level of sequence identity, yapK is distinct from yapJ in its contribution to disseminated Y. pestis infection. In addition, a mutant lacking both of these genes exhibits an additive attenuation, suggesting nonredundant roles for yapJ and yapK in systemic Y. pestis infection. However, the deletion of the homologous genes in Y. pseudotuberculosis does not seem to impact the virulence of this organism in orogastric or systemic infection models.

Impact Initiation of Rods of Pressed Polytetrafluoroethylene (PTFE) and Aluminum Powders

NASA Astrophysics Data System (ADS)

Mock, Willis, Jr.; Drotar, Jason T.

2007-06-01

A gas gun has been used to investigate the impact initiation of rods consisting of a mixture of 72 wt% PTFE (28 μm particle size) and 28 wt% aluminum (95 micron particle size) powders. The rods were 7.6 mm in diameter by 51 mm long, and were fabricated from material that had been pressed and sintered to a full density of 2.27 gm/cm^ 3. They were sabot-launched into steel anvils at impact velocities ranging from 468 to 970 m/sec. This corresponds to calculated initial impact stresses of 25 to 64 kbar, respectively. A framing camera was used to observe the time sequence of events. These include change in rod shape, fracture, and the initiation and evolution of the reaction phenomena. The time of observation of first light after impact was taken as the initiation time. Initiation occurred at discrete locations in the impacted material. At the lowest impact stress of 25 kbar no light was observed; this value was taken as the initiation threshold stress for this material. Above the initiation threshold, the initiation time dropped abruptly from 74 μs just above threshold to 14 μs at the highest impact velocity of 970 m/s. These results are compared with rod impact experiments for a similar material [1] in which the only major difference is a smaller aluminum particle size (9 micron). [1] W. Mock, Jr. and W. H. Holt, in Proc. APS Shock Compression of Condensed Matter--2005, p.1097.

Highly sensitive detection of mutations in CHO cell recombinant DNA using multi-parallel single molecule real-time DNA sequencing.

PubMed

Cartwright, Joseph F; Anderson, Karin; Longworth, Joseph; Lobb, Philip; James, David C

2018-06-01

High-fidelity replication of biologic-encoding recombinant DNA sequences by engineered mammalian cell cultures is an essential pre-requisite for the development of stable cell lines for the production of biotherapeutics. However, immortalized mammalian cells characteristically exhibit an increased point mutation frequency compared to mammalian cells in vivo, both across their genomes and at specific loci (hotspots). Thus unforeseen mutations in recombinant DNA sequences can arise and be maintained within producer cell populations. These may affect both the stability of recombinant gene expression and give rise to protein sequence variants with variable bioactivity and immunogenicity. Rigorous quantitative assessment of recombinant DNA integrity should therefore form part of the cell line development process and be an essential quality assurance metric for instances where synthetic/multi-component assemblies are utilized to engineer mammalian cells, such as the assessment of recombinant DNA fidelity or the mutability of single-site integration target loci. Based on Pacific Biosciences (Menlo Park, CA) single molecule real-time (SMRT™) circular consensus sequencing (CCS) technology we developed a rDNA sequence analysis tool to process the multi-parallel sequencing of ∼40,000 single recombinant DNA molecules. After statistical filtering of raw sequencing data, we show that this analytical method is capable of detecting single point mutations in rDNA to a minimum single mutation frequency of 0.0042% (<1/24,000 bases). Using a stable CHO transfectant pool harboring a randomly integrated 5 kB plasmid construct encoding GFP we found that 28% of recombinant plasmid copies contained at least one low frequency (<0.3%) point mutation. These mutations were predominantly found in GC base pairs (85%) and that there was no positional bias in mutation across the plasmid sequence. There was no discernable difference between the mutation frequencies of coding and non-coding DNA. The putative ratio of non-synonymous and synonymous changes within the open reading frames (ORFs) in the plasmid sequence indicates that natural selection does not impact upon the prevalence of these mutations. Here we have demonstrated the abundance of mutations that fall outside of the reported range of detection of next generation sequencing (NGS) and second generation sequencing (SGS) platforms, providing a methodology capable of being utilized in cell line development platforms to identify the fidelity of recombinant genes throughout the production process. © 2018 Wiley Periodicals, Inc.

Effects of Ceftiofur and Chlortetracycline on the Resistomes of Feedlot Cattle.

PubMed

Weinroth, Margaret D; Scott, H Morgan; Norby, Bo; Loneragan, Guy H; Noyes, Noelle R; Rovira, Pablo; Doster, Enrique; Yang, Xiang; Woerner, Dale R; Morley, Paul S; Belk, Keith E

2018-07-01

Treatment of food-producing animals with antimicrobial drugs (AMD) is controversial because of concerns regarding promotion of antimicrobial resistance (AMR). To investigate this concern, resistance genes in metagenomic bovine fecal samples during a clinical trial were analyzed to assess the impacts of treatment on beef feedlot cattle resistomes. Four groups of cattle were exposed, using a 2-by-2 factorial design, to different regimens of antimicrobial treatment. Injections of ceftiofur crystalline-free acid (a third-generation cephalosporin) were used to treat all cattle in treatment pens or only a single animal, and either chlortetracycline was included in the feed of all cattle in a pen or the feed was untreated. On days 0 and 26, respectively, pre- and posttrial fecal samples were collected, and resistance genes were characterized using shotgun metagenomics. Treatment with ceftiofur was not associated with changes to β-lactam resistance genes. However, cattle fed chlortetracycline had a significant increase in relative abundance of tetracycline resistance genes. There was also an increase of an AMR class not administered during the study, which is a possible indicator of coselection of resistance genes. Samples analyzed in this study had previously been evaluated by culture characterization ( Escherichia coli and Salmonella ) and quantitative PCR (qPCR) of metagenomic fecal DNA, which allowed comparison of results with this study. In the majority of samples, genes that were selectively enriched through culture and qPCR were not identified through shotgun metagenomic sequencing in this study, suggesting that changes previously documented did not reflect changes affecting the majority of bacterial genetic elements found in the predominant fecal resistome. IMPORTANCE Despite significant concerns about public health implications of AMR in relation to use of AMD in food animals, there are many unknowns about the long- and short-term impact of common uses of AMD for treatment, control, and prevention of disease. Additionally, questions commonly arise regarding how to best measure and quantify AMR genes in relation to public health risks and how to determine which genes are most important. These data provide an introductory view of the utility of using shotgun metagenomic sequencing data as an outcome for clinical trials evaluating the impact of using AMD in food animals. Copyright © 2018 Weinroth et al.

Changes in environmental conditions as the cause of the marine biota Great Mass Extinction at the Triassic-Jurassic boundary

NASA Astrophysics Data System (ADS)

Barash, M. S.

2016-02-01

In the interval of the Triassic-Jurassic boundary, 80% of the marine species became extinct. Four main hypotheses about the causes of this mass extinction are considered: volcanism, climatic oscillations, sea level variations accompanied by anoxia, and asteroid impact events. The extinction was triggered by an extensive flooding of basalts in the Central Atlantic Magmatic Province. Furthermore, a number of meteoritic craters have been found. Under the effect of cosmic causes, two main sequences of events developed on the Earth: terrestrial ones, leading to intensive volcanism, and cosmic ones (asteroid impacts). Their aftermaths, however, were similar in terms of the chemical compounds and aerosols released. As a consequence, the greenhouse effect, dimming of the atmosphere (impeding photosynthesis), ocean stagnation, and anoxia emerged. Then, biological productivity decreased and food chains were destroyed. Thus, the entire ecosystem was disturbed and a considerable part of the biota became extinct.

Effect of carbon and manganese on the microstructure and mechanical properties of 9Cr2WVTa deposited metals

NASA Astrophysics Data System (ADS)

Wang, Jian; Rong, Lijian; Li, Dianzhong; Lu, Shanping

2017-03-01

Six 9Cr2WVTa deposited metals with different carbon and manganese contents have been studied to reveal the role of major elements, which guide for the design of welding consumables for reduced activation ferritic/martensitic steel and meet for the requirements of accelerator driven systems-lead fusion reactors. The typical microstructure for the 9Cr2WVTa deposited metals is the lath martensite along with the fine stripe δ-ferrite. The chemical compositions influence the solidification sequence and therefore, change the δ-ferrite content in the deposited metal. The impact toughness for the 9Cr2WVTa deposited metals decreases remarkably when the δ-ferrite content is more than 5.2 vol%, also the impact toughness decreases owing to the high quenching martensite formation. Increasing the level of manganese addition, α phase of each alloy shifts to the bottom right according to the CCT diagram.

Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes.

PubMed

Semenkovich, Nicholas P; Planer, Joseph D; Ahern, Philip P; Griffin, Nicholas W; Lin, Charles Y; Gordon, Jeffrey I

2016-12-20

The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to define chromatin accessibility in predicted enhancer regions of intestinal αβ + and γδ + intraepithelial lymphocytes purified from germ-free mice, their conventionally raised (CONV-R) counterparts, and mice reared germ free and then colonized with CONV-R gut microbiota at the end of the suckling-weaning transition. Characterizing genes adjacent to traditional enhancers and super-enhancers revealed signaling networks, metabolic pathways, and enhancer-associated transcription factors affected by the microbiota. Our results support the notion that epigenetic modifications help define microbial community-affiliated functional features of host immune cell lineages.

Sequencing of hepatitis C virus for detection of resistance to direct-acting antiviral therapy: A systematic review.

PubMed

Bartlett, Sofia R; Grebely, Jason; Eltahla, Auda A; Reeves, Jacqueline D; Howe, Anita Y M; Miller, Veronica; Ceccherini-Silberstein, Francesca; Bull, Rowena A; Douglas, Mark W; Dore, Gregory J; Harrington, Patrick; Lloyd, Andrew R; Jacka, Brendan; Matthews, Gail V; Wang, Gary P; Pawlotsky, Jean-Michel; Feld, Jordan J; Schinkel, Janke; Garcia, Federico; Lennerstrand, Johan; Applegate, Tanya L

2017-07-01

The significance of the clinical impact of direct-acting antiviral (DAA) resistance-associated substitutions (RASs) in hepatitis C virus (HCV) on treatment failure is unclear. No standardized methods or guidelines for detection of DAA RASs in HCV exist. To facilitate further evaluations of the impact of DAA RASs in HCV, we conducted a systematic review of RAS sequencing protocols, compiled a comprehensive public library of sequencing primers, and provided expert guidance on the most appropriate methods to screen and identify RASs. The development of standardized RAS sequencing protocols is complicated due to a high genetic variability and the need for genotype- and subtype-specific protocols for multiple regions. We have identified several limitations of the available methods and have highlighted areas requiring further research and development. The development, validation, and sharing of standardized methods for all genotypes and subtypes should be a priority. ( Hepatology Communications 2017;1:379-390).

Systematic evaluation of the impact of ChIP-seq read designs on genome coverage, peak identification, and allele-specific binding detection.

PubMed

Zhang, Qi; Zeng, Xin; Younkin, Sam; Kawli, Trupti; Snyder, Michael P; Keleş, Sündüz

2016-02-24

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) experiments revolutionized genome-wide profiling of transcription factors and histone modifications. Although maturing sequencing technologies allow these experiments to be carried out with short (36-50 bps), long (75-100 bps), single-end, or paired-end reads, the impact of these read parameters on the downstream data analysis are not well understood. In this paper, we evaluate the effects of different read parameters on genome sequence alignment, coverage of different classes of genomic features, peak identification, and allele-specific binding detection. We generated 101 bps paired-end ChIP-seq data for many transcription factors from human GM12878 and MCF7 cell lines. Systematic evaluations using in silico variations of these data as well as fully simulated data, revealed complex interplay between the sequencing parameters and analysis tools, and indicated clear advantages of paired-end designs in several aspects such as alignment accuracy, peak resolution, and most notably, allele-specific binding detection. Our work elucidates the effect of design on the downstream analysis and provides insights to investigators in deciding sequencing parameters in ChIP-seq experiments. We present the first systematic evaluation of the impact of ChIP-seq designs on allele-specific binding detection and highlights the power of pair-end designs in such studies.

Finding positives after disaster: Insights from nurses following the 2010-2011 Canterbury, NZ earthquake sequence.

PubMed

Johal, Sarbjit S; Mounsey, Zoe R

2015-11-01

This paper identifies positive aspects of nurse experiences during the Canterbury 2010-2011 earthquake sequence and subsequent recovery process. Qualitative semi-structured interviews were undertaken with 11 nurses from the Christchurch area to explore the challenges faced by the nurses during and following the earthquakes. The interviews took place three years after the start of the earthquake experience to enable exploration of the longer term recovery process. The interview transcripts were analysed and coded using a grounded theory approach. The data analysis identified that despite the many challenges faced by the nurses during and following the earthquakes they were able to identify positives from their experience. A number of themes were identified that are related to posttraumatic growth, including; improvement in relationships with others, change in perspective/values, changed views of self and acknowledgement of the value of the experience. The research indicates that nurses were able to identify positive aspects of their experiences of the earthquakes and recovery process, suggesting that both positive and negative impacts on wellbeing can co-exist. These insights have value for employers designing support processes following disasters as focusing on positive elements could enhance nurse wellbeing during stressful times. Copyright © 2015 College of Emergency Nursing Australasia Ltd. Published by Elsevier Ltd. All rights reserved.

Long-term impacts of human harvesting on shellfish: North Iberian top shells and limpets from the Upper Palaeolithic to the present

NASA Astrophysics Data System (ADS)

Turrero, Pablo; Muñoz-Colmenero, A. Marta; Prado, Andrea; Garcia-Vazquez, Eva

2014-11-01

Humans have contributed to phenotypic and demographic changes in their prey from very early on in the colonization of Europe, including the harvesting of shellfish in coastal ecosystems. We estimated trends in population growth (variation in the number of individuals) from DNA sequences of modern specimens in two North Iberian molluscs, top shells (Osilinus lineatus, from 24 sequences and 14 haplotypes) and limpets (Patella vulgata, taken from the bibliography), which were subjected to very different levels of harvesting pressure during the Upper Palaeolithic (~ 20000 to ~ 6000 years ago). The less harvested Osilinus top shells experienced fluctuations in population numbers coincident with climatic oscillations. Patella limpets, which were harvested in greater numbers, suffered clear and uninterrupted decreases in their numbers during the Upper Palaeolithic. These trends coincided with morphological changes in shell size (length or width) in the same direction (i.e., shell size decreased when population size decreased and vice versa). The differing trends seen in taxa subjected to different intensities of harvesting pressure suggest that climate effects were overcome by anthropogenic selection (leading to a smaller average length) in limpets. We suggest that intense fishing pressure may have induced irreversible shell length decreases in the most exploited species.

Stable Patterns of CENH3 Occupancy Through Maize Lineages Containing Genetically Similar Centromeres.

PubMed

Gent, Jonathan I; Wang, Kai; Jiang, Jiming; Dawe, R Kelly

2015-08-01

While the approximate chromosomal position of centromeres has been identified in many species, little is known about the dynamics and diversity of centromere positions within species. Multiple lines of evidence indicate that DNA sequence has little or no impact in specifying centromeres in maize and in most multicellular organisms. Given that epigenetically defined boundaries are expected to be dynamic, we hypothesized that centromere positions would change rapidly over time, which would result in a diversity of centromere positions in isolated populations. To test this hypothesis, we used CENP-A/cenH3 (CENH3 in maize) chromatin immunoprecipitation to define centromeres in breeding pedigrees that included the B73 inbred as a common parent. While we found a diversity of CENH3 profiles for centromeres with divergent sequences that were not inherited from B73, the CENH3 profiles from centromeres that were inherited from B73 were indistinguishable from each other. We propose that specific genetic elements in centromeric regions favor or inhibit CENH3 accumulation, leading to reproducible patterns of CENH3 occupancy. These data also indicate that dramatic shifts in centromere position normally originate from accumulated or large-scale genetic changes rather than from epigenetic positional drift. Copyright © 2015 by the Genetics Society of America.

Abundance, composition and activity of denitrifier communities in metal polluted paddy soils

PubMed Central

Liu, Yuan; Liu, Yongzhuo; Zhou, Huimin; Li, Lianqing; Zheng, Jinwei; Zhang, Xuhui; Zheng, Jufeng; Pan, Genxing

2016-01-01

Denitrification is one of the most important soil microbial processes leading to the production of nitrous oxide (N2O). The potential changes with metal pollution in soil microbial community for N2O production and reduction are not well addressed. In this study, topsoil samples were collected both from polluted and non-polluted rice paddy fields and denitrifier communities were characterized with molecular fingerprinting procedures. All the retrieved nirK sequences could be grouped into neither α- nor β- proteobacteria, while most of the nosZ sequences were affiliated with α-proteobacteria. The abundances of the nirK and nosZ genes were reduced significantly in the two polluted soils. Thus, metal pollution markedly affected composition of both nirK and nosZ denitrifiers. While the total denitrifying activity and N2O production rate were both reduced under heavy metal pollution of the two sites, the N2O reduction rate showed no significant change. These findings suggest that N2O production activity could be sensitive to heavy metal pollution, which could potentially lead to a decrease in N2O emission in polluted paddies. Therefore, metal pollution could have potential impacts on soil N transformation and thus on N2O emission from paddy soils. PMID:26739424

Long period astronomical cycles from the Triassic to Jurassic bedded chert sequence (Inuyama, Japan); Geologic evidences for the chaotic behavior of solar planets

NASA Astrophysics Data System (ADS)

Ikeda, Masayuki; Tada, Ryuji

2013-04-01

Astronomical theory predicts that ~2 Myr eccentricity cycle have changed its periodicity and amplitude through time because of the chaotic behavior of solar planets, especially Earth-Mars secular resonance. Although the ~2 Myr eccentricity cycle has been occasionally recognized in geological records, their frequency transitions have never been reported. To explore the frequency evolution of ~2 Myr eccentricity cycle, we used the bedded chert sequence in Inuyama, Japan, of which rhythms were proven to be of astronomical origin, covering the ~30 Myr long spanning from the Triassic to Jurassic. The frequency modulation of ~2 Myr cycle between ~1.6 and ~1.8 Myr periodicity detected from wavelet analysis of chert bed thickness variation are the first geologic record of chaotic transition of Earth-Mars secular resonance. The frequency modulation of ~2 Myr cycle will provide new constraints for the orbital models. Additionally, ~8 Myr cycle detected as chert bed thickness variation and its amplitude modulation of ~2 Myr cycle may be related to the amplitude modulation of ~2 Myr eccentricity cycle through non-linear process(es) of Earth system dynamics, suggesting possible impact of the chaotic behavior of Solar planets on climate change.

An accurate bacterial DNA quantification assay for HTS library preparation of human biological samples.

PubMed

Seashols-Williams, Sarah; Green, Raquel; Wohlfahrt, Denise; Brand, Angela; Tan-Torres, Antonio Limjuco; Nogales, Francy; Brooks, J Paul; Singh, Baneshwar

2018-05-17

Sequencing and classification of microbial taxa within forensically relevant biological fluids has the potential for applications in the forensic science and biomedical fields. The quantity of bacterial DNA from human samples is currently estimated based on quantity of total DNA isolated. This method can miscalculate bacterial DNA quantity due to the mixed nature of the sample, and consequently library preparation is often unreliable. We developed an assay that can accurately and specifically quantify bacterial DNA within a mixed sample for reliable 16S ribosomal DNA (16S rDNA) library preparation and high throughput sequencing (HTS). A qPCR method was optimized using universal 16S rDNA primers, and a commercially available bacterial community DNA standard was used to develop a precise standard curve. Following qPCR optimization, 16S rDNA libraries from saliva, vaginal and menstrual secretions, urine, and fecal matter were amplified and evaluated at various DNA concentrations; successful HTS data were generated with as low as 20 pg of bacterial DNA. Changes in bacterial DNA quantity did not impact observed relative abundances of major bacterial taxa, but relative abundance changes of minor taxa were observed. Accurate quantification of microbial DNA resulted in consistent, successful library preparations for HTS analysis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temporal changes in the diazotrophic bacterial communities associated with Caribbean sponges Ircinia stroblina and Mycale laxissima

PubMed Central

Zhang, Fan; Vicente, Jan; Hill, Russell T.

2014-01-01

Sponges that harbor microalgal or, cyanobacterial symbionts may benefit from photosynthetically derived carbohydrates, which are rich in carbon but devoid of nitrogen, and may therefore encounter nitrogen limitation. Diazotrophic communities associated with two Caribbean sponges, Ircinia strobilina and Mycale laxissima were studied in a time series during which three individuals of each sponge were collected in four time points (5:00 AM, 12:00 noon, 5:00 PM, 10:00 PM). nifH genes were successfully amplified from the corresponding gDNA and cDNA pools and sequenced by high throughput 454 amplicon sequencing. In both sponges, over half the nifH transcripts were classified as from cyanobacteria and the remainder from heterotrophic bacteria. We found various groups of bacteria actively expressing the nifH gene during the entire day-night cycle, an indication that the nitrogen fixation potential was fully exploited by different nitrogen fixing bacteria groups associated with their hosts. This study showed for the first time the dynamic changes in the activity of the diazotrophic bacterial communities in marine sponges. Our study expands understanding of the diazotrophic groups that contribute to the fixed nitrogen pool in the benthic community. Sponge bacterial community-associated diazotrophy may have an important impact on the nitrogen biogeochemical cycle in the coral reef ecosystem. PMID:25389420

Temporal changes in the diazotrophic bacterial communities associated with Caribbean sponges Ircinia stroblina and Mycale laxissima.

PubMed

Zhang, Fan; Vicente, Jan; Hill, Russell T

2014-01-01

Sponges that harbor microalgal or, cyanobacterial symbionts may benefit from photosynthetically derived carbohydrates, which are rich in carbon but devoid of nitrogen, and may therefore encounter nitrogen limitation. Diazotrophic communities associated with two Caribbean sponges, Ircinia strobilina and Mycale laxissima were studied in a time series during which three individuals of each sponge were collected in four time points (5:00 AM, 12:00 noon, 5:00 PM, 10:00 PM). nifH genes were successfully amplified from the corresponding gDNA and cDNA pools and sequenced by high throughput 454 amplicon sequencing. In both sponges, over half the nifH transcripts were classified as from cyanobacteria and the remainder from heterotrophic bacteria. We found various groups of bacteria actively expressing the nifH gene during the entire day-night cycle, an indication that the nitrogen fixation potential was fully exploited by different nitrogen fixing bacteria groups associated with their hosts. This study showed for the first time the dynamic changes in the activity of the diazotrophic bacterial communities in marine sponges. Our study expands understanding of the diazotrophic groups that contribute to the fixed nitrogen pool in the benthic community. Sponge bacterial community-associated diazotrophy may have an important impact on the nitrogen biogeochemical cycle in the coral reef ecosystem.

