WorldWideScience

Sample records for survey provide insight

  1. Fed manufacturing surveys provide insight into national economy

    OpenAIRE

    Kerr, Emily; Pia M. Orrenius; Wang, Jack; Canas, Jesus

    2014-01-01

    Regional Federal Reserve Banks’ manufacturing surveys provide important insight into national economic conditions. The Dallas Fed’s Texas Manufacturing Outlook Survey performs well forecasting the ISM manufacturing index and U.S. industrial production.

  2. FIELD SURVEY PROVIDENCE COUNTY, RI

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — Survey data includes spatial datasets and data tables necessary to digitally represent data collected in the survey phase of the study. (Source: FEMA Guidelines and...

  3. Satellites provide new insights into polar geophysics

    Science.gov (United States)

    Laxon, Seymour; McAdoo, David

    A revolution in polar geophysics is under way thanks to altimeter data, which the ERS satellites have been collecting since 1991. Geophysical surveys in the polar regions have long been hampered by inaccessibility, particularly in areas that are covered yearround by sea ice or land ice. As a result the major remaining uncertainties in global tectonic models of the Mesozoic and Cenozoic tend to lie in the Arctic and Antarctic regions. In fact, major tectonic plate boundaries have been hypothesized, but not confirmed, for both regions. In the Arctic, a divergent plate boundary associated with the Mesozoic opening of the Canada Basin has been proposed [e.g., Lawver et al., 1990] while in the Antarctic a divergent boundary, active during the late Cretaceous in the Amundsen Sea, has been hypothesized [Cande et al., 1995; Stock and Molnar, 1987]. Due to the acute sparseness of seafloor surveys in these areas, however, no one has been able to prove that these plate boundaries actually existed, nor has anyone been able to locate extinct remnants of the boundaries. High-resolution marine gravity fields (Figures 1 and 2) derived from satellite altimeter data are now redressing this problem of sparse surveys.

  4. Insights into rare diseases from social media surveys.

    Science.gov (United States)

    Davies, William

    2016-11-09

    The internet, and social media platforms, are increasingly being used by substantial sectors of the worldwide population. By engaging effectively with online and social media, scientists and clinicians can obtain unprecedented access to relatively large cohorts of individuals with rare diseases, as well as their relatives, carers and professionals involved in their healthcare. Online surveys of these stakeholder groups may provide important new insights into rare conditions and their management relatively quickly and easily, with the possibility of rapid translation into healthcare interventions and policy. Here, I describe our recent positive experience with the online survey approach to a rare disease (X-linked ichthyosis), and review its advantages and limitations.

  5. The South African wine industry: Insights survey 2013

    CSIR Research Space (South Africa)

    Blok, T

    2013-09-01

    Full Text Available professionals who understand the specific challenges the industry faces. Our aim remains to make a meaningful contribution to the industry with projects like this insights survey, and to work alongside industry leaders to provide advice and seek solutions...-sector, as well as persistent increases in energy costs, it is not surprising to see labour and electricity as the expenses that executives are most concerned about over the next 12 to 36 months. Labour Marketing and sales Bottling and packaging Chemicals...

  6. Genomic analyses provide insights into the history of tomato breeding.

    Science.gov (United States)

    Lin, Tao; Zhu, Guangtao; Zhang, Junhong; Xu, Xiangyang; Yu, Qinghui; Zheng, Zheng; Zhang, Zhonghua; Lun, Yaoyao; Li, Shuai; Wang, Xiaoxuan; Huang, Zejun; Li, Junming; Zhang, Chunzhi; Wang, Taotao; Zhang, Yuyang; Wang, Aoxue; Zhang, Yancong; Lin, Kui; Li, Chuanyou; Xiong, Guosheng; Xue, Yongbiao; Mazzucato, Andrea; Causse, Mathilde; Fei, Zhangjun; Giovannoni, James J; Chetelat, Roger T; Zamir, Dani; Städler, Thomas; Li, Jingfu; Ye, Zhibiao; Du, Yongchen; Huang, Sanwen

    2014-11-01

    The histories of crop domestication and breeding are recorded in genomes. Although tomato is a model species for plant biology and breeding, the nature of human selection that altered its genome remains largely unknown. Here we report a comprehensive analysis of tomato evolution based on the genome sequences of 360 accessions. We provide evidence that domestication and improvement focused on two independent sets of quantitative trait loci (QTLs), resulting in modern tomato fruit ∼100 times larger than its ancestor. Furthermore, we discovered a major genomic signature for modern processing tomatoes, identified the causative variants that confer pink fruit color and precisely visualized the linkage drag associated with wild introgressions. This study outlines the accomplishments as well as the costs of historical selection and provides molecular insights toward further improvement.

  7. Insights Gained From 4 Years of EOSDIS User Surveys

    Science.gov (United States)

    Behnke, J.; Boquist, C. L.

    2007-12-01

    The Earth Observation System Data and Information System (EOSDIS) is a large, complex data system currently supporting over 18 operational NASA satellite missions including the flagship EOS missions: Terra, Aqua, and Aura. A critical underpinning for management of EOSDIS is developing a thorough knowledge of the EOSDIS user community and how they use the EOSDIS products in their research. It is important to know whether the system is meeting the users' needs and expectations. Thus, in 2004 NASA commissioned a comprehensive survey to determine user satisfaction using the American Customer Satisfaction Index (ACSI) approach. NASA has continued to survey users yearly since. Users continue to rate EOSDIS systems and services highly as the EOSDIS ACSI score has outperformed both the averages for U.S. companies and for Federal Agencies. In addition, users' comments have provided valuable insight into the effect of data center processes on users' experiences. Although their satisfaction has remained high, their preferences have changed with the rapid advances in web-based services. We now have four years of data on user satisfaction from these surveys. The results of each survey highlight areas that, if improved, could lead to increased user satisfaction, including overall product quality, product documentation, and product selection and ordering processes. This paper will present the survey results and how they compare from year to year.

  8. Comparative genomics provide insights into evolution of trichoderma nutrition style.

    Science.gov (United States)

    Xie, Bin-Bin; Qin, Qi-Long; Shi, Mei; Chen, Lei-Lei; Shu, Yan-Li; Luo, Yan; Wang, Xiao-Wei; Rong, Jin-Cheng; Gong, Zhi-Ting; Li, Dan; Sun, Cai-Yun; Liu, Gui-Ming; Dong, Xiao-Wei; Pang, Xiu-Hua; Huang, Feng; Liu, Weifeng; Chen, Xiu-Lan; Zhou, Bai-Cheng; Zhang, Yu-Zhong; Song, Xiao-Yan

    2014-02-01

    Saprotrophy on plant biomass is a recently developed nutrition strategy for Trichoderma. However, the physiology and evolution of this new nutrition strategy is still elusive. We report the deep sequencing and analysis of the genome of Trichoderma longibrachiatum, an efficient cellulase producer. The 31.7-Mb genome, smallest among the sequenced Trichoderma species, encodes fewer nutrition-related genes than saprotrophic T. reesei (Tr), including glycoside hydrolases and nonribosomal peptide synthetase-polyketide synthase. Homology and phylogenetic analyses suggest that a large number of nutrition-related genes, including GH18 chitinases, β-1,3/1,6-glucanases, cellulolytic enzymes, and hemicellulolytic enzymes, were lost in the common ancestor of T. longibrachiatum (Tl) and Tr. dN/dS (ω) calculation indicates that all the nutrition-related genes analyzed are under purifying selection. Cellulolytic enzymes, the key enzymes for saprotrophy on plant biomass, are under stronger purifying selection pressure in Tl and Tr than in mycoparasitic species, suggesting that development of the nutrition strategy of saprotrophy on plant biomass has increased the selection pressure. In addition, aspartic proteases, serine proteases, and metalloproteases are subject to stronger purifying selection pressure in Tl and Tr, suggesting that these enzymes may also play important roles in the nutrition. This study provides insights into the physiology and evolution of the nutrition strategy of Trichoderma.

  9. Marsupial Genome Sequences: Providing Insight into Evolution and Disease

    Directory of Open Access Journals (Sweden)

    Janine E. Deakin

    2012-01-01

    Full Text Available Marsupials (metatherians, with their position in vertebrate phylogeny and their unique biological features, have been studied for many years by a dedicated group of researchers, but it has only been since the sequencing of the first marsupial genome that their value has been more widely recognised. We now have genome sequences for three distantly related marsupial species (the grey short-tailed opossum, the tammar wallaby, and Tasmanian devil, with the promise of many more genomes to be sequenced in the near future, making this a particularly exciting time in marsupial genomics. The emergence of a transmissible cancer, which is obliterating the Tasmanian devil population, has increased the importance of obtaining and analysing marsupial genome sequence for understanding such diseases as well as for conservation efforts. In addition, these genome sequences have facilitated studies aimed at answering questions regarding gene and genome evolution and provided insight into the evolution of epigenetic mechanisms. Here I highlight the major advances in our understanding of evolution and disease, facilitated by marsupial genome projects, and speculate on the future contributions to be made by such sequences.

  10. The complex jujube genome provides insights into fruit tree biology.

    Science.gov (United States)

    Liu, Meng-Jun; Zhao, Jin; Cai, Qing-Le; Liu, Guo-Cheng; Wang, Jiu-Rui; Zhao, Zhi-Hui; Liu, Ping; Dai, Li; Yan, Guijun; Wang, Wen-Jiang; Li, Xian-Song; Chen, Yan; Sun, Yu-Dong; Liu, Zhi-Guo; Lin, Min-Juan; Xiao, Jing; Chen, Ying-Ying; Li, Xiao-Feng; Wu, Bin; Ma, Yong; Jian, Jian-Bo; Yang, Wei; Yuan, Zan; Sun, Xue-Chao; Wei, Yan-Li; Yu, Li-Li; Zhang, Chi; Liao, Sheng-Guang; He, Rong-Jun; Guang, Xuan-Min; Wang, Zhuo; Zhang, Yue-Yang; Luo, Long-Hai

    2014-10-28

    The jujube (Ziziphus jujuba Mill.), a member of family Rhamnaceae, is a major dry fruit and a traditional herbal medicine for more than one billion people. Here we present a high-quality sequence for the complex jujube genome, the first genome sequence of Rhamnaceae, using an integrated strategy. The final assembly spans 437.65 Mb (98.6% of the estimated) with 321.45 Mb anchored to the 12 pseudo-chromosomes and contains 32,808 genes. The jujube genome has undergone frequent inter-chromosome fusions and segmental duplications, but no recent whole-genome duplication. Further analyses of the jujube-specific genes and transcriptome data from 15 tissues reveal the molecular mechanisms underlying some specific properties of the jujube. Its high vitamin C content can be attributed to a unique high level expression of genes involved in both biosynthesis and regeneration. Our study provides insights into jujube-specific biology and valuable genomic resources for the improvement of Rhamnaceae plants and other fruit trees.

  11. Small teleost fish provide new insights into human skeletal diseases.

    Science.gov (United States)

    Witten, P E; Harris, M P; Huysseune, A; Winkler, C

    2017-01-01

    Small teleost fish such as zebrafish and medaka are increasingly studied as models for human skeletal diseases. Efficient new genome editing tools combined with advances in the analysis of skeletal phenotypes provide new insights into fundamental processes of skeletal development. The skeleton among vertebrates is a highly conserved organ system, but teleost fish and mammals have evolved unique traits or have lost particular skeletal elements in each lineage. Several unique features of the skeleton relate to the extremely small size of early fish embryos and the small size of adult fish used as models. A detailed analysis of the plethora of interesting skeletal phenotypes in zebrafish and medaka pushes available skeletal imaging techniques to their respective limits and promotes the development of new imaging techniques. Impressive numbers of zebrafish and medaka mutants with interesting skeletal phenotypes have been characterized, complemented by transgenic zebrafish and medaka lines. The advent of efficient genome editing tools, such as TALEN and CRISPR/Cas9, allows to introduce targeted deficiencies in genes of model teleosts to generate skeletal phenotypes that resemble human skeletal diseases. This review will also discuss other attractive aspects of the teleost skeleton. This includes the capacity for lifelong tooth replacement and for the regeneration of dermal skeletal elements, such as scales and fin rays, which further increases the value of zebrafish and medaka models for skeletal research. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Survey on Knowledge of Healthcare Providers about Childhood ...

    African Journals Online (AJOL)

    IRORO YARHERE

    Key words: Survey, Knowledge, Diabetes Mellitus, Health care providers, ... this is not so in many developing and Sub-Saharan countries.4 Patients usually ..... Survey on knowledge and attitudes regarding diabetic inpatient management by.

  13. Can tobacco dependence provide insights into other drug addictions?

    Science.gov (United States)

    DiFranza, Joseph R

    2016-10-27

    Within the field of addiction research, individuals tend to operate within silos of knowledge focused on specific drug classes. The discovery that tobacco dependence develops in a progression of stages and that the latency to the onset of withdrawal symptoms after the last use of tobacco changes over time have provided insights into how tobacco dependence develops that might be applied to the study of other drugs.As physical dependence on tobacco develops, it progresses through previously unrecognized clinical stages of wanting, craving and needing. The latency to withdrawal is a measure of the asymptomatic phase of withdrawal, extending from the last use of tobacco to the emergence of withdrawal symptoms. Symptomatic withdrawal is characterized by a wanting phase, a craving phase, and a needing phase. The intensity of the desire to smoke that is triggered by withdrawal correlates with brain activity in addiction circuits. With repeated tobacco use, the latency to withdrawal shrinks from as long as several weeks to as short as several minutes. The shortening of the asymptomatic phase of withdrawal drives an escalation of smoking, first in terms of the number of smoking days/month until daily smoking commences, then in terms of cigarettes smoked/day.The discoveries of the stages of physical dependence and the latency to withdrawal raises the question, does physical dependence develop in stages with other drugs? Is the latency to withdrawal for other substances measured in weeks at the onset of dependence? Does it shorten over time? The research methods that uncovered how tobacco dependence emerges might be fruitfully applied to the investigation of other addictions.

  14. Social network analysis provides insights into African swine fever epidemiology.

    Science.gov (United States)

    Lichoti, Jacqueline Kasiiti; Davies, Jocelyn; Kitala, Philip M; Githigia, Samuel M; Okoth, Edward; Maru, Yiheyis; Bukachi, Salome A; Bishop, Richard P

    2016-04-01

    Pig movements play a significant role in the spread of economically important infectious diseases such as the African swine fever. Characterization of movement networks between pig farms and through other types of farm and household enterprises that are involved in pig value chains can provide useful information on the role that different participants in the networks play in pathogen transmission. Analysis of social networks that underpin these pig movements can reveal pathways that are important in the transmission of disease, trade in commodities, the dissemination of information and the influence of behavioural norms. We assessed pig movements among pig keeping households within West Kenya and East Uganda and across the shared Kenya-Uganda border in the study region, to gain insight into within-country and trans-boundary pig movements. Villages were sampled using a randomized cluster design. Data were collected through interviews in 2012 and 2013 from 683 smallholder pig-keeping households in 34 villages. NodeXL software was used to describe pig movement networks at village level. The pig movement and trade networks were localized and based on close social networks involving family ties, friendships and relationships with neighbours. Pig movement network modularity ranged from 0.2 to 0.5 and exhibited good community structure within the network implying an easy flow of knowledge and adoption of new attitudes and beliefs, but also promoting an enhanced rate of disease transmission. The average path length of 5 defined using NodeXL, indicated that disease could easily reach every node in a cluster. Cross-border boar service between Uganda and Kenya was also recorded. Unmonitored trade in both directions was prevalent. While most pig transactions in the absence of disease, were at a small scale (10km. The close social relationships between actors in pig movement networks indicate the potential for possible interventions to develop shared norms and mutually accepted

  15. Sparse regularization techniques provide novel insights into outcome integration processes.

    Science.gov (United States)

    Mohr, Holger; Wolfensteller, Uta; Frimmel, Steffi; Ruge, Hannes

    2015-01-01

    By exploiting information that is contained in the spatial arrangement of neural activations, multivariate pattern analysis (MVPA) can detect distributed brain activations which are not accessible by standard univariate analysis. Recent methodological advances in MVPA regularization techniques have made it feasible to produce sparse discriminative whole-brain maps with highly specific patterns. Furthermore, the most recent refinement, the Graph Net, explicitly takes the 3D-structure of fMRI data into account. Here, these advanced classification methods were applied to a large fMRI sample (N=70) in order to gain novel insights into the functional localization of outcome integration processes. While the beneficial effect of differential outcomes is well-studied in trial-and-error learning, outcome integration in the context of instruction-based learning has remained largely unexplored. In order to examine neural processes associated with outcome integration in the context of instruction-based learning, two groups of subjects underwent functional imaging while being presented with either differential or ambiguous outcomes following the execution of varying stimulus-response instructions. While no significant univariate group differences were found in the resulting fMRI dataset, L1-regularized (sparse) classifiers performed significantly above chance and also clearly outperformed the standard L2-regularized (dense) Support Vector Machine on this whole-brain between-subject classification task. Moreover, additional L2-regularization via the Elastic Net and spatial regularization by the Graph Net improved interpretability of discriminative weight maps but were accompanied by reduced classification accuracies. Most importantly, classification based on sparse regularization facilitated the identification of highly specific regions differentially engaged under ambiguous and differential outcome conditions, comprising several prefrontal regions previously associated with

  16. Eggshell Porosity Provides Insight on Evolution of Nesting in Dinosaurs.

    Directory of Open Access Journals (Sweden)