What you learn is more than what you see: what can sequencing effects tell us about inductive category learning?

PubMed Central

Carvalho, Paulo F.; Goldstone, Robert L.

2015-01-01

Inductive category learning takes place across time. As such, it is not surprising that the sequence in which information is studied has an impact in what is learned and how efficient learning is. In this paper we review research on different learning sequences and how this impacts learning. We analyze different aspects of interleaved (frequent alternation between categories during study) and blocked study (infrequent alternation between categories during study) that might explain how and when one sequence of study results in improved learning. While these different sequences of study differ in the amount of temporal spacing and temporal juxtaposition between items of different categories, these aspects do not seem to account for the majority of the results available in the literature. However, differences in the type of category being studied and the duration of the retention interval between study and test may play an important role. We conclude that there is no single aspect that is able to account for all the evidence available. Understanding learning as a process of sequential comparisons in time and how different sequences fundamentally alter the statistics of this experience offers a promising framework for understanding sequencing effects in category learning. We use this framework to present novel predictions and hypotheses for future research on sequencing effects in inductive category learning. PMID:25983699

A coupled synoptic-hydrological model for climate change impact assessment

NASA Astrophysics Data System (ADS)

Wilby, Robert; Greenfield, Brian; Glenny, Cathy

1994-01-01

A coupled atmospheric-hydrological model is presented. Sequences of daily rainfall occurrence for the 20 year period 1971-1990 at sites in the British Isles are related to the Lamb's Weather Types (LWT) by using conditional probabilities. Time series of circulation patterns and hence rainfall were then generated using a Markov representation of matrices of transition probabilities between weather types. The resultant precipitation data were used as input to a semidistributed catchment model to simulate daily flows. The combined model successfully reproduced aspects of the daily weather, precipitation and flow regimes. A range of synoptic scenarios were further investigated with particular reference to low flows in the River Coln, UK. The modelling approach represents a means of translating general circulation model (GCM) climate change predictions at the macro-scale into hydrological concerns at the catchment scale.

The Effect of Stress and Speech Rate on Vowel Coarticulation in Catalan Vowel-Consonant-Vowel Sequences

ERIC Educational Resources Information Center

Recasens, Daniel

2015-01-01

Purpose: The goal of this study was to ascertain the effect of changes in stress and speech rate on vowel coarticulation in vowel-consonant-vowel sequences. Method: Data on second formant coarticulatory effects as a function of changing /i/ versus /a/ were collected for five Catalan speakers' productions of vowel-consonant-vowel sequences with the…

Rapid Diagnostics of Onboard Sequences

NASA Technical Reports Server (NTRS)

Starbird, Thomas W.; Morris, John R.; Shams, Khawaja S.; Maimone, Mark W.

2012-01-01

Keeping track of sequences onboard a spacecraft is challenging. When reviewing Event Verification Records (EVRs) of sequence executions on the Mars Exploration Rover (MER), operators often found themselves wondering which version of a named sequence the EVR corresponded to. The lack of this information drastically impacts the operators diagnostic capabilities as well as their situational awareness with respect to the commands the spacecraft has executed, since the EVRs do not provide argument values or explanatory comments. Having this information immediately available can be instrumental in diagnosing critical events and can significantly enhance the overall safety of the spacecraft. This software provides auditing capability that can eliminate that uncertainty while diagnosing critical conditions. Furthermore, the Restful interface provides a simple way for sequencing tools to automatically retrieve binary compiled sequence SCMFs (Space Command Message Files) on demand. It also enables developers to change the underlying database, while maintaining the same interface to the existing applications. The logging capabilities are also beneficial to operators when they are trying to recall how they solved a similar problem many days ago: this software enables automatic recovery of SCMF and RML (Robot Markup Language) sequence files directly from the command EVRs, eliminating the need for people to find and validate the corresponding sequences. To address the lack of auditing capability for sequences onboard a spacecraft during earlier missions, extensive logging support was added on the Mars Science Laboratory (MSL) sequencing server. This server is responsible for generating all MSL binary SCMFs from RML input sequences. The sequencing server logs every SCMF it generates into a MySQL database, as well as the high-level RML file and dictionary name inputs used to create the SCMF. The SCMF is then indexed by a hash value that is automatically included in all command EVRs by the onboard flight software. Second, both the binary SCMF result and the RML input file can be retrieved simply by specifying the hash to a Restful web interface. This interface enables command line tools as well as large sophisticated programs to download the SCMF and RMLs on-demand from the database, enabling a vast array of tools to be built on top of it. One such command line tool can retrieve and display RML files, or annotate a list of EVRs by interleaving them with the original sequence commands. This software has been integrated with the MSL sequencing pipeline where it will serve sequences useful in diagnostics, debugging, and situational awareness throughout the mission.

Common 5S rRNA variants are likely to be accepted in many sequence contexts

NASA Technical Reports Server (NTRS)

Zhang, Zhengdong; D'Souza, Lisa M.; Lee, Youn-Hyung; Fox, George E.

2003-01-01

Over evolutionary time RNA sequences which are successfully fixed in a population are selected from among those that satisfy the structural and chemical requirements imposed by the function of the RNA. These sequences together comprise the structure space of the RNA. In principle, a comprehensive understanding of RNA structure and function would make it possible to enumerate which specific RNA sequences belong to a particular structure space and which do not. We are using bacterial 5S rRNA as a model system to attempt to identify principles that can be used to predict which sequences do or do not belong to the 5S rRNA structure space. One promising idea is the very intuitive notion that frequently seen sequence changes in an aligned data set of naturally occurring 5S rRNAs would be widely accepted in many other 5S rRNA sequence contexts. To test this hypothesis, we first developed well-defined operational definitions for a Vibrio region of the 5S rRNA structure space and what is meant by a highly variable position. Fourteen sequence variants (10 point changes and 4 base-pair changes) were identified in this way, which, by the hypothesis, would be expected to incorporate successfully in any of the known sequences in the Vibrio region. All 14 of these changes were constructed and separately introduced into the Vibrio proteolyticus 5S rRNA sequence where they are not normally found. Each variant was evaluated for its ability to function as a valid 5S rRNA in an E. coli cellular context. It was found that 93% (13/14) of the variants tested are likely valid 5S rRNAs in this context. In addition, seven variants were constructed that, although present in the Vibrio region, did not meet the stringent criteria for a highly variable position. In this case, 86% (6/7) are likely valid. As a control we also examined seven variants that are seldom or never seen in the Vibrio region of 5S rRNA sequence space. In this case only two of seven were found to be potentially valid. The results demonstrate that changes that occur multiple times in a local region of RNA sequence space in fact usually will be accepted in any sequence context in that same local region.

Impact of rainfall pattern on interrill erosion process

USDA-ARS?s Scientific Manuscript database

The impact of rainfall pattern on the interrill erosion process is not fully understood despite its importance. Systematic rainfall simulation experiments involving different rain intensities, stages, intensity sequences, and surface cover conditions were conducted to investigate the impacts of rain...

Depositional framework and sequence stratigraphic aspects of the Coniacian Santonian mixed siliciclastic/carbonate Matulla sediments in Nezzazat and Ekma blocks, Gulf of Suez, Egypt

NASA Astrophysics Data System (ADS)

El-Azabi, M. H.; El-Araby, A.

2007-04-01

Superb outcrops of mixed siliciclastic/carbonate rocks mark the Coniacian-Santonian Matulla Formation exposed in Nezzazat and Ekma blocks, west central Sinai. They are built up of various lithofacies that reflect minor fluctuations in relative sea-level from lower intertidal to slightly deep subtidal settings. Relying on the facies characteristics and stratal geometries, the siliciclastic rocks are divided into seven depositional facies, including beach foreshore laminated sands, upper shoreface cross-bedded sandstone, lower shoreface massive bioturbated and wave-rippled sandstones, shallow subtidal siltstone and deep subtidal shale/claystone. The carbonate rocks comprise lower intertidal lime-mudstone, floatstone and dolostone, shallow subtidal skeletal shoal of oyster rudstone/bioclastic grainstone, and shoal margin packstone. Oolitic grain-ironstone and ferribands are partially intervened the facies types. Deposition has taken place under varied conditions of restricted, partly open marine circulation, low to high wave energy and normal to raised salinity during alternating periods of abundant and ceased clastic supply. The facies types are arranged into asymmetric upward-shallowing cycles that record multiple small-scale transgressive-regressive events. Lime-mudstone and sandstone normally terminate the regressive events. Four sequence boundaries marking regional relative sea-level falls divide the Matulla Formation into three stratigraphic units. These boundaries are Turonian/Coniacian, intra-Coniacian, Coniacian/Santonian and Santonian/Campanian. They do not fit with those sequence boundaries proposed in Haq et al.'s global eustatic curves (1988) except for the sea-level fall associated with the intra-Coniacian boundary. Other sequence boundaries have resulted from regional tectonic impact of the Syrian Arc Fold System that has been initiated in north Egypt during the Latest Turonian-Coniacian. These boundaries enclose three well-defined 3rd order depositional sequences; their enclosing shallowing-upward cycles (i.e. parasequences) record the 4th order relative sea-level fluctuations. 34 and 20 parasequence sets, in the order of a few meters to tens of meters thick, mark the Matulla sequences in Nezzazat and Ekma blocks respectively. Each sequence shows an initial phase of rapid sea-level rise with retrogradational sets, followed by lowering sea-level and progradation/aggradation of the parasequence sets. The transgressive deposits display predominance of deep subtidal lagoonal facies, while highstand deposits show an increase in siliciclastic and carbonate facies with the progressive decrease of lagoonal facies. The sedimentary patterns and environments suggest that the regional, partly eustatic sea-level (i.e. intra-Coniacian) changes controlled the overall architecture of the sequence distribution, whereas changes in the clastic input controlled the variations in facies associations within each depositional sequence.

Differential gene expression in the siphonophore Nanomia bijuga (Cnidaria) assessed with multiple next-generation sequencing workflows.

PubMed

Siebert, Stefan; Robinson, Mark D; Tintori, Sophia C; Goetz, Freya; Helm, Rebecca R; Smith, Stephen A; Shaner, Nathan; Haddock, Steven H D; Dunn, Casey W

2011-01-01

We investigated differential gene expression between functionally specialized feeding polyps and swimming medusae in the siphonophore Nanomia bijuga (Cnidaria) with a hybrid long-read/short-read sequencing strategy. We assembled a set of partial gene reference sequences from long-read data (Roche 454), and generated short-read sequences from replicated tissue samples that were mapped to the references to quantify expression. We collected and compared expression data with three short-read expression workflows that differ in sample preparation, sequencing technology, and mapping tools. These workflows were Illumina mRNA-Seq, which generates sequence reads from random locations along each transcript, and two tag-based approaches, SOLiD SAGE and Helicos DGE, which generate reads from particular tag sites. Differences in expression results across workflows were mostly due to the differential impact of missing data in the partial reference sequences. When all 454-derived gene reference sequences were considered, Illumina mRNA-Seq detected more than twice as many differentially expressed (DE) reference sequences as the tag-based workflows. This discrepancy was largely due to missing tag sites in the partial reference that led to false negatives in the tag-based workflows. When only the subset of reference sequences that unambiguously have tag sites was considered, we found broad congruence across workflows, and they all identified a similar set of DE sequences. Our results are promising in several regards for gene expression studies in non-model organisms. First, we demonstrate that a hybrid long-read/short-read sequencing strategy is an effective way to collect gene expression data when an annotated genome sequence is not available. Second, our replicated sampling indicates that expression profiles are highly consistent across field-collected animals in this case. Third, the impacts of partial reference sequences on the ability to detect DE can be mitigated through workflow choice and deeper reference sequencing.

Differential Gene Expression in the Siphonophore Nanomia bijuga (Cnidaria) Assessed with Multiple Next-Generation Sequencing Workflows

PubMed Central

Siebert, Stefan; Robinson, Mark D.; Tintori, Sophia C.; Goetz, Freya; Helm, Rebecca R.; Smith, Stephen A.; Shaner, Nathan; Haddock, Steven H. D.; Dunn, Casey W.

2011-01-01

We investigated differential gene expression between functionally specialized feeding polyps and swimming medusae in the siphonophore Nanomia bijuga (Cnidaria) with a hybrid long-read/short-read sequencing strategy. We assembled a set of partial gene reference sequences from long-read data (Roche 454), and generated short-read sequences from replicated tissue samples that were mapped to the references to quantify expression. We collected and compared expression data with three short-read expression workflows that differ in sample preparation, sequencing technology, and mapping tools. These workflows were Illumina mRNA-Seq, which generates sequence reads from random locations along each transcript, and two tag-based approaches, SOLiD SAGE and Helicos DGE, which generate reads from particular tag sites. Differences in expression results across workflows were mostly due to the differential impact of missing data in the partial reference sequences. When all 454-derived gene reference sequences were considered, Illumina mRNA-Seq detected more than twice as many differentially expressed (DE) reference sequences as the tag-based workflows. This discrepancy was largely due to missing tag sites in the partial reference that led to false negatives in the tag-based workflows. When only the subset of reference sequences that unambiguously have tag sites was considered, we found broad congruence across workflows, and they all identified a similar set of DE sequences. Our results are promising in several regards for gene expression studies in non-model organisms. First, we demonstrate that a hybrid long-read/short-read sequencing strategy is an effective way to collect gene expression data when an annotated genome sequence is not available. Second, our replicated sampling indicates that expression profiles are highly consistent across field-collected animals in this case. Third, the impacts of partial reference sequences on the ability to detect DE can be mitigated through workflow choice and deeper reference sequencing. PMID:21829563

High-throughput interpretation of gene structure changes in human and nonhuman resequencing data, using ACE

USDA-ARS?s Scientific Manuscript database

We describe a suite of software tools for identifying possible functional changes in gene structure that may result from sequence variants. ACE (“Assessing Changes to Exons”) converts phased genotype calls to a collection of explicit haplotype sequences, maps transcript annotations onto them, detect...

Rewriting the blueprint of life by synthetic genomics and genome engineering.

PubMed

Annaluru, Narayana; Ramalingam, Sivaprakash; Chandrasegaran, Srinivasan

2015-06-16

Advances in DNA synthesis and assembly methods over the past decade have made it possible to construct genome-size fragments from oligonucleotides. Early work focused on synthesis of small viral genomes, followed by hierarchical synthesis of wild-type bacterial genomes and subsequently on transplantation of synthesized bacterial genomes into closely related recipient strains. More recently, a synthetic designer version of yeast Saccharomyces cerevisiae chromosome III has been generated, with numerous changes from the wild-type sequence without having an impact on cell fitness and phenotype, suggesting plasticity of the yeast genome. A project to generate the first synthetic yeast genome--the Sc2.0 Project--is currently underway.

Corn and culture in central andean prehistory.

PubMed

Johannessen, S; Hastorf, C A

1989-05-12

The prehistoric development and spread of domesticated maize varieties in the highlands of Peru, unlike the drier coastal deserts, is little known because ancient maize remains in this area survive mainly as fragments, kernels, and cob parts. An analysis of fragmented charred maize from prehistoric households (A.D.450 to 1500) in the Mantaro Valley reveals a developmental sequence of maize varieties for Highland Peru. The evidence indicates an adoption of large-kernelled maize varieties beginning in the Late Intermediate (A.D. 1000). This is centuries later than a similar change in maize, associated with the Wari expansion, that occurred in coastal areas, and indicates minimal Wari impact in the Mantaro Valley.

Managing the impact of climate change on the hydrology of the Gallocanta Basin, NE-Spain.

PubMed

Kuhn, Nikolaus J; Baumhauer, Roland; Schütt, Brigitta

2011-02-01

The Gallocanta Basin represents an environment highly sensitive to climate change. Over the past 60 years, the Laguna de Gallocanta, an ephemeral lake situated in the closed Gallocanta basin, experienced a sequence of wet and dry phases. The lake and its surrounding wetlands are one of only a few bird sanctuaries left in NE-Spain for grey cranes on their annual migration from Scandinavia to northern Africa. Understanding the impact of climate change on basin hydrology is therefore of utmost importance for the appropriate management of the bird sanctuary. Changes in lake level are only weakly linked to annual rainfall, with reaction times between hours and months after rainfall. Both the total amount of rainfall over the reaction period, as well as individual extreme events, affect lake level. In this study the characteristics and frequencies of daily, event, monthly and bi-monthly rainfall over the past 60 years were analysed. The results revealed a clear link between increased frequencies of high magnitude rainfall and phases of water filling in the Laguna de Gallocanta. In the middle of the 20th century, the absolute amount of rainfall appears to have been more important for lake level, while more recently the frequency of high magnitude rainfall has emerged as the dominant variable. In the Gallocanta Basin, climate change and the distinct and continuing land use change since Spain joined the EU in 1986 have created an environment that is in a more or less constant state of transition. This highlights two challenges faced by hydrologists and climatologists involved in developing water management tools for the Gallocanta Basin in particular, but also other areas with sensitive and rapidly changing environments. Hydrologists have to understand the processes and the spatial and temporal patterns of surface-climate interaction in a watershed to assess the impact of climate change on its hydrology. Climatologists, on the other hand, have to develop climate models which provide the appropriate output data, such as reliable information on rainfall characteristics relevant for environmental management. Copyright © 2009. Published by Elsevier Ltd.

Phenolic compositions of 50 and 30 year sequences of Australian red wines: the impact of wine age.

PubMed

McRae, Jacqui M; Dambergs, Robert G; Kassara, Stella; Parker, Mango; Jeffery, David W; Herderich, Markus J; Smith, Paul A

2012-10-10

The phenolic composition of red wine impacts upon the color and mouthfeel and thus quality of the wine. Both of these characteristics differ depending on the age of a wine, with the purple of young wines changing to brick red and the puckering or aggressive astringency softening in older wines. This study investigated the color parameters, tannin concentrations and tannin composition of a 50 year series of Cabernet Sauvignon wines from a commercial label as well as 30 year series of Cabernet Sauvignon and Shiraz wines from a separate commercial label to assess the impact of wine age on phenolic composition and concentration. The wine color density in wines of 40 to 50 years old was around 5 AU compared with 16 AU of wine less than 12 months old, which correlated well with the concentration of non-bleachable pigments and pigmented polymers. Conversely, the anthocyanin concentrations in 10 year old wines were substantially lower than that of recently bottled wines (around 100 mg/L compared with 627 mg/L, respectively), adding further evidence that non-bleachable pigments including pigmented polymers play a much larger role in long-term wine color than anthocyanins. No age-related trend was observed for tannin concentration, indicating that the widely noted softer astringency of older red wines cannot necessarily be directly related to lower concentrations of soluble wine tannin and is potentially a consequence of changes in tannin structure. Wine tannins from older wines were generally larger than tannins from younger wines and showed structural changes consistent with oxidation.

Influence of carbon source on nutrient removal performance and physical-chemical characteristics of aerobic granular sludge.

PubMed

Lashkarizadeh, Monireh; Yuan, Qiuyan; Oleszkiewicz, Jan A

2015-01-01

The impact of carbon source variation on the physical and chemical characteristics of aerobic granular sludge and its biological nutrient (nitrogen and phosphorus) removal performance was investigated. Two identical sequencing batch reactors, R1 and R2, were set up. Granular biomass was cultivated to maturity using acetate-based synthetic wastewater. After mature granules in both reactors with simultaneous chemical oxygen demand (COD), ammonium and phosphorus removal capability were achieved, the feed of R2 was changed to municipal wastewater and R1 was continued on synthetic feed as control. Biological phosphorus removal was completely inhibited in R2 due to lack of readily biodegradable COD; however, the biomass maintained high ammonium and COD removal efficiencies. The disintegration of the granules in R2 occurred during the first two weeks after the change of feed, but it did not have significant impacts on settling properties of the sludge. Re-granulation of the biomass in R2 was then observed within 30 d after granules' disintegration when the biomass acclimated to the new substrate. The granular biomass in R1 and R2 maintained a Sludge Volume Index close to 60 and 47 mL g(-1), respectively, during the experimental period. It was concluded that changing the carbon source from readily biodegradable acetate to the more complex ones present in municipal wastewater did not have significant impacts on aerobic granular sludge characteristics; it particularly did not affect its settling properties. However, sufficient readily biodegradable carbon would have to be provided to maintain simultaneous biological nitrate and phosphorus removal.

Microcraters formed in glass by projectiles of various densities

NASA Technical Reports Server (NTRS)

Vedder, J. F.; Mandeville, J.-C.

1974-01-01

An experiment was conducted investigating the effect of projectile density on the structure and size of craters in soda lime glass and fused quartz. The projectiles were spheres of polystyrene-divinylbenzene (PS-DVB), aluminum, and iron with velocities between 0.5 and 15 km/sec and diameters between 0.4 and 5 microns. The projectile densities spanned the range expected for primary and secondary particles of micrometer size at the lunar surface, and the velocities spanned the lower range of micrometeoroid velocities and the upper range of secondary projectile velocities. There are changes in crater morphology as the impact velocity increases, and the transitions occur at lower velocities for the projectiles of higher density. The sequence of morphological features of the craters found for PS-DVB impacting soda lime glass for increasing impact velocity, described in a previous work (Mandeville and Vedder, 1971), also occurs in fused quartz and in both targets with the more dense aluminum and iron projectiles. Each transition in morphology occurs at impact velocities generating a certain pressure in the target. High density projectiles require a lower velocity than low-density projectiles to generate a given shock pressure.