    Kohei Tanaka

    Full Text Available Knowledge about the types of nests built by dinosaurs can provide insight into the evolution of nesting and reproductive behaviors among archosaurs. However, the low preservation potential of their nesting materials and nesting structures means that most information can only be gleaned indirectly through comparison with extant archosaurs. Two general nest types are recognized among living archosaurs: 1 covered nests, in which eggs are incubated while fully covered by nesting material (as in crocodylians and megapodes, and 2 open nests, in which eggs are exposed in the nest and brooded (as in most birds. Previously, dinosaur nest types had been inferred by estimating the water vapor conductance (i.e., diffusive capacity of their eggs, based on the premise that high conductance corresponds to covered nests and low conductance to open nests. However, a lack of statistical rigor and inconsistencies in this method render its application problematic and its validity questionable. As an alternative we propose a statistically rigorous approach to infer nest type based on large datasets of eggshell porosity and egg mass compiled for over 120 extant archosaur species and 29 archosaur extinct taxa/ootaxa. The presence of a strong correlation between eggshell porosity and nest type among extant archosaurs indicates that eggshell porosity can be used as a proxy for nest type, and thus discriminant analyses can help predict nest type in extinct taxa. Our results suggest that: 1 covered nests are likely the primitive condition for dinosaurs (and probably archosaurs, and 2 open nests first evolved among non-avian theropods more derived than Lourinhanosaurus and were likely widespread in non-avian maniraptorans, well before the appearance of birds. Although taphonomic evidence suggests that basal open nesters (i.e., oviraptorosaurs and troodontids were potentially the first dinosaurs to brood their clutches, they still partially buried their eggs in sediment

  17. Eggshell Porosity Provides Insight on Evolution of Nesting in Dinosaurs.

    Science.gov (United States)

    Tanaka, Kohei; Zelenitsky, Darla K; Therrien, François

    2015-01-01

    Knowledge about the types of nests built by dinosaurs can provide insight into the evolution of nesting and reproductive behaviors among archosaurs. However, the low preservation potential of their nesting materials and nesting structures means that most information can only be gleaned indirectly through comparison with extant archosaurs. Two general nest types are recognized among living archosaurs: 1) covered nests, in which eggs are incubated while fully covered by nesting material (as in crocodylians and megapodes), and 2) open nests, in which eggs are exposed in the nest and brooded (as in most birds). Previously, dinosaur nest types had been inferred by estimating the water vapor conductance (i.e., diffusive capacity) of their eggs, based on the premise that high conductance corresponds to covered nests and low conductance to open nests. However, a lack of statistical rigor and inconsistencies in this method render its application problematic and its validity questionable. As an alternative we propose a statistically rigorous approach to infer nest type based on large datasets of eggshell porosity and egg mass compiled for over 120 extant archosaur species and 29 archosaur extinct taxa/ootaxa. The presence of a strong correlation between eggshell porosity and nest type among extant archosaurs indicates that eggshell porosity can be used as a proxy for nest type, and thus discriminant analyses can help predict nest type in extinct taxa. Our results suggest that: 1) covered nests are likely the primitive condition for dinosaurs (and probably archosaurs), and 2) open nests first evolved among non-avian theropods more derived than Lourinhanosaurus and were likely widespread in non-avian maniraptorans, well before the appearance of birds. Although taphonomic evidence suggests that basal open nesters (i.e., oviraptorosaurs and troodontids) were potentially the first dinosaurs to brood their clutches, they still partially buried their eggs in sediment. Open nests

  18. Numerical Experiments Providing New Insights into Plasma Focus Fusion Devices

    Directory of Open Access Journals (Sweden)

    Sing Lee

    2010-04-01

    Full Text Available Recent extensive and systematic numerical experiments have uncovered new insights into plasma focus fusion devices including the following: (1 a plasma current limitation effect, as device static inductance is reduced towards very small values; (2 scaling laws of neutron yield and soft x-ray yield as functions of storage energies and currents; (3 a global scaling law for neutron yield as a function of storage energy combining experimental and numerical data showing that scaling deterioration has probably been interpreted as neutron ‘saturation’; and (4 a fundamental cause of neutron ‘saturation’. The ground-breaking insights thus gained may completely change the directions of plasma focus fusion research.

  19. The relationship between consumer insight and provider-consumer agreement regarding consumer's quality of life.

    Science.gov (United States)

    Hasson-Ohayon, Ilanit; Roe, David; Kravetz, Shlomo; Levy-Frank, Itamar; Meir, Taly

    2011-10-01

    This study examined the relationship between insight and mental health consumers and providers agreement regarding consumers rated quality of life (QoL). Seventy mental health consumers and their 23 care providers filled-out parallel questionnaires designed to measure consumer QoL. Consumers' insight was also assessed. For most QoL domains, agreement between consumers and providers was higher for persons with high insight. For the Psychological well being dimension a negative correlation was uncovered for persons with low insight indicating disagreement between consumer and provider. These findings are discussed within the context of the literature on insight and agreement between consumer and provider as related to the therapeutic alliance.

  20. Military Medics Insight into Providing Womens Health Services

    Science.gov (United States)

    2015-12-22

    Health Protection: Fit and ready force Deploy with and care for the warrior Care for all entrusted to our care Nursing Competencies...worry. The consultation of the family by the military women was apparent in both studies prior to seeking formal health care . However, younger...algorithms for deployed military women. Nursing Research 59:2-10 Thomson BA, Nielsen PE. 2006. Women’s health care in Operation Iraqi Freedom: a survey

  1. NIH scientists provide new insight into rare kidney cancer

    Science.gov (United States)

    NIH scientists have discovered a unique feature of a rare, hereditary form of kidney cancer that may provide a better understanding of its progression and metastasis, possibly laying the foundation for the development of new targeted therapies.

  2. Athena: Providing Insight into the History of the Universe

    Science.gov (United States)

    Murphy, Gloria A.

    2010-01-01

    The American Institute for Aeronautics and Astronautics has provided a Request for Proposal which calls for a manned mission to a Near-Earth Object. It is the goal of Team COLBERT to respond to their request by providing a reusable system that can be implemented as a solid stepping stone for future manned trips to Mars and beyond. Despite Team COLBERT consisting of only students in Aerospace Engineering, in order to achieve this feat, the team must employ the use of Systems Engineering. Tools and processes from Systems Engineering will provide quantitative and semi-quantitative tools for making design decisions and evaluating items such as budgets and schedules. This paper will provide an in-depth look at some of the Systems Engineering processes employed and will step through the design process of a Human Asteroid Exploration System.

  3. Elephant Transcriptome Provides Insights into the Evolution of Eutherian Placentation

    OpenAIRE

    Hou, Zhuo-Cheng; Sterner, Kirstin N.; Romero, Roberto; Than, Nandor Gabor; Gonzalez, Juan M.; Weckle, Amy; Xing, Jun; Benirschke, Kurt; Goodman, Morris; Wildman, Derek E.

    2012-01-01

    The chorioallantoic placenta connects mother and fetus in eutherian pregnancies. In order to understand the evolution of the placenta and provide further understanding of placenta biology, we sequenced the transcriptome of a term placenta of an African elephant (Loxodonta africana) and compared these data with RNA sequence and microarray data from other eutherian placentas including human, mouse, and cow. We characterized the composition of 55,910 expressed sequence tag (i.e., cDNA) contigs u...

  4. DNA markers provide insight about common lime in historicalplantings

    DEFF Research Database (Denmark)

    Hansen, Ole Kim; Thomsen, Pernille; Rasmussen, Christine Waage

    2014-01-01

    nurseries in the Netherlands and Germany. It also provides evidence that it is possible to obtain the same genetic material as originally planted when common lime trees are to be replaced in historical plantings. Furthermore, the utility of DNA markers in the management of plant material in parks......As part of the restoration process of an avenue of common lime (Tilia × europaea) from 1760 in the Royal Danish Gardens, all remaining trees were genotyped with DNA markers before they were felled. As such, information about the nature of the plant material (clonal versus non-clonal) and mode...

  5. Metaproteomics provides functional insight into activated sludge wastewater treatment.

    Directory of Open Access Journals (Sweden)

    Paul Wilmes

    Full Text Available BACKGROUND: Through identification of highly expressed proteins from a mixed culture activated sludge system this study provides functional evidence of microbial transformations important for enhanced biological phosphorus removal (EBPR. METHODOLOGY/PRINCIPAL FINDINGS: A laboratory-scale sequencing batch reactor was successfully operated for different levels of EBPR, removing around 25, 40 and 55 mg/l P. The microbial communities were dominated by the uncultured polyphosphate-accumulating organism "Candidatus Accumulibacter phosphatis". When EBPR failed, the sludge was dominated by tetrad-forming alpha-Proteobacteria. Representative and reproducible 2D gel protein separations were obtained for all sludge samples. 638 protein spots were matched across gels generated from the phosphate removing sludges. 111 of these were excised and 46 proteins were identified using recently available sludge metagenomic sequences. Many of these closely match proteins from "Candidatus Accumulibacter phosphatis" and could be directly linked to the EBPR process. They included enzymes involved in energy generation, polyhydroxyalkanoate synthesis, glycolysis, gluconeogenesis, glycogen synthesis, glyoxylate/TCA cycle, fatty acid beta oxidation, fatty acid synthesis and phosphate transport. Several proteins involved in cellular stress response were detected. CONCLUSIONS/SIGNIFICANCE: Importantly, this study provides direct evidence linking the metabolic activities of "Accumulibacter" to the chemical transformations observed in EBPR. Finally, the results are discussed in relation to current EBPR metabolic models.

  6. Noise provides new insights on contrast sensitivity function.

    Directory of Open Access Journals (Sweden)

    Ge Chen

    Full Text Available Sensitivity to luminance difference, or contrast sensitivity, is critical for animals to survive in and interact with the external world. The contrast sensitivity function (CSF, which measures visual sensitivity to spatial patterns over a wide range of spatial frequencies, provides a comprehensive characterization of the visual system. Despite its popularity and significance in both basic research and clinical practice, it hasn't been clear what determines the CSF and how the factors underlying the CSF change in different conditions. In the current study, we applied the external noise method and perceptual template model to a wide range of external noise and spatial frequency (SF conditions, and evaluated how the various sources of observer inefficiency changed with SF and determined the limiting factors underlying the CSF. We found that only internal additive noise and template gain changed significantly with SF, while the transducer non-linearity and coefficient for multiplicative noise were constant. The 12-parameter model provided a very good account of all the data in the 200 tested conditions (86.5%, 86.2%, 89.5%, and 96.4% for the four subjects, respectively. Our results suggest a re-consideration of the popular spatial vision model that employs the CSF as the front-end filter and constant internal additive noise across spatial frequencies. The study will also be of interest to scientists and clinicians engaged in characterizing spatial vision deficits and/or developing rehabilitation methods to restore spatial vision in clinical populations.

  7. Isothermal microcalorimetry provides new insight into terrestrial carbon cycling.

    Science.gov (United States)

    Herrmann, Anke M; Coucheney, Elsa; Nunan, Naoise

    2014-04-15

    Energy is continuously transformed in environmental systems through the metabolic activities of living organisms, but little is known about the relationship between the two. In this study, we tested the hypothesis that microbial energetics are controlled by microbial community composition in terrestrial ecosystems. We determined the functional diversity profiles of the soil biota (i.e., multiple substrate-induced respiration and microbial energetics) in soils from an arable ecosystem with contrasting long-term management regimes (54 years). These two functional profiling methods were then related to the soils' microbial community composition. Using isothermal microcalorimetry, we show that direct measures of energetics provide a functional link between energy flows and the composition of below-ground microbial communities at a high taxonomic level (Mantel R = 0.4602, P = 0.006). In contrast, this link was not apparent when carbon dioxide (CO2) was used as an aggregate measure of microbial metabolism (Mantel R = 0.2291, P = 0.11). Our work advocates that the microbial energetics approach provides complementary information to soil respiration for investigating the involvement of microbial communities in below-ground carbon dynamics. Empirical data of our proposed microbial energetics approach can feed into carbon-climate based ecosystem feedback modeling with the suggested conceptual ecological model as a base.

  8. Metaproteomics Provides Functional Insight into Activated Sludge Wastewater Treatment

    Science.gov (United States)

    Wilmes, Paul; Wexler, Margaret; Bond, Philip L.

    2008-01-01

    Background Through identification of highly expressed proteins from a mixed culture activated sludge system this study provides functional evidence of microbial transformations important for enhanced biological phosphorus removal (EBPR). Methodology/Principal Findings A laboratory-scale sequencing batch reactor was successfully operated for different levels of EBPR, removing around 25, 40 and 55 mg/l P. The microbial communities were dominated by the uncultured polyphosphate-accumulating organism “Candidatus Accumulibacter phosphatis”. When EBPR failed, the sludge was dominated by tetrad-forming α-Proteobacteria. Representative and reproducible 2D gel protein separations were obtained for all sludge samples. 638 protein spots were matched across gels generated from the phosphate removing sludges. 111 of these were excised and 46 proteins were identified using recently available sludge metagenomic sequences. Many of these closely match proteins from “Candidatus Accumulibacter phosphatis” and could be directly linked to the EBPR process. They included enzymes involved in energy generation, polyhydroxyalkanoate synthesis, glycolysis, gluconeogenesis, glycogen synthesis, glyoxylate/TCA cycle, fatty acid β oxidation, fatty acid synthesis and phosphate transport. Several proteins involved in cellular stress response were detected. Conclusions/Significance Importantly, this study provides direct evidence linking the metabolic activities of “Accumulibacter” to the chemical transformations observed in EBPR. Finally, the results are discussed in relation to current EBPR metabolic models. PMID:18392150

  9. Animal NLRs provide structural insights into plant NLR function.

    Science.gov (United States)

    Bentham, Adam; Burdett, Hayden; Anderson, Peter A; Williams, Simon J; Kobe, Bostjan

    2017-03-01

    The plant immune system employs intracellular NLRs (nucleotide binding [NB], leucine-rich repeat [LRR]/nucleotide-binding oligomerization domain [NOD]-like receptors) to detect effector proteins secreted into the plant cell by potential pathogens. Activated plant NLRs trigger a range of immune responses, collectively known as the hypersensitive response (HR), which culminates in death of the infected cell. Plant NLRs show structural and functional resemblance to animal NLRs involved in inflammatory and innate immune responses. Therefore, knowledge of the activation and regulation of animal NLRs can help us understand the mechanism of action of plant NLRs, and vice versa. This review provides an overview of the innate immune pathways in plants and animals, focusing on the available structural and biochemical information available for both plant and animal NLRs. We highlight the gap in knowledge between the animal and plant systems, in particular the lack of structural information for plant NLRs, with crystal structures only available for the N-terminal domains of plant NLRs and an integrated decoy domain, in contrast to the more complete structures available for animal NLRs. We assess the similarities and differences between plant and animal NLRs, and use the structural information on the animal NLR pair NAIP/NLRC4 to derive a plausible model for plant NLR activation. Signalling by cooperative assembly formation (SCAF) appears to operate in most innate immunity pathways, including plant and animal NLRs. Our proposed model of plant NLR activation includes three key steps: (1) initially, the NLR exists in an inactive auto-inhibited state; (2) a combination of binding by activating elicitor and ATP leads to a structural rearrangement of the NLR; and (3) signalling occurs through cooperative assembly of the resistosome. Further studies, structural and biochemical in particular, will be required to provide additional evidence for the different features of this model and

  10. Participation willingness in web surveys: exploring effect of sponsoring corporation's and survey provider's reputation.

    Science.gov (United States)

    Fang, Jiaming; Wen, Chao; Pavur, Robert

    2012-04-01

    Prior research involving response rates in Web-based surveys has not adequately addressed the effect of the reputation of a sponsoring corporation that contracts with a survey provider. This study investigates the effect of two factors, namely, the reputation of a survey's provider and the reputation of a survey's sponsoring corporation, on the willingness of potential respondents to participate in a Web survey. Results of an experimental design with these two factors reveal that the sponsoring corporation's and the survey provider's strong reputations can induce potential respondents to participate in a Web survey. A sponsoring corporation's reputation has a greater effect on the participation willingness of potential respondents of a Web survey than the reputation of the survey provider. A sponsoring corporation with a weak reputation who contracts with a survey provider having a strong reputation results in increased participation willingness from potential respondents if the identity of the sponsoring corporation is disguised in a survey. This study identifies the most effective strategy to increase participation willingness for a Web-based survey by considering both the reputations of the sponsoring corporation and survey provider and whether to reveal their identities.

  11. Insights into early pig domestication provided by ancient DNA analysis

    Science.gov (United States)

    Caliebe, Amke; Nebel, Almut; Makarewicz, Cheryl; Krawczak, Michael; Krause-Kyora, Ben

    2017-01-01

    Pigs (Sus scrofa) were first domesticated between 8,500 and 8,000 cal BC in the Near East, from where they were subsequently brought into Europe by agriculturalists. Soon after the arrival of the first domestic pigs in northern Europe (~4500 BC), farmers are thought to have started to incorporate local wild boars into their swine herds. This husbandry strategy ultimately resulted in the domestication of European wild boars. Here, we set out to provide a more precise geographic and temporal framework of the early management of suid populations in northern Europe, drawing upon mitochondrial DNA haplotype data from 116 Neolithic Sus specimens. We developed a quantitative mathematical model tracing the haplotypes of the domestic pigs back to their most likely geographic origin. Our modelling results suggest that, between 5000 and 4000 BC, almost all matrilines in the north originated from domesticated animals from the south of central Europe. In the following period (4000–3000 BC), an estimated 78–100% of domesticates in the north were of northern matrilineal origin, largely from local wild boars. These findings point towards a dramatic change in suid management strategies taking place throughout south-central and northern Europe after 4000 BC. PMID:28300151

  12. The African coelacanth genome provides insights into tetrapod evolution.

    Science.gov (United States)

    Amemiya, Chris T; Alföldi, Jessica; Lee, Alison P; Fan, Shaohua; Philippe, Hervé; Maccallum, Iain; Braasch, Ingo; Manousaki, Tereza; Schneider, Igor; Rohner, Nicolas; Organ, Chris; Chalopin, Domitille; Smith, Jeramiah J; Robinson, Mark; Dorrington, Rosemary A; Gerdol, Marco; Aken, Bronwen; Biscotti, Maria Assunta; Barucca, Marco; Baurain, Denis; Berlin, Aaron M; Blatch, Gregory L; Buonocore, Francesco; Burmester, Thorsten; Campbell, Michael S; Canapa, Adriana; Cannon, John P; Christoffels, Alan; De Moro, Gianluca; Edkins, Adrienne L; Fan, Lin; Fausto, Anna Maria; Feiner, Nathalie; Forconi, Mariko; Gamieldien, Junaid; Gnerre, Sante; Gnirke, Andreas; Goldstone, Jared V; Haerty, Wilfried; Hahn, Mark E; Hesse, Uljana; Hoffmann, Steve; Johnson, Jeremy; Karchner, Sibel I; Kuraku, Shigehiro; Lara, Marcia; Levin, Joshua Z; Litman, Gary W; Mauceli, Evan; Miyake, Tsutomu; Mueller, M Gail; Nelson, David R; Nitsche, Anne; Olmo, Ettore; Ota, Tatsuya; Pallavicini, Alberto; Panji, Sumir; Picone, Barbara; Ponting, Chris P; Prohaska, Sonja J; Przybylski, Dariusz; Saha, Nil Ratan; Ravi, Vydianathan; Ribeiro, Filipe J; Sauka-Spengler, Tatjana; Scapigliati, Giuseppe; Searle, Stephen M J; Sharpe, Ted; Simakov, Oleg; Stadler, Peter F; Stegeman, John J; Sumiyama, Kenta; Tabbaa, Diana; Tafer, Hakim; Turner-Maier, Jason; van Heusden, Peter; White, Simon; Williams, Louise; Yandell, Mark; Brinkmann, Henner; Volff, Jean-Nicolas; Tabin, Clifford J; Shubin, Neil; Schartl, Manfred; Jaffe, David B; Postlethwait, John H; Venkatesh, Byrappa; Di Palma, Federica; Lander, Eric S; Meyer, Axel; Lindblad-Toh, Kerstin

    2013-04-18

    The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.

  13. The Atlantic salmon genome provides insights into rediploidization.

    Science.gov (United States)

    Lien, Sigbjørn; Koop, Ben F; Sandve, Simen R; Miller, Jason R; Kent, Matthew P; Nome, Torfinn; Hvidsten, Torgeir R; Leong, Jong S; Minkley, David R; Zimin, Aleksey; Grammes, Fabian; Grove, Harald; Gjuvsland, Arne; Walenz, Brian; Hermansen, Russell A; von Schalburg, Kris; Rondeau, Eric B; Di Genova, Alex; Samy, Jeevan K A; Olav Vik, Jon; Vigeland, Magnus D; Caler, Lis; Grimholt, Unni; Jentoft, Sissel; Våge, Dag Inge; de Jong, Pieter; Moen, Thomas; Baranski, Matthew; Palti, Yniv; Smith, Douglas R; Yorke, James A; Nederbragt, Alexander J; Tooming-Klunderud, Ave; Jakobsen, Kjetill S; Jiang, Xuanting; Fan, Dingding; Hu, Yan; Liberles, David A; Vidal, Rodrigo; Iturra, Patricia; Jones, Steven J M; Jonassen, Inge; Maass, Alejandro; Omholt, Stig W; Davidson, William S

    2016-04-18

    The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.

  14. Fractal image perception provides novel insights into hierarchical cognition.

    Science.gov (United States)

    Martins, M J; Fischmeister, F P; Puig-Waldmüller, E; Oh, J; Geissler, A; Robinson, S; Fitch, W T; Beisteiner, R

    2014-08-01

    Hierarchical structures play a central role in many aspects of human cognition, prominently including both language and music. In this study we addressed hierarchy in the visual domain, using a novel paradigm based on fractal images. Fractals are self-similar patterns generated by repeating the same simple rule at multiple hierarchical levels. Our hypothesis was that the brain uses different resources for processing hierarchies depending on whether it applies a "fractal" or a "non-fractal" cognitive strategy. We analyzed the neural circuits activated by these complex hierarchical patterns in an event-related fMRI study of 40 healthy subjects. Brain activation was compared across three different tasks: a similarity task, and two hierarchical tasks in which subjects were asked to recognize the repetition of a rule operating transformations either within an existing hierarchical level, or generating new hierarchical levels. Similar hierarchical images were generated by both rules and target images were identical. We found that when processing visual hierarchies, engagement in both hierarchical tasks activated the visual dorsal stream (occipito-parietal cortex, intraparietal sulcus and dorsolateral prefrontal cortex). In addition, the level-generating task specifically activated circuits related to the integration of spatial and categorical information, and with the integration of items in contexts (posterior cingulate cortex, retrosplenial cortex, and medial, ventral and anterior regions of temporal cortex). These findings provide interesting new clues about the cognitive mechanisms involved in the generation of new hierarchical levels as required for fractals.

  15. Elephant transcriptome provides insights into the evolution of eutherian placentation.

    Science.gov (United States)

    Hou, Zhuo-Cheng; Sterner, Kirstin N; Romero, Roberto; Than, Nandor Gabor; Gonzalez, Juan M; Weckle, Amy; Xing, Jun; Benirschke, Kurt; Goodman, Morris; Wildman, Derek E

    2012-01-01

    The chorioallantoic placenta connects mother and fetus in eutherian pregnancies. In order to understand the evolution of the placenta and provide further understanding of placenta biology, we sequenced the transcriptome of a term placenta of an African elephant (Loxodonta africana) and compared these data with RNA sequence and microarray data from other eutherian placentas including human, mouse, and cow. We characterized the composition of 55,910 expressed sequence tag (i.e., cDNA) contigs using our custom annotation pipeline. A Markov algorithm was used to cluster orthologs of human, mouse, cow, and elephant placenta transcripts. We found 2,963 genes are commonly expressed in the placentas of these eutherian mammals. Gene ontology categories previously suggested to be important for placenta function (e.g., estrogen receptor signaling pathway, cell motion and migration, and adherens junctions) were significantly enriched in these eutherian placenta-expressed genes. Genes duplicated in different lineages and also specifically expressed in the placenta contribute to the great diversity observed in mammalian placenta anatomy. We identified 1,365 human lineage-specific, 1,235 mouse lineage-specific, 436 cow lineage-specific, and 904 elephant-specific placenta-expressed (PE) genes. The most enriched clusters of human-specific PE genes are signal/glycoprotein and immunoglobulin, and humans possess a deeply invasive human hemochorial placenta that comes into direct contact with maternal immune cells. Inference of phylogenetically conserved and derived transcripts demonstrates the power of comparative transcriptomics to trace placenta evolution and variation across mammals and identified candidate genes that may be important in the normal function of the human placenta, and their dysfunction may be related to human pregnancy complications.

  16. The genome of Laccaria bicolor provides insights into

    Energy Technology Data Exchange (ETDEWEB)

    Martin, F [UMR, France; Aerts, A. [U.S. Department of Energy, Joint Genome Institute; Ahren, D [Lund University, Sweden; Brun, A [UMR, France; Danchin, E [Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS and Unive; Duchaussoy, F [UMR, France; Gibon, J [UMR, France; Kohler, A [UMR, France; Lindquist, E [U.S. Department of Energy, Joint Genome Institute; Pereda, V [UMR, France; Salamov, A. [U.S. Department of Energy, Joint Genome Institute; Shapiro, HJ [U.S. Department of Energy, Joint Genome Institute; Wuyts, J [UMR, France; Blaudez, D. [Institut National de la Recherche Agronomique, France; Buee, M [UMR, France; Brokstein, P [U.S. Department of Energy, Joint Genome Institute; Canbeck, B [Lund University, Sweden; Cohen, D [UMR, France; Courty, PE [UMR, France; Coutinho, PM [Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS and Unive; Delaruelle, C [UMR, France; Detter, J C [U.S. Department of Energy, Joint Genome Institute; Deveau, A [UMR, France; DiFazio, Stephen P [West Virginia University; Duplessis, S [UMR, France; Fraissinet-Tachet, L [Universite de Lyon, France; Lucic, E [UMR, France; Frey-Klett, P [UMR, France; Fourrey, C [UMR, France; Feussner, I [Georg-August Universitat Gottingen Germany; Gay, G [Universite de Lyon, France; Grimwood, Jane [Stanford University; Hoegger, P J [Georg-August Universitat Gottingen Germany; Jain, P [University of Alabama, Huntsville; Kilaru, S [Georg-August Universitat Gottingen Germany; Labbe, J [UMR, France; Lin, Y C [Ghent University, Belgium; Legue, V [UMR, France; Le Tacon, F [UMR, France; Marmeisse, R [Universite de Lyon, France; Melayah, D [Universite de Lyon, France; Montanini, B [UMR, France; Muratet, M [University of Alabama, Huntsville; Nehls, U [Eberhard-Karls-Universitat, Tubingen, Germany; Niculita-Hirzel, H [University of Lausanne, Switzerland; Oudot-Le Secq, M P [UMR, France; Peter, M [UMR, France; Quesneville, H [Unite de Recherches en Genomique-Info,Evry Cedex; Rajashekar, B [Lund University, Sweden; Reich, M [UMR, France; Rouhler, N [UMR, France; Schmutz, Jeremy [Stanford University; Yin, Tongming [ORNL; Tuskan, Gerald A [ORNL; Chalot, M [UMR, France; Henrissat, B [Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS and Unive; Kues, U [Georg-August Universitat Gottingen Germany; Lucas, S [U.S. Department of Energy, Joint Genome Institute; Van de Peer, Y [Ghent University, Belgium; Podila, G [University of Alabama, Huntsville; Polle, A [Georg-August Universitat Gottingen Germany; Pukkila, P J [University of North Carolina, Chapel Hill; Richardson, P M [U.S. Department of Energy, Joint Genome Institute; Rouze, P [Ghent University, Belgium; Sanders, I R [University of Lausanne, Switzerland; Stajich, J E [University of California, Berkeley; Tunlid, A [Lund University, Sweden; Grigoriev, I. [U.S. Department of Energy, Joint Genome Institute

    2008-01-01

    Mycorrhizal symbioses the union of roots and soil fungi are universal in terrestrial ecosystems and may have been fundamental to land colonization by plants1,2. Boreal, temperate and montane forests all depend on ectomycorrhizae1. Identification of the primary factors that regulate symbiotic development and metabolic activity will therefore open the door to understanding the role of ectomycorrhizae in plant development and physiology, allowing the full ecological significance of this symbiosis to be explored. Here we report the genome sequence of the ectomycorrhizal basidiomycete Laccaria bicolor (Fig. 1) and highlight gene sets involved in rhizosphere colonization and symbiosis. This 65-megabase genome assembly contains 20,000 predicted protein-encoding genes and a very large number of transposons and repeated sequences. We detected unexpected genomic features, most notably a battery of effector-type small secreted proteins (SSPs) with unknown function, several of which are only expressed in symbiotic tissues. The most highly expressed SSP accumulates in the proliferating hyphae colonizing the host root. The ectomycorrhizae-specific SSPs probably have a decisive role in the establishment of the symbiosis. The unexpected observation that the genome of L. bicolor lacks carbohydrate-active enzymes involved in degradation of plant cell walls, but maintains the ability to degrade non-plant cell wall polysaccharides, reveals the dual saprotrophic and biotrophic lifestyle of the mycorrhizal fungus that enables it to grow within both soil and living plant roots. The predicted gene inventory of the L. bicolor genome, therefore, points to previously unknown mechanisms of symbiosis operating in biotrophic mycorrhizal fungi. The availability of this genome provides an unparalleled opportunity to develop a deeper understanding of the processes by which symbionts interact with plants within their ecosystem to perform vital functions in the carbon and nitrogen cycles that are

  17. The genome of Laccaria bicolor provides insights into mycorrhizal symbiosis

    Energy Technology Data Exchange (ETDEWEB)

    Martin, F.; Aerts, A.; Ahren, D.; Brun, A.; Danchin, E. G. J.; Duchaussoy, F.; Gibon, J.; Kohler, A.; Lindquist, E.; Peresa, V.; Salamov, A.; Shapiro, H. J.; Wuyts, J.; Blaudez, D.; Buee, M.; Brokstein, P.; Canback, B.; Cohen, D.; Courty, P. E.; Coutinho, P. M.; Delaruelle, C.; Detter, J. C.; Deveau, A.; DiFazio, S.; Duplessis, S.; Fraissinet-Tachet, L.; Lucic, E.; Frey-Klett, P.; Fourrey, C.; Feussner, I.; Gay, G.; Grimwood, J.; Hoegger, P. J.; Jain, P.; Kilaru, S.; Labbe, J.; Lin, Y. C.; Legue, V.; Le Tacon, F.; Marmeisse, R.; Melayah, D.; Montanini, B.; Muratet, M.; Nehls, U.; Niculita-Hirzel, H.; Secq, M. P. Oudot-Le; Peter, M.; Quesneville, H.; Rajashekar, B.; Reich, M.; Rouhier, N.; Schmutz, J.; Yin, T.; Chalot, M.; Henrissat, B.; Kues, U.; Lucas, S.; Van de Peer, Y.; Podila, G. K.; Polle, A.; Pukkila, P. J.; Richardson, P. M.; Rouze, P.; Sanders, I. R.; Stajich, J. E.; Tunlid, A.; Tuskan, G.; Grigoriev, I. V.

    2007-08-10

    Mycorrhizal symbioses the union of roots and soil fungi are universal in terrestrial ecosystems and may have been fundamental to land colonization by plants 1, 2. Boreal, temperate and montane forests all depend on ectomycorrhizae1. Identification of the primary factors that regulate symbiotic development and metabolic activity will therefore open the door to understanding the role of ectomycorrhizae in plant development and physiology, allowing the full ecological significance of this symbiosis to be explored. Here we report the genome sequence of the ectomycorrhizal basidiomycete Laccaria bicolor (Fig. 1) and highlight gene sets involved in rhizosphere colonization and symbiosis. This 65-megabase genome assembly contains 20,000 predicted protein-encoding genes and a very large number of transposons and repeated sequences. We detected unexpected genomic features, most notably a battery of effector-type small secreted proteins (SSPs) with unknown function, several of which are only expressed in symbiotic tissues. The most highly expressed SSP accumulates in the proliferating hyphae colonizing the host root. The ectomycorrhizae-specific SSPs probably have a decisive role in the establishment of the symbiosis. The unexpected observation that the genome of L. bicolor lacks carbohydrate-active enzymes involved in degradation of plant cell walls, but maintains the ability to degrade non-plant cell wall polysaccharides, reveals the dual saprotrophic and biotrophic lifestyle of the mycorrhizal fungus that enables it to grow within both soil and living plant roots. The predicted gene inventory of the L. bicolor genome, therefore, points to previously unknown mechanisms of symbiosis operating in biotrophic mycorrhizal fungi. The availability of this genome provides an unparalleled opportunity to develop a deeper understanding of the processes by which symbionts interact with plants within their ecosystem to perform vital functions in the carbon and nitrogen cycles that are

  18. Fusion transcriptome profiling provides insights into alveolar rhabdomyosarcoma.

    Science.gov (United States)

    Xie, Zhongqiu; Babiceanu, Mihaela; Kumar, Shailesh; Jia, Yuemeng; Qin, Fujun; Barr, Frederic G; Li, Hui

    2016-11-15

    Gene fusions and fusion products were thought to be unique features of neoplasia. However, more and more studies have identified fusion RNAs in normal physiology. Through RNA sequencing of 27 human noncancer tissues, a large number of fusion RNAs were found. By analyzing fusion transcriptome, we observed close clusterings between samples of same or similar tissues, supporting the feasibility of using fusion RNA profiling to reveal connections between biological samples. To put the concept into use, we selected alveolar rhabdomyosarcoma (ARMS), a myogenic pediatric cancer whose exact cell of origin is not clear. PAX3-FOXO1 (paired box gene 3 fused with forkhead box O1) fusion RNA, which is considered a hallmark of ARMS, was recently found during normal muscle cell differentiation. We performed and analyzed RNA sequencing from various time points during myogenesis and uncovered many chimeric fusion RNAs. Interestingly, we found that the fusion RNA profile of RH30, an ARMS cell line, is most similar to the myogenesis time point when PAX3-FOXO1 is expressed. In contrast, full transcriptome clustering analysis failed to uncover this connection. Strikingly, all of the 18 chimeric RNAs in RH30 cells could be detected at the same myogenic time point(s). In addition, the seven chimeric RNAs that follow the exact transient expression pattern as PAX3-FOXO1 are specific to rhabdomyosarcoma cells. Further testing with clinical samples also confirmed their specificity to rhabdomyosarcoma. These results provide further support for the link between at least some ARMSs and the PAX3-FOXO1-expressing myogenic cells and demonstrate that fusion RNA profiling can be used to investigate the etiology of fusion-gene-associated cancers.