Deep sequencing of evolving pathogen populations: applications, errors, and bioinformatic solutions

PubMed Central

2014-01-01

Deep sequencing harnesses the high throughput nature of next generation sequencing technologies to generate population samples, treating information contained in individual reads as meaningful. Here, we review applications of deep sequencing to pathogen evolution. Pioneering deep sequencing studies from the virology literature are discussed, such as whole genome Roche-454 sequencing analyses of the dynamics of the rapidly mutating pathogens hepatitis C virus and HIV. Extension of the deep sequencing approach to bacterial populations is then discussed, including the impacts of emerging sequencing technologies. While it is clear that deep sequencing has unprecedented potential for assessing the genetic structure and evolutionary history of pathogen populations, bioinformatic challenges remain. We summarise current approaches to overcoming these challenges, in particular methods for detecting low frequency variants in the context of sequencing error and reconstructing individual haplotypes from short reads. PMID:24428920

Complementary molecular information changes our perception of food web structure

PubMed Central

Wirta, Helena K.; Hebert, Paul D. N.; Kaartinen, Riikka; Prosser, Sean W.; Várkonyi, Gergely; Roslin, Tomas

2014-01-01

How networks of ecological interactions are structured has a major impact on their functioning. However, accurately resolving both the nodes of the webs and the links between them is fraught with difficulties. We ask whether the new resolution conferred by molecular information changes perceptions of network structure. To probe a network of antagonistic interactions in the High Arctic, we use two complementary sources of molecular data: parasitoid DNA sequenced from the tissues of their hosts and host DNA sequenced from the gut of adult parasitoids. The information added by molecular analysis radically changes the properties of interaction structure. Overall, three times as many interaction types were revealed by combining molecular information from parasitoids and hosts with rearing data, versus rearing data alone. At the species level, our results alter the perceived host specificity of parasitoids, the parasitoid load of host species, and the web-wide role of predators with a cryptic lifestyle. As the northernmost network of host–parasitoid interactions quantified, our data point exerts high leverage on global comparisons of food web structure. However, how we view its structure will depend on what information we use: compared with variation among networks quantified at other sites, the properties of our web vary as much or much more depending on the techniques used to reconstruct it. We thus urge ecologists to combine multiple pieces of evidence in assessing the structure of interaction webs, and suggest that current perceptions of interaction structure may be strongly affected by the methods used to construct them. PMID:24449902

Error and Error Mitigation in Low-Coverage Genome Assemblies

PubMed Central

Hubisz, Melissa J.; Lin, Michael F.; Kellis, Manolis; Siepel, Adam

2011-01-01

The recent release of twenty-two new genome sequences has dramatically increased the data available for mammalian comparative genomics, but twenty of these new sequences are currently limited to ∼2× coverage. Here we examine the extent of sequencing error in these 2× assemblies, and its potential impact in downstream analyses. By comparing 2× assemblies with high-quality sequences from the ENCODE regions, we estimate the rate of sequencing error to be 1–4 errors per kilobase. While this error rate is fairly modest, sequencing error can still have surprising effects. For example, an apparent lineage-specific insertion in a coding region is more likely to reflect sequencing error than a true biological event, and the length distribution of coding indels is strongly distorted by error. We find that most errors are contributed by a small fraction of bases with low quality scores, in particular, by the ends of reads in regions of single-read coverage in the assembly. We explore several approaches for automatic sequencing error mitigation (SEM), making use of the localized nature of sequencing error, the fact that it is well predicted by quality scores, and information about errors that comes from comparisons across species. Our automatic methods for error mitigation cannot replace the need for additional sequencing, but they do allow substantial fractions of errors to be masked or eliminated at the cost of modest amounts of over-correction, and they can reduce the impact of error in downstream phylogenomic analyses. Our error-mitigated alignments are available for download. PMID:21340033

Is Whole-Exome Sequencing an Ethically Disruptive Technology? Perspectives of Pediatric Oncologists and Parents of Pediatric Patients With Solid Tumors.

PubMed

McCullough, Laurence B; Slashinski, Melody J; McGuire, Amy L; Street, Richard L; Eng, Christine M; Gibbs, Richard A; Parsons, D William; Plon, Sharon E

2016-03-01

It has been anticipated that physician and parents will be ill prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive. As a part of the Baylor Advancing Sequencing in Childhood Cancer Care study, we conducted semistructured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis to provide inductive insights into their views of sequencing. Our major findings reveal that neither pediatric oncologists nor parents anticipate sequencing to be an ethically disruptive technology, because they expect to be prepared to integrate sequencing results into their existing approaches to learning and using new clinical information for care. Pediatric oncologists do not expect sequencing results to be more complex than other diagnostic information and plan simply to incorporate these data into their evidence-based approach to clinical practice, although they were concerned about impact on parents. For parents, there is an urgency to protect their child's health and in this context they expect genomic information to better prepare them to participate in decisions about their child's care. Our data do not support the concern that introducing genome sequencing into childhood cancer care will be ethically disruptive, that is, leave physicians or parents ill prepared or unprepared to make responsible decisions about patient care. © 2015 Wiley Periodicals, Inc.

Is Whole Exome Sequencing an Ethically Disruptive Technology? Perspectives of Pediatric Oncologists and Parents of Pediatric Patients with Solid Tumors

PubMed Central

McCullough, Laurence B.; Slashinski, Melody J.; McGuire, Amy L.; Street, Richard L.; Eng, Christine M.; Gibbs, Richard A.; Parsons, D. Williams; Plon, Sharon E.

2016-01-01

Background Some anticipate that physician and parents will be ill-prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive. Procedure As part of the Baylor Advancing Sequencing in Childhood Cancer Care (BASIC3) study, we conducted semi-structured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision-making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis to provide inductive insights into their views of sequencing. Results Our major findings reveal that neither pediatric oncologists nor parents anticipate sequencing to be an ethically disruptive technology, because they expect to be prepared to integrate sequencing results into their existing approaches to learning and using new clinical information for care. Pediatric oncologists do not expect sequencing results to be more complex than other diagnostic information and plan simply to incorporate these data into their evidence-based approach to clinical practice although they were concerned about impact on parents. For parents, there is an urgency to protect their chil's health and in this context they expect genomic information to better prepare them to participate in decisions about their chil's care. Conclusion Our data do not support concern that introducing genome sequencing into childhood cancer care will be ethically disruptive, i.e., leave physicians or parents ill-prepared or unprepared to make responsible decisions about patient care. PMID:26505993

MPS Editor

NASA Technical Reports Server (NTRS)

Mathews, William S.; Liu, Ning; Francis, Laurie K.; OReilly, Taifun L.; Schrock, Mitchell; Page, Dennis N.; Morris, John R.; Joswig, Joseph C.; Crockett, Thomas M.; Shams, Khawaja S.

2011-01-01

Previously, it was time-consuming to hand-edit data and then set up simulation runs to find the effect and impact of the input data on a spacecraft. MPS Editor provides the user the capability to create/edit/update models and sequences, and immediately try them out using what appears to the user as one piece of software. MPS Editor provides an integrated sequencing environment for users. It provides them with software that can be utilized during development as well as actual operations. In addition, it provides them with a single, consistent, user friendly interface. MPS Editor uses the Eclipse Rich Client Platform to provide an environment that can be tailored to specific missions. It provides the capability to create and edit, and includes an Activity Dictionary to build the simulation spacecraft models, build and edit sequences of commands, and model the effects of those commands on the spacecraft. MPS Editor is written in Java using the Eclipse Rich Client Platform. It is currently built with four perspectives: the Activity Dictionary Perspective, the Project Adaptation Perspective, the Sequence Building Perspective, and the Sequence Modeling Perspective. Each perspective performs a given task. If a mission doesn't require that task, the unneeded perspective is not added to that project's delivery. In the Activity Dictionary Perspective, the user builds the project-specific activities, observations, calibrations, etc. Typically, this is used during the development phases of the mission, although it can be used later to make changes and updates to the Project Activity Dictionary. In the Adaptation Perspective, the user creates the spacecraft models such as power, data store, etc. Again, this is typically used during development, but will be used to update or add models of the spacecraft. The Sequence Building Perspective allows the user to create a sequence of activities or commands that go to the spacecraft. It provides a simulation of the activities and commands that have been created.

The complete amino acid sequence of human skeletal-muscle fructose-bisphosphate aldolase.

PubMed Central

Freemont, P S; Dunbar, B; Fothergill-Gilmore, L A

1988-01-01

The complete amino acid sequence of human skeletal-muscle fructose-bisphosphate aldolase, comprising 363 residues, was determined. The sequence was deduced by automated sequencing of CNBr-cleavage, o-iodosobenzoic acid-cleavage, trypsin-digest and staphylococcal-proteinase-digest fragments. Comparison of the sequence with other class I aldolase sequences shows that the mammalian muscle isoenzyme is one of the most highly conserved enzymes known, with only about 2% of the residues changing per 100 million years. Non-mammalian aldolases appear to be evolving at the same rate as other glycolytic enzymes, with about 4% of the residues changing per 100 million years. Secondary-structure predictions are analysed in an accompanying paper [Sawyer, Fothergill-Gilmore & Freemont (1988) Biochem. J. 249, 789-793]. PMID:3355497

Teaching Task Sequencing via Verbal Mediation.

ERIC Educational Resources Information Center

Rusch, Frank R.; And Others

1987-01-01

Verbal sequence training was used to teach a moderately mentally retarded woman to sequence job-related tasks. Learning to say the tasks in the proper sequence resulted in the employee performing her tasks in that sequence, and the employee was capable of mediating her own work behavior when scheduled changes occurred. (Author/JDD)

Multi-layered mutation in hedgehog-related genes in Gorlin syndrome may affect the phenotype.

PubMed

Onodera, Shoko; Saito, Akiko; Hasegawa, Daigo; Morita, Nana; Watanabe, Katsuhito; Nomura, Takeshi; Shibahara, Takahiko; Ohba, Shinsuke; Yamaguchi, Akira; Azuma, Toshifumi

2017-01-01

Gorlin syndrome is a genetic disorder of autosomal dominant inheritance that predisposes the affected individual to a variety of disorders that are attributed largely to heterozygous germline patched1 (PTCH1) mutations. PTCH1 is a hedgehog (Hh) receptor as well as a repressor, mutation of which leads to constitutive activation of Hh pathway. Hh pathway encompasses a wide variety of cellular signaling cascades, which involve several molecules; however, no associated genotype-phenotype correlations have been reported. Recently, mutations in Suppressor of fused homolog (SUFU) or PTCH2 were reported in patients with Gorlin syndrome. These facts suggest that multi-layered mutations in Hh pathway may contribute to the development of Gorlin syndrome. We demonstrated multiple mutations of Hh-related genes in addition to PTCH1, which possibly act in an additive or multiplicative manner and lead to Gorlin syndrome. High-throughput sequencing was performed to analyze exome sequences in four unrelated Gorlin syndrome patient genomes. Mutations in PTCH1 gene were detected in all four patients. Specific nucleotide variations or frameshift variations of PTCH1 were identified along with the inferred amino acid changes in all patients. We further filtered 84 different genes which are closely related to Hh signaling. Fifty three of these had enough coverage of over ×30. The sequencing results were filtered and compared to reduce the number of sequence variants identified in each of the affected individuals. We discovered three genes, PTCH2, BOC, and WNT9b, with mutations with a predicted functional impact assessed by MutationTaster2 or PolyPhen-2 (Polymorphism Phenotyping v2) analysis. It is noticeable that PTCH2 and BOC are Hh receptor molecules. No significant mutations were observed in SUFU. Multi-layered mutations in Hh pathway may change the activation level of the Hh signals, which may explain the wide phenotypic variability of Gorlin syndrome.

Induced Seismicity: Balancing the Scientific Process With the Need for Rapid Communication of Evolving Seismic Hazards

NASA Astrophysics Data System (ADS)

Cochran, E. S.; Ellsworth, W. L.; Llenos, A. L.; Rubinstein, J. L.

2014-12-01

In this presentation, we outline the USGS response to dramatically increased earthquake activity in the central and eastern US, with a focus on Oklahoma. Using the November 2011 Prague, OK earthquake sequence as an example, we describe the tensions between the need to conduct thorough scientific investigations while providing timely information to local, state, and federal government agencies, and the public. In the early morning hours of November 5, 2011 a M4.8 earthquake struck near the town of Prague, Oklahoma and was followed by a M5.6 earthquake just over 20 hours later. The mainshock was widely felt across the central US, causing damage to homes close to the epicenter and injuring at least 2 people. Within hours of the initial event several portable instruments were installed and following the mainshock a larger seismic deployment was mounted (Keranen et al., 2013). A sizeable earthquake in the central or eastern US is always of scientific interest due to the dearth of seismic data available for assessing seismic hazard. The Prague sequence garnered especially strong scientific and public interest when a link between the sequence and injection of wastewater at several local deep wells was postulated. Therefore, there was a need to provide immediate information as it became available. However, in the first few days to months it was impossible to confidently confirm or refute whether the seismicity was linked to injection, but it was known that the foreshock occurred close to several deep injection wells and many of the events were shallow; thus, the sequence warranted further study. Over the course of the next few years, several studies built the case that the Prague sequence was likely induced by wastewater injection (Keranen et al., 2013; Sumy et al., 2014; McGarr, 2014) and additional studies suggested that the changes in seismicity throughout Oklahoma were not due to natural variations in seismicity rates (Llenos and Michael, 2013; Ellsworth, 2013). These studies changed the public discourse from providing primary information about the on-going earthquake sequences to how to mitigate the hazard associated with wastewater injection. And, scientific studies are now focused on how to include the impact of induced events within the National Seismic Hazard Maps (e.g. Peterson et al., 2014).

The complete chloroplast genome sequence of Gossypium hirsutum: organization and phylogenetic relationships to other angiosperms

PubMed Central

Lee, Seung-Bum; Kaittanis, Charalambos; Jansen, Robert K; Hostetler, Jessica B; Tallon, Luke J; Town, Christopher D; Daniell, Henry

2006-01-01

Background Cotton (Gossypium hirsutum) is the most important fiber crop grown in 90 countries. In 2004–2005, US farmers planted 79% of the 5.7-million hectares of nuclear transgenic cotton. Unfortunately, genetically modified cotton has the potential to hybridize with other cultivated and wild relatives, resulting in geographical restrictions to cultivation. However, chloroplast genetic engineering offers the possibility of containment because of maternal inheritance of transgenes. The complete chloroplast genome of cotton provides essential information required for genetic engineering. In addition, the sequence data were used to assess phylogenetic relationships among the major clades of rosids using cotton and 25 other completely sequenced angiosperm chloroplast genomes. Results The complete cotton chloroplast genome is 160,301 bp in length, with 112 unique genes and 19 duplicated genes within the IR, containing a total of 131 genes. There are four ribosomal RNAs, 30 distinct tRNA genes and 17 intron-containing genes. The gene order in cotton is identical to that of tobacco but lacks rpl22 and infA. There are 30 direct and 24 inverted repeats 30 bp or longer with a sequence identity ≥ 90%. Most of the direct repeats are within intergenic spacer regions, introns and a 72 bp-long direct repeat is within the psaA and psaB genes. Comparison of protein coding sequences with expressed sequence tags (ESTs) revealed nucleotide substitutions resulting in amino acid changes in ndhC, rpl23, rpl20, rps3 and clpP. Phylogenetic analysis of a data set including 61 protein-coding genes using both maximum likelihood and maximum parsimony were performed for 28 taxa, including cotton and five other angiosperm chloroplast genomes that were not included in any previous phylogenies. Conclusion Cotton chloroplast genome lacks rpl22 and infA and contains a number of dispersed direct and inverted repeats. RNA editing resulted in amino acid changes with significant impact on their hydropathy. Phylogenetic analysis provides strong support for the position of cotton in the Malvales in the eurosids II clade sister to Arabidopsis in the Brassicales. Furthermore, there is strong support for the placement of the Myrtales sister to the eurosid I clade, although expanded taxon sampling is needed to further test this relationship. PMID:16553962

Sasquatch: predicting the impact of regulatory SNPs on transcription factor binding from cell- and tissue-specific DNase footprints.

PubMed

Schwessinger, Ron; Suciu, Maria C; McGowan, Simon J; Telenius, Jelena; Taylor, Stephen; Higgs, Doug R; Hughes, Jim R

2017-10-01

In the era of genome-wide association studies (GWAS) and personalized medicine, predicting the impact of single nucleotide polymorphisms (SNPs) in regulatory elements is an important goal. Current approaches to determine the potential of regulatory SNPs depend on inadequate knowledge of cell-specific DNA binding motifs. Here, we present Sasquatch, a new computational approach that uses DNase footprint data to estimate and visualize the effects of noncoding variants on transcription factor binding. Sasquatch performs a comprehensive k -mer-based analysis of DNase footprints to determine any k -mer's potential for protein binding in a specific cell type and how this may be changed by sequence variants. Therefore, Sasquatch uses an unbiased approach, independent of known transcription factor binding sites and motifs. Sasquatch only requires a single DNase-seq data set per cell type, from any genotype, and produces consistent predictions from data generated by different experimental procedures and at different sequence depths. Here we demonstrate the effectiveness of Sasquatch using previously validated functional SNPs and benchmark its performance against existing approaches. Sasquatch is available as a versatile webtool incorporating publicly available data, including the human ENCODE collection. Thus, Sasquatch provides a powerful tool and repository for prioritizing likely regulatory SNPs in the noncoding genome. © 2017 Schwessinger et al.; Published by Cold Spring Harbor Laboratory Press.

Impact Lithologies and Post-Impact Hydrothermal Alteration Exposed by the Chicxulub Scientific Drilling Project, Yaxcopoil, Mexico

NASA Technical Reports Server (NTRS)

Kring, David A.; Zurcher, Lukas; Horz, Friedrich

2003-01-01

The Chicxulub Scientific Drilling Project recovered a continuous core from the Yaxcopoil-1 (YAX-1) borehole, which is approx.60-65 km from the center of the Chicxulub structure, approx.15 km beyond the limit of the estimated approx.50 km radius transient crater (excavation cavity), but within the rim of the estimated approx.90 km radius final crater. Approximately approx.100 m of melt-bearing impactites were recoverd from a depth of 794 to 895 m, above approx.600 m of underlying megablocks of Cretaceous target sediments, before bottoming at 1511 m. Compared to lithologies at impact craters like the Ries, the YAX-1 impactite sequence is incredibly rich in impact melts of unusual textural variety and complexity. The impactite sequence has also been altered by hydrothermal activity that may have largely been produced by the impact event.

Hybrid composite laminates reinforced with Kevlar/carbon/glass woven fabrics for ballistic impact testing.

PubMed

Randjbaran, Elias; Zahari, Rizal; Jalil, Nawal Aswan Abdul; Majid, Dayang Laila Abang Abdul

2014-01-01

Current study reported a facile method to investigate the effects of stacking sequence layers of hybrid composite materials on ballistic energy absorption by running the ballistic test at the high velocity ballistic impact conditions. The velocity and absorbed energy were accordingly calculated as well. The specimens were fabricated from Kevlar, carbon, and glass woven fabrics and resin and were experimentally investigated under impact conditions. All the specimens possessed equal mass, shape, and density; nevertheless, the layers were ordered in different stacking sequence. After running the ballistic test at the same conditions, the final velocities of the cylindrical AISI 4340 Steel pellet showed how much energy was absorbed by the samples. The energy absorption of each sample through the ballistic impact was calculated; accordingly, the proper ballistic impact resistance materials could be found by conducting the test. This paper can be further studied in order to characterise the material properties for the different layers.

Overcoming bias and systematic errors in next generation sequencing data.

PubMed

Taub, Margaret A; Corrada Bravo, Hector; Irizarry, Rafael A

2010-12-10

Considerable time and effort has been spent in developing analysis and quality assessment methods to allow the use of microarrays in a clinical setting. As is the case for microarrays and other high-throughput technologies, data from new high-throughput sequencing technologies are subject to technological and biological biases and systematic errors that can impact downstream analyses. Only when these issues can be readily identified and reliably adjusted for will clinical applications of these new technologies be feasible. Although much work remains to be done in this area, we describe consistently observed biases that should be taken into account when analyzing high-throughput sequencing data. In this article, we review current knowledge about these biases, discuss their impact on analysis results, and propose solutions.

Statistical learning of music- and language-like sequences and tolerance for spectral shifts.

PubMed

Daikoku, Tatsuya; Yatomi, Yutaka; Yumoto, Masato

2015-02-01

In our previous study (Daikoku, Yatomi, & Yumoto, 2014), we demonstrated that the N1m response could be a marker for the statistical learning process of pitch sequence, in which each tone was ordered by a Markov stochastic model. The aim of the present study was to investigate how the statistical learning of music- and language-like auditory sequences is reflected in the N1m responses based on the assumption that both language and music share domain generality. By using vowel sounds generated by a formant synthesizer, we devised music- and language-like auditory sequences in which higher-ordered transitional rules were embedded according to a Markov stochastic model by controlling fundamental (F0) and/or formant frequencies (F1-F2). In each sequence, F0 and/or F1-F2 were spectrally shifted in the last one-third of the tone sequence. Neuromagnetic responses to the tone sequences were recorded from 14 right-handed normal volunteers. In the music- and language-like sequences with pitch change, the N1m responses to the tones that appeared with higher transitional probability were significantly decreased compared with the responses to the tones that appeared with lower transitional probability within the first two-thirds of each sequence. Moreover, the amplitude difference was even retained within the last one-third of the sequence after the spectral shifts. However, in the language-like sequence without pitch change, no significant difference could be detected. The pitch change may facilitate the statistical learning in language and music. Statistically acquired knowledge may be appropriated to process altered auditory sequences with spectral shifts. The relative processing of spectral sequences may be a domain-general auditory mechanism that is innate to humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Cenozoic global sea level, sequences, and the New Jersey transect: Results from coastal plain and continental slope drilling

USGS Publications Warehouse

Miller, K.G.; Mountain, Gregory S.; Browning, J.V.; Kominz, M.; Sugarman, P.J.; Christie-Blick, N.; Katz, M.E.; Wright, J.D.

1998-01-01

The New Jersey Sea Level Transect was designed to evaluate the relationships among global sea level (eustatic) change, unconformity-bounded sequences, and variations in subsidence, sediment supply, and climate on a passive continental margin. By sampling and dating Cenozoic strata from coastal plain and continental slope locations, we show that sequence boundaries correlate (within ??0.5 myr) regionally (onshore-offshore) and interregionally (New Jersey-Alabama-Bahamas), implicating a global cause. Sequence boundaries correlate with ??18O increases for at least the past 42 myr, consistent with an ice volume (glacioeustatic) control, although a causal relationship is not required because of uncertainties in ages and correlations. Evidence for a causal connection is provided by preliminary Miocene data from slope Site 904 that directly link ??18O increases with sequence boundaries. We conclude that variation in the size of ice sheets has been a primary control on the formation of sequence boundaries since ~42 Ma. We speculate that prior to this, the growth and decay of small ice sheets caused small-amplitude sea level changes (<20 m) in this supposedly ice-free world because Eocene sequence boundaries also appear to correlate with minor ??18O increases. Subsidence estimates (backstripping) indicate amplitudes of short-term (million-year scale) lowerings that are consistent with estimates derived from ??18O studies (25-50 m in the Oligocene-middle Miocene and 10-20 m in the Eocene) and a long-term lowering of 150-200 m over the past 65 myr, consistent with estimates derived from volume changes on mid-ocean ridges. Although our results are consistent with the general number and timing of Paleocene to middle Miocene sequences published by workers at Exxon Production Research Company, our estimates of sea level amplitudes are substantially lower than theirs. Lithofacies patterns within sequences follow repetitive, predictable patterns: (1) coastal plain sequences consist of basal transgressive sands overlain by regressive highstand silts and quartz sands; and (2) although slope lithofacies variations are subdued, reworked sediments constitute lowstand deposits, causing the strongest, most extensive seismic reflections. Despite a primary eustatic control on sequence boundaries, New Jersey sequences were also influenced by changes in tectonics, sediment supply, and climate. During the early to middle Eocene, low siliciclastic and high pelagic input associated with warm climates resulted in widespread carbonate deposition and thin sequences. Late middle Eocene and earliest Oligocene cooling events curtailed carbonate deposition in the coastal plain and slope, respectively, resulting in a switch to siliciclastic sedimentation. In onshore areas, Oligocene sequences are thin owing to low siliciclastic and pelagic input, and their distribution is patchy, reflecting migration or progradation of depocenters; in contrast, Miocene onshore sequences are thicker, reflecting increased sediment supply, and they are more complete downdip owing to simple tectonics. We conclude that the New Jersey margin provides a natural laboratory for unraveling complex interactions of eustasy, tectonics, changes in sediment supply, and climate change.

Molecular diagnosis of bloodstream infections: planning to (physically) reach the bedside.

PubMed

Leggieri, N; Rida, A; François, P; Schrenzel, Jacques

2010-08-01

Faster identification of infecting microorganisms and treatment options is a first-ranking priority in the infectious disease area, in order to prevent inappropriate treatment and overuse of broad-spectrum antibiotics. Standard bacterial identification is intrinsically time-consuming, and very recently there has been a burst in the number of commercially available nonphenotype-based techniques and in the documentation of a possible clinical impact of these techniques. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is now a standard diagnostic procedure on cultures and hold promises on spiked blood. Meanwhile, commercial PCR-based techniques have improved with the use of bacterial DNA enrichment methods, the diversity of amplicon analysis techniques (melting curve analysis, microarrays, gel electrophoresis, sequencing and analysis by mass spectrometry) leading to the ability to challenge bacterial culture as the gold standard for providing earlier diagnosis with a better 'clinical' sensitivity and additional prognostic information. Laboratory practice has already changed with MALDI-TOF MS, but a change in clinical practice, driven by emergent nucleic acid-based techniques, will need the demonstration of real-life applicability as well as robust clinical-impact-oriented studies.

Intense Exercise and Aerobic Conditioning Associated with Chromium or L-Carnitine Supplementation Modified the Fecal Microbiota of Fillies

PubMed Central

Feringer, Walter Heinz; Carvalho, Júlia Ribeiro Garcia; Rodrigues, Isadora Mestriner; Jordão, Lilian Rezende; Fonseca, Mayara Gonçalves; Carneiro de Rezende, Adalgiza Souza; de Queiroz Neto, Antonio; Weese, J. Scott; da Costa, Márcio Carvalho

2016-01-01

Recent studies performed in humans and rats have reported that exercise can alter the intestinal microbiota. Athletic horses perform intense exercise regularly, but studies characterizing horse microbiome during aerobic conditioning programs are still limited. Evidence has indicated that this microbial community is involved in the metabolic homeostasis of the host. Research on ergogenic substances using new sequencing technologies have been limited to the intestinal microbiota and there is a considerable demand for scientific studies that verify the effectiveness of these supplements in horses. L-carnitine and chromium are potentially ergogenic substances for athletic humans and horses since they are possibly able to modify the metabolism of carbohydrates and lipids. This study aimed to assess the impact of acute exercise and aerobic conditioning, associated either with L-carnitine or chromium supplementation, on the intestinal microbiota of fillies. Twelve “Mangalarga Marchador” fillies in the incipient fitness stage were distributed into four groups: control (no exercise), exercise, L-carnitine (10g/day) and chelated chromium (10mg/day). In order to investigate the impact of acute exercise or aerobic conditioning on fecal microbiota all fillies undergoing the conditioning program were analyzed as a separate treatment. The fillies underwent two incremental exercise tests before and after training on a treadmill for 42 days at 70–80% of the lactate threshold intensity. Fecal samples were obtained before and 48 h after acute exercise (incremental exercise test). Bacterial populations were characterized by sequencing the V4 region of the 16S rRNA gene using the MiSeq Illumina platform, and 5,224,389 sequences were obtained from 48 samples. The results showed that, overall, the two most abundant phyla were Firmicutes (50.22%) followed by Verrucomicrobia (15.13%). The taxa with the highest relative abundances were unclassified Clostridiales (17.06%) and "5 genus incertae sedis" from the phylum Verrucomicrobia (12.98%). There was a decrease in the phylum Chlamydiae and in the genus Mycobacterium after the second incremental exercise test. Intense exercise changed the community’s structure and aerobic conditioning was associated with changes in the composition and structure of the intestinal bacterial population of fillies. The intra-group comparison showed that chromium or L-carnitine induced moderate changes in the fecal microbiota of fillies, but the microbiota did not differ from the control group, which was exercised with no supplementation. Fecal pH correlated positively with Simpson’s index, while plasma pH correlated negatively. Our results show that exercise and aerobic conditioning can change in the microbiota and provide a basis for further studies enrolling a larger number of horses at different fitness levels to better understand the effects of exercise and training on the intestinal microbiota of horses. PMID:27935992

Intense Exercise and Aerobic Conditioning Associated with Chromium or L-Carnitine Supplementation Modified the Fecal Microbiota of Fillies.

PubMed

Almeida, Maria Luiza Mendes de; Feringer, Walter Heinz; Carvalho, Júlia Ribeiro Garcia; Rodrigues, Isadora Mestriner; Jordão, Lilian Rezende; Fonseca, Mayara Gonçalves; Carneiro de Rezende, Adalgiza Souza; de Queiroz Neto, Antonio; Weese, J Scott; Costa, Márcio Carvalho da; Lemos, Eliana Gertrudes de Macedo; Ferraz, Guilherme de Camargo

2016-01-01

Recent studies performed in humans and rats have reported that exercise can alter the intestinal microbiota. Athletic horses perform intense exercise regularly, but studies characterizing horse microbiome during aerobic conditioning programs are still limited. Evidence has indicated that this microbial community is involved in the metabolic homeostasis of the host. Research on ergogenic substances using new sequencing technologies have been limited to the intestinal microbiota and there is a considerable demand for scientific studies that verify the effectiveness of these supplements in horses. L-carnitine and chromium are potentially ergogenic substances for athletic humans and horses since they are possibly able to modify the metabolism of carbohydrates and lipids. This study aimed to assess the impact of acute exercise and aerobic conditioning, associated either with L-carnitine or chromium supplementation, on the intestinal microbiota of fillies. Twelve "Mangalarga Marchador" fillies in the incipient fitness stage were distributed into four groups: control (no exercise), exercise, L-carnitine (10g/day) and chelated chromium (10mg/day). In order to investigate the impact of acute exercise or aerobic conditioning on fecal microbiota all fillies undergoing the conditioning program were analyzed as a separate treatment. The fillies underwent two incremental exercise tests before and after training on a treadmill for 42 days at 70-80% of the lactate threshold intensity. Fecal samples were obtained before and 48 h after acute exercise (incremental exercise test). Bacterial populations were characterized by sequencing the V4 region of the 16S rRNA gene using the MiSeq Illumina platform, and 5,224,389 sequences were obtained from 48 samples. The results showed that, overall, the two most abundant phyla were Firmicutes (50.22%) followed by Verrucomicrobia (15.13%). The taxa with the highest relative abundances were unclassified Clostridiales (17.06%) and "5 genus incertae sedis" from the phylum Verrucomicrobia (12.98%). There was a decrease in the phylum Chlamydiae and in the genus Mycobacterium after the second incremental exercise test. Intense exercise changed the community's structure and aerobic conditioning was associated with changes in the composition and structure of the intestinal bacterial population of fillies. The intra-group comparison showed that chromium or L-carnitine induced moderate changes in the fecal microbiota of fillies, but the microbiota did not differ from the control group, which was exercised with no supplementation. Fecal pH correlated positively with Simpson's index, while plasma pH correlated negatively. Our results show that exercise and aerobic conditioning can change in the microbiota and provide a basis for further studies enrolling a larger number of horses at different fitness levels to better understand the effects of exercise and training on the intestinal microbiota of horses.

Parallel changes of taxonomic interaction networks in lacustrine bacterial communities induced by a polymetallic perturbation

PubMed Central

Laplante, Karine; Sébastien, Boutin; Derome, Nicolas

2013-01-01

Heavy metals released by anthropogenic activities such as mining trigger profound changes to bacterial communities. In this study we used 16S SSU rRNA gene high-throughput sequencing to characterize the impact of a polymetallic perturbation and other environmental parameters on taxonomic networks within five lacustrine bacterial communities from sites located near Rouyn-Noranda, Quebec, Canada. The results showed that community equilibrium was disturbed in terms of both diversity and structure. Moreover, heavy metals, especially cadmium combined with water acidity, induced parallel changes among sites via the selection of resistant OTUs (Operational Taxonomic Unit) and taxonomic dominance perturbations favoring the Alphaproteobacteria. Furthermore, under a similar selective pressure, covariation trends between phyla revealed conservation and parallelism within interphylum interactions. Our study sheds light on the importance of analyzing communities not only from a phylogenetic perspective but also including a quantitative approach to provide significant insights into the evolutionary forces that shape the dynamic of the taxonomic interaction networks in bacterial communities. PMID:23789031

From road to lab to math: the co-evolution of technological, regulatory, and organizational innovations for automotive crash testing.

PubMed

Leonardi, Paul M

2010-04-01

Today, in the midst of economic crisis, senior executives at US automakers and influential industry analysts frequently reflect on the progression that safety testing has taken from the crude trials done on the road, to controlled laboratory experiments, and to today's complex math-based simulation models. They use stories of this seemingly linear and natural sequence to justify further investment in simulation technologies. The analysis presented in this paper shows that change in the structures of automakers' organizations co-evolved with regulations specifying who was at fault in vehicle impacts, how vehicles should be built to withstand the force of an impact, and how testing should be done to assure that vehicles met those requirements. Changes in the regulatory environment were bolstered by new theories about crash test dynamics and changing technologies with which to test those theories. Thus, as new technological and regulatory innovations co-evolved with innovations in organizational structuring, ideas about how to best conduct crash tests shifted and catalyzed new cycles of technological, regulatory, and organizational innovation. However, this co-evolutionary story tells us that the move from road to lab to math was not natural or linear as today's managerial rhetoric would have us believe. Rather, the logic of math-based simulation was the result of technological, regulatory and organizational changes that created an industry-wide ideology that supported the move toward math while making it appear natural within the shifting structure of the industry.

Understanding soil health by capitalizing on long-term field studies

NASA Astrophysics Data System (ADS)

Tavakkoli, Ehsan; Wang, Zhe; VanZweieten, Lukas; Rose, Michael

2017-04-01

Microbial biodiversity in Australian agricultural soils is of paramount importance as it plays a critical role in regulating soil health, plant productivity, and the cycling of carbon, nitrogen, and other nutrients. Agricultural practices strongly affect soil microbial communities by changing the physical and chemical characteristics of the soil in which microorganisms live, thereby affecting their abundance, diversity, and activity. Despite its importance, the specific responses of various microbial groups to changing environmental conditions (e.g. increased/decreased carbon in response to land management) in agricultural soils are not well understood. This knowledge gap is largely due to previous methodological limitations that, until recently, did not allow microbial diversity and functioning to be meaningfully investigated on large numbers of samples. We sampled soils from a field trial on the effect of strategic tillage in no-till systems to examine the potential impact of tillage and stubble management on soil microbial composition. To determine the relative abundance of bacteria and fungi, we used quantitative PCR (qPCR), and to analyze the composition and diversity of the bacterial and fungal communities, we used bar-coded high-throughput sequencing. Bioinformatics of the sequencing generated data was performed using a previously scripted and tested pipeline, and involved allocation of the relevant sequences to their samples of origin according to the bar-code. In parallel, changes in soil quality and microbial functionality were determined using multi-enzyme activity assay and multiple substrate-induced respiration. The extracellular enzyme activities that were measured include: β-1,4-glucosidase, β-D-cellobiohydrolase, β-Xylosidase, and α-1,4-glucosidase which are all relevant to the C cycle; β-1,4-N-acetylglucosaminidase and L-leucine aminopeptidase which are both relevant to the N cycle associated and associated with protein catabolism. In this presentation, analyses of soil health and functionality in relation to its response to various agronomic practices and implications for C sequestration and nutrient cycling will be discussed.

Rapid Measurement and Correction of Phase Errors from B0 Eddy Currents: Impact on Image Quality for Non-Cartesian Imaging

PubMed Central

Brodsky, Ethan K.; Klaers, Jessica L.; Samsonov, Alexey A.; Kijowski, Richard; Block, Walter F.

2014-01-01

Non-Cartesian imaging sequences and navigational methods can be more sensitive to scanner imperfections that have little impact on conventional clinical sequences, an issue which has repeatedly complicated the commercialization of these techniques by frustrating transitions to multi-center evaluations. One such imperfection is phase errors caused by resonant frequency shifts from eddy currents induced in the cryostat by time-varying gradients, a phenomemon known as B0 eddy currents. These phase errors can have a substantial impact on sequences that use ramp sampling, bipolar gradients, and readouts at varying azimuthal angles. We present a method for measuring and correcting phase errors from B0 eddy currents and examine the results on two different scanner models. This technique yields significant improvements in image quality for high-resolution joint imaging on certain scanners. The results suggest that correction of short time B0 eddy currents in manufacturer provided service routines would simplify adoption of non-Cartesian sampling methods. PMID:22488532

Optimal control of a hybrid rhythmic-discrete task: the bouncing ball revisited.

PubMed

Ronsse, Renaud; Wei, Kunlin; Sternad, Dagmar

2010-05-01

Rhythmically bouncing a ball with a racket is a hybrid task that combines continuous rhythmic actuation of the racket with the control of discrete impact events between racket and ball. This study presents experimental data and a two-layered modeling framework that explicitly addresses the hybrid nature of control: a first discrete layer calculates the state to reach at impact and the second continuous layer smoothly drives the racket to this desired state, based on optimality principles. The testbed for this hybrid model is task performance at a range of increasingly slower tempos. When slowing the rhythm of the bouncing actions, the continuous cycles become separated into a sequence of discrete movements interspersed by dwell times and directed to achieve the desired impact. Analyses of human performance show increasing variability of performance measures with slower tempi, associated with a change in racket trajectories from approximately sinusoidal to less symmetrical velocity profiles. Matching results of model simulations give support to a hybrid control model based on optimality, and therefore suggest that optimality principles are applicable to the sensorimotor control of complex movements such as ball bouncing.

Validation of Methods to Assess the Immunoglobulin Gene Repertoire in Tissues Obtained from Mice on the International Space Station.

PubMed

Rettig, Trisha A; Ward, Claire; Pecaut, Michael J; Chapes, Stephen K

2017-07-01

Spaceflight is known to affect immune cell populations. In particular, splenic B cell numbers decrease during spaceflight and in ground-based physiological models. Although antibody isotype changes have been assessed during and after space flight, an extensive characterization of the impact of spaceflight on antibody composition has not been conducted in mice. Next Generation Sequencing and bioinformatic tools are now available to assess antibody repertoires. We can now identify immunoglobulin gene- segment usage, junctional regions, and modifications that contribute to specificity and diversity. Due to limitations on the International Space Station, alternate sample collection and storage methods must be employed. Our group compared Illumina MiSeq sequencing data from multiple sample preparation methods in normal C57Bl/6J mice to validate that sample preparation and storage would not bias the outcome of antibody repertoire characterization. In this report, we also compared sequencing techniques and a bioinformatic workflow on the data output when we assessed the IgH and Igκ variable gene usage. This included assessments of our bioinformatic workflow on Illumina HiSeq and MiSeq datasets and is specifically designed to reduce bias, capture the most information from Ig sequences, and produce a data set that provides other data mining options. We validated our workflow by comparing our normal mouse MiSeq data to existing murine antibody repertoire studies validating it for future antibody repertoire studies.

The impact of reduced pH on the microbial community of the coral Acropora eurystoma

PubMed Central

Meron, Dalit; Atias, Elinor; Iasur Kruh, Lilach; Elifantz, Hila; Minz, Dror; Fine, Maoz; Banin, Ehud

2011-01-01

Rising concentrations of atmospheric carbon dioxide are acidifying the world's oceans. Surface seawater pH is 0.1 units lower than pre-industrial values and is predicted to decrease by up to 0.4 units by the end of the century. This change in pH may result in changes in the physiology of ocean organisms, in particular, organisms that build their skeletons/shells from calcium carbonate, such as corals. This physiological change may also affect other members of the coral holobiont, for example, the microbial communities associated with the coral, which in turn may affect the coral physiology and health. In the present study, we examined changes in bacterial communities in the coral mucus, tissue and skeleton following exposure of the coral Acropora eurystoma to two different pH conditions: 7.3 and 8.2 (ambient seawater). The microbial community was different at the two pH values, as determined by denaturing gradient gel electrophoresis and 16S rRNA gene sequence analysis. Further analysis of the community in the corals maintained at the lower pH revealed an increase in bacteria associated with diseased and stressed corals, such as Vibrionaceae and Alteromonadaceae. In addition, an increase in the number of potential antibacterial activity was recorded among the bacteria isolated from the coral maintained at pH 7.3. Taken together, our findings highlight the impact that changes in the pH may have on the coral-associated bacterial community and their potential contribution to the coral host. PMID:20668489

Maternal high fat diet and its consequence on the gut microbiome: A rat model.

PubMed

Mann, Phyllis E; Huynh, Kevin; Widmer, Giovanni

2017-11-14

The biological changes that occur during pregnancy in the female mammal include shifts in hormonal regulation in preparation for parturition and lactation, and changes in energy metabolism. In women, studies have also shown that during pregnancy there is a reduction in bacterial species richness in the gut. In the current experiment rats were used to model the interaction of diet, reproductive status, and intestinal bacterial microbiota during pregnancy and lactation. In Experiment 1 rats were exposed to either standard chow or high-fat chow (60%) and were divided into two groups: unmated (NULL) or mated (RE). In Experiment 2, both NULL and RE rats were exposed to high-fat chow for a 30-day period. High-throughput sequencing of the 16S rRNA gene revealed that pregnancy impacted the gut microbiota in a similar manner to humans. The impact of reproductive status on microbiota composition, however, was stronger in rats fed a high-fat (HF) diet. Diet-induced changes replicated some of the changes observed in humans, such as increasing the Firmicutes/Bacteroidetes ratio. However, in contrast to humans, pregnancy in rats did not increase β-diversity between microbiota from different animals. These results indicate that during pregnancy in rats, the gut microbiota is altered in a similar manner to that which occurs in women, and that these changes are further exaggerated by exposure to a HF diet. Thus, the rat may allow modelling the effects of consumption of HF food during pregnancy and enable future studies to determine the risks of HF diets during pregnancy and its consequences on the offspring.

Evaluation of 16S Rrna amplicon sequencing using two next-generation sequencing technologies for phylogenetic analysis of the rumen bacterial community in steers

USDA-ARS?s Scientific Manuscript database

Next generation sequencing technologies have vastly changed the approach of sequencing of the 16S rRNA gene for studies in microbial ecology. Three distinct technologies are available for large-scale 16S sequencing. All three are subject to biases introduced by sequencing error rates, amplificatio...

Evaluation of 16S rRNA amplicon sequencing using two next-generation sequencing technologies for phylogenetic analysis of the rumen bacterial community in steers

USDA-ARS?s Scientific Manuscript database

Next generation sequencing technologies have vastly changed the approach of sequencing of the 16S rRNA gene for studies in microbial ecology. Three distinct technologies are available for large-scale 16S sequencing. All three are subject to biases introduced by sequencing error rates, amplificatio...

Accurate and High-Coverage Immune Repertoire Sequencing Reveals Characteristics of Antibody Repertoire Diversification in Young Children with Malaria

NASA Astrophysics Data System (ADS)

Jiang, Ning

Accurately measuring the immune repertoire sequence composition, diversity, and abundance is important in studying repertoire response in infections, vaccinations, and cancer immunology. Using molecular identifiers (MIDs) to tag mRNA molecules is an effective method in improving the accuracy of immune repertoire sequencing (IR-seq). However, it is still difficult to use IR-seq on small amount of clinical samples to achieve a high coverage of the repertoire diversities. This is especially challenging in studying infections and vaccinations where B cell subpopulations with fewer cells, such as memory B cells or plasmablasts, are often of great interest to study somatic mutation patterns and diversity changes. Here, we describe an approach of IR-seq based on the use of MIDs in combination with a clustering method that can reveal more than 80% of the antibody diversity in a sample and can be applied to as few as 1,000 B cells. We applied this to study the antibody repertoires of young children before and during an acute malaria infection. We discovered unexpectedly high levels of somatic hypermutation (SHM) in infants and revealed characteristics of antibody repertoire development in young children that would have a profound impact on immunization in children.

Investigation of the microbial communities colonizing prepainted steel used for roofing and walling.