  19. A survey of pharmacists' preparedness for provider status implementation.

    Science.gov (United States)

    Tolle, Erica M; Al Jumali, Ali Azeez Ali; Catney, Christine M; McDonough, Randal P; Veach, Stevie; Doucette, William R

    1) To measure pharmacists' preparedness for the implementation of provider status; and 2) to measure pharmacists' perceived stakeholder readiness for provider status implementation. An anonymous 24-item electronic survey was sent to a convenience sample of approximately 1500 licensed Iowa pharmacists. They were contacted by means of their membership in the Iowa Pharmacists Association, 1 of 6 regional associations; Drake University and University of Iowa faculty listservs; and the University of Iowa alumni office. Pharmacists received initial contact through e-mail, private groups on social media, or respective organizations' websites requesting participation. Respondents' confidence to provide clinical skills and perceived preparedness for provider status implementation were measured. One hundred thirty-two pharmacists completed the survey. Participants perceived high confidence in themselves to serve as providers and low confidence in the preparedness of payers to support pharmacist provider status. Participants reported feeling most confident in obtaining a medication history and past medical history and least confident in obtaining vital signs and providing point-of-care testing. If provider status for pharmacists becomes law, Iowa pharmacists should expand on initiatives in collaboration with stakeholders to make a smoother transition into provider status. Iowa pharmacists may benefit from educational programming focused on delivering components of clinical services, such as measuring vital signs and point-of-care testing. Future research can be conducted to explain pharmacists' confidence levels as well as intentions to implement provider status services. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Measuring stigma among abortion providers: assessing the Abortion Provider Stigma Survey instrument.

    Science.gov (United States)

    Martin, Lisa A; Debbink, Michelle; Hassinger, Jane; Youatt, Emily; Eagen-Torkko, Meghan; Harris, Lisa H

    2014-01-01

    We explored the psychometric properties of 15 survey questions that assessed abortion providers' perceptions of stigma and its impact on providers' professional and personal lives referred to as the Abortion Provider Stigma Survey (APSS). We administered the survey to a sample of abortion providers recruited for the Providers' Share Workshop (N = 55). We then completed analyses using Stata SE/12.0. Exploratory factor analysis, which resulted in 13 retained items and identified three subscales: disclosure management, resistance and resilience, and discrimination. Stigma was salient in abortion provider's lives: they identified difficulties surrounding disclosure (66%) and felt unappreciated by society (89%). Simultaneously, workers felt they made a positive contribution to society (92%) and took pride in their work (98%). Paired t-test analyses of the pre- and post-Workshop APSS scores showed no changes in the total score. However, the Disclosure Management subscale scores were significantly lower (indicating decreased stigma) for two subgroups of participants: those over the age of 30 and those with children. This analysis is a promising first step in the development of a quantitative tool for capturing abortion providers' experiences of and responses to pervasive abortion stigma.

  1. Abortion practice in Mexico: a survey of health care providers.

    Science.gov (United States)

    Dayananda, Ila; Walker, Dilys; Atienzo, Erika E; Haider, Sadia

    2012-03-01

    Little is known about abortion practice in Mexico postlegalization of abortion in Mexico City in 2007. In 2009, we anonymously surveyed 418 Mexican health care providers at the Colegio Mexicano de Especialistas en Ginecologia y Obstetricia meeting using audio computer-assisted self-interview technology. The majority of respondents were obstetrician gynecologists (376, 90%), Catholic (341, 82%), 35-60 years old (332, 79%) and male (222, 53%) and worked with trainees (307, 74%). Prior to 2007, 11% (46) and 17% (71) provided medical and surgical abortions; now, 15% (62) and 21% (86) provide these services, respectively. Practitioners from Mexico City were more likely to provide services than those from other areas. Most medical abortion providers (50, 81%) used ineffective protocols. Surgical abortion providers mainly used either manual vacuum aspiration (39, 45%) or sharp curettage (27, 32%). Most abortion providers were trained in residency and wanted more training in medical (54, 87%) and surgical (59, 69%) abortion. Among nonproviders, 49% (175) and 27% (89) expressed interest in learning to perform medical and surgical abortion, respectively. Given the interest in learning to provide safe abortion services and the prevalent use of ineffective medical abortion regimens and sharp curettage, abortion training in Mexico should be strengthened. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. A survey of assistive technology service providers in the USA.

    Science.gov (United States)

    Arthanat, Sajay; Elsaesser, Linda-Jeanne; Bauer, Stephen

    2017-01-26

    This study investigates perspectives of assistive technology service (ATS) providers regarding their education and training, interdisciplinary standards of practice, use of a common language framework, funding policies, utilization of evidence and outcomes measurement. A survey underpinned by AT legislations and established guidelines for practice was completed by 318 certified AT providers. More than 30% of the providers reported their education and training as inadequate to fulfil four of the seven primary roles of ATS. Nearly 90% of providers expressed awareness of the International Classification of Functioning, Disability and Health (ICF) domains for interdisciplinary communication. However, only 45% felt that they could effectively utilize the ICF in their documentation. About 75% of the providers acknowledged the lack of a recognized standard for the provision of services. Prevailing inadequacies in funding were negatively impacting the quality of ATS, as expressed by 88% of respondents. Translation of evidence to practice was identified as a major challenge by 41% of service providers. Providers were predominantly documenting outcomes through informal interviews (54%) or non-standard instruments (26%). Findings support the need for strengthening professional curriculum, pre-service and in-service training and an established standard to support effective, interdisciplinary AT services and data collection to support public policy decisions. Implications for Rehabilitation This study validates the need to strengthen education and training of AT service providers by enhancing professional curriculum as well as their engagement in pre-service and in-service training activities. This study draws attention to health care funding policies and practices that critically impact the quality of AT services. This study signifies the need for an established interdisciplinary standard among AT professionals to support effective communication, service coordination and

  3. Domestic violence during pregnancy: survey of patients and healthcare providers.

    Science.gov (United States)

    Jeanjot, Isabelle; Barlow, Patricia; Rozenberg, Serge

    2008-05-01

    Domestic violence is a major public health problem; surveys report that 3%-17% of pregnant women suffer from it during their pregnancy, endangering fetal and maternal health. First, we aim (1) to estimate the prevalence of domestic violence in women who had been admitted to the maternity department of a public hospital that provides healthcare to a multicultural population, (2) to identify risk factors for domestic violence, and (3) to evaluate obstetrical complications. Second, we aim (4) to evaluate the attitude of healthcare providers toward screening for domestic violence. For six consecutive weeks, 200 women were systematically interviewed and screened for domestic violence in the early postpartum; 56 healthcare providers were interviewed. Twenty-two women [11%] were victims of violence during their recent pregnancy. These women have less family and social support than nonabused women, have fewer stable relationships, and suffer more frequently from affective disorders. There were no differences in terms of obstetrical complications. Most healthcare providers do not systematically screen for domestic violence during pregnancy because of language and cultural barriers, fear of shocking the patient, and lack of competence in how to manage the problem. Systematic screening for domestic violence should be recommended during pregnancy, considering its high prevalence.

  4. Provider confidence in opioid prescribing and chronic pain management: results of the Opioid Therapy Provider Survey.

    Science.gov (United States)

    Pearson, Amy Cs; Moman, Rajat N; Moeschler, Susan M; Eldrige, Jason S; Hooten, W Michael

    2017-01-01

    Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics. The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman's rho. Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8%) did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1) following an opioid therapy protocol (P=0.001), 2) the perceived ability to identify patients at risk for opioid misuse (P=0.006), and 3) using a consistent practice-based approach to improve their comfort level with prescribing opioids (Pconfidence was negatively correlated with the perception that treating pain patients was a "problem in my practice" (P=0.005). In this study, the majority of providers did not feel confident managing chronic pain. However, provider confidence was associated with a protocolized and consistent practice-based approach toward managing opioids and the perceived ability to identify patients at risk for opioid misuse. Future studies should investigate whether provider confidence is associated with measurable competence in managing chronic pain and explore approaches to enhance appropriate levels of confidence in caring for patients with chronic pain.

  5. The Clean Energy Manufacturing Analysis Center (CEMAC): Providing Analysis and Insights on Clean Technology Manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Nicholi S [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-28

    The U.S. Department of Energy's Clean Energy Manufacturing Analysis Center (CEMAC) provides objective analysis and up-to-date data on global supply chains and manufacturing of clean energy technologies. Policymakers and industry leaders seek CEMAC insights to inform choices to promote economic growth and the transition to a clean energy economy.

  6. Segmentation studies provide insights to better understanding attitudes towards science and technology.

    Science.gov (United States)

    Cormick, Craig; Romanach, Lygia Malzoni

    2014-03-01

    Values-based studies of people's attitudes towards science and technology not only provide great insights into what drives different attitudes to issues like climate change and genetically modified foods, but allow for segmenting the general public by homogeneous values. Such segmentations both provide better predictions of people's attitudes to new technologies or contentious science issues than age, sex, or other standard demographics, and allow a better matching of different messages with different community values.

  7. Open innovation and universities. Insights from an interregional survey

    Directory of Open Access Journals (Sweden)

    Tibor Dory

    2013-07-01

    Full Text Available The article presents the results of an empirical study carried out within the “Open Research Platform” (ORP subproject of “European Collaborative and Open regional Innovation Strategies” (EURIS. In the frame of this subproject a survey was carried out to investigate companies’ technology transfer practices with universities in four regions of the European Union, i.e. Navarra (Spain, Lodz region (Poland, Stuttgart region (Germany and Western-Transdanubia (Hungary. The main objectives of the investigation were to explore: i to what extent knowledge transfer activities at higher education institutions and research organizations serve the open innovation model? and ii what the role is of higher education institutions in the technology transfer system of the examined regions? In the first section, the relevance of the survey under the open innovation paradigm is discussed then the main conclusions of the survey are presented. Finally, an open innovation collaboration model is introduced that provides both companies and universities with some suggestions to make their collaboration more effective

  8. Echolocation detections and digital video surveys provide reliable estimates of the relative density of harbour porpoises

    National Research Council Canada - National Science Library

    Williamson, Laura D; Brookes, Kate L; Scott, Beth E; Graham, Isla M; Bradbury, Gareth; Hammond, Philip S; Thompson, Paul M; McPherson, Jana

    2016-01-01

    ...‐based visual surveys. Surveys of cetaceans using acoustic loggers or digital cameras provide alternative methods to estimate relative density that have the potential to reduce cost and provide a verifiable record of all detections...

  9. Complexes of Thermotoga maritima S-adenosylmethionine decarboxylase provide insights into substrate specificity

    Energy Technology Data Exchange (ETDEWEB)

    Bale, Shridhar; Baba, Kavita; McCloskey, Diane E.; Pegg, Anthony E.; Ealick, Steven E.

    2010-06-25

    The polyamines putrescine, spermidine and spermine are ubiquitous aliphatic cations and are essential for cellular growth and differentiation. S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical pyruvoyl-dependent enzyme in the polyamine-biosynthetic pathway. The crystal structures of AdoMetDC from humans and plants and of the AdoMetDC proenzyme from Thermotoga maritima have been obtained previously. Here, the crystal structures of activated T. maritima AdoMetDC (TmAdoMetDC) and of its complexes with S-adenosylmethionine methyl ester and 5{prime}-deoxy-5{prime}-dimethylthioadenosine are reported. The results demonstrate for the first time that TmAdoMetDC autoprocesses without the need for additional factors and that the enzyme contains two complete active sites, both of which use residues from both chains of the homodimer. The complexes provide insights into the substrate specificity and ligand binding of AdoMetDC in prokaryotes. The conservation of the ligand-binding mode and the active-site residues between human and T. maritima AdoMetDC provides insight into the evolution of AdoMetDC.

  10. Parameter sensitivity analysis of stochastic models provides insights into cardiac calcium sparks.

    Science.gov (United States)

    Lee, Young-Seon; Liu, Ona Z; Hwang, Hyun Seok; Knollmann, Bjorn C; Sobie, Eric A

    2013-03-05

    We present a parameter sensitivity analysis method that is appropriate for stochastic models, and we demonstrate how this analysis generates experimentally testable predictions about the factors that influence local Ca(2+) release in heart cells. The method involves randomly varying all parameters, running a single simulation with each set of parameters, running simulations with hundreds of model variants, then statistically relating the parameters to the simulation results using regression methods. We tested this method on a stochastic model, containing 18 parameters, of the cardiac Ca(2+) spark. Results show that multivariable linear regression can successfully relate parameters to continuous model outputs such as Ca(2+) spark amplitude and duration, and multivariable logistic regression can provide insight into how parameters affect Ca(2+) spark triggering (a probabilistic process that is all-or-none in a single simulation). Benchmark studies demonstrate that this method is less computationally intensive than standard methods by a factor of 16. Importantly, predictions were tested experimentally by measuring Ca(2+) sparks in mice with knockout of the sarcoplasmic reticulum protein triadin. These mice exhibit multiple changes in Ca(2+) release unit structures, and the regression model both accurately predicts changes in Ca(2+) spark amplitude (30% decrease in model, 29% decrease in experiments) and provides an intuitive and quantitative understanding of how much each alteration contributes to the result. This approach is therefore an effective, efficient, and predictive method for analyzing stochastic mathematical models to gain biological insight.

  11. The challenge of training for family medicine across different contexts: Insights from providing training in China

    Directory of Open Access Journals (Sweden)

    John Sandars

    2016-05-01

    Full Text Available Physicians with expertise in providing training for family medicine, at both undergraduate level and postgraduate level, are frequently invited to run training workshops in countries with developing systems of family medicine but this approach is often a challenge for the incoming external trainers. There are general challenges in working across different contexts, especially cultural factors, the different approaches to training, including the aims, methods, and assessment, and additional organizational factors, influenced by the wider sociopolitical environment of the host country. Practical responses to these challenges are discussed, with relevance to both external trainers and those responsible for requesting training. This commentary contains insights from the experiences of the authors in providing training for family medicine in China.

  12. Structure of the Hantavirus Nucleoprotein Provides Insights into the Mechanism of RNA Encapsidation.

    Science.gov (United States)

    Olal, Daniel; Daumke, Oliver

    2016-03-08

    Hantaviruses are etiological agents of life-threatening hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. The nucleoprotein (N) of hantavirus is essential for viral transcription and replication, thus representing an attractive target for therapeutic intervention. We have determined the crystal structure of hantavirus N to 3.2 Å resolution. The structure reveals a two-lobed, mostly α-helical structure that is distantly related to that of orthobunyavirus Ns. A basic RNA binding pocket is located at the intersection between the two lobes. We provide evidence that oligomerization is mediated by amino- and C-terminal arms that bind to the adjacent monomers. Based on these findings, we suggest a model for the oligomeric ribonucleoprotein (RNP) complex. Our structure provides mechanistic insights into RNA encapsidation in the genus Hantavirus and constitutes a template for drug discovery efforts aimed at combating hantavirus infections.

  13. The HapMap Resource is Providing New Insights into Ourselves and its Application to Pharmacogenomics.

    Science.gov (United States)

    Zhang, Wei; Ratain, Mark J; Dolan, M Eileen

    2008-01-01

    The exploration of quantitative variation in complex traits such as gene expression and drug response in human populations has become one of the major priorities for medical genetics. The International HapMap Project provides a key resource of genotypic data on human lymphoblastoid cell lines derived from four major world populations of European, African, Chinese and Japanese ancestry for researchers to associate with various phenotypic data to find genes affecting health, disease and response to drugs. Recent progress in dissecting genetic contribution to natural variation in gene expression within and among human populations and variation in drug response are two examples in which researchers have utilized the HapMap resource. The HapMap Project provides new insights into the human genome and has applicability to pharmacogenomics studies leading to personalized medicine.

  14. Mechanisms of bacterial morphogenesis: evolutionary cell biology approaches provide new insights.

    Science.gov (United States)

    Jiang, Chao; Caccamo, Paul D; Brun, Yves V

    2015-04-01

    How Darwin's "endless forms most beautiful" have evolved remains one of the most exciting questions in biology. The significant variety of bacterial shapes is most likely due to the specific advantages they confer with respect to the diverse environments they occupy. While our understanding of the mechanisms generating relatively simple shapes has improved tremendously in the last few years, the molecular mechanisms underlying the generation of complex shapes and the evolution of shape diversity are largely unknown. The emerging field of bacterial evolutionary cell biology provides a novel strategy to answer this question in a comparative phylogenetic framework. This relatively novel approach provides hypotheses and insights into cell biological mechanisms, such as morphogenesis, and their evolution that would have been difficult to obtain by studying only model organisms. We discuss the necessary steps, challenges, and impact of integrating "evolutionary thinking" into bacterial cell biology in the genomic era.