PubMed

Huynh, Tran T; Jamil, Ili; Pianegonda, Nicole A; Blanksby, Stephen J; Barker, Philip J; Manefield, Mike; Rice, Scott A

2017-04-01

Microbial colonization of prepainted steel, commonly used in roofing applications, impacts their aesthetics, durability, and functionality. Understanding the relevant organisms and the mechanisms by which colonization occurs would provide valuable information that can be subsequently used to design fouling prevention strategies. Here, next-generation sequencing and microbial community finger printing (T-RFLP) were used to study the community composition of microbes colonizing prepainted steel roofing materials at Burrawang, Australia and Kapar, Malaysia over a 52-week period. Community diversity was low and was dominated by Bacillus spp., cyanobacteria, actinobacteria, Cladosporium sp., Epicoccum nigrum, and Teratosphaeriaceae sp. Cultivation-based methods isolated approximately 20 different fungi and bacteria, some of which, such as E. nigrum and Cladosporium sp., were represented in the community sequence data. Fluorescence in situ hybridization imaging showed that fungi were the most dominant organisms present. Analysis of the sequence and T-RFLP data indicated that the microbial communities differed significantly between locations and changed significantly over time. The study demonstrates the utility of molecular ecology tools to identify and characterize microbial communities associated with the fouling of painted steel surfaces and ultimately can enable the targeted development of control strategies based on the dominant species responsible for fouling. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Next-generation sequencing identifies major DNA methylation changes during progression of Ph+ chronic myeloid leukemia

PubMed Central

Heller, G; Topakian, T; Altenberger, C; Cerny-Reiterer, S; Herndlhofer, S; Ziegler, B; Datlinger, P; Byrgazov, K; Bock, C; Mannhalter, C; Hörmann, G; Sperr, W R; Lion, T; Zielinski, C C; Valent, P; Zöchbauer-Müller, S

2016-01-01

Little is known about the impact of DNA methylation on the evolution/progression of Ph+ chronic myeloid leukemia (CML). We investigated the methylome of CML patients in chronic phase (CP-CML), accelerated phase (AP-CML) and blast crisis (BC-CML) as well as in controls by reduced representation bisulfite sequencing. Although only ~600 differentially methylated CpG sites were identified in samples obtained from CP-CML patients compared with controls, ~6500 differentially methylated CpG sites were found in samples from BC-CML patients. In the majority of affected CpG sites, methylation was increased. In CP-CML patients who progressed to AP-CML/BC-CML, we identified up to 897 genes that were methylated at the time of progression but not at the time of diagnosis. Using RNA-sequencing, we observed downregulated expression of many of these genes in BC-CML compared with CP-CML samples. Several of them are well-known tumor-suppressor genes or regulators of cell proliferation, and gene re-expression was observed by the use of epigenetic active drugs. Together, our results demonstrate that CpG site methylation clearly increases during CML progression and that it may provide a useful basis for revealing new targets of therapy in advanced CML. PMID:27211271

Apigenin Impacts the Growth of the Gut Microbiota and Alters the Gene Expression of Enterococcus.

PubMed

Wang, Minqian; Firrman, Jenni; Zhang, Liqing; Arango-Argoty, Gustavo; Tomasula, Peggy; Liu, LinShu; Xiao, Weidong; Yam, Kit

2017-08-03

Apigenin is a major dietary flavonoid with many bioactivities, widely distributed in plants. Apigenin reaches the colon region intact and interacts there with the human gut microbiota, however there is little research on how apigenin affects the gut bacteria. This study investigated the effect of pure apigenin on human gut bacteria, at both the single strain and community levels. The effect of apigenin on the single gut bacteria strains Bacteroides galacturonicus , Bifidobacterium catenulatum , Lactobacillus rhamnosus GG, and Enterococcus caccae , was examined by measuring their anaerobic growth profiles. The effect of apigenin on a gut microbiota community was studied by culturing a fecal inoculum under in vitro conditions simulating the human ascending colon. 16S rRNA gene sequencing and GC-MS analysis quantified changes in the community structure. Single molecule RNA sequencing was used to reveal the response of Enterococcus caccae to apigenin. Enterococcus caccae was effectively inhibited by apigenin when cultured alone, however, the genus Enterococcus was enhanced when tested in a community setting. Single molecule RNA sequencing found that Enterococcus caccae responded to apigenin by up-regulating genes involved in DNA repair, stress response, cell wall synthesis, and protein folding. Taken together, these results demonstrate that apigenin affects both the growth and gene expression of Enterococcus caccae .

Corexit 9500 Enhances Oil Biodegradation and Changes ...

EPA Pesticide Factsheets

While COREXIT 9500 is widely applied after oil spills for its reported dispersing activity, there is still a debate on the effectiveness on enhancing oil biodegradation and its potential toxic effect on microbial communities. To better understand the impact of COREXIT 9500 on the structure and activity levels of hydrocarbon degrading microbial communities, we analyzed next-generation 16S rRNA gene sequencing libraries of hydrocarbon enrichments grown at cryophilic and mesophilic conditions and using both DNA and RNA extracts as sequencing templates. Oil biodegradation patterns in both cryophilic and mesophilic enrichments were consistent with those reported in the literature (i.e., aliphatics were degraded faster than aromatics). A slight increase in biodegradation was observed in the presence of COREXIT at both 25°C and 5°C experiments. Differences in community structure were observed between treatment conditions in the DNA-based libraries. The 25°C consortia was dominated by unclassified members of the Vibrio, Pseudoidiomarina, Marinobacter, Alcanivorax, and Thallassospira species, while the 5°C consortia were dominated by several genera of Flavobacteria, Alcanivorax and Oleispira. With the exception of Vibrio-like species, members of these genera have been linked to hydrocarbon degradation and have been observed after oil spills. Colwellia and Cycloclasticus, known aromatic degraders, was also found in these enrichments. RNA-based sequencing of 25°C

Transcriptome Profiling of Buffalograss Challenged with the Leaf Spot Pathogen Curvularia inaequalis.

PubMed

Amaradasa, Bimal S; Amundsen, Keenan

2016-01-01

Buffalograss (Bouteloua dactyloides) is a low maintenance U. S. native turfgrass species with exceptional drought, heat, and cold tolerance. Leaf spot caused by Curvularia inaequalis negatively impacts buffalograss visual quality. Two leaf spot susceptible and two resistant buffalograss lines were challenged with C. inaequalis. Samples were collected from treated and untreated leaves when susceptible lines showed symptoms. Transcriptome sequencing was done and differentially expressed genes were identified. Approximately 27 million raw sequencing reads were produced per sample. More than 86% of the sequencing reads mapped to an existing buffalograss reference transcriptome. De novo assembly of unmapped reads was merged with the existing reference to produce a more complete transcriptome. There were 461 differentially expressed transcripts between the resistant and susceptible lines when challenged with the pathogen and 1552 in its absence. Previously characterized defense-related genes were identified among the differentially expressed transcripts. Twenty one resistant line transcripts were similar to genes regulating pattern triggered immunity and 20 transcripts were similar to genes regulating effector triggered immunity. There were also nine up-regulated transcripts in resistance lines which showed potential to initiate systemic acquired resistance (SAR) and three transcripts encoding pathogenesis-related proteins which are downstream products of SAR. This is the first study characterizing changes in the buffalograss transcriptome when challenged with C. inaequalis.

Computational analysis of sequence selection mechanisms.

PubMed

Meyerguz, Leonid; Grasso, Catherine; Kleinberg, Jon; Elber, Ron

2004-04-01

Mechanisms leading to gene variations are responsible for the diversity of species and are important components of the theory of evolution. One constraint on gene evolution is that of protein foldability; the three-dimensional shapes of proteins must be thermodynamically stable. We explore the impact of this constraint and calculate properties of foldable sequences using 3660 structures from the Protein Data Bank. We seek a selection function that receives sequences as input, and outputs survival probability based on sequence fitness to structure. We compute the number of sequences that match a particular protein structure with energy lower than the native sequence, the density of the number of sequences, the entropy, and the "selection" temperature. The mechanism of structure selection for sequences longer than 200 amino acids is approximately universal. For shorter sequences, it is not. We speculate on concrete evolutionary mechanisms that show this behavior.

Genomic Sequencing Procedure Microcosting Analysis and Health Economic Cost-Impact Analysis: A Report of the Association for Molecular Pathology.

PubMed

Sabatini, Linda M; Mathews, Charles; Ptak, Devon; Doshi, Shivang; Tynan, Katherine; Hegde, Madhuri R; Burke, Tara L; Bossler, Aaron D

2016-05-01

The increasing use of advanced nucleic acid sequencing technologies for clinical diagnostics and therapeutics has made vital understanding the costs of performing these procedures and their value to patients, providers, and payers. The Association for Molecular Pathology invested in a cost and value analysis of specific genomic sequencing procedures (GSPs) newly coded by the American Medical Association Current Procedural Terminology Editorial Panel. Cost data and work effort, including the development and use of data analysis pipelines, were gathered from representative laboratories currently performing these GSPs. Results were aggregated to generate representative cost ranges given the complexity and variability of performing the tests. Cost-impact models for three clinical scenarios were generated with assistance from key opinion leaders: impact of using a targeted gene panel in optimizing care for patients with advanced non-small-cell lung cancer, use of a targeted gene panel in the diagnosis and management of patients with sensorineural hearing loss, and exome sequencing in the diagnosis and management of children with neurodevelopmental disorders of unknown genetic etiology. Each model demonstrated value by either reducing health care costs or identifying appropriate care pathways. The templates generated will aid laboratories in assessing their individual costs, considering the value structure in their own patient populations, and contributing their data to the ongoing dialogue regarding the impact of GSPs on improving patient care. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

The transfer of movement sequences: effects of decreased and increased load.

PubMed

Muehlbauer, Thomas; Panzer, Stefan; Shea, Charles H

2007-06-01

A number of recent experiments have demonstrated that a movement structure develops during the course of learning a movement sequence that provides the basis for transfer. After learning a movement sequence participants have been shown to be able to effectively produce the sequence when movement demands require that the sequence be rescaled in amplitude or produced with an unpractised set of effectors. The purpose of the present experiment was to determine whether participants, after learning a complex 16-element movement sequence with a 0.567-kg load, could also effectively produce the sequence when the load was decreased (0.0 kg) or increased (1.134 kg). The results indicated that participants were able to effectively compensate for decreased and increased load with virtually no changes in performance characteristics (displacement, velocity, acceleration, and pattern of element durations) while electromyographic (EMG) signals demonstrated that smaller (reduced load) or larger forces (increased load) were spontaneously generated to compensate for the change in load. The muscle activation patterns of the biceps and triceps as well as the level of coactivation appeared to be generally upscaled to generate and dissipate the changes in force requirement needed to compensate for the increased load.

Age effects on discrimination of timing in auditory sequences

NASA Astrophysics Data System (ADS)

Fitzgibbons, Peter J.; Gordon-Salant, Sandra

2004-08-01

The experiments examined age-related changes in temporal sensitivity to increments in the interonset intervals (IOI) of components in tonal sequences. Discrimination was examined using reference sequences consisting of five 50-ms tones separated by silent intervals; tone frequencies were either fixed at 4 kHz or varied within a 2-4-kHz range to produce spectrally complex patterns. The tonal IOIs within the reference sequences were either equal (200 or 600 ms) or varied individually with an average value of 200 or 600 ms to produce temporally complex patterns. The difference limen (DL) for increments of IOI was measured. Comparison sequences featured either equal increments in all tonal IOIs or increments in a single target IOI, with the sequential location of the target changing randomly across trials. Four groups of younger and older adults with and without sensorineural hearing loss participated. Results indicated that DLs for uniform changes of sequence rate were smaller than DLs for single target intervals, with the largest DLs observed for single targets embedded within temporally complex sequences. Older listeners performed more poorly than younger listeners in all conditions, but the largest age-related differences were observed for temporally complex stimulus conditions. No systematic effects of hearing loss were observed.

Event-Related Potentials Elicited by Pre-Attentive Emotional Changes in Temporal Context

PubMed Central

Fujimura, Tomomi; Okanoya, Kazuo

2013-01-01

The ability to detect emotional change in the environment is essential for adaptive behavior. The current study investigated whether event-related potentials (ERPs) can reflect emotional change in a visual sequence. To assess pre-attentive processing, we examined visual mismatch negativity (vMMN): the negative potentials elicited by a deviant (infrequent) stimulus embedded in a sequence of standard (frequent) stimuli. Participants in two experiments pre-attentively viewed visual sequences of Japanese kanji with different emotional connotations while ERPs were recorded. The visual sequence in Experiment 1 consisted of neutral standards and two types of emotional deviants with a strong and weak intensity. Although the results indicated that strongly emotional deviants elicited more occipital negativity than neutral standards, it was unclear whether these negativities were derived from emotional deviation in the sequence or from the emotional significance of the deviants themselves. In Experiment 2, the two identical emotional deviants were presented against different emotional standards. One type of deviants was emotionally incongruent with the standard and the other type of deviants was emotionally congruent with the standard. The results indicated that occipital negativities elicited by deviants resulted from perceptual changes in a visual sequence at a latency of 100–200 ms and from emotional changes at latencies of 200–260 ms. Contrary to the results of the ERP experiment, reaction times to deviants showed no effect of emotional context; negative stimuli were consistently detected more rapidly than were positive stimuli. Taken together, the results suggest that brain signals can reflect emotional change in a temporal context. PMID:23671693

Event-related potentials elicited by pre-attentive emotional changes in temporal context.

PubMed

Fujimura, Tomomi; Okanoya, Kazuo

2013-01-01

The ability to detect emotional change in the environment is essential for adaptive behavior. The current study investigated whether event-related potentials (ERPs) can reflect emotional change in a visual sequence. To assess pre-attentive processing, we examined visual mismatch negativity (vMMN): the negative potentials elicited by a deviant (infrequent) stimulus embedded in a sequence of standard (frequent) stimuli. Participants in two experiments pre-attentively viewed visual sequences of Japanese kanji with different emotional connotations while ERPs were recorded. The visual sequence in Experiment 1 consisted of neutral standards and two types of emotional deviants with a strong and weak intensity. Although the results indicated that strongly emotional deviants elicited more occipital negativity than neutral standards, it was unclear whether these negativities were derived from emotional deviation in the sequence or from the emotional significance of the deviants themselves. In Experiment 2, the two identical emotional deviants were presented against different emotional standards. One type of deviants was emotionally incongruent with the standard and the other type of deviants was emotionally congruent with the standard. The results indicated that occipital negativities elicited by deviants resulted from perceptual changes in a visual sequence at a latency of 100-200 ms and from emotional changes at latencies of 200-260 ms. Contrary to the results of the ERP experiment, reaction times to deviants showed no effect of emotional context; negative stimuli were consistently detected more rapidly than were positive stimuli. Taken together, the results suggest that brain signals can reflect emotional change in a temporal context.

UNAM Scientific Drilling Program of Chicxulub Impact Structure-Evidence for a 300 kilometer crater diameter

NASA Astrophysics Data System (ADS)

Urrutia-Fucugauchi, J.; Marin, L.; Trejo-Garcia, A.

As part of the UNAM drilling program at the Chicxulub structure, two 700 m deep continuously cored boreholes were completed between April and July, 1995. The Peto UNAM-6 and Tekax UNAM-7 drilling sites are ˜150 km and 125 km, respectively, SSE of Chicxulub Puerto, near the crater's center. Core samples from both sites show a sequence of post-crater carbonates on top of a thick impact breccia pile covering the disturbed Mesozoic platform rocks. At UNAM-7, two impact breccia units were encountered: (1) an upper breccia, mean magnetic susceptibility is high (˜55 × 10-6 SI units), indicating a large component of silicate basement has been incorporated into this breccia, and (2) an evaporite-rich, low susceptibility impact breccia similar in character to the evaporite-rich breccias observed at the PEMEX drill sites further out. The upper breccia was encountered at ˜226 m below the surface and is ˜125 m thick; the lower breccia is immediately subjacent and is >240 m thick. This two-breccia sequence is typical of the suevite-Bunte breccia sequence found within other well preserved impact craters. The suevitic upper unit is not present at UNAM-6. Instead, a >240 m thick evaporite-rich breccia unit, similar to the lower breccia at UNAM-7, was encountered at a depth of ˜280 m. The absence of an upper breccia equivalent at UNAM-6 suggests some portion of the breccia sequence has been removed by erosion. This is consistent with interpretations that place the high-standing crater rim at 130-150 km from the center. Consequently, the stratigraphic observations and magnetic susceptibiity records on the upper and lower breccias (depth and thickness) support a ˜300 km diameter crater model.

Conversion of Amazon rainforest to agriculture alters community traits of methane-cycling organisms.

PubMed

Meyer, Kyle M; Klein, Ann M; Rodrigues, Jorge L M; Nüsslein, Klaus; Tringe, Susannah G; Mirza, Babur S; Tiedje, James M; Bohannan, Brendan J M

2017-03-01

Land use change is one of the greatest environmental impacts worldwide, especially to tropical forests. The Amazon rainforest has been subject to particularly high rates of land use change, primarily to cattle pasture. A commonly observed response to cattle pasture establishment in the Amazon is the conversion of soil from a methane sink in rainforest, to a methane source in pasture. However, it is not known how the microorganisms that mediate methane flux are altered by land use change. Here, we use the deepest metagenomic sequencing of Amazonian soil to date to investigate differences in methane-cycling microorganisms and their traits across rainforest and cattle pasture soils. We found that methane-cycling microorganisms responded to land use change, with the strongest responses exhibited by methane-consuming, rather than methane-producing, microorganisms. These responses included a reduction in the relative abundance of methanotrophs and a significant decrease in the abundance of genes encoding particulate methane monooxygenase. We also observed compositional changes to methanotroph and methanogen communities as well as changes to methanotroph life history strategies. Our observations suggest that methane-cycling microorganisms are vulnerable to land use change, and this vulnerability may underlie the response of methane flux to land use change in Amazon soils. © 2017 John Wiley & Sons Ltd.

Habits as action sequences: hierarchical action control and changes in outcome value

PubMed Central

Dezfouli, Amir; Lingawi, Nura W.; Balleine, Bernard W.

2014-01-01

Goal-directed action involves making high-level choices that are implemented using previously acquired action sequences to attain desired goals. Such a hierarchical schema is necessary for goal-directed actions to be scalable to real-life situations, but results in decision-making that is less flexible than when action sequences are unfolded and the decision-maker deliberates step-by-step over the outcome of each individual action. In particular, from this perspective, the offline revaluation of any outcomes that fall within action sequence boundaries will be invisible to the high-level planner resulting in decisions that are insensitive to such changes. Here, within the context of a two-stage decision-making task, we demonstrate that this property can explain the emergence of habits. Next, we show how this hierarchical account explains the insensitivity of over-trained actions to changes in outcome value. Finally, we provide new data that show that, under extended extinction conditions, habitual behaviour can revert to goal-directed control, presumably as a consequence of decomposing action sequences into single actions. This hierarchical view suggests that the development of action sequences and the insensitivity of actions to changes in outcome value are essentially two sides of the same coin, explaining why these two aspects of automatic behaviour involve a shared neural structure. PMID:25267824

Direct repeat sequences in the Streptomyces chitinase-63 promoter direct both glucose repression and chitin induction

PubMed Central

Ni, Xiangyang; Westpheling, Janet

1997-01-01

The chi63 promoter directs glucose-sensitive, chitin-dependent transcription of a gene involved in the utilization of chitin as carbon source. Analysis of 5′ and 3′ deletions of the promoter region revealed that a 350-bp segment is sufficient for wild-type levels of expression and regulation. The analysis of single base changes throughout the promoter region, introduced by random and site-directed mutagenesis, identified several sequences to be important for activity and regulation. Single base changes at −10, −12, −32, −33, −35, and −37 upstream of the transcription start site resulted in loss of activity from the promoter, suggesting that bases in these positions are important for RNA polymerase interaction. The sequences centered around −10 (TATTCT) and −35 (TTGACC) in this promoter are, in fact, prototypical of eubacterial promoters. Overlapping the RNA polymerase binding site is a perfect 12-bp direct repeat sequence. Some base changes within this direct repeat resulted in constitutive expression, suggesting that this sequence is an operator for negative regulation. Other base changes resulted in loss of glucose repression while retaining the requirement for chitin induction, suggesting that this sequence is also involved in glucose repression. The fact that cis-acting mutations resulted in glucose resistance but not inducer independence rules out the possibility that glucose repression acts exclusively by inducer exclusion. The fact that mutations that affect glucose repression and chitin induction fall within the same direct repeat sequence module suggests that the direct repeat sequence facilitates both chitin induction and glucose repression. PMID:9371809

How does bias correction of RCM precipitation affect modelled runoff?

NASA Astrophysics Data System (ADS)

Teng, J.; Potter, N. J.; Chiew, F. H. S.; Zhang, L.; Vaze, J.; Evans, J. P.

2014-09-01

Many studies bias correct daily precipitation from climate models to match the observed precipitation statistics, and the bias corrected data are then used for various modelling applications. This paper presents a review of recent methods used to bias correct precipitation from regional climate models (RCMs). The paper then assesses four bias correction methods applied to the weather research and forecasting (WRF) model simulated precipitation, and the follow-on impact on modelled runoff for eight catchments in southeast Australia. Overall, the best results are produced by either quantile mapping or a newly proposed two-state gamma distribution mapping method. However, the difference between the tested methods is small in the modelling experiments here (and as reported in the literature), mainly because of the substantial corrections required and inconsistent errors over time (non-stationarity). The errors remaining in bias corrected precipitation are typically amplified in modelled runoff. The tested methods cannot overcome limitation of RCM in simulating precipitation sequence, which affects runoff generation. Results further show that whereas bias correction does not seem to alter change signals in precipitation means, it can introduce additional uncertainty to change signals in high precipitation amounts and, consequently, in runoff. Future climate change impact studies need to take this into account when deciding whether to use raw or bias corrected RCM results. Nevertheless, RCMs will continue to improve and will become increasingly useful for hydrological applications as the bias in RCM simulations reduces.

Reintroduction of locally extinct vertebrates impacts arid soil fungal communities.

PubMed

Clarke, Laurence J; Weyrich, Laura S; Cooper, Alan

2015-06-01

Introduced species have contributed to extinction of native vertebrates in many parts of the world. Changes to vertebrate assemblages are also likely to alter microbial communities through coextinction of some taxa and the introduction of others. Many attempts to restore degraded habitats involve removal of exotic vertebrates (livestock and feral animals) and reintroduction of locally extinct species, but the impact of such reintroductions on microbial communities is largely unknown. We used high-throughput DNA sequencing of the fungal internal transcribed spacer I (ITS1) region to examine whether replacing exotic vertebrates with reintroduced native vertebrates led to changes in soil fungal communities at a reserve in arid central Australia. Soil fungal diversity was significantly different between dune and swale (interdune) habitats. Fungal communities also differed significantly between sites with exotic or reintroduced native vertebrates after controlling for the effect of habitat. Several fungal operational taxonomic units (OTUs) found exclusively inside the reserve were present in scats from reintroduced native vertebrates, providing a direct link between the vertebrate assemblage and soil microbial communities. Our results show that changes to vertebrate assemblages through local extinctions and the invasion of exotic species can alter soil fungal communities. If local extinction of one or several species results in the coextinction of microbial taxa, the full complement of ecological interactions may never be restored. © 2015 John Wiley & Sons Ltd.

Response of Gut Microbiota to Metabolite Changes Induced by Endurance Exercise.

PubMed

Zhao, Xia; Zhang, Zhujun; Hu, Bin; Huang, Wei; Yuan, Chao; Zou, Lingyun

2018-01-01

A few animal studies have shown that wheel running could reverse an unhealthy status by shifting the gut microbial composition, but no investigations have studied the effect of endurance running, such as marathon running, on human gut microbial communities. Since many findings have shown that marathon running immediately causes metabolic changes in blood, urine, muscles and lymph that potentially impact the gut microbiota (GM) within several hours. Here, we investigated whether the GM immediately responds to the enteric changes in amateur half-marathon runners. Alterations in the metabolic profile and microbiota were investigated in fecal samples based on an untargeted metabolomics methodology and 16S rDNA sequencing analysis. A total of 40 fecal metabolites were found significantly changed after finishing a half-marathon race. The most significantly different metabolites were organic acids (the major increased metabolites) and nucleic acid components (the major decreased metabolites). The enteric changes induced by running did not affect the α-diversity of the GM, but the abundances of certain microbiota members were shown to be significantly different before and after running. The family Coriobacteriaceae was identified as a potential biomarker that links exercise with health improvement. Functional prediction showed a significantly activated "Cell motility" function of GM within participants after running. Correlation analysis indicated that the observed differential GM in our study might have been the shared outcome of running and diet. This study provided knowledge regarding the health impacts of marathon running from the perspective of GM for the first time. Our data indicated that long-distance endurance running can immediately cause striking metabolic changes in the gut environment. Gut microbes can rapidly respond to the altered fecal metabolites by adjusting certain bacterial taxa. These findings highlighted the health-promoting benefits of exercise from the perspective of GM.

New Investigations of the Gow Lake Impact Structure, Saskatchewan, Canada: Impact Melt Rocks, Astronaut Training, and More

NASA Astrophysics Data System (ADS)

Osinski, G. R.; Singleton, A. C.; Ozaruk, A.; Hansen, J. R.

2012-03-01

New investigations of the Gow Lake impact structure has revealed an almost complete sequence of impactites from the crater floor upward through a series of melt-free and melt-bearing rocks. This research involved an astronaut training component.

Some Effects of Changes in Question Structure and Sequence on Performance in a Multiple Choice Chemistry Test.

ERIC Educational Resources Information Center

Hodson, D.

1984-01-01

Investigated the effect on student performance of changes in question structure and sequence on a GCE 0-level multiple-choice chemistry test. One finding noted is that there was virtually no change in test reliability on reducing the number of options (from five to per test item). (JN)

The annotation-enriched non-redundant patent sequence databases.

PubMed

Li, Weizhong; Kondratowicz, Bartosz; McWilliam, Hamish; Nauche, Stephane; Lopez, Rodrigo

2013-01-01

The EMBL-European Bioinformatics Institute (EMBL-EBI) offers public access to patent sequence data, providing a valuable service to the intellectual property and scientific communities. The non-redundant (NR) patent sequence databases comprise two-level nucleotide and protein sequence clusters (NRNL1, NRNL2, NRPL1 and NRPL2) based on sequence identity (level-1) and patent family (level-2). Annotation from the source entries in these databases is merged and enhanced with additional information from the patent literature and biological context. Corrections in patent publication numbers, kind-codes and patent equivalents significantly improve the data quality. Data are available through various user interfaces including web browser, downloads via FTP, SRS, Dbfetch and EBI-Search. Sequence similarity/homology searches against the databases are available using BLAST, FASTA and PSI-Search. In this article, we describe the data collection and annotation and also outline major changes and improvements introduced since 2009. Apart from data growth, these changes include additional annotation for singleton clusters, the identifier versioning for tracking entry change and the entry mappings between the two-level databases. Database URL: http://www.ebi.ac.uk/patentdata/nr/

The Annotation-enriched non-redundant patent sequence databases

PubMed Central

Li, Weizhong; Kondratowicz, Bartosz; McWilliam, Hamish; Nauche, Stephane; Lopez, Rodrigo

2013-01-01

The EMBL-European Bioinformatics Institute (EMBL-EBI) offers public access to patent sequence data, providing a valuable service to the intellectual property and scientific communities. The non-redundant (NR) patent sequence databases comprise two-level nucleotide and protein sequence clusters (NRNL1, NRNL2, NRPL1 and NRPL2) based on sequence identity (level-1) and patent family (level-2). Annotation from the source entries in these databases is merged and enhanced with additional information from the patent literature and biological context. Corrections in patent publication numbers, kind-codes and patent equivalents significantly improve the data quality. Data are available through various user interfaces including web browser, downloads via FTP, SRS, Dbfetch and EBI-Search. Sequence similarity/homology searches against the databases are available using BLAST, FASTA and PSI-Search. In this article, we describe the data collection and annotation and also outline major changes and improvements introduced since 2009. Apart from data growth, these changes include additional annotation for singleton clusters, the identifier versioning for tracking entry change and the entry mappings between the two-level databases. Database URL: http://www.ebi.ac.uk/patentdata/nr/ PMID:23396323

DNA sequence of the lymphotropic variant of minute virus of mice, MVM(i), and comparison with the DNA sequence of the fibrotropic prototype strain.

PubMed

Astell, C R; Gardiner, E M; Tattersall, P

1986-02-01

The sequence of molecular clones of the genome of MVM(i), a lymphotropic variant of minute virus of mice, was determined and compared with that of MVM(p), the fibrotropic prototype strain. At the nucleotide level there are 163 base changes: 129 transitions and 34 transversions. Most nucleotide changes are silent, with only 27 amino acids changes predicted, of which 22 are conservative. Notable differences between the MVM(i) and MVM(p) genomes which may account for the cell specificities of these viruses occur within the 3' nontranslated regions. The differences discussed include the absence of a 65-base-pair direct in MVM(i), the presence of only two polyadenylation sites in MVM(i) compared with four in MVM(p), and sequences that bear a resemblance to enhancer sequences. Also included in this paper is an important correction to the MVM(p) sequence (C.R. Astell, M. Thomson, M. Merchlinsky, and D. C. Ward, Nucleic Acids Res. 11:999-1018, 1983).

Continuous aesthetic judgment of image sequences.

PubMed

Khaw, Mel W; Freedberg, David

2018-05-18

Perceptual judgments are said to be reference-dependent as they change on the basis of recent experiences. Here we quantify sequence effects within two types of aesthetic judgments: (i) individual ratings of single images (during self-paced trials) and (ii) continuous ratings of image sequences. As in the case of known contrast effects, trial-by-trial aesthetic responses are negatively correlated with judgments made toward the preceding image. During continuous judgment, a different type of bias is observed. The onset of change within a sequence introduces a persistent increase in ratings (relative to when the same images are judged in isolation). Furthermore, subjects indicate adjustment patterns and choices that selectively favor sequences that are rich in change. Sequence effects in aesthetic judgments thus differ greatly depending on the continuity and arrangement of presented stimuli. The effects highlighted here are important in understanding sustained aesthetic responses over time, such as those elicited during choreographic and musical arrangements. In contrast, standard measurements of aesthetic responses (over trials) may represent a series of distinct aesthetic experiences (e.g., viewing artworks in a museum). Copyright © 2018 Elsevier B.V. All rights reserved.

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

Allen, J; Velsko, S

This report explores the question of whether meaningful conclusions can be drawn regarding the transmission relationship between two microbial samples on the basis of differences observed between the two sample's respective genomes. Unlike similar forensic applications using human DNA, the rapid rate of microbial genome evolution combined with the dynamics of infectious disease require a shift in thinking on what it means for two samples to 'match' in support of a forensic hypothesis. Previous outbreaks for SARS-CoV, FMDV and HIV were examined to investigate the question of how microbial sequence data can be used to draw inferences that link twomore » infected individuals by direct transmission. The results are counter intuitive with respect to human DNA forensic applications in that some genetic change rather than exact matching improve confidence in inferring direct transmission links, however, too much genetic change poses challenges, which can weaken confidence in inferred links. High rates of infection coupled with relatively weak selective pressure observed in the SARS-CoV and FMDV data lead to fairly low confidence for direct transmission links. Confidence values for forensic hypotheses increased when testing for the possibility that samples are separated by at most a few intermediate hosts. Moreover, the observed outbreak conditions support the potential to provide high confidence values for hypothesis that exclude direct transmission links. Transmission inferences are based on the total number of observed or inferred genetic changes separating two sequences rather than uniquely weighing the importance of any one genetic mismatch. Thus, inferences are surprisingly robust in the presence of sequencing errors provided the error rates are randomly distributed across all samples in the reference outbreak database and the novel sequence samples in question. When the number of observed nucleotide mutations are limited due to characteristics of the outbreak or the availability of only partial rather than whole genome sequencing, indel information was shown to have the potential to improve performance but only for select outbreak conditions. In examined HIV transmission cases, extended evolution proved to be the limiting factor in assigning high confidence to transmission links, however, the potential to correct for extended evolution not associated with transmission events is demonstrated. Outbreak specific conditions such as selective pressure (in the form of varying mutation rate), are shown to impact the strength of inference made and a Monte Carlo simulation tool is introduced, which is used to provide upper and lower bounds on the confidence values associated with a forensic hypothesis.« less

A survey of transposable element classification systems--a call for a fundamental update to meet the challenge of their diversity and complexity.

PubMed

Piégu, Benoît; Bire, Solenne; Arensburger, Peter; Bigot, Yves

2015-05-01

The increase of publicly available sequencing data has allowed for rapid progress in our understanding of genome composition. As new information becomes available we should constantly be updating and reanalyzing existing and newly acquired data. In this report we focus on transposable elements (TEs) which make up a significant portion of nearly all sequenced genomes. Our ability to accurately identify and classify these sequences is critical to understanding their impact on host genomes. At the same time, as we demonstrate in this report, problems with existing classification schemes have led to significant misunderstandings of the evolution of both TE sequences and their host genomes. In a pioneering publication Finnegan (1989) proposed classifying all TE sequences into two classes based on transposition mechanisms and structural features: the retrotransposons (class I) and the DNA transposons (class II). We have retraced how ideas regarding TE classification and annotation in both prokaryotic and eukaryotic scientific communities have changed over time. This has led us to observe that: (1) a number of TEs have convergent structural features and/or transposition mechanisms that have led to misleading conclusions regarding their classification, (2) the evolution of TEs is similar to that of viruses by having several unrelated origins, (3) there might be at least 8 classes and 12 orders of TEs including 10 novel orders. In an effort to address these classification issues we propose: (1) the outline of a universal TE classification, (2) a set of methods and classification rules that could be used by all scientific communities involved in the study of TEs, and (3) a 5-year schedule for the establishment of an International Committee for Taxonomy of Transposable Elements (ICTTE). Copyright © 2015 Elsevier Inc. All rights reserved.

Homoplastic microinversions and the avian tree of life

PubMed Central

2011-01-01

Background Microinversions are cytologically undetectable inversions of DNA sequences that accumulate slowly in genomes. Like many other rare genomic changes (RGCs), microinversions are thought to be virtually homoplasy-free evolutionary characters, suggesting that they may be very useful for difficult phylogenetic problems such as the avian tree of life. However, few detailed surveys of these genomic rearrangements have been conducted, making it difficult to assess this hypothesis or understand the impact of microinversions upon genome evolution. Results We surveyed non-coding sequence data from a recent avian phylogenetic study and found substantially more microinversions than expected based upon prior information about vertebrate inversion rates, although this is likely due to underestimation of these rates in previous studies. Most microinversions were lineage-specific or united well-accepted groups. However, some homoplastic microinversions were evident among the informative characters. Hemiplasy, which reflects differences between gene trees and the species tree, did not explain the observed homoplasy. Two specific loci were microinversion hotspots, with high numbers of inversions that included both the homoplastic as well as some overlapping microinversions. Neither stem-loop structures nor detectable sequence motifs were associated with microinversions in the hotspots. Conclusions Microinversions can provide valuable phylogenetic information, although power analysis indicates that large amounts of sequence data will be necessary to identify enough inversions (and similar RGCs) to resolve short branches in the tree of life. Moreover, microinversions are not perfect characters and should be interpreted with caution, just as with any other character type. Independent of their use for phylogenetic analyses, microinversions are important because they have the potential to complicate alignment of non-coding sequences. Despite their low rate of accumulation, they have clearly contributed to genome evolution, suggesting that active identification of microinversions will prove useful in future phylogenomic studies. PMID:21612607

BDNF Val66Met polymorphism is associated with abnormal interhemispheric transfer of a newly acquired motor skill.

PubMed

Morin-Moncet, Olivier; Beaumont, Vincent; de Beaumont, Louis; Lepage, Jean-Francois; Théoret, Hugo

2014-05-01

Recent data suggest that the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene can alter cortical plasticity within the motor cortex of carriers, which exhibits abnormally low rates of cortical reorganization after repetitive motor tasks. To verify whether long-term retention of a motor skill is also modulated by the presence of the polymorphism, 20 participants (10 Val66Val, 10 Val66Met) were tested twice at a 1-wk interval. During each visit, excitability of the motor cortex was measured by transcranial magnetic stimulations (TMS) before and after performance of a procedural motor learning task (serial reaction time task) designed to study sequence-specific learning of the right hand and sequence-specific transfer from the right to the left hand. Behavioral results showed a motor learning effect that persisted for at least a week and task-related increases in corticospinal excitability identical for both sessions and without distinction for genetic group. Sequence-specific transfer of the motor skill from the right hand to the left hand was greater in session 2 than in session 1 only in the Val66Met genetic group. Further analysis revealed that the sequence-specific transfer occurred equally at both sessions in the Val66Val genotype group. In the Val66Met genotype group, sequence-specific transfer did not occur at session 1 but did at session 2. These data suggest a limited impact of Val66Met polymorphism on the learning and retention of a complex motor skill and its associated changes in corticospinal excitability over time, and a possible modulation of the interhemispheric transfer of procedural learning. Copyright © 2014 the American Physiological Society.

Optimizing de novo transcriptome assembly and extending genomic resources for striped catfish (Pangasianodon hypophthalmus).

PubMed

Thanh, Nguyen Minh; Jung, Hyungtaek; Lyons, Russell E; Njaci, Isaac; Yoon, Byoung-Ha; Chand, Vincent; Tuan, Nguyen Viet; Thu, Vo Thi Minh; Mather, Peter

2015-10-01

Striped catfish (Pangasianodon hypophthalmus) is a commercially important freshwater fish used in inland aquaculture in the Mekong Delta, Vietnam. The culture industry is facing a significant challenge however from saltwater intrusion into many low topographical coastal provinces across the Mekong Delta as a result of predicted climate change impacts. Developing genomic resources for this species can facilitate the production of improved culture lines that can withstand raised salinity conditions, and so we have applied high-throughput Ion Torrent sequencing of transcriptome libraries from six target osmoregulatory organs from striped catfish as a genomic resource for use in future selection strategies. We obtained 12,177,770 reads after trimming and processing with an average length of 97bp. De novo assemblies were generated using CLC Genomic Workbench, Trinity and Velvet/Oases with the best overall contig performance resulting from the CLC assembly. De novo assembly using CLC yielded 66,451 contigs with an average length of 478bp and N50 length of 506bp. A total of 37,969 contigs (57%) possessed significant similarity with proteins in the non-redundant database. Comparative analyses revealed that a significant number of contigs matched sequences reported in other teleost fishes, ranging in similarity from 45.2% with Atlantic cod to 52% with zebrafish. In addition, 28,879 simple sequence repeats (SSRs) and 55,721 single nucleotide polymorphisms (SNPs) were detected in the striped catfish transcriptome. The sequence collection generated in the current study represents the most comprehensive genomic resource for P. hypophthalmus available to date. Our results illustrate the utility of next-generation sequencing as an efficient tool for constructing a large genomic database for marker development in non-model species. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of sequence changes in live attenuated goose parvovirus vaccine strains developed in Asia and Europe.

PubMed

Shien, J-H; Wang, Y-S; Chen, C-H; Shieh, H K; Hu, C-C; Chang, P-C

2008-10-01

Live attenuated vaccines have been used for control of the disease caused by goose parvovirus (GPV), but the mechanism involved in attenuation of GPV remains elusive. This report presents the complete nucleotide sequences of two live attenuated strains of GPV (82-0321V and VG32/1) that were independently developed in Taiwan and Europe, together with the parental strain of 82-0321V and a field strain isolated in Taiwan in 2006. Sequence comparisons showed that 82-0321V and VG32/1 had multiple deletions and substitutions in the inverted terminal repeats region when compared with their parental strain or the field virus, but these changes did not affect the formation of the hairpin structure essential for viral replication. Moreover, 82-0321V and VG32/1 had five amino acid changes in the non-structural protein, but these changes were located at positions distant from known functional motifs in the non-structural protein. In contrast, 82-0321V had nine changes and VG32/1 had 11 changes in their capsid proteins (VP1), and the majority of these changes occurred at positions close to the putative receptor binding sites of VP1, as predicted using the structure of adeno-associated virus 2 as the model system. Taken together, the results suggest that changes in sequence near the receptor binding sites of VP1 might be responsible for attenuation of GPV. This is the first report of complete nucleotide sequences of GPV other than the virulent B strain, and suggests a possible mechanism for attenuation of GPV.

Single nucleotide variations: Biological impact and theoretical interpretation

PubMed Central

Katsonis, Panagiotis; Koire, Amanda; Wilson, Stephen Joseph; Hsu, Teng-Kuei; Lua, Rhonald C; Wilkins, Angela Dawn; Lichtarge, Olivier

2014-01-01

Genome-wide association studies (GWAS) and whole-exome sequencing (WES) generate massive amounts of genomic variant information, and a major challenge is to identify which variations drive disease or contribute to phenotypic traits. Because the majority of known disease-causing mutations are exonic non-synonymous single nucleotide variations (nsSNVs), most studies focus on whether these nsSNVs affect protein function. Computational studies show that the impact of nsSNVs on protein function reflects sequence homology and structural information and predict the impact through statistical methods, machine learning techniques, or models of protein evolution. Here, we review impact prediction methods and discuss their underlying principles, their advantages and limitations, and how they compare to and complement one another. Finally, we present current applications and future directions for these methods in biological research and medical genetics. PMID:25234433

Time sequence photography of Roosters Comb

USDA-ARS?s Scientific Manuscript database

The importance of understanding natural landscape changes is key in properly determining rangeland ecology. Time sequence photography allows a landscape snapshot to be documented and enables the ability to compare natural changes overtime. Photographs of Roosters Comb were taken from the same vantag...

Scaling up discovery of hidden diversity in fungi: impacts of barcoding approaches.

PubMed

Yahr, Rebecca; Schoch, Conrad L; Dentinger, Bryn T M

2016-09-05

The fungal kingdom is a hyperdiverse group of multicellular eukaryotes with profound impacts on human society and ecosystem function. The challenge of documenting and describing fungal diversity is exacerbated by their typically cryptic nature, their ability to produce seemingly unrelated morphologies from a single individual and their similarity in appearance to distantly related taxa. This multiplicity of hurdles resulted in the early adoption of DNA-based comparisons to study fungal diversity, including linking curated DNA sequence data to expertly identified voucher specimens. DNA-barcoding approaches in fungi were first applied in specimen-based studies for identification and discovery of taxonomic diversity, but are now widely deployed for community characterization based on sequencing of environmental samples. Collectively, fungal barcoding approaches have yielded important advances across biological scales and research applications, from taxonomic, ecological, industrial and health perspectives. A major outstanding issue is the growing problem of 'sequences without names' that are somewhat uncoupled from the traditional framework of fungal classification based on morphology and preserved specimens. This review summarizes some of the most significant impacts of fungal barcoding, its limitations, and progress towards the challenge of effective utilization of the exponentially growing volume of data gathered from high-throughput sequencing technologies.This article is part of the themed issue 'From DNA barcodes to biomes'. © 2016 The Authors.

Ragweed (Ambrosia artemisiifolia) pollen allergenicity: SuperSAGE transcriptomic analysis upon elevated CO2 and drought stress

PubMed Central

2014-01-01

Background Pollen of common ragweed (Ambrosia artemisiifolia) is a main cause of allergic diseases in Northern America. The weed has recently become spreading as a neophyte in Europe, while climate change may also affect the growth of the plant and additionally may also influence pollen allergenicity. To gain better insight in the molecular mechanisms in the development of ragweed pollen and its allergenic proteins under global change scenarios, we generated SuperSAGE libraries to identify differentially expressed transcripts. Results Ragweed plants were grown in a greenhouse under 380 ppm CO2 and under elevated level of CO2 (700 ppm). In addition, drought experiments under both CO2 concentrations were performed. The pollen viability was not altered under elevated CO2, whereas drought stress decreased its viability. Increased levels of individual flavonoid metabolites were found under elevated CO2 and/or drought. Total RNA was isolated from ragweed pollen, exposed to the four mentioned scenarios and four SuperSAGE libraries were constructed. The library dataset included 236,942 unique sequences, showing overlapping as well as clear differently expressed sequence tags (ESTs). The analysis targeted ESTs known in Ambrosia, as well as in pollen of other plants. Among the identified ESTs, those encoding allergenic ragweed proteins (Amb a) increased under elevated CO2 and drought stress. In addition, ESTs encoding allergenic proteins in other plants were also identified. Conclusions The analysis of changes in the transcriptome of ragweed pollen upon CO2 and drought stress using SuperSAGE indicates that under global change scenarios the pollen transcriptome was altered, and impacts the allergenic potential of ragweed pollen. PMID:24972689

Response of Spring Diatoms to CO2 Availability in the Western North Pacific as Determined by Next-Generation Sequencing.

PubMed

Endo, Hisashi; Sugie, Koji; Yoshimura, Takeshi; Suzuki, Koji

2016-01-01

Next-generation sequencing (NGS) technologies have enabled us to determine phytoplankton community compositions at high resolution. However, few studies have adopted this approach to assess the responses of natural phytoplankton communities to environmental change. Here, we report the impact of different CO2 levels on spring diatoms in the Oyashio region of the western North Pacific as estimated by NGS of the diatom-specific rbcL gene (DNA), which encodes the large subunit of RubisCO. We also examined the abundance and composition of rbcL transcripts (cDNA) in diatoms to assess their physiological responses to changing CO2 levels. A short-term (3-day) incubation experiment was carried out on-deck using surface Oyashio waters under different pCO2 levels (180, 350, 750, and 1000 μatm) in May 2011. During the incubation, the transcript abundance of the diatom-specific rbcL gene decreased with an increase in seawater pCO2 levels. These results suggest that CO2 fixation capacity of diatoms decreased rapidly under elevated CO2 levels. In the high CO2 treatments (750 and 1000 μatm), diversity of diatom-specific rbcL gene and its transcripts decreased relative to the control treatment (350 μatm), as well as contributions of Chaetocerataceae, Thalassiosiraceae, and Fragilariaceae to the total population, but the contributions of Bacillariaceae increased. In the low CO2 treatment, contributions of Bacillariaceae also increased together with other eukaryotes. These suggest that changes in CO2 levels can alter the community composition of spring diatoms in the Oyashio region. Overall, the NGS technology provided us a deeper understanding of the response of diatoms to changes in CO2 levels in terms of their community composition, diversity, and photosynthetic physiology.