  15. Drosophila Cappuccino alleles provide insight into formin mechanism and role in oogenesis.

    Science.gov (United States)

    Yoo, Haneul; Roth-Johnson, Elizabeth A; Bor, Batbileg; Quinlan, Margot E

    2015-05-15

    During Drosophila development, the formin actin nucleator Cappuccino (Capu) helps build a cytoplasmic actin mesh throughout the oocyte. Loss of Capu leads to female sterility, presumably because polarity determinants fail to localize properly in the absence of the mesh. To gain deeper insight into how Capu builds this actin mesh, we systematically characterized seven capu alleles, which have missense mutations in Capu's formin homology 2 (FH2) domain. We report that all seven alleles have deleterious effects on fly fertility and the actin mesh in vivo but have strikingly different effects on Capu's biochemical activity in vitro. Using a combination of bulk and single- filament actin-assembly assays, we find that the alleles differentially affect Capu's ability to nucleate and processively elongate actin filaments. We also identify a unique "loop" in the lasso region of Capu's FH2 domain. Removing this loop enhances Capu's nucleation, elongation, and F-actin-bundling activities in vitro. Together our results on the loop and the seven missense mutations provides mechanistic insight into formin function in general and Capu's role in the Drosophila oocyte in particular.

  16. Pediatric Primary Care Providers' Relationships with Mental Health Care Providers: Survey Results

    Science.gov (United States)

    Pidano, Anne E.; Honigfeld, Lisa; Bar-Halpern, Miri; Vivian, James E.

    2014-01-01

    Background: As many as 20 % of children have diagnosable mental health conditions and nearly all of them receive pediatric primary health care. However, most children with serious mental health concerns do not receive mental health services. This study tested hypotheses that pediatric primary care providers (PPCPs) in relationships with mental…

  17. A Renaissance in Nepovirus Research Provides New Insights Into Their Molecular Interface With Hosts and Vectors.

    Science.gov (United States)

    Fuchs, M; Schmitt-Keichinger, C; Sanfaçon, H

    2017-01-01

    Nepoviruses supplied seminal landmarks to the historical trail of plant virology. Among the first agriculturally relevant viruses recognized in the late 1920s and among the first plant viruses officially classified in the early 1970s, nepoviruses also comprise the first species for which a soil-borne ectoparasitic nematode vector was identified. Early research on nepoviruses shed light on the genome structure and expression, biological properties of the two genomic RNAs, and mode of transmission. In recent years, research on nepoviruses enjoyed an extraordinary renaissance. This resurgence provided new insights into the molecular interface between viruses and their plant hosts, and between viruses and dagger nematode vectors to advance our understanding of some of the major steps of the infectious cycle. Here we examine these recent findings, highlight ongoing work, and offer some perspectives for future research. © 2017 Elsevier Inc. All rights reserved.

  18. Genomic analyses of primitive, wild and cultivated citrus provide insights into asexual reproduction.

    Science.gov (United States)

    Wang, Xia; Xu, Yuantao; Zhang, Siqi; Cao, Li; Huang, Yue; Cheng, Junfeng; Wu, Guizhi; Tian, Shilin; Chen, Chunli; Liu, Yan; Yu, Huiwen; Yang, Xiaoming; Lan, Hong; Wang, Nan; Wang, Lun; Xu, Jidi; Jiang, Xiaolin; Xie, Zongzhou; Tan, Meilian; Larkin, Robert M; Chen, Ling-Ling; Ma, Bin-Guang; Ruan, Yijun; Deng, Xiuxin; Xu, Qiang

    2017-05-01

    The emergence of apomixis-the transition from sexual to asexual reproduction-is a prominent feature of modern citrus. Here we de novo sequenced and comprehensively studied the genomes of four representative citrus species. Additionally, we sequenced 100 accessions of primitive, wild and cultivated citrus. Comparative population analysis suggested that genomic regions harboring energy- and reproduction-associated genes are probably under selection in cultivated citrus. We also narrowed the genetic locus responsible for citrus polyembryony, a form of apomixis, to an 80-kb region containing 11 candidate genes. One of these, CitRWP, is expressed at higher levels in ovules of polyembryonic cultivars. We found a miniature inverted-repeat transposable element insertion in the promoter region of CitRWP that cosegregated with polyembryony. This study provides new insights into citrus apomixis and constitutes a promising resource for the mining of agriculturally important genes.

  19. A new raptorial dinosaur with exceptionally long feathering provides insights into dromaeosaurid flight performance.

    Science.gov (United States)

    Han, Gang; Chiappe, Luis M; Ji, Shu-An; Habib, Michael; Turner, Alan H; Chinsamy, Anusuya; Liu, Xueling; Han, Lizhuo

    2014-07-15

    Microraptorines are a group of predatory dromaeosaurid theropod dinosaurs with aerodynamic capacity. These close relatives of birds are essential for testing hypotheses explaining the origin and early evolution of avian flight. Here we describe a new 'four-winged' microraptorine, Changyuraptor yangi, from the Early Cretaceous Jehol Biota of China. With tail feathers that are nearly 30 cm long, roughly 30% the length of the skeleton, the new fossil possesses the longest known feathers for any non-avian dinosaur. Furthermore, it is the largest theropod with long, pennaceous feathers attached to the lower hind limbs (that is, 'hindwings'). The lengthy feathered tail of the new fossil provides insight into the flight performance of microraptorines and how they may have maintained aerial competency at larger body sizes. We demonstrate how the low-aspect-ratio tail of the new fossil would have acted as a pitch control structure reducing descent speed and thus playing a key role in landing.

  20. Comparative analysis of bat genomes provides insight into the evolution of flight and immunity.

    Science.gov (United States)

    Zhang, Guojie; Cowled, Christopher; Shi, Zhengli; Huang, Zhiyong; Bishop-Lilly, Kimberly A; Fang, Xiaodong; Wynne, James W; Xiong, Zhiqiang; Baker, Michelle L; Zhao, Wei; Tachedjian, Mary; Zhu, Yabing; Zhou, Peng; Jiang, Xuanting; Ng, Justin; Yang, Lan; Wu, Lijun; Xiao, Jin; Feng, Yue; Chen, Yuanxin; Sun, Xiaoqing; Zhang, Yong; Marsh, Glenn A; Crameri, Gary; Broder, Christopher C; Frey, Kenneth G; Wang, Lin-Fa; Wang, Jun

    2013-01-25

    Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related species, fruit bat Pteropus alecto and insectivorous bat Myotis davidii. We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor κB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.

  1. The Lingula genome provides insights into brachiopod evolution and the origin of phosphate biomineralization

    Science.gov (United States)

    Luo, Yi-Jyun; Takeuchi, Takeshi; Koyanagi, Ryo; Yamada, Lixy; Kanda, Miyuki; Khalturina, Mariia; Fujie, Manabu; Yamasaki, Shin-ichi; Endo, Kazuyoshi; Satoh, Noriyuki

    2015-01-01

    The evolutionary origins of lingulid brachiopods and their calcium phosphate shells have been obscure. Here we decode the 425-Mb genome of Lingula anatina to gain insights into brachiopod evolution. Comprehensive phylogenomic analyses place Lingula close to molluscs, but distant from annelids. The Lingula gene number has increased to ∼34,000 by extensive expansion of gene families. Although Lingula and vertebrates have superficially similar hard tissue components, our genomic, transcriptomic and proteomic analyses show that Lingula lacks genes involved in bone formation, indicating an independent origin of their phosphate biominerals. Several genes involved in Lingula shell formation are shared by molluscs. However, Lingula has independently undergone domain combinations to produce shell matrix collagens with EGF domains and carries lineage-specific shell matrix proteins. Gene family expansion, domain shuffling and co-option of genes appear to be the genomic background of Lingula's unique biomineralization. This Lingula genome provides resources for further studies of lophotrochozoan evolution. PMID:26383154

  2. Feathered non-avian dinosaurs from North America provide insight into wing origins.

    Science.gov (United States)

    Zelenitsky, Darla K; Therrien, François; Erickson, Gregory M; DeBuhr, Christopher L; Kobayashi, Yoshitsugu; Eberth, David A; Hadfield, Frank

    2012-10-26

    Previously described feathered dinosaurs reveal a fascinating record of feather evolution, although substantial phylogenetic gaps remain. Here we report the occurrence of feathers in ornithomimosaurs, a clade of non-maniraptoran theropods for which fossilized feathers were previously unknown. The Ornithomimus specimens, recovered from Upper Cretaceous deposits of Alberta, Canada, provide new insights into dinosaur plumage and the origin of the avian wing. Individuals from different growth stages reveal the presence of a filamentous feather covering throughout life and winglike structures on the forelimbs of adults. The appearance of winglike structures in older animals indicates that they may have evolved in association with reproductive behaviors. These specimens show that primordial wings originated earlier than previously thought, among non-maniraptoran theropods.

  3. Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity

    DEFF Research Database (Denmark)

    Zhang, Guojie; Cowled, Christopher; Shi, Zhengli

    2013-01-01

    Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific......Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat...... that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution....

  4. Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

    Energy Technology Data Exchange (ETDEWEB)

    Sidhu, Navdeep S. [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Schreiber, Kathrin [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); Pröpper, Kevin [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Becker, Stefan [Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany); Usón, Isabel [Instituto de Biologia Molecular de Barcelona (IBMB–CSIC), Barcelona Science Park, Baldiri Reixach 15, 08028 Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), (Spain); Sheldrick, George M. [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Gärtner, Jutta; Krätzner, Ralph, E-mail: rkraetz@gwdg.de; Steinfeld, Robert, E-mail: rkraetz@gwdg.de [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany)

    2014-05-01

    Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.

  5. Whole Genome Analysis of Leptospira licerasiae Provides Insight into Leptospiral Evolution and Pathogenicity

    Science.gov (United States)

    Selengut, Jeremy D.; Harkins, Derek M.; Patra, Kailash P.; Moreno, Angelo; Lehmann, Jason S.; Purushe, Janaki; Sanka, Ravi; Torres, Michael; Webster, Nicholas J.; Vinetz, Joseph M.; Matthias, Michael A.

    2012-01-01

    The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835) provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae) that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010T and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for its infectiousness

  6. Obesity and prostate cancer detection: insights from three national surveys.

    Science.gov (United States)

    Parekh, Niyati; Lin, Yong; Dipaola, Robert S; Marcella, Stephen; Lu-Yao, Grace

    2010-09-01

    Previous studies suggest that obesity is associated with higher prostate cancer progression and mortality despite an association with lower prostate cancer incidence. This study aims to better understand these apparently inconsistent relationships among obese men by combining evidence from 3 nationally representative cross-sectional surveys. We evaluated relationships between obesity and 1) testosterone concentrations in the Third National Health and Nutrition Examination Survey (NHANES III; n=845); 2) prostate-specific antigen (PSA) in NHANES 2001-2004 (n=2458); and 3) prostate biopsy rates in the National Health Interview Survey (NHIS 2000; n=4789) population. Mean testosterone, PSA concentrations, and biopsy rates were computed for Body Mass Index (BMI) categories. Testosterone concentrations were inversely associated with obesity (P-trend obese (BMI >35) versus lean (BMI 4 ng/mL (3% vs 8%; P 30 versus 16% with BMI 30 versus BMI Obesity was associated with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates.

  7. Obesity and prostate cancer detection: insights from three national surveys

    Science.gov (United States)

    Parekh, Niyati; Lin, Yong; DiPaola, Robert S.; Marcella, Stephen; Lu-Yao, Grace

    2013-01-01

    Background Previous studies suggest that obesity is associated with higher prostate cancer progression and mortality despite an association with lower prostate cancer incidence. This study aims to better understand these apparently inconsistent relationships among obese men, by combining evidence from three nationally representative cross-sectional surveys. Methods We evaluated relationships between obesity and (1) testosterone concentrations in the Third National Health and Nutrition Examination Survey (NHANES III; n=845), (2) prostate-specific antigen (PSA) in NHANES 2001–2004 (n=2,458) and (3) prostate biopsy rates in the National Health Interview Survey (NHIS 2000; n=4,789) population. Mean testosterone, PSA concentrations and biopsy rates were computed for body mass index (BMI) categories. Results Testosterone concentrations were inversely associated with obesity (p-trendobese (BMI >35) versus lean (BMI 4 ng/ml (3% versus 8%; p30 versus 16% with BMI 30 versus BMI Obesity was associated with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates. PMID:20800152

  8. The Microbial Signature Provides Insight into the Mechanistic Basis of Coral Success across Reef Habitats

    Science.gov (United States)

    Leggat, William; Bongaerts, Pim

    2016-01-01

    ABSTRACT For ecosystems vulnerable to environmental change, understanding the spatiotemporal stability of functionally crucial symbioses is fundamental to determining the mechanisms by which these ecosystems may persist. The coral Pachyseris speciosa is a successful environmental generalist that succeeds in diverse reef habitats. The generalist nature of this coral suggests it may have the capacity to form functionally significant microbial partnerships to facilitate access to a range of nutritional sources within different habitats. Here, we propose that coral is a metaorganism hosting three functionally distinct microbial interactions: a ubiquitous core microbiome of very few symbiotic host-selected bacteria, a microbiome of spatially and/or regionally explicit core microbes filling functional niches (100,000 phylotypes). We find that this coral hosts upwards of 170,000 distinct phylotypes and provide evidence for the persistence of a select group of bacteria in corals across environmental habitats of the Great Barrier Reef and Coral Sea. We further show that a higher number of bacteria are consistently associated with corals on mesophotic reefs than on shallow reefs. An increase in microbial diversity with depth suggests reliance by this coral on bacteria for nutrient acquisition on reefs exposed to nutrient upwelling. Understanding the complex microbial communities of host organisms across broad biotic and abiotic environments as functionally distinct microbiomes can provide insight into those interactions that are ubiquitous niche symbioses and those that provide competitive advantage within the hosts’ environment. PMID:27460792

  9. The Microbial Signature Provides Insight into the Mechanistic Basis of Coral Success across Reef Habitats

    Directory of Open Access Journals (Sweden)

    Alejandra Hernandez-Agreda

    2016-07-01

    Full Text Available For ecosystems vulnerable to environmental change, understanding the spatiotemporal stability of functionally crucial symbioses is fundamental to determining the mechanisms by which these ecosystems may persist. The coral Pachyseris speciosa is a successful environmental generalist that succeeds in diverse reef habitats. The generalist nature of this coral suggests it may have the capacity to form functionally significant microbial partnerships to facilitate access to a range of nutritional sources within different habitats. Here, we propose that coral is a metaorganism hosting three functionally distinct microbial interactions: a ubiquitous core microbiome of very few symbiotic host-selected bacteria, a microbiome of spatially and/or regionally explicit core microbes filling functional niches (100,000 phylotypes. We find that this coral hosts upwards of 170,000 distinct phylotypes and provide evidence for the persistence of a select group of bacteria in corals across environmental habitats of the Great Barrier Reef and Coral Sea. We further show that a higher number of bacteria are consistently associated with corals on mesophotic reefs than on shallow reefs. An increase in microbial diversity with depth suggests reliance by this coral on bacteria for nutrient acquisition on reefs exposed to nutrient upwelling. Understanding the complex microbial communities of host organisms across broad biotic and abiotic environments as functionally distinct microbiomes can provide insight into those interactions that are ubiquitous niche symbioses and those that provide competitive advantage within the hosts’ environment.

  10. Hyper-dry conditions provide new insights into the cause of extreme floods after wildfire

    Science.gov (United States)

    Moody, John A.; Ebel, Brian A.

    2012-01-01

    A catastrophic wildfire in the foothills of the Rocky Mountains near Boulder, Colorado provided a unique opportunity to investigate soil conditions immediately after a wildfire and before alteration by rainfall. Measurements of near-surface (θ; and matric suction, ψ), rainfall, and wind velocity were started 8 days after the wildfire began. These measurements established that hyper-dryconditions (θ 3 cm-3; ψ > ~ 3 x 105 cm) existed and provided an in-situ retention curve for these conditions. These conditions exacerbate the effects of water repellency (natural and fire-induced) and limit the effectiveness of capillarity and gravity driven infiltration into fire-affected soils. The important consequence is that given hyper-dryconditions, the critical rewetting process before the first rain is restricted to the diffusion–adsorption of water-vapor. This process typically has a time scale of days to weeks (especially when the hydrologic effects of the ash layer are included) that is longer than the typical time scale (minutes to hours) of some rainstorms, such that under hyper-dryconditions essentially no rain infiltrates. The existence of hyper-dryconditions provides insight into why, frequently during the first rain storm after a wildfire, nearly all rainfall becomes runoff causing extremefloods and debris flows.