Hotspots, Lifelines, and the Safrr Haywired Earthquake Sequence

NASA Astrophysics Data System (ADS)

Ratliff, J. L.; Porter, K.

2014-12-01

Though California has experienced many large earthquakes (San Francisco, 1906; Loma Prieta, 1989; Northridge, 1994), the San Francisco Bay Area has not had a damaging earthquake for 25 years. Earthquake risk and surging reliance on smartphones and the Internet to handle everyday tasks raise the question: is an increasingly technology-reliant Bay Area prepared for potential infrastructure impacts caused by a major earthquake? How will a major earthquake on the Hayward Fault affect lifelines (roads, power, water, communication, etc.)? The U.S. Geological Survey Science Application for Risk Reduction (SAFRR) program's Haywired disaster scenario, a hypothetical two-year earthquake sequence triggered by a M7.05 mainshock on the Hayward Fault, addresses these and other questions. We explore four geographic aspects of lifeline damage from earthquakes: (1) geographic lifeline concentrations, (2) areas where lifelines pass through high shaking or potential ground-failure zones, (3) areas with diminished lifeline service demand due to severe building damage, and (4) areas with increased lifeline service demand due to displaced residents and businesses. Potential mainshock lifeline vulnerability and spatial demand changes will be discerned by superimposing earthquake shaking, liquefaction probability, and landslide probability damage thresholds with lifeline concentrations and with large-capacity shelters. Intersecting high hazard levels and lifeline clusters represent potential lifeline susceptibility hotspots. We will also analyze possible temporal vulnerability and demand changes using an aftershock shaking threshold. The results of this analysis will inform regional lifeline resilience initiatives and response and recovery planning, as well as reveal potential redundancies and weaknesses for Bay Area lifelines. Identified spatial and temporal hotspots can provide stakeholders with a reference for possible systemic vulnerability resulting from an earthquake sequence.

Translating natural genetic variation to gene expression in a computational model of the Drosophila gap gene regulatory network

PubMed Central

Kozlov, Konstantin N.; Kulakovskiy, Ivan V.; Zubair, Asif; Marjoram, Paul; Lawrie, David S.; Nuzhdin, Sergey V.; Samsonova, Maria G.

2017-01-01

Annotating the genotype-phenotype relationship, and developing a proper quantitative description of the relationship, requires understanding the impact of natural genomic variation on gene expression. We apply a sequence-level model of gap gene expression in the early development of Drosophila to analyze single nucleotide polymorphisms (SNPs) in a panel of natural sequenced D. melanogaster lines. Using a thermodynamic modeling framework, we provide both analytical and computational descriptions of how single-nucleotide variants affect gene expression. The analysis reveals that the sequence variants increase (decrease) gene expression if located within binding sites of repressors (activators). We show that the sign of SNP influence (activation or repression) may change in time and space and elucidate the origin of this change in specific examples. The thermodynamic modeling approach predicts non-local and non-linear effects arising from SNPs, and combinations of SNPs, in individual fly genotypes. Simulation of individual fly genotypes using our model reveals that this non-linearity reduces to almost additive inputs from multiple SNPs. Further, we see signatures of the action of purifying selection in the gap gene regulatory regions. To infer the specific targets of purifying selection, we analyze the patterns of polymorphism in the data at two phenotypic levels: the strengths of binding and expression. We find that combinations of SNPs show evidence of being under selective pressure, while individual SNPs do not. The model predicts that SNPs appear to accumulate in the genotypes of the natural population in a way biased towards small increases in activating action on the expression pattern. Taken together, these results provide a systems-level view of how genetic variation translates to the level of gene regulatory networks via combinatorial SNP effects. PMID:28898266

Benthic foraminifera baseline assemblages from a coastal nearshore reef complex on the central Great Barrier Reef

NASA Astrophysics Data System (ADS)

Johnson, Jamie; Perry, Chris; Smithers, Scott; Morgan, Kyle

2016-04-01

Declining water quality due to river catchment modification since European settlement (c. 1850 A.D.) represents a major threat to the health of coral reefs on Australia's Great Barrier Reef (GBR), particularly for those located in the coastal waters of the GBR's inner-shelf. These nearshore reefs are widely perceived to be most susceptible to declining water quality owing to their close proximity to river point sources. Despite this, nearshore reefs have been relatively poorly studied with the impacts and magnitudes of environmental degradation still remaining unclear. This is largely due to ongoing debates concerning the significance of increased sediment yields against naturally high background sedimentary regimes. Benthic foraminifera are increasingly used as tools for monitoring environmental and ecological change on coral reefs. On the GBR, the majority of studies have focussed on the spatial distributions of contemporary benthic foraminiferal assemblages. While baseline assemblages from other environments (e.g. inshore reefs and mangroves) have been described, very few records exist for nearshore reefs. Here, we present preliminary results from the first palaeoecological study of foraminiferal assemblages of nearshore reefs on the central GBR. Cores were recovered from the nearshore reef complex at Paluma Shoals using percussion techniques. Recovery was 100%, capturing the entire Holocene reef sequence of the selected reef structures. Radiocarbon dating and subsequent age-depth modelling techniques were used to identify reef sequences pre-dating European settlement. Benthic foraminifera assemblages were reconstructed from the identified sequences to establish pre-European ecological baselines with the aim of providing a record of foraminiferal distribution during vertical reef accretion and against which contemporary ecological change may be assessed.

Characterization of the first complete genome sequence of an Impatiens necrotic spot orthotospovirus isolate from the United States and worldwide phylogenetic analyses of INSV isolates.

PubMed

Zhao, Kaixi; Margaria, Paolo; Rosa, Cristina

2018-05-10

Impatiens necrotic spot orthotospovirus (INSV) can impact economically important ornamental plants and vegetables worldwide. Characterization studies on INSV are limited. For most INSV isolates, there are no complete genome sequences available. This lack of genomic information has a negative impact on the understanding of the INSV genetic diversity and evolution. Here we report the first complete nucleotide sequence of a US INSV isolate. INSV-UP01 was isolated from an impatiens in Pennsylvania, US. RT-PCR was used to clone its full-length genome and Vector NTI to assemble overlapping sequences. Phylogenetic trees were constructed by using MEGA7 software to show the phylogenetic relationships with other available INSV sequences worldwide. This US isolate has genome and biological features classical of INSV species and clusters in the Western Hemisphere clade, but its origin appears to be recent. Furthermore, INSV-UP01 might have been involved in a recombination event with an Italian isolate belonging to the Asian clade. Our analyses support that INSV isolates infect a broad plant-host range they group by geographic origin and not by host, and are subjected to frequent recombination events. These results justify the need to generate and analyze complete genome sequences of orthotospoviruses in general and INSV in particular.

Cancer Chemoprotection Through Nutrient-mediated Histone Modifications

PubMed Central

Gao, Yifeng; Tollefsbol, Trygve O.

2016-01-01

Epigenetics, the study of heritable changes in gene expression without modifying the nucleotide sequence, is among the most important topics in medicinal chemistry and cancer chemoprotection. Among those changes, DNA methylation and histone modification have been shown to be associated with various types of cancers in a number of ways, many of which are regulated by dietary components that are mostly found in plants. Although, mechanisms of nutrient components affecting histone acetylation/deacetylation in cancer are widely studied, how those natural compounds affect cancer through other histone modifications, such as methylation, phosphorylation and ubiquitylation, is rarely reviewed. Thus, this review article discusses impacts recently studied on histone acetylation as well as other histone modifications by dietary components, such as genistein, resveratrol, curcumin, epigallocatechin-3-gallate (EGCG), 3,3′-diindolylmethane (DIM), diallyl disulfide, garcinol, procyanidin B3, quercetin, sulforaphane and other isothiocyanates, in various types of cancer. PMID:25891109

Transmissible microbial and metabolomic remodeling by soluble dietary fiber improves metabolic homeostasis

PubMed Central

He, Baokun; Nohara, Kazunari; Ajami, Nadim J.; Michalek, Ryan D.; Tian, Xiangjun; Wong, Matthew; Losee-Olson, Susan H.; Petrosino, Joseph F.; Yoo, Seung-Hee; Shimomura, Kazuhiro; Chen, Zheng

2015-01-01

Dietary fibers are increasingly appreciated as beneficial nutritional components. However, a requisite role of gut microbiota in fiber function and the overall impact of fibers on metabolomic flux remain unclear. We herein showed enhancing effects of a soluble resistant maltodextrin (RM) on glucose homeostasis in mouse metabolic disease models. Remarkably, fecal microbiota transplantation (FMT) caused pronounced and time-dependent improvement in glucose tolerance in RM recipient mice, indicating a causal relationship between microbial remodeling and metabolic efficacy. Microbial 16S sequencing revealed transmissible taxonomic changes correlated with improved metabolism, notably enrichment of probiotics and reduction of Alistipes and Bacteroides known to associate with high fat/protein diets. Metabolomic profiling further illustrated broad changes, including enrichment of phenylpropionates and decreases in key intermediates of glucose utilization, cholesterol biosynthesis and amino acid fermentation. These studies elucidate beneficial roles of RM-dependent microbial remodeling in metabolic homeostasis, and showcase prevalent health-promoting potentials of dietary fibers. PMID:26040234

Impact of depressive symptoms, self-esteem and neuroticism on trajectories of overgeneral autobiographical memory over repeated trials.

PubMed

Kashdan, Todd B; Roberts, John E; Carlos, Erica L

2006-04-01

The present study examined trajectories of change in the frequency of overgeneral autobiographical memory (OGM) over the course of repeated trials, and tested whether particular dimensions of depressive symptomatology (somatic and cognitive-affective distress), self-esteem, and neuroticism account for individual differences in these trajectories. Given that depression is associated with impairments in effortful processing, we predicted that over repeated trials depression would be associated with increasingly OGM. Generalised Linear Mixed Models with Penalised Quasi-Likelihood demonstrated significant linear and quadratic trends in OGM over repeated trials, and somatic distress and self-esteem moderated these slopes. The form of these interactions suggested that somatic distress and low self-esteem primarily contribute to OGM during the second half of the trial sequence. The present findings demonstrate the value of a novel analytical approach to OGM that estimates individual trajectories of change over repeated trials.

Impacts of storm chronology on the morphological changes of the Formby beach and dune system, UK

NASA Astrophysics Data System (ADS)

Dissanayake, P.; Brown, J.; Karunarathna, H.

2015-07-01

Impacts of storm chronology within a storm cluster on beach/dune erosion are investigated by applying the state-of-the-art numerical model XBeach to the Sefton coast, northwest England. Six temporal storm clusters of different storm chronologies were formulated using three storms observed during the 2013/2014 winter. The storm power values of these three events nearly halve from the first to second event and from the second to third event. Cross-shore profile evolution was simulated in response to the tide, surge and wave forcing during these storms. The model was first calibrated against the available post-storm survey profiles. Cumulative impacts of beach/dune erosion during each storm cluster were simulated by using the post-storm profile of an event as the pre-storm profile for each subsequent event. For the largest event the water levels caused noticeable retreat of the dune toe due to the high water elevation. For the other events the greatest evolution occurs over the bar formations (erosion) and within the corresponding troughs (deposition) of the upper-beach profile. The sequence of events impacting the size of this ridge-runnel feature is important as it consequently changes the resilience of the system to the most extreme event that causes dune retreat. The highest erosion during each single storm event was always observed when that storm initialised the storm cluster. The most severe storm always resulted in the most erosion during each cluster, no matter when it occurred within the chronology, although the erosion volume due to this storm was reduced when it was not the primary event. The greatest cumulative cluster erosion occurred with increasing storm severity; however, the variability in cumulative cluster impact over a beach/dune cross section due to storm chronology is minimal. Initial storm impact can act to enhance or reduce the system resilience to subsequent impact, but overall the cumulative impact is controlled by the magnitude and number of the storms. This model application provides inter-survey information about morphological response to repeated storm impact. This will inform local managers of the potential beach response and dune vulnerability to variable storm configurations.

Impacts of storm chronology on the morphological changes of the Formby beach and dune system, UK

NASA Astrophysics Data System (ADS)

Dissanayake, P.; Brown, J.; Karunarathna, H.

2015-04-01

Impacts of storm chronology within a storm cluster on beach/dune erosion are investigated by applying the state-of-the-art numerical model XBeach to the Sefton coast, northwest England. Six temporal storm clusters of different storm chronologies were formulated using three storms observed during the 2013/14 winter. The storm power values of these three events nearly halve from the first to second event and from the second to third event. Cross-shore profile evolution was simulated in response to the tide, surge and wave forcing during these storms. The model was first calibrated against the available post-storm survey profiles. Cumulative impacts of beach/dune erosion during each storm cluster were simulated by using the post-storm profile of an event as the pre-storm profile for each subsequent event. For the largest event the water levels caused noticeable retreat of the dune toe due to the high water elevation. For the other events the greatest evolution occurs over the bar formations (erosion) and within the corresponding troughs (deposition) of the upper beach profile. The sequence of events impacting the size of this ridge-runnel feature is important as it consequently changes the resilience of the system to the most extreme event that causes dune retreat. The highest erosion during each single storm event was always observed when that storm initialised the storm cluster. The most severe storm always resulted in the most erosion during each cluster, no matter when it occurred within the chronology, although the erosion volume due to this storm was reduced when it was not the primary event. The greatest cumulative cluster erosion occurred with increasing storm severity; however, the variability in cumulative cluster impact over a beach/dune cross-section due to storm chronology is minimal. Initial storm impact can act to enhance or reduce the system resilience to subsequent impact, but overall the cumulative impact is controlled by the magnitude and number of the storms. This model application provides inter-survey information about morphological response to repeated storm impact. This will inform local managers of the potential beach response and dune vulnerability to variable storm configurations.

Flexible, Mastery-Oriented Astrophysics Sequence.

ERIC Educational Resources Information Center

Zeilik, Michael, II

1981-01-01

Describes the implementation and impact of a two-semester mastery-oriented astrophysics sequence for upper-level physics/astrophysics majors designed to handle flexibly a wide range of student backgrounds. A Personalized System of Instruction (PSI) format was used fostering frequent student-instructor interaction and role-modeling behavior in…

Sequencing Computer-Assisted Learning of Transformations of Trigonometric Functions

ERIC Educational Resources Information Center

Ross, John A.; Bruce, Catherine D.; Sibbald, Timothy M.

2011-01-01

Studies incorporating technology into the teaching of trigonometry, although sparse, have demonstrated positive effects on student achievement. The optimal sequence for integrating technology with teacher-led mathematics instruction has not been determined. Our research investigated whether technology has a greater impact on student achievement…

Increasing the reach of forensic genetics with massively parallel sequencing.

PubMed

Budowle, Bruce; Schmedes, Sarah E; Wendt, Frank R

2017-09-01

The field of forensic genetics has made great strides in the analysis of biological evidence related to criminal and civil matters. More so, the discipline has set a standard of performance and quality in the forensic sciences. The advent of massively parallel sequencing will allow the field to expand its capabilities substantially. This review describes the salient features of massively parallel sequencing and how it can impact forensic genetics. The features of this technology offer increased number and types of genetic markers that can be analyzed, higher throughput of samples, and the capability of targeting different organisms, all by one unifying methodology. While there are many applications, three are described where massively parallel sequencing will have immediate impact: molecular autopsy, microbial forensics and differentiation of monozygotic twins. The intent of this review is to expose the forensic science community to the potential enhancements that have or are soon to arrive and demonstrate the continued expansion the field of forensic genetics and its service in the investigation of legal matters.

Evolution and molecular epidemiology of classical swine fever virus during a multi-annual outbreak amongst European wild boar.

PubMed

Goller, Katja V; Gabriel, Claudia; Dimna, Mireille Le; Le Potier, Marie-Frédérique; Rossi, Sophie; Staubach, Christoph; Merboth, Matthias; Beer, Martin; Blome, Sandra

2016-03-01

Classical swine fever is a viral disease of pigs that carries tremendous socio-economic impact. In outbreak situations, genetic typing is carried out for the purpose of molecular epidemiology in both domestic pigs and wild boar. These analyses are usually based on harmonized partial sequences. However, for high-resolution analyses towards the understanding of genetic variability and virus evolution, full-genome sequences are more appropriate. In this study, a unique set of representative virus strains was investigated that was collected during an outbreak in French free-ranging wild boar in the Vosges-du-Nord mountains between 2003 and 2007. Comparative sequence and evolutionary analyses of the nearly full-length sequences showed only slow evolution of classical swine fever virus strains over the years and no impact of vaccination on mutation rates. However, substitution rates varied amongst protein genes; furthermore, a spatial and temporal pattern could be observed whereby two separate clusters were formed that coincided with physical barriers.

Variants of the D{sub 5} dopamine receptor gene found in patients with schizophrenia: Identification of a nonsense mutation and multiple missense changes

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

Sobell, J.L.; Lind, T.J.; Sommer, S.S.

To determine whether mutations in the D{sub 5} dopamine receptor (D{sub 5}DR) gene are associated with schizophrenia, the gene was examined in 78 unrelated schizophrenic individuals. After amplification by the polymerase chain reaction, products were examined by dideoxy fingerprinting (ddF), a highly sensitive screening method related to single strand conformational polymorphism analysis. All samples with unusual ddF patterns were sequenced to precisely identify the sequence change. In the 156 D{sub 5}DR alleles examined, nine sequence changes were identified. Four of the nine did not affect protein structure; of these, three were silent changes and one was a transition in themore » 3{prime} untranslated region. The remaining five sequence changes result in protein alterations: of these, one is a missense change in a non-conserved amino acid, 3 are missense changes in amino acids that are conserved in some dopamine D{sub 5} receptors and the last is a nonsense mutation. To investigate whether the nonsense mutation was associated with schizophrenia, 400 additional schizophrenic cases of western European descent and 1914 ethnically-similar controls were screened for the change. One additional schizophrenic carrier was identified and verified by direct genomic sequencing (allele frequency: .0013), but eight carriers also were found and confirmed among the non-schizophrenics (allele frequency: .0021)(p>.25). The gene was re-examined in all newly identified carriers of the nonsense mutation by direct sequencing and/or ddF in search of additional mutations. None were identified. Family studies also were conducted to investigate possible cosegregation of the mutation with other neuropsychiatric diseases, but this was not demonstrated. Thus, the mutation does not appear to be associated with an increased risk of schizophrenia nor does an initial analysis suggest cosegregation with other neuropsychiatric disorders or symptom complexes.« less

Increased fMRI Sensitivity at Equal Data Burden Using Averaged Shifted Echo Acquisition

PubMed Central

Witt, Suzanne T.; Warntjes, Marcel; Engström, Maria

2016-01-01

There is growing evidence as to the benefits of collecting BOLD fMRI data with increased sampling rates. However, many of the newly developed acquisition techniques developed to collect BOLD data with ultra-short TRs require hardware, software, and non-standard analytic pipelines that may not be accessible to all researchers. We propose to incorporate the method of shifted echo into a standard multi-slice, gradient echo EPI sequence to achieve a higher sampling rate with a TR of <1 s with acceptable spatial resolution. We further propose to incorporate temporal averaging of consecutively acquired EPI volumes to both ameliorate the reduced temporal signal-to-noise inherent in ultra-fast EPI sequences and reduce the data burden. BOLD data were collected from 11 healthy subjects performing a simple, event-related visual-motor task with four different EPI sequences: (1) reference EPI sequence with TR = 1440 ms, (2) shifted echo EPI sequence with TR = 700 ms, (3) shifted echo EPI sequence with every two consecutively acquired EPI volumes averaged and effective TR = 1400 ms, and (4) shifted echo EPI sequence with every four consecutively acquired EPI volumes averaged and effective TR = 2800 ms. Both the temporally averaged sequences exhibited increased temporal signal-to-noise over the shifted echo EPI sequence. The shifted echo sequence with every two EPI volumes averaged also had significantly increased BOLD signal change compared with the other three sequences, while the shifted echo sequence with every four EPI volumes averaged had significantly decreased BOLD signal change compared with the other three sequences. The results indicated that incorporating the method of shifted echo into a standard multi-slice EPI sequence is a viable method for achieving increased sampling rate for collecting event-related BOLD data. Further, consecutively averaging every two consecutively acquired EPI volumes significantly increased the measured BOLD signal change and the subsequently calculated activation map statistics. PMID:27932947

Is sequence awareness mandatory for perceptual sequence learning: An assessment using a pure perceptual sequence learning design.

PubMed

Deroost, Natacha; Coomans, Daphné

2018-02-01

We examined the role of sequence awareness in a pure perceptual sequence learning design. Participants had to react to the target's colour that changed according to a perceptual sequence. By varying the mapping of the target's colour onto the response keys, motor responses changed randomly. The effect of sequence awareness on perceptual sequence learning was determined by manipulating the learning instructions (explicit versus implicit) and assessing the amount of sequence awareness after the experiment. In the explicit instruction condition (n = 15), participants were instructed to intentionally search for the colour sequence, whereas in the implicit instruction condition (n = 15), they were left uninformed about the sequenced nature of the task. Sequence awareness after the sequence learning task was tested by means of a questionnaire and the process-dissociation-procedure. The results showed that the instruction manipulation had no effect on the amount of perceptual sequence learning. Based on their report to have actively applied their sequence knowledge during the experiment, participants were subsequently regrouped in a sequence strategy group (n = 14, of which 4 participants from the implicit instruction condition and 10 participants from the explicit instruction condition) and a no-sequence strategy group (n = 16, of which 11 participants from the implicit instruction condition and 5 participants from the explicit instruction condition). Only participants of the sequence strategy group showed reliable perceptual sequence learning and sequence awareness. These results indicate that perceptual sequence learning depends upon the continuous employment of strategic cognitive control processes on sequence knowledge. Sequence awareness is suggested to be a necessary but not sufficient condition for perceptual learning to take place. Copyright © 2018 Elsevier B.V. All rights reserved.

Alternation blindness in the representation of binary sequences.