  11. The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

    Directory of Open Access Journals (Sweden)

    Tintoré M

    2016-12-01

    Full Text Available Mar Tintoré,1 Maggie Alexander,2 Kathleen Costello,3 Martin Duddy,4 David E Jones,5 Nancy Law,6 Gilmore O’Neill,7 Antonio Uccelli,8 Robert Weissert,9 Sibyl Wray10 1Multiple Sclerosis Centre of Catalonia, Hospital Vall d’Hebron, Barcelona, Spain; 2European Multiple Sclerosis Platform, Brussels, Belgium; 3National Multiple Sclerosis Society, Denver, CO, USA; 4Royal Victoria Infirmary, Newcastle-upon-Tyne, UK; 5Department of Neurology, University of Virginia, Charlottesville, VA, USA; 6Nancy Law Consulting LLC, Parker, CO, USA; 7Biogen, Cambridge, MA, USA; 8Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; 9Department of Neurology, University of Regensburg, Regensburg, Germany; 10Hope Neurology Multiple Sclerosis Center, Knoxville, TN, USA Background: Managing multiple sclerosis (MS treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods: A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results: A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT; satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment

  12. New technologies provide insights into genetic basis of psychiatric disorders and explain their co-morbidity.

    Science.gov (United States)

    Rudan, Igor

    2010-06-01

    The completion of Human Genome Project and the "HapMap" project was followed by translational activities from companies within the private sector. This led to the introduction of genome-wide scans based on hundreds of thousands of single nucleotide polymorphysms (SNP). These scans were based on common genetic variants in human populations. This new and powerful technology was then applied to the existing DNA-based datasets with information on psychiatric disorders. As a result, an unprecedented amount of novel scientific insights related to the underlying biology and genetics of psychiatric disorders was obtained. The dominant design of these studies, so called "genome-wide association studies" (GWAS), used statistical methods which minimized the risk of false positive reports and provided much greater power to detect genotype-phenotype associations. All findings were entirely data-driven rather than hypothesis-driven, which often made it difficult for researchers to understand or interpret the findings. Interestingly, this work in genetics is indicating how non-specific some genes are for psychiatric disorders, having associations in common for schizophrenia, bipolar disorder and autism. This suggests that the earlier stages of psychiatric disorders may be multi-valent and that early detection, coupled with a clearer understanding of the environmental factors, may allow prevention. At the present time, the rich "harvest" from GWAS still has very limited power to predict the variation in psychiatric disease status at individual level, typically explaining less than 5% of the total risk variance. The most recent studies of common genetic variation implicated the role of major histocompatibility complex in schizophrenia and other disorders. They also provided molecular evidence for a substantial polygenic component to the risk of psychiatric diseases, involving thousands of common alleles of very small effect. The studies of structural genetic variation, such as copy

  13. Transcriptome Analysis of Manganese-deficient Chlamydomonas reinhardtii Provides Insight on the Chlorophyll Biosynthesis Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lockhart, Ainsley; Zvenigorodsky, Natasha; Pedraza, Mary Ann; Lindquist, Erika

    2011-08-11

    The biosynthesis of chlorophyll and other tetrapyrroles is a vital but poorly understood process. Recent genomic advances with the unicellular green algae Chlamydomonas reinhardtii have created opportunity to more closely examine the mechanisms of the chlorophyll biosynthesis pathway via transcriptome analysis. Manganese is a nutrient of interest for complex reactions because of its multiple stable oxidation states and role in molecular oxygen coordination. C. reinhardtii was cultured in Manganese-deplete Tris-acetate-phosphate (TAP) media for 24 hours and used to create cDNA libraries for sequencing using Illumina TruSeq technology. Transcriptome analysis provided intriguing insight on possible regulatory mechanisms in the pathway. Evidence supports similarities of GTR (Glutamyl-tRNA synthase) to its Chlorella vulgaris homolog in terms of Mn requirements. Data was also suggestive of Mn-related compensatory up-regulation for pathway proteins CHLH1 (Manganese Chelatase), GUN4 (Magnesium chelatase activating protein), and POR1 (Light-dependent protochlorophyllide reductase). Intriguingly, data suggests possible reciprocal expression of oxygen dependent CPX1 (coproporphyrinogen III oxidase) and oxygen independent CPX2. Further analysis using RT-PCR could provide compelling evidence for several novel regulatory mechanisms in the chlorophyll biosynthesis pathway.

  14. Dynamic transcriptional profiling provides insights into tuberous root development in Rehmannia glutinosa

    Directory of Open Access Journals (Sweden)

    Peng eSun

    2015-06-01

    Full Text Available Rehmannia glutinosa, a herb of the Scrophulariaceae family, is widely cultivated in the Northern part of China. The tuberous root has well known medicinal properties; however, yield and quality are threatened by abiotic and biotic stresses. Understanding the molecular process of tuberous root development may help identify novel targets for its control. In the present study, we used Illumina sequencing and de novo assembly strategies to obtain a reference transcriptome that is relevant to tuberous root development. We then conducted RNA-seq quantification analysis to determine gene expression profiles of the adventitious root (AR, thickening adventitious root (TAR, and the developing tuberous root (DTR. Expression profiling identified a total of 6,974 differentially expressed unigenes during root developmental. Bioinformatics analysis and gene expression profiling revealed changes in phenylpropanoid biosynthesis, starch and sucrose metabolism, and plant hormone biosynthesis during root development. Moreover, we identified and allocated putative functions to the genes involved in tuberous root development, including genes related to major carbohydrate metabolism, hormone metabolism, and transcription regulation. The present study provides the initial description of gene expression profiles of AR, TAR, and DTR, which facilitates identification of genes of interest. Moreover, our work provides insights into the molecular mechanisms underlying tuberous root development and may assist in the design and development of improved breeding schemes for different R. glutinosa varieties through genetic manipulation.

  15. Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms

    Science.gov (United States)

    Guo, Michael H.; Nandakumar, Satish K.; Ulirsch, Jacob C.; Zekavat, Seyedeh M.; Buenrostro, Jason D.; Natarajan, Pradeep; Salem, Rany M.; Chiarle, Roberto; Mitt, Mario; Kals, Mart; Pärn, Kalle; Fischer, Krista; Milani, Lili; Mägi, Reedik; Palta, Priit; Gabriel, Stacey B.; Metspalu, Andres; Lander, Eric S.; Kathiresan, Sekar; Hirschhorn, Joel N.; Esko, Tõnu; Sankaran, Vijay G.

    2017-01-01

    Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil count-associated locus near the master hematopoietic transcription factor CEBPA. The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance. PMID:28031487

  16. Dissecting the genetics of complex inheritance: linkage disequilibrium mapping provides insight into Crohn disease.

    Science.gov (United States)

    Elding, Heather; Lau, Winston; Swallow, Dallas M; Maniatis, Nikolas

    2011-12-09

    Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q and pinpoint NOD2 as a possible causative locus. However, linkage is also observed in families that do not bear the most frequent NOD2 causative mutations, but no other signals on 16q have been found so far in published genome-wide association studies. Our aim is to identify this missing genetic contribution. We apply a powerful genetic mapping approach to the Wellcome Trust Case-Control Consortium and the National Institute of Diabetes and Digestive and Kidney Diseases genome-wide association data on CD. This method takes into account the underlying structure of linkage disequilibrium (LD) by using genetic distances from LD maps and provides a location for the causal agent. We find genetic heterogeneity within the NOD2 locus and also show an independent and unsuspected involvement of the neighboring gene, CYLD. We find associations with the IRF8 region and the region containing CDH1 and CDH3, as well as substantial phenotypic and genetic heterogeneity for CD itself. The genes are known to be involved in inflammation and immune dysregulation. These findings provide insight into the genetics of CD and suggest promising directions for understanding disease heterogeneity. The application of this method thus paves the way for understanding complex inheritance in general, leading to the dissection of different pathways and ultimately, personalized treatment. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  17. The charophycean green algae provide insights into the early origins of plant cell walls.

    Science.gov (United States)

    Sørensen, Iben; Pettolino, Filomena A; Bacic, Antony; Ralph, John; Lu, Fachuang; O'Neill, Malcolm A; Fei, Zhangzhun; Rose, Jocelyn K C; Domozych, David S; Willats, William G T

    2011-10-01

    Numerous evolutionary innovations were required to enable freshwater green algae to colonize terrestrial habitats and thereby initiate the evolution of land plants (embryophytes). These adaptations probably included changes in cell-wall composition and architecture that were to become essential for embryophyte development and radiation. However, it is not known to what extent the polymers that are characteristic of embryophyte cell walls, including pectins, hemicelluloses, glycoproteins and lignin, evolved in response to the demands of the terrestrial environment or whether they pre-existed in their algal ancestors. Here we show that members of the advanced charophycean green algae (CGA), including the Charales, Coleochaetales and Zygnematales, but not basal CGA (Klebsormidiales and Chlorokybales), have cell walls that are comparable in several respects to the primary walls of embryophytes. Moreover, we provide both chemical and immunocytochemical evidence that selected Coleochaete species have cell walls that contain small amounts of lignin or lignin-like polymers derived from radical coupling of hydroxycinnamyl alcohols. Thus, the ability to synthesize many of the components that characterize extant embryophyte walls evolved during divergence within CGA. Our study provides new insight into the evolutionary window during which the structurally complex walls of embryophytes originated, and the significance of the advanced CGA during these events. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  18. Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

    Science.gov (United States)

    Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R.

    2016-01-01

    Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients. PMID:27725636

  19. Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R. (Sanofi Aventis); (UMASS, Amherst)

    2016-10-26

    Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients.

  20. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

    Science.gov (United States)

    Moreau, Christophe; Cioci, Gianluca; Iannello, Marina; Laffly, Emmanuelle; Chouquet, Anne; Ferreira, Arturo; Thielens, Nicole M.; Gaboriaud, Christine

    2016-01-01

    Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant ‘eat-me’ prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences. PMID:27840680

  1. Neanderthal brain size at birth provides insights into the evolution of human life history.

    Science.gov (United States)

    Ponce de León, Marcia S; Golovanova, Lubov; Doronichev, Vladimir; Romanova, Galina; Akazawa, Takeru; Kondo, Osamu; Ishida, Hajime; Zollikofer, Christoph P E

    2008-09-16

    From birth to adulthood, the human brain expands by a factor of 3.3, compared with 2.5 in chimpanzees [DeSilva J and Lesnik J (2006) Chimpanzee neonatal brain size: Implications for brain growth in Homo erectus. J Hum Evol 51: 207-212]. How the required extra amount of human brain growth is achieved and what its implications are for human life history and cognitive development are still a matter of debate. Likewise, because comparative fossil evidence is scarce, when and how the modern human pattern of brain growth arose during evolution is largely unknown. Virtual reconstructions of a Neanderthal neonate from Mezmaiskaya Cave (Russia) and of two Neanderthal infant skeletons from Dederiyeh Cave (Syria) now provide new comparative insights: Neanderthal brain size at birth was similar to that in recent Homo sapiens and most likely subject to similar obstetric constraints. Neanderthal brain growth rates during early infancy were higher, however. This pattern of growth resulted in larger adult brain sizes but not in earlier completion of brain growth. Because large brains growing at high rates require large, late-maturing, mothers [Leigh SR and Blomquist GE (2007) in Campbell CJ et al. Primates in perspective; pp 396-407], it is likely that Neanderthal life history was similarly slow, or even slower-paced, than in recent H. sapiens.

  2. Peeping at TOMs-Diverse Entry Gates to Mitochondria Provide Insights into the Evolution of Eukaryotes.

    Science.gov (United States)

    Mani, Jan; Meisinger, Chris; Schneider, André

    2016-02-01

    Mitochondria are essential for eukaryotic life and more than 95% of their proteins are imported as precursors from the cytosol. The targeting signals for this posttranslational import are conserved in all eukaryotes. However, this conservation does not hold true for the protein translocase of the mitochondrial outer membrane that serves as entry gate for essentially all precursor proteins. Only two of its subunits, Tom40 and Tom22, are conserved and thus likely were present in the last eukaryotic common ancestor. Tom7 is found in representatives of all supergroups except the Excavates. This suggests that it was added to the core of the translocase after the Excavates segregated from all other eukaryotes. A comparative analysis of the biochemically and functionally characterized outer membrane translocases of yeast, plants, and trypanosomes, which represent three eukaryotic supergroups, shows that the receptors that recognize the conserved import signals differ strongly between the different systems. They present a remarkable example of convergent evolution at the molecular level. The structural diversity of the functionally conserved import receptors therefore provides insight into the early evolutionary history of mitochondria. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Crystal structure of Manduca sexta prophenoloxidase provides insights into the mechanism of type 3 copper enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yongchao; Wang, Yang; Jiang, Haobo; Deng, Junpeng; (OKLU)

    2010-02-22

    Arthropod phenoloxidase (PO) generates quinones and other toxic compounds to sequester and kill pathogens during innate immune responses. It is also involved in wound healing and other physiological processes. Insect PO is activated from its inactive precursor, prophenoloxidase (PPO), by specific proteolysis via a serine protease cascade. Here, we report the crystal structure of PPO from a lepidopteran insect at a resolution of 1.97 {angstrom}, which is the initial structure for a PPO from the type 3 copper protein family. Manduca sexta PPO is a heterodimer consisting of 2 homologous polypeptide chains, PPO1 and PPO2. The active site of each subunit contains a canonical type 3 di-nuclear copper center, with each copper ion coordinated with 3 structurally conserved histidines. The acidic residue Glu-395 located at the active site of PPO2 may serve as a general base for deprotonation of monophenolic substrates, which is key to the ortho-hydroxylase activity of PO. The structure provides unique insights into the mechanism by which type 3 copper proteins differ in their enzymatic activities, albeit sharing a common active center. A drastic change in electrostatic surface induced on cleavage at Arg-51 allows us to propose a model for localized PPO activation in insects.

  4. Combining 3D structure with glycan array data provides insight into the origin of glycan specificity.

    Science.gov (United States)

    Grant, Oliver C; Tessier, Matthew B; Meche, Lawrence; Mahal, Lara K; Foley, Bethany L; Woods, Robert J

    2016-07-01

    Defining how a glycan-binding protein (GBP) specifically selects its cognate glycan from among the ensemble of glycans within the cellular glycome is an area of intense study. Powerful insight into recognition mechanisms can be gained from 3D structures of GBPs complexed to glycans; however, such structures remain difficult to obtain experimentally. Here an automated 3D structure generation technique, called computational carbohydrate grafting, is combined with the wealth of specificity information available from glycan array screening. Integration of the array data with modeling and crystallography allows generation of putative co-complex structures that can be objectively assessed and iteratively altered until a high level of agreement with experiment is achieved. Given an accurate model of the co-complexes, grafting is also able to discern which binding determinants are active when multiple potential determinants are present within a glycan. In some cases, induced fit in the protein or glycan was necessary to explain the observed specificity, while in other examples a revised definition of the minimal binding determinants was required. When applied to a collection of 10 GBP-glycan complexes, for which crystallographic and array data have been reported, grafting provided a structural rationalization for the binding specificity of >90% of 1223 arrayed glycans. A webtool that enables researchers to perform computational carbohydrate grafting is available at www.glycam.org/gr (accessed 03 March 2016).

  5. Whole-Genome Sequencing of Native Sheep Provides Insights into Rapid Adaptations to Extreme Environments.

    Science.gov (United States)

    Yang, Ji; Li, Wen-Rong; Lv, Feng-Hua; He, San-Gang; Tian, Shi-Lin; Peng, Wei-Feng; Sun, Ya-Wei; Zhao, Yong-Xin; Tu, Xiao-Long; Zhang, Min; Xie, Xing-Long; Wang, Yu-Tao; Li, Jin-Quan; Liu, Yong-Gang; Shen, Zhi-Qiang; Wang, Feng; Liu, Guang-Jian; Lu, Hong-Feng; Kantanen, Juha; Han, Jian-Lin; Li, Meng-Hua; Liu, Ming-Jun

    2016-10-01

    Global climate change has a significant effect on extreme environments and a profound influence on species survival. However, little is known of the genome-wide pattern of livestock adaptations to extreme environments over a short time frame following domestication. Sheep (Ovis aries) have become well adapted to a diverse range of agroecological zones, including certain extreme environments (e.g., plateaus and deserts), during their post-domestication (approximately 8-9 kya) migration and differentiation. Here, we generated whole-genome sequences from 77 native sheep, with an average effective sequencing depth of ∼5× for 75 samples and ∼42× for 2 samples. Comparative genomic analyses among sheep in contrasting environments, that is, plateau (>4,000 m above sea level) versus lowland (1500 m) versus low-altitude region (600 mm), and arid zone (400 mm), detected a novel set of candidate genes as well as pathways and GO categories that are putatively associated with hypoxia responses at high altitudes and water reabsorption in arid environments. In addition, candidate genes and GO terms functionally related to energy metabolism and body size variations were identified. This study offers novel insights into rapid genomic adaptations to extreme environments in sheep and other animals, and provides a valuable resource for future research on livestock breeding in response to climate change.

  6. Structural and mutational analysis of the nonribosomal peptide synthetase heterocyclization domain provides insight into catalysis.

    Science.gov (United States)

    Bloudoff, Kristjan; Fage, Christopher D; Marahiel, Mohamed A; Schmeing, T Martin

    2017-01-03

    Nonribosomal peptide synthetases (NRPSs) are a family of multidomain, multimodule enzymes that synthesize structurally and functionally diverse peptides, many of which are of great therapeutic or commercial value. The central chemical step of peptide synthesis is amide bond formation, which is typically catalyzed by the condensation (C) domain. In many NRPS modules, the C domain is replaced by the heterocyclization (Cy) domain, a homologous domain that performs two consecutive reactions by using hitherto unknown catalytic mechanisms. It first catalyzes amide bond formation, and then the intramolecular cyclodehydration between a Cys, Ser, or Thr side chain and the backbone carbonyl carbon to form a thiazoline, oxazoline, or methyloxazoline ring. The rings are important for the form and function of the peptide product. We present the crystal structure of an NRPS Cy domain, Cy2 of bacillamide synthetase, at a resolution of 2.3 Å. Despite sharing the same fold, the active sites of C and Cy domains have important differences. The structure allowed us to probe the roles of active-site residues by using mutational analyses in a peptide synthesis assay with intact bacillamide synthetase. The drastically different effects of these mutants, interpreted by using our structural and bioinformatic results, provide insight into the catalytic mechanisms of the Cy domain and implicate a previously unexamined Asp-Thr dyad in catalysis of the cyclodehydration reaction.

  7. Comparative transcriptome analysis of chemosensory genes in two sister leaf beetles provides insights into chemosensory speciation.

    Science.gov (United States)

    Zhang, Bin; Zhang, Wei; Nie, Rui-E; Li, Wen-Zhu; Segraves, Kari A; Yang, Xing-Ke; Xue, Huai-Jun

    2016-12-01

    Divergence in chemosensory traits has been posited as an important component of chemosensory speciation in insects. In particular, chemosensory genes expressed in the peripheral sensory neurons are likely to influence insect behaviors such as preference for food, oviposition sites, and mates. Despite their key role in insect behavior and potentially speciation, the underlying genetic basis for divergence in chemosensory traits remains largely unexplored. One way to ascertain the role of chemosensory genes in speciation is to make comparisons of these genes across closely related species to detect the genetic signatures of divergence. Here, we used high throughput transcriptome analysis to compare chemosensory genes of the sister leaf beetles species Pyrrhalta maculicollis and P. aenescens, whose sexual isolation and host plant preference are mediated by divergent chemical signals. Although there was low overall divergence between transcriptome profiles, there were a number of genes that were differentially expressed between the species. Furthermore, we also detected two chemosensory genes under positive selection, one of which that was also differentially expressed between the species, suggesting a possible role for these genes in chemical-based premating reproductive isolation and host use. Combined with the available chemical and ecological work in this system, further studies of the divergent chemosensory genes presented here will provide insight into the process of chemosensory speciation among Pyrrhalta beetles.

  8. Structure-function analysis of peroxidasin provides insight into the mechanism of collagen IV crosslinking.

    Science.gov (United States)

    Lázár, Enikő; Péterfi, Zalán; Sirokmány, Gábor; Kovács, Hajnal A; Klement, Eva; Medzihradszky, Katalin F; Geiszt, Miklós

    2015-06-01

    Basement membranes provide structural support and convey regulatory signals to cells in diverse tissues. Assembly of collagen IV into a sheet-like network is a fundamental mechanism during the formation of basement membranes. Peroxidasin (PXDN) was recently described to catalyze crosslinking of collagen IV through the formation of sulfilimine bonds. Despite the significance of this pathway in tissue genesis, our understanding of PXDN function is far from complete. In this work we demonstrate that collagen IV crosslinking is a physiological function of mammalian PXDN. Moreover, we carried out structure-function analysis of PXDN to gain a better insight into its role in collagen IV synthesis. We identify conserved cysteines in PXDN that mediate the oligomerization of the protein into a trimeric complex. We also demonstrate that oligomerization is not an absolute requirement for enzymatic activity, but optimal collagen IV coupling is only catalyzed by the PXDN trimers. Localization experiments of different PXDN mutants in two different cell models revealed that PXDN oligomers, but not monomers, adhere on the cell surface in "hot spots," which represent previously unknown locations of collagen IV crosslinking.

  9. Systematic characterization of the peroxidase gene family provides new insights into fungal pathogenicity in Magnaporthe oryzae.

    Science.gov (United States)

    Mir, Albely Afifa; Park, Sook-Young; Abu Sadat, Md; Kim, Seongbeom; Choi, Jaeyoung; Jeon, Junhyun; Lee, Yong-Hwan

    2015-07-02

    Fungal pathogens have evolved antioxidant defense against reactive oxygen species produced as a part of host innate immunity. Recent studies proposed peroxidases as components of antioxidant defense system. However, the role of fungal peroxidases during interaction with host plants has not been explored at the genomic level. Here, we systematically identified peroxidase genes and analyzed their impact on fungal pathogenesis in a model plant pathogenic fungus, Magnaporthe oryzae. Phylogeny reconstruction placed 27 putative peroxidase genes into 15 clades. Expression profiles showed that majority of them are responsive to in planta condition and in vitro H2O2. Our analysis of individual deletion mutants for seven selected genes including MoPRX1 revealed that these genes contribute to fungal development and/or pathogenesis. We identified significant and positive correlations among sensitivity to H2O2, peroxidase activity and fungal pathogenicity. In-depth analysis of MoPRX1 demonstrated that it is a functional ortholog of thioredoxin peroxidase in Saccharomyces cerevisiae and is required for detoxification of the oxidative burst within host cells. Transcriptional profiling of other peroxidases in ΔMoprx1 suggested interwoven nature of the peroxidase-mediated antioxidant defense system. The results from this study provide insight into the infection strategy built on evolutionarily conserved peroxidases in the rice blast fungus.

  10. Analysis of the FGF gene family provides insights into aquatic adaptation in cetaceans

    Science.gov (United States)

    Nam, Kiwoong; Lee, Kyeong Won; Chung, Oksung; Yim, Hyung-Soon; Cha, Sun-Shin; Lee, Sae-Won; Jun, JeHoon; Cho, Yun Sung; Bhak, Jong; Magalhães, João Pedro de; Lee, Jung-Hyun; Jeong, Jae-Yeon

    2017-01-01

    Cetacean body structure and physiology exhibit dramatic adaptations to their aquatic environment. Fibroblast growth factors (FGFs) are a family of essential factors that regulate animal development and physiology; however, their role in cetacean evolution is not clearly understood. Here, we sequenced the fin whale genome and analysed FGFs from 8 cetaceans. FGF22, a hair follicle-enriched gene, exhibited pseudogenization, indicating that the function of this gene is no longer necessary in cetaceans that have lost most of their body hair. An evolutionary analysis revealed signatures of positive selection for FGF3 and FGF11, genes related to ear and tooth development and hypoxia, respectively. We found a D203G substitution in cetacean FGF9, which was predicted to affect FGF9 homodimerization, suggesting that this gene plays a role in the acquisition of rigid flippers for efficient manoeuvring. Cetaceans utilize low bone density as a buoyancy control mechanism, but the underlying genes are not known. We found that the expression of FGF23, a gene associated with reduced bone density, is greatly increased in the cetacean liver under hypoxic conditions, thus implicating FGF23 in low bone density in cetaceans. Altogether, our results provide novel insights into the roles of FGFs in cetacean adaptation to the aquatic environment. PMID:28074842

  11. The sacred lotus genome provides insights into the evolution of flowering plants.

    Science.gov (United States)

    Wang, Yun; Fan, Guangyi; Liu, Yiman; Sun, Fengming; Shi, Chengcheng; Liu, Xin; Peng, Jing; Chen, Wenbin; Huang, Xinfang; Cheng, Shifeng; Liu, Yuping; Liang, Xinming; Zhu, Honglian; Bian, Chao; Zhong, Lan; Lv, Tian; Dong, Hongxia; Liu, Weiqing; Zhong, Xiao; Chen, Jing; Quan, Zhiwu; Wang, Zhihong; Tan, Benzhong; Lin, Chufa; Mu, Feng; Xu, Xun; Ding, Yi; Guo, An-Yuan; Wang, Jun; Ke, Weidong

    2013-11-01

    Sacred lotus (Nelumbo nucifera) is an ornamental plant that is also used for food and medicine. This basal eudicot species is especially important from an evolutionary perspective, as it occupies a critical phylogenetic position in flowering plants. Here we report the draft genome of a wild strain of sacred lotus. The assembled genome is 792 Mb, which is approximately 85-90% of genome size estimates. We annotated 392 Mb of repeat sequences and 36,385 protein-coding genes within the genome. Using these sequence data, we constructed a phylogenetic tree and confirmed the basal location of sacred lotus within eudicots. Importantly, we found evidence for a relatively recent whole-genome duplication event; any indication of the ancient paleo-hexaploid event was, however, absent. Genomic analysis revealed evidence of positive selection within 28 embryo-defective genes and one annexin gene that may be related to the long-term viability of sacred lotus seed. We also identified a significant expansion of starch synthase genes, which probably elevated starch levels within the rhizome of sacred lotus. Sequencing this strain of sacred lotus thus provided important insights into the evolution of flowering plant and revealed genetic mechanisms that influence seed dormancy and starch synthesis.

  12. Crystal structure of the Epithiospecifier Protein, ESP from Arabidopsis thaliana provides insights into its product specificity.

    Science.gov (United States)

    Zhang, Weiwei; Wang, Wenhe; Liu, Zihe; Xie, Yongchao; Wang, Hao; Mu, Yajuan; Huang, Yao; Feng, Yue

    2016-09-16

    Specifier proteins are important components of the glucosinolate-myrosinase system, which mediate plant defense against herbivory and pathogen attacks. Upon tissue disruption, glucosinolates are hydrolyzed to instable aglucones by myrosinases, and then aglucones will rearrange to form defensive isothiocyanates. Specifier proteins can redirect this reaction to form other products, such as simple nitriles, epithionitriles and organic thiocyanates instead of isothiocyanates based on the side chain structure of glucosinolate and the type of the specifier proteins. Nevertheless, the molecular mechanism underlying the different product spectrums of various specifier proteins was not fully understood. Here in this study, we solved the crystal structure of the Epithiospecifier Protein, ESP from Arabidopsis thaliana (AtESP) at 2.3 Å resolution. Structural comparisons with the previously solved structure of thiocyanate forming protein, TFP from Thlaspi arvense (TaTFP) reveal that AtESP shows a dimerization pattern different from TaTFP. Moreover, AtESP harbors a slightly larger active site pocket than TaTFP and several residues around the active site are different between the two proteins, which might account for the different product spectrums of the two proteins. Together, our structural study provides important insights into the molecular mechanisms of specifier proteins and shed light on the basis of their different product spectrums.

  13. Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution

    Science.gov (United States)

    Rutledge, Gavin G.; Böhme, Ulrike; Sanders, Mandy; Reid, Adam J.; Cotton, James A.; Maiga-Ascofare, Oumou; Djimdé, Abdoulaye A.; Apinjoh, Tobias O.; Amenga-Etego, Lucas; Manske, Magnus; Barnwell, John W.; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck; Anstey, Nicholas M.; Auburn, Sarah; Price, Ric N.; McCarthy, James S.; Kwiatkowski, Dominic P.; Newbold, Chris I.; Berriman, Matthew; Otto, Thomas D.

    2017-01-01

    Elucidation of the evolutionary history and interrelatedness of Plasmodium species that infect humans has been hampered by a lack of genetic information for three human-infective species: P. malariae and two P. ovale species (P. o. curtisi and P. o. wallikeri)1. These species are prevalent across most regions in which malaria is endemic2,3 and are often undetectable by light microscopy4, rendering their study in human populations difficult5. The exact evolutionary relationship of these species to the other human-infective species has been contested6,7. Using a new reference genome for P. malariae and a manually curated draft P. o. curtisi genome, we are now able to accurately place these species within the Plasmodium phylogeny. Sequencing of a P. malariae relative that infects chimpanzees reveals similar signatures of selection in the P. malariae lineage to another Plasmodium lineage shown to be capable of colonization of both human and chimpanzee hosts. Molecular dating suggests that these host adaptations occurred over similar evolutionary timescales. In addition to the core genome that is conserved between species, differences in gene content can be linked to their specific biology. The genome suggests that P. malariae expresses a family of heterodimeric proteins on its surface that have structural similarities to a protein crucial for invasion of red blood cells. The data presented here provide insight into the evolution of the Plasmodium genus as a whole. PMID:28117441

  14. Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans

    Science.gov (United States)

    Wang, Zhengfei; Xu, Shixia; Du, Kexing; Huang, Fang; Chen, Zhuo; Zhou, Kaiya; Ren, Wenhua; Yang, Guang

    2016-01-01

    Although cetaceans (whales, porpoises, and dolphins) have multi-chambered stomachs, feeding habits of modern cetaceans have dramatically changed from herbivorous to carnivorous. However, the genetic basis underlying this dietary switch remains unexplored. Here, we present the first systematic investigation of 10 digestive enzymes genes (i.e., CYP7A1, CTRC, LIPC, LIPF, PNLIP, PGC, PRSS1, SI, SLC5A1, and TMPRSS15) of representative cetaceans, and the evolutionary trajectory of RNASE1 in cetartiodactylans. Positive selections were detected with proteinases (i.e., CTRC, PRSS1, and TMPRSS15) and lipases (i.e., CYP7A1, LIPF, and PNLIP) suggesting that cetaceans have evolved an enhanced digestion capacity for proteins and lipids, the major nutritional components of their prey (fishes and invertebrates). In addition, it was found that RNASE1 gene duplicated after the cetartiodactylan speciation and two independent gene duplication events took place in Camelidae and Ruminantia. Positive selection was detected with RNASE1 of Camelidae and Bovidae, suggesting enhanced digestive efficiency in the ruminants. Remarkably, even though the ancestors of cetaceans were terrestrial artiodactyls that are herbivorous, modern cetaceans lost the pancreatic RNASE1 copy with digestive function, which is in accordance with the dietary change from herbivorous to carnivorous. In sum, this is the first study that provides new insights into the evolutionary mechanism of dietary switch in cetaceans. PMID:27651393

  15. New insight into the Solar System's transition disk phase provided by the unusual meteorite Isheyevo

    CERN Document Server

    Morris, Melissa A; Knauth, L Paul

    2014-01-01

    Many aspects of planet formation are controlled by the amount of gas remaining in the natal protoplanetary disk (PPDs). Infrared observations show that PPDs undergo a transition stage at several Myr, during which gas densities are reduced. Our Solar System would have experienced such a stage. However, there is currently no data that provides insight into this crucial time in our PPD's evolution. We show that the Isheyevo meteorite contains the first definitive evidence for a transition disk stage in our Solar System. Isheyevo belongs to a class of metal-rich meteorites whose components have been dated at almost 5 Myr after the first solids in the Solar System, and exhibits unique sedimentary layers that imply formation through gentle sedimentation. We show that such layering can occur via gentle sweep-up of material found in the impact plume resulting from the collision of two planetesimals. Such sweep-up requires gas densities consistent with observed transition disks. As such, Isheyevo presents the first ev...

  16. Obsessive compulsive disorder networks: positron emission tomography and neuropsychology provide new insights.

    Directory of Open Access Journals (Sweden)

    Bruno Millet

    Full Text Available BACKGROUND: Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC in obsessive compulsive disorder (OCD. We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. METHODS AND FINDINGS: This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level on resting-state (18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices, the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. CONCLUSION: As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes.

  17. The genome of Ganoderma lucidum provides insights into triterpenes biosynthesis and wood degradation [corrected].

    Directory of Open Access Journals (Sweden)

    Dongbo Liu

    Full Text Available BACKGROUND: Ganoderma lucidum (Reishi or Ling Zhi is one of the most famous Traditional Chinese Medicines and has been widely used in the treatment of various human diseases in Asia countries. It is also a fungus with strong wood degradation ability with potential in bioenergy production. However, genes, pathways and mechanisms of these functions are still unknown. METHODOLOGY/PRINCIPAL FINDINGS: The genome of G. lucidum was sequenced and assembled into a 39.9 megabases (Mb draft genome, which encoded 12,080 protein-coding genes and ∼83% of them were similar to public sequences. We performed comprehensive annotation for G. lucidum genes and made comparisons with genes in other fungi genomes. Genes in the biosynthesis of the main G. lucidum active ingredients, ganoderic acids (GAs, were characterized. Among the GAs synthases, we identified a fusion gene, the N and C terminal of which are homologous to two different enzymes. Moreover, the fusion gene was only found in basidiomycetes. As a white rot fungus with wood degradation ability, abundant carbohydrate-active enzymes and ligninolytic enzymes were identified in the G. lucidum genome and were compared with other fungi. CONCLUSIONS/SIGNIFICANCE: The genome sequence and well annotation of G. lucidum will provide new insights in function analyses including its medicinal mechanism. The characterization of genes in the triterpene biosynthesis and wood degradation will facilitate bio-engineering research in the production of its active ingredients and bioenergy.

  18. The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

    Science.gov (United States)

    Tintoré, Mar; Alexander, Maggie; Costello, Kathleen; Duddy, Martin; Jones, David E; Law, Nancy; O’Neill, Gilmore; Uccelli, Antonio; Weissert, Robert; Wray, Sibyl

    2017-01-01

    Background Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Conclusion Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment. PMID:28053511

  19. Patient and physician asthma deterioration terminology: results from the 2009 Asthma Insight and Management survey.

    Science.gov (United States)

    Blaiss, Michael S; Nathan, Robert A; Stoloff, Stuart W; Meltzer, Eli O; Murphy, Kevin R; Doherty, Dennis E

    2012-01-01

    Long-term achievement of asthma control is dependent in part on the use of mutually understandable asthma terminology in all verbal and written patient-physician communications. Using data from the Asthma Insight and Management (AIM) survey, the objective of this analysis is to provide a contemporary depiction of asthma deterioration terminology as used by current asthma patients and physicians in the United States. As part of the 2009 AIM survey, current asthma patients (≥12 years of age; weighted n = 2499) and physicians (n = 309) were queried about their recognition, understanding, and/or use of the terms "asthma attack," "asthma flare-up," and "asthma exacerbation" in telephone interviews. Nearly all patients had heard the term "asthma attack" (97%), but relatively few had heard the term "asthma exacerbation" (24%); 71% had heard "asthma flare-up." In contrast, physicians reported using the term "asthma attack" least (65%) and the term "asthma exacerbation" most (77%) when discussing asthma with their patients; 70% reported using "asthma flare-up." Among patients familiar with "asthma flare-up" and "asthma exacerbation" (n = 502), only 38% said that the terms mean the same thing; nearly all physicians (94%) said that the terms mean the same thing. Collectively, data from the AIM survey suggest that patients and physicians use different asthma deterioration terminology and, more importantly, that they do not necessarily understand each other's terms. Standardizing asthma deterioration terminology may help optimize asthma patient-physician communication to improve patient understanding of written asthma action plans and therefore, enhance patient outcomes.