PubMed

Yu, Ru Qi; Osherson, Daniel; Zhao, Jiaying

2018-03-01

Binary information is prevalent in the environment and contains 2 distinct outcomes. Binary sequences consist of a mixture of alternation and repetition. Understanding how people perceive such sequences would contribute to a general theory of information processing. In this study, we examined how people process alternation and repetition in binary sequences. Across 4 paradigms involving estimation, working memory, change detection, and visual search, we found that the number of alternations is underestimated compared with repetitions (Experiment 1). Moreover, recall for binary sequences deteriorates as the sequence alternates more (Experiment 2). Changes in bits are also harder to detect as the sequence alternates more (Experiment 3). Finally, visual targets superimposed on bits of a binary sequence take longer to process as alternation increases (Experiment 4). Overall, our results indicate that compared with repetition, alternation in a binary sequence is less salient in the sense of requiring more attention for successful encoding. The current study thus reveals the cognitive constraints in the representation of alternation and provides a new explanation for the overalternation bias in randomness perception. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

40Ar/39Ar dating of a Langhian biotite-rich clay layer in the pelagic sequence of the Cònero Riviera, Ancona, Italy

NASA Astrophysics Data System (ADS)

Mader, Dieter; Montanari, Alessandro; Gattacceca, Jérôme; Koeberl, Christian; Handler, Robert; Coccioni, Rodolfo

2001-12-01

A nearly complete and undisturbed Miocene carbonate sequence is present in the easternmost part of the Umbria-Marche basin, Italy, which is ideal for detailed and integrated stratigraphic investigations of the Miocene Epoch. In this study, we were trying to obtain evidence for the presence or absence of distal ejecta from the 15 Ma Ries impact structure in southern Germany, located about 600 km to the north-northwest of the Umbria-Marche basin. The first step is to find coeval strata in the Umbria-Marche sequence. At the La Vedova section, Cònero Riviera, we dated a volcaniclastic biotite-rich clay layer, the Aldo Level, which is situated within planktonic foraminiferal Zone N8, at 14.9±0.2 Ma, using the 40Ar/39Ar method. Together with detailed geologic and stratigraphic information about the Aldo Level, the resulting age can be used confidentially to calibrate the Langhian stage. Besides providing new constraints on Miocene geochronology, this age can now be used for impact stratigraphic studies. To directly correlate the biotite ages of the La Vedova section with rocks from the Ries impact event, Ries impact glass was also analyzed and found to be coeval. Although unrelated to this impact event, the biotite-rich clay layer should help in the search for evidence of distal ejecta related to the Ries crater.

P53 Gene Mutagenesis in Breast Cancer

DTIC Science & Technology

2005-03-01

the wild type T peak. 12 Table 1. Sonic ntations dected by SINtA Individual Cell Sequence Amino Acid Species Conservation 3 ID’ ID Change2 Change... differences in the content of toxic substances in the diet (Biggs et al., 1993; Blaszyk et al., 1996). The development of this p53 mutation load...Changes in the P53 Gene in Single Cells Individual Sequence Amino acid Species conservation ’ ID’ Cell ID change’ change Monkey Mouse Rat Chicken

Responses of soil respiration to soil management changes in an agropastoral ecotone in Inner Mongolia, China.

PubMed

Xue, Haili; Tang, Haiping

2018-01-01

Studying the responses of soil respiration ( R s ) to soil management changes is critical for enhancing our understanding of the global carbon cycle and has practical implications for grassland management. Therefore, the objectives of this study were (1) quantify daily and seasonal patterns of R s , (2) evaluate the influence of abiotic factors on R s , and (3) detect the effects of soil management changes on R s . We hypothesized that (1) most of daily and seasonal variation in R s could be explained by soil temperature ( T s ) and soil water content ( S w ), (2) soil management changes could significantly affect R s , and (3) soil management changes affected R s via the significant change in abiotic and biotic factors. In situ R s values were monitored in an agropastoral ecotone in Inner Mongolia, China, during the growing seasons in 2009 (August to October) and 2010 (May to October). The soil management changes sequences included free grazing grassland (FG), cropland (CL), grazing enclosure grassland (GE), and abandoned cultivated grassland (AC). During the growing season in 2010, cumulative R s for FG, CL, GE, and AC averaged 265.97, 344.74, 236.70, and 226.42 gC m -2  year -1 , respectively. The T s and S w significantly influenced R s and explained 66%-86% of the variability in daily R s . Monthly mean temperature and precipitation explained 78%-96% of the variability in monthly R s . The results clearly showed that R s was increased by 29% with the conversion of FG to CL and decreased by 35% and 11% with the conversion of CL to AC and FG to GE. The factors impacting the change in R s under different soil management changes sequences varied. Our results confirm the tested hypotheses. The increase in Q 1 0 and litter biomass induced by conversion of FG to GE could lead to increased R s if the climate warming. We suggest that after proper natural restoration period, grasslands should be utilized properly to decrease R s .

Environmental Impact on DNA Methylation in the Germline: State of the Art and Gaps of Knowledge

PubMed Central

Pacchierotti, Francesca; Spanò, Marcello

2015-01-01

The epigenome consists of chemical changes in DNA and chromatin that without modifying the DNA sequence modulate gene expression and cellular phenotype. The epigenome is highly plastic and reacts to changing external conditions with modifications that can be inherited to daughter cells and across generations. Whereas this innate plasticity allows for adaptation to a changing environment, it also implies the potential of epigenetic derailment leading to so-called epimutations. DNA methylation is the most studied epigenetic mark. DNA methylation changes have been associated with cancer, infertility, cardiovascular, respiratory, metabolic, immunologic, and neurodegenerative pathologies. Experiments in rodents demonstrate that exposure to a variety of chemical stressors, occurring during the prenatal or the adult life, may induce DNA methylation changes in germ cells, which may be transmitted across generations with phenotypic consequences. An increasing number of human biomonitoring studies show environmentally related DNA methylation changes mainly in blood leukocytes, whereas very few data have been so far collected on possible epigenetic changes induced in the germline, even by the analysis of easily accessible sperm. In this paper, we review the state of the art on factors impinging on DNA methylation in the germline, highlight gaps of knowledge, and propose priorities for future studies. PMID:26339587

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.

PubMed

Fishman, G A; Stone, E M; Grover, S; Derlacki, D J; Haines, H L; Hockey, R R

1999-04-01

To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.

Impacts of Seasonal Housing and Teat Preparation on Raw Milk Microbiota: a High-Throughput Sequencing Study.

PubMed

Doyle, Conor J; Gleeson, David; O'Toole, Paul W; Cotter, Paul D

2017-01-15

In pasture-based systems, changes in dairy herd habitat due to seasonality results in the exposure of animals to different environmental niches. These niches contain distinct microbial communities that may be transferred to raw milk, with potentially important food quality and safety implications for milk producers. It is postulated that the extent to which these microorganisms are transferred could be limited by the inclusion of a teat preparation step prior to milking. High-throughput sequencing on a variety of microbial niches on farms was used to study the patterns of microbial movement through the dairy production chain and, in the process, to investigate the impact of seasonal housing and the inclusion/exclusion of a teat preparation regime on the raw milk microbiota from the same herd over two sampling periods, i.e., indoor and outdoor. Beta diversity and network analyses showed that environmental and milk microbiotas separated depending on whether they were sourced from an indoor or outdoor environment. Within these respective habitats, similarities between the milk microbiota and that of teat swab samples and, to a lesser extent, fecal samples were apparent. Indeed, SourceTracker identified the teat surface as the most significant source of contamination, with herd feces being the next most prevalent source of contamination. In milk from cows grazing outdoors, teat prep significantly increased the numbers of total bacteria present. In summary, sequence-based microbiota analysis identified possible sources of raw milk contamination and highlighted the influence of environment and farm management practices on the raw milk microbiota. The composition of the raw milk microbiota is an important consideration from both a spoilage perspective and a food safety perspective and has implications for milk targeted for direct consumption and for downstream processing. Factors that influence contamination have been examined previously, primarily through the use of culture-based techniques. We describe here the extensive application of high-throughput DNA sequencing technologies to study the relationship between the milk production environment and the raw milk microbiota. The results show that the environment in which the herd was kept was the primary driver of the composition of the milk microbiota composition. Copyright © 2016 American Society for Microbiology.

Impacts of Seasonal Housing and Teat Preparation on Raw Milk Microbiota: a High-Throughput Sequencing Study

PubMed Central

Doyle, Conor J.; Gleeson, David; O'Toole, Paul W.

2016-01-01

ABSTRACT In pasture-based systems, changes in dairy herd habitat due to seasonality results in the exposure of animals to different environmental niches. These niches contain distinct microbial communities that may be transferred to raw milk, with potentially important food quality and safety implications for milk producers. It is postulated that the extent to which these microorganisms are transferred could be limited by the inclusion of a teat preparation step prior to milking. High-throughput sequencing on a variety of microbial niches on farms was used to study the patterns of microbial movement through the dairy production chain and, in the process, to investigate the impact of seasonal housing and the inclusion/exclusion of a teat preparation regime on the raw milk microbiota from the same herd over two sampling periods, i.e., indoor and outdoor. Beta diversity and network analyses showed that environmental and milk microbiotas separated depending on whether they were sourced from an indoor or outdoor environment. Within these respective habitats, similarities between the milk microbiota and that of teat swab samples and, to a lesser extent, fecal samples were apparent. Indeed, SourceTracker identified the teat surface as the most significant source of contamination, with herd feces being the next most prevalent source of contamination. In milk from cows grazing outdoors, teat prep significantly increased the numbers of total bacteria present. In summary, sequence-based microbiota analysis identified possible sources of raw milk contamination and highlighted the influence of environment and farm management practices on the raw milk microbiota. IMPORTANCE The composition of the raw milk microbiota is an important consideration from both a spoilage perspective and a food safety perspective and has implications for milk targeted for direct consumption and for downstream processing. Factors that influence contamination have been examined previously, primarily through the use of culture-based techniques. We describe here the extensive application of high-throughput DNA sequencing technologies to study the relationship between the milk production environment and the raw milk microbiota. The results show that the environment in which the herd was kept was the primary driver of the composition of the milk microbiota composition. PMID:27815277

High depth, whole-genome sequencing of cholera isolates from Haiti and the Dominican Republic.

PubMed

Sealfon, Rachel; Gire, Stephen; Ellis, Crystal; Calderwood, Stephen; Qadri, Firdausi; Hensley, Lisa; Kellis, Manolis; Ryan, Edward T; LaRocque, Regina C; Harris, Jason B; Sabeti, Pardis C

2012-09-11

Whole-genome sequencing is an important tool for understanding microbial evolution and identifying the emergence of functionally important variants over the course of epidemics. In October 2010, a severe cholera epidemic began in Haiti, with additional cases identified in the neighboring Dominican Republic. We used whole-genome approaches to sequence four Vibrio cholerae isolates from Haiti and the Dominican Republic and three additional V. cholerae isolates to a high depth of coverage (>2000x); four of the seven isolates were previously sequenced. Using these sequence data, we examined the effect of depth of coverage and sequencing platform on genome assembly and identification of sequence variants. We found that 50x coverage is sufficient to construct a whole-genome assembly and to accurately call most variants from 100 base pair paired-end sequencing reads. Phylogenetic analysis between the newly sequenced and thirty-three previously sequenced V. cholerae isolates indicates that the Haitian and Dominican Republic isolates are closest to strains from South Asia. The Haitian and Dominican Republic isolates form a tight cluster, with only four variants unique to individual isolates. These variants are located in the CTX region, the SXT region, and the core genome. Of the 126 mutations identified that separate the Haiti-Dominican Republic cluster from the V. cholerae reference strain (N16961), 73 are non-synonymous changes, and a number of these changes cluster in specific genes and pathways. Sequence variant analyses of V. cholerae isolates, including multiple isolates from the Haitian outbreak, identify coverage-specific and technology-specific effects on variant detection, and provide insight into genomic change and functional evolution during an epidemic.

LenVarDB: database of length-variant protein domains.

PubMed

Mutt, Eshita; Mathew, Oommen K; Sowdhamini, Ramanathan

2014-01-01

Protein domains are functionally and structurally independent modules, which add to the functional variety of proteins. This array of functional diversity has been enabled by evolutionary changes, such as amino acid substitutions or insertions or deletions, occurring in these protein domains. Length variations (indels) can introduce changes at structural, functional and interaction levels. LenVarDB (freely available at http://caps.ncbs.res.in/lenvardb/) traces these length variations, starting from structure-based sequence alignments in our Protein Alignments organized as Structural Superfamilies (PASS2) database, across 731 structural classification of proteins (SCOP)-based protein domain superfamilies connected to 2 730 625 sequence homologues. Alignment of sequence homologues corresponding to a structural domain is available, starting from a structure-based sequence alignment of the superfamily. Orientation of the length-variant (indel) regions in protein domains can be visualized by mapping them on the structure and on the alignment. Knowledge about location of length variations within protein domains and their visual representation will be useful in predicting changes within structurally or functionally relevant sites, which may ultimately regulate protein function. Non-technical summary: Evolutionary changes bring about natural changes to proteins that may be found in many organisms. Such changes could be reflected as amino acid substitutions or insertions-deletions (indels) in protein sequences. LenVarDB is a database that provides an early overview of observed length variations that were set among 731 protein families and after examining >2 million sequences. Indels are followed up to observe if they are close to the active site such that they can affect the activity of proteins. Inclusion of such information can aid the design of bioengineering experiments.

Sequence of Changes in Maize Responding to Soil Water Deficit and Related Critical Thresholds

PubMed Central

Ma, Xueyan; He, Qijin; Zhou, Guangsheng

2018-01-01

The sequence of changes in crop responding to soil water deficit and related critical thresholds are essential for better drought damage classification and drought monitoring indicators. This study was aimed to investigate the critical thresholds of maize growth and physiological characteristics responding to changing soil water and to reveal the sequence of changes in maize responding to soil water deficit both in seedling and jointing stages based on 2-year’s maize field experiment responding to six initial soil water statuses conducted in 2013 and 2014. Normal distribution tolerance limits were newly adopted to identify critical thresholds of maize growth and physiological characteristics to a wide range of soil water status. The results showed that in both stages maize growth characteristics related to plant water status [stem moisture content (SMC) and leaf moisture content (LMC)], leaf gas exchange [net photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs)], and leaf area were sensitive to soil water deficit, while biomass-related characteristics were less sensitive. Under the concurrent weather conditions and agronomic managements, the critical soil water thresholds in terms of relative soil moisture of 0–30 cm depth (RSM) of maize SMC, LMC, net Pn, Tr, Gs, and leaf area were 72, 65, 62, 60, 58, and 46%, respectively, in seedling stage, and 64, 64, 51, 53, 48, and 46%, respectively, in jointing stage. It indicated that there is a sequence of changes in maize responding to soil water deficit, i.e., their response sequences as soil water deficit intensified: SMC ≥ LMC > leaf gas exchange > leaf area in both stages. This sequence of changes in maize responding to soil water deficit and related critical thresholds may be better indicators of damage classification and drought monitoring. PMID:29765381

Impacts of Glutaraldehyde on Microbial Community Structure and Degradation Potential in Streams Impacted by Hydraulic Fracturing.

PubMed

Campa, Maria Fernanda; Techtmann, Stephen M; Gibson, Caleb M; Zhu, Xiaojuan; Patterson, Megan; Garcia de Matos Amaral, Amanda; Ulrich, Nikea; Campagna, Shawn R; Grant, Christopher J; Lamendella, Regina; Hazen, Terry C

2018-05-15

The environmental impacts of hydraulic fracturing, particularly those of surface spills in aquatic ecosystems, are not fully understood. The goals of this study were to (1) understand the effect of previous exposure to hydraulic fracturing fluids on aquatic microbial community structure and (2) examine the impacts exposure has on biodegradation potential of the biocide glutaraldehyde. Microcosms were constructed from hydraulic fracturing-impacted and nonhydraulic fracturing-impacted streamwater within the Marcellus shale region in Pennsylvania. Microcosms were amended with glutaraldehyde and incubated aerobically for 56 days. Microbial community adaptation to glutaraldehyde was monitored using 16S rRNA gene amplicon sequencing and quantification by qPCR. Abiotic and biotic glutaraldehyde degradation was measured using ultra-performance liquid chromatography--high resolution mass spectrometry and total organic carbon. It was found that nonhydraulic fracturing-impacted microcosms biodegraded glutaraldehyde faster than the hydraulic fracturing-impacted microcosms, showing a decrease in degradation potential after exposure to hydraulic fracturing activity. Hydraulic fracturing-impacted microcosms showed higher richness after glutaraldehyde exposure compared to unimpacted streams, indicating an increased tolerance to glutaraldehyde in hydraulic fracturing impacted streams. Beta diversity and differential abundance analysis of sequence count data showed different bacterial enrichment for hydraulic fracturing-impacted and nonhydraulic fracturing-impacted microcosms after glutaraldehyde addition. These findings demonstrated a lasting effect on microbial community structure and glutaraldehyde degradation potential in streams impacted by hydraulic fracturing operations.

Dynamic peptide libraries for the discovery of supramolecular nanomaterials

NASA Astrophysics Data System (ADS)

Pappas, Charalampos G.; Shafi, Ramim; Sasselli, Ivan R.; Siccardi, Henry; Wang, Tong; Narang, Vishal; Abzalimov, Rinat; Wijerathne, Nadeesha; Ulijn, Rein V.

2016-11-01

Sequence-specific polymers, such as oligonucleotides and peptides, can be used as building blocks for functional supramolecular nanomaterials. The design and selection of suitable self-assembling sequences is, however, challenging because of the vast combinatorial space available. Here we report a methodology that allows the peptide sequence space to be searched for self-assembling structures. In this approach, unprotected homo- and heterodipeptides (including aromatic, aliphatic, polar and charged amino acids) are subjected to continuous enzymatic condensation, hydrolysis and sequence exchange to create a dynamic combinatorial peptide library. The free-energy change associated with the assembly process itself gives rise to selective amplification of self-assembling candidates. By changing the environmental conditions during the selection process, different sequences and consequent nanoscale morphologies are selected.

Dynamic peptide libraries for the discovery of supramolecular nanomaterials.

PubMed

Pappas, Charalampos G; Shafi, Ramim; Sasselli, Ivan R; Siccardi, Henry; Wang, Tong; Narang, Vishal; Abzalimov, Rinat; Wijerathne, Nadeesha; Ulijn, Rein V

2016-11-01

Sequence-specific polymers, such as oligonucleotides and peptides, can be used as building blocks for functional supramolecular nanomaterials. The design and selection of suitable self-assembling sequences is, however, challenging because of the vast combinatorial space available. Here we report a methodology that allows the peptide sequence space to be searched for self-assembling structures. In this approach, unprotected homo- and heterodipeptides (including aromatic, aliphatic, polar and charged amino acids) are subjected to continuous enzymatic condensation, hydrolysis and sequence exchange to create a dynamic combinatorial peptide library. The free-energy change associated with the assembly process itself gives rise to selective amplification of self-assembling candidates. By changing the environmental conditions during the selection process, different sequences and consequent nanoscale morphologies are selected.

Applications and Case Studies of the Next-Generation Sequencing Technologies in Food, Nutrition and Agriculture.

USDA-ARS?s Scientific Manuscript database

Next-generation sequencing technologies are able to produce high-throughput short sequence reads in a cost-effective fashion. The emergence of these technologies has not only facilitated genome sequencing but also changed the landscape of life sciences. Here I survey their major applications ranging...

Recent Applications of DNA Sequencing Technologies in Food, Nutrition and Agriculture

USDA-ARS?s Scientific Manuscript database

Next-generation DNA sequencing technologies are able to produce millions of short sequence reads in a high-throughput, cost-effective fashion. The emergence of these technologies has not only facilitated genome sequencing but also changed the landscape of life sciences. This review surveys their rec...

Next generation sequencers: methods and applications in food-borne pathogens

USDA-ARS?s Scientific Manuscript database

Next generation sequencers are able to produce millions of short sequence reads in a high-throughput, low-cost way. The emergence of these technologies has not only facilitated genome sequencing but also started to change the landscape of life sciences. This chapter will survey their methods and app...

Metagenomic and near full-length 16S rRNA sequence data in support of the phylogenetic analysis of the rumen bacterial community in steers

USDA-ARS?s Scientific Manuscript database

Next generation sequencing technologies have vastly changed the approach of sequencing of the 16S rRNA gene for studies in microbial ecology. Three distinct technologies are available for large-scale 16S sequencing. All three are subject to biases introduced by sequencing error rates, amplificatio...

Chemistry, the Central Science? The History of the High School Science Sequence

ERIC Educational Resources Information Center

Sheppard, Keith; Robbins, Dennis M.

2005-01-01

Chemistry became the ''central science'' not by design but by accident in the US high schools. The three important factors, which had their influence on the high school science, are sequenced and their impact on the development of US science education, are mentioned.

The impact of horizontal gene transfer on the biology of Clostridium difficile.

PubMed

Roberts, Adam P; Allan, Elaine; Mullany, Peter

2014-01-01

Clostridium difficile infection (CDI) is now recognised as the main cause of healthcare associated diarrhoea. Over the recent years there has been a change in the epidemiology of CDI with certain related strains dominating infection. These strains have been termed hyper-virulent and have successfully spread across the globe. Many C. difficile strains have had their genomes completely sequenced allowing researchers to build up a very detailed picture of the contribution of horizontal gene transfer to the adaptive potential, through the acquisition of mobile DNA, of this organism. Here, we review and discuss the contribution of mobile genetic elements to the biology of this clinically important pathogen. © 2014 Elsevier Ltd All rights reserved.

Drug decriminalization and the price of illicit drugs.

PubMed

Félix, Sónia; Portugal, Pedro

2017-01-01

This study is an empirical assessment of the impact of the drug decriminalization policy followed by Portugal in July 2001, on the price of illicit drugs. The analysis is performed using a difference-in-differences approach and the Synthetic Control Method in order to construct a synthetic control unit from a convex combination of countries. The results suggest that the prices of opiates and cocaine in the post-treatment period did not decrease in the sequence of the policy change. We conclude that the drug decriminalization policy seems to have caused no harm through lower illicit drugs prices, which would lead to higher drug usage and dependence. Copyright © 2016 Elsevier B.V. All rights reserved.

A Search for Impact Debris in the Pliocene Age Sirius Group, Transantarctic Mountains

NASA Technical Reports Server (NTRS)

Harvey, Ralph P.; Boyd, Hiram

2003-01-01

The Sirius Group is a mixed sequence of interbedded diamictite and mudstone of Pliocene age found at scattered locations along the length of the Transantarctic Mountains. Sirius Group rocks are usually considered tillites, but contain some very "un-tillite" elements. Within section and from site to site, Sirius Group rocks vary considerably in terms of texture and relative abundance of clast lithologies, recording a history that includes shifting influences of glacial, lacustrine, fluvial and wetland processes. The colorful heritage of the Sirius Group has generated a lot of interest due to its potential as a record of changes in the behavior of the East Antarctic icesheet during a climatologically interesting period.