  20. Comparative Genome Analysis Provides Insights into the Pathogenicity of Flavobacterium psychrophilum

    Science.gov (United States)

    Castillo, Daniel; Christiansen, Rói Hammershaimb; Dalsgaard, Inger; Madsen, Lone; Espejo, Romilio

    2016-01-01

    phenotypic properties may provide new insights to the mechanisms of pathogenicity in F. psychrophilum. PMID:27071075

  1. Proteomic analysis of FUS interacting proteins provides insights into FUS function and its role in ALS.

    Science.gov (United States)

    Kamelgarn, Marisa; Chen, Jing; Kuang, Lisha; Arenas, Alexandra; Zhai, Jianjun; Zhu, Haining; Gal, Jozsef

    2016-10-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Mutations in the Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) gene cause a subset of familial ALS cases and are also implicated in sporadic ALS. FUS is typically localized to the nucleus. The ALS-related FUS mutations cause cytoplasmic mis-localization and the formation of stress granule-like structures. Abnormal cytoplasmic FUS localization was also found in a subset of frontotemporal dementia (FTLD) cases without FUS mutations. To better understand the function of FUS, we performed wild-type and mutant FUS pull-downs followed by proteomic identification of the interacting proteins. The FUS interacting partners we identified are involved in multiple pathways, including chromosomal organization, transcription, RNA splicing, RNA transport, localized translation, and stress response. FUS interacted with hnRNPA1 and Matrin-3, RNA binding proteins whose mutations were also reported to cause familial ALS, suggesting that hnRNPA1 and Matrin-3 may play common pathogenic roles with FUS. The FUS interactions displayed varied RNA dependence. Numerous FUS interacting partners that we identified are components of exosomes. We found that FUS itself was present in exosomes, suggesting that the secretion of FUS might contribute to the cell-to-cell spreading of FUS pathology. FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. Our results provide insights into the physiological functions of FUS as well as important pathways where mutant FUS can interfere with cellular processes and potentially contribute to the pathogenesis of ALS.

  2. Insights into the mechanisms of absence seizure generation provided by EEG with Functional MRI.

    Directory of Open Access Journals (Sweden)

    Patrick William Carney

    2014-09-01

    Full Text Available Absence seizures are brief epileptic events characterized by loss of awareness with subtle motor features. They may be very frequent, and impact on attention, learning and memory. A number of pathophysiological models have been developed to explain the mechanism of absence seizure generation which rely heavily on observations from animal studies. Studying the structural and functional relationships between large-scale brain networks in humans is only practical with non-invasive whole brain techniques. EEG with functional MRI (EEG-fMRI is one such technique that provides an opportunity to explore the interactions between brain structures involved in AS generation. A number of fMRI techniques including event-related analysis, time course analysis and functional connectivity have identified a common network of structures involved in AS seizures. This network comprises the thalamus, midline and lateral parietal cortex (the default mode network [DMN], caudate nuclei and the reticular structures of the pons. The main component displaying an increase in BOLD signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN. Time course analysis shows that, rather than some structures being activated or inactivated during AS, there appears to be increase in activity across components of the network preceding or following the electro-clinical onset of the seizure. The earliest change in BOLD signal occurs in the DMN, prior to the onset of epileptiform events. This region also shows altered functional connectivity in patients with absence seizures. Hence it appears that engagement of this network is central to absence seizures. In this review we will explore the insights EEG-fMRI studies into the mechanisms of AS and considers how the DMN is likely to be the major large scale brain network central to both seizure generation and the seizure manifestations.

  3. 3D-structured illumination microscopy provides novel insight into architecture of human centrosomes

    Directory of Open Access Journals (Sweden)

    Katharina F. Sonnen

    2012-08-01

    Centrioles are essential for the formation of cilia and flagella. They also form the core of the centrosome, which organizes microtubule arrays important for cell shape, polarity, motility and division. Here, we have used super-resolution 3D-structured illumination microscopy to analyse the spatial relationship of 18 centriole and pericentriolar matrix (PCM components of human centrosomes at different cell cycle stages. During mitosis, PCM proteins formed extended networks with interspersed γ-Tubulin. During interphase, most proteins were arranged at specific distances from the walls of centrioles, resulting in ring staining, often with discernible density masses. Through use of site-specific antibodies, we found the C-terminus of Cep152 to be closer to centrioles than the N-terminus, illustrating the power of 3D-SIM to study protein disposition. Appendage proteins showed rings with multiple density masses, and the number of these masses was strongly reduced during mitosis. At the proximal end of centrioles, Sas-6 formed a dot at the site of daughter centriole assembly, consistent with its role in cartwheel formation. Plk4 and STIL co-localized with Sas-6, but Cep135 was associated mostly with mother centrioles. Remarkably, Plk4 formed a dot on the surface of the mother centriole before Sas-6 staining became detectable, indicating that Plk4 constitutes an early marker for the site of nascent centriole formation. Our study provides novel insights into the architecture of human centrosomes and illustrates the power of super-resolution microscopy in revealing the relative localization of centriole and PCM proteins in unprecedented detail.

  4. Genome-wide analysis of Pax8 binding provides new insights into thyroid functions

    Directory of Open Access Journals (Sweden)

    Ruiz-Llorente Sergio

    2012-04-01

    Full Text Available Abstract Background The transcription factor Pax8 is essential for the differentiation of thyroid cells. However, there are few data on genes transcriptionally regulated by Pax8 other than thyroid-related genes. To better understand the role of Pax8 in the biology of thyroid cells, we obtained transcriptional profiles of Pax8-silenced PCCl3 thyroid cells using whole genome expression arrays and integrated these signals with global cis-regulatory sequencing studies performed by ChIP-Seq analysis Results Exhaustive analysis of Pax8 immunoprecipitated peaks demonstrated preferential binding to intragenic regions and CpG-enriched islands, which suggests a role of Pax8 in transcriptional regulation of orphan CpG regions. In addition, ChIP-Seq allowed us to identify Pax8 partners, including proteins involved in tertiary DNA structure (CTCF and chromatin remodeling (Sp1, and these direct transcriptional interactions were confirmed in vivo. Moreover, both factors modulate Pax8-dependent transcriptional activation of the sodium iodide symporter (Nis gene promoter. We ultimately combined putative and novel Pax8 binding sites with actual target gene expression regulation to define Pax8-dependent genes. Functional classification suggests that Pax8-regulated genes may be directly involved in important processes of thyroid cell function such as cell proliferation and differentiation, apoptosis, cell polarity, motion and adhesion, and a plethora of DNA/protein-related processes. Conclusion Our study provides novel insights into the role of Pax8 in thyroid biology, exerted through transcriptional regulation of important genes involved in critical thyrocyte processes. In addition, we found new transcriptional partners of Pax8, which functionally cooperate with Pax8 in the regulation of thyroid gene transcription. Besides, our data demonstrate preferential location of Pax8 in non-promoter CpG regions. These data point to an orphan CpG island-mediated mechanism

  5. Multiple kisspeptin receptors in early osteichthyans provide new insights into the evolution of this receptor family.

    Directory of Open Access Journals (Sweden)

    Jérémy Pasquier

    Full Text Available Deorphanization of GPR54 receptor a decade ago led to the characterization of the kisspeptin receptor (Kissr in mammals and the discovery of its major role in the brain control of reproduction. While a single gene encodes for Kissr in eutherian mammals including human, other vertebrates present a variable number of Kissr genes, from none in birds, one or two in teleosts, to three in an amphibian, xenopus. In order to get more insight into the evolution of Kissr gene family, we investigated the presence of Kissr in osteichthyans of key-phylogenetical positions: the coelacanth, a representative of early sarcopterygians, the spotted gar, a non-teleost actinopterygian, and the European eel, a member of an early group of teleosts (elopomorphs. We report the occurrence of three Kissr for the first time in a teleost, the eel. As measured by quantitative RT-PCR, the three eel Kissr were differentially expressed in the brain-pituitary-gonadal axis, and differentially regulated in experimentally matured eels, as compared to prepubertal controls. Subfunctionalisation, as shown by these differences in tissue distribution and regulation, may have represented significant evolutionary constraints for the conservation of multiple Kissr paralogs in this species. Furthermore, we identified four Kissr in both coelacanth and spotted gar genomes, providing the first evidence for the presence of four Kissr in vertebrates. Phylogenetic and syntenic analyses supported the existence of four Kissr paralogs in osteichthyans and allowed to propose a clarified nomenclature of Kissr (Kissr-1 to -4 based on these paralogs. Syntenic analysis suggested that the four Kissr paralogs arose through the two rounds of whole genome duplication (1R and 2R in early vertebrates, followed by multiple gene loss events in the actinopterygian and sarcopterygian lineages. Due to gene loss there was no impact of the teleost-specific whole genome duplication (3R on the number of Kissr paralogs

  6. Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

    Directory of Open Access Journals (Sweden)

    Naoto Tanaka

    Full Text Available Cyclic nucleotide-gated (CNG ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM. ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients.

  7. Perigone Lobe Transcriptome Analysis Provides Insights into Rafflesia cantleyi Flower Development

    Science.gov (United States)

    Lee, Xin-Wei; Mat-Isa, Mohd-Noor; Mohd-Elias, Nur-Atiqah; Aizat-Juhari, Mohd Afiq; Goh, Hoe-Han; Dear, Paul H.; Chow, Keng-See; Haji Adam, Jumaat; Mohamed, Rahmah; Firdaus-Raih, Mohd; Wan, Kiew-Lian

    2016-01-01

    Rafflesia is a biologically enigmatic species that is very rare in occurrence and possesses an extraordinary morphology. This parasitic plant produces a gigantic flower up to one metre in diameter with no leaves, stem or roots. However, little is known about the floral biology of this species especially at the molecular level. In an effort to address this issue, we have generated and characterised the transcriptome of the Rafflesia cantleyi flower, and performed a comparison with the transcriptome of its floral bud to predict genes that are expressed and regulated during flower development. Approximately 40 million sequencing reads were generated and assembled de novo into 18,053 transcripts with an average length of 641 bp. Of these, more than 79% of the transcripts had significant matches to annotated sequences in the public protein database. A total of 11,756 and 7,891 transcripts were assigned to Gene Ontology categories and clusters of orthologous groups respectively. In addition, 6,019 transcripts could be mapped to 129 pathways in Kyoto Encyclopaedia of Genes and Genomes Pathway database. Digital abundance analysis identified 52 transcripts with very high expression in the flower transcriptome of R. cantleyi. Subsequently, analysis of differential expression between developing flower and the floral bud revealed a set of 105 transcripts with potential role in flower development. Our work presents a deep transcriptome resource analysis for the developing flower of R. cantleyi. Genes potentially involved in the growth and development of the R. cantleyi flower were identified and provide insights into biological processes that occur during flower development. PMID:27977777

  8. Macroscale patterns in body size of intertidal crustaceans provide insights on climate change effects.

    Science.gov (United States)

    Jaramillo, Eduardo; Dugan, Jenifer E; Hubbard, David M; Contreras, Heraldo; Duarte, Cristian; Acuña, Emilio; Schoeman, David S

    2017-01-01

    Predicting responses of coastal ecosystems to altered sea surface temperatures (SST) associated with global climate change, requires knowledge of demographic responses of individual species. Body size is an excellent metric because it scales strongly with growth and fecundity for many ectotherms. These attributes can underpin demographic as well as community and ecosystem level processes, providing valuable insights for responses of vulnerable coastal ecosystems to changing climate. We investigated contemporary macroscale patterns in body size among widely distributed crustaceans that comprise the majority of intertidal abundance and biomass of sandy beach ecosystems of the eastern Pacific coasts of Chile and California, USA. We focused on ecologically important species representing different tidal zones, trophic guilds and developmental modes, including a high-shore macroalga-consuming talitrid amphipod (Orchestoidea tuberculata), two mid-shore scavenging cirolanid isopods (Excirolana braziliensis and E. hirsuticauda), and a low-shore suspension-feeding hippid crab (Emerita analoga) with an amphitropical distribution. Significant latitudinal patterns in body sizes were observed for all species in Chile (21° - 42°S), with similar but steeper patterns in Emerita analoga, in California (32°- 41°N). Sea surface temperature was a strong predictor of body size (-4% to -35% °C-1) in all species. Beach characteristics were subsidiary predictors of body size. Alterations in ocean temperatures of even a few degrees associated with global climate change are likely to affect body sizes of important intertidal ectotherms, with consequences for population demography, life history, community structure, trophic interactions, food-webs, and indirect effects such as ecosystem function. The consistency of results for body size and temperature across species with different life histories, feeding modes, ecological roles, and microhabitats inhabiting a single widespread coastal

  9. Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

    Science.gov (United States)

    Tanaka, Naoto; Dutrow, Emily V; Miyadera, Keiko; Delemotte, Lucie; MacDermaid, Christopher M; Reinstein, Shelby L; Crumley, William R; Dixon, Christopher J; Casal, Margret L; Klein, Michael L; Aguirre, Gustavo D; Tanaka, Jacqueline C; Guziewicz, Karina E

    2015-01-01

    Cyclic nucleotide-gated (CNG) ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM). ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD) simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ) domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients.

  10. Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities.

    Science.gov (United States)

    Traven, Ana; Jänicke, Amrei; Harrison, Paul; Swaminathan, Angavai; Seemann, Torsten; Beilharz, Traude H

    2012-01-01

    Understanding multicellular fungal structures is important for designing better strategies against human fungal pathogens. For example, the ability to form multicellular biofilms is a key virulence property of the yeast Candida albicans. C. albicans biofilms form on indwelling medical devices and are drug resistant, causing serious infections in hospital settings. Multicellular fungal communities are heterogeneous, consisting of cells experiencing different environments. Heterogeneity is likely important for the phenotypic characteristics of communities, yet it is poorly understood. Here we used colonies of the yeast Saccharomyces cerevisiae as a model fungal multicellular structure. We fractionated the outside colony layers from the cells in the center by FACS, using a Cit1-GFP marker expressed exclusively on the outside. Transcriptomics analysis of the two subpopulations revealed that the outside colony layers are actively growing by fermentative metabolism, while the cells residing on the inside are in a resting state and experience changes to mitochondrial activity. Our data shows several parallels with C. albicans biofilms providing insight into the contributions of heterogeneity to biofilm phenotypes. Hallmarks of C. albicans biofilms - the expression of ribosome and translation functions and activation of glycolysis and ergosterol biosynthesis occur on the outside of colonies, while expression of genes associates with sulfur assimilation is observed in the colony center. Cell wall restructuring occurs in biofilms, and cell wall functions are enriched in both fractions: the outside cells display enrichment of cell wall biosynthesis enzymes and cell wall proteins, while the inside cells express cell wall degrading enzymes. Our study also suggests that noncoding transcription and posttranscriptional mRNA regulation play important roles during growth of yeast in colonies, setting the scene for investigating these pathways in the development of multicellular

  11. Transcriptional profiling of a yeast colony provides new insight into the heterogeneity of multicellular fungal communities.

    Directory of Open Access Journals (Sweden)

    Ana Traven

    Full Text Available Understanding multicellular fungal structures is important for designing better strategies against human fungal pathogens. For example, the ability to form multicellular biofilms is a key virulence property of the yeast Candida albicans. C. albicans biofilms form on indwelling medical devices and are drug resistant, causing serious infections in hospital settings. Multicellular fungal communities are heterogeneous, consisting of cells experiencing different environments. Heterogeneity is likely important for the phenotypic characteristics of communities, yet it is poorly understood. Here we used colonies of the yeast Saccharomyces cerevisiae as a model fungal multicellular structure. We fractionated the outside colony layers from the cells in the center by FACS, using a Cit1-GFP marker expressed exclusively on the outside. Transcriptomics analysis of the two subpopulations revealed that the outside colony layers are actively growing by fermentative metabolism, while the cells residing on the inside are in a resting state and experience changes to mitochondrial activity. Our data shows several parallels with C. albicans biofilms providing insight into the contributions of heterogeneity to biofilm phenotypes. Hallmarks of C. albicans biofilms - the expression of ribosome and translation functions and activation of glycolysis and ergosterol biosynthesis occur on the outside of colonies, while expression of genes associates with sulfur assimilation is observed in the colony center. Cell wall restructuring occurs in biofilms, and cell wall functions are enriched in both fractions: the outside cells display enrichment of cell wall biosynthesis enzymes and cell wall proteins, while the inside cells express cell wall degrading enzymes. Our study also suggests that noncoding transcription and posttranscriptional mRNA regulation play important roles during growth of yeast in colonies, setting the scene for investigating these pathways in the development

  12. Gene expression profiling provides insights into pathways of oxaliplatin-related sinusoidal obstruction syndrome in humans.

    Science.gov (United States)

    Rubbia-Brandt, Laura; Tauzin, Sébastien; Brezault, Catherine; Delucinge-Vivier, Céline; Descombes, Patrick; Dousset, Bertand; Majno, Pietro E; Mentha, Gilles; Terris, Benoit

    2011-04-01

    Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS.

  13. Comparative proteomic analysis provides new insights into cadmium accumulation in rice grain under cadmium stress

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Dawei, E-mail: dwxue@hznu.edu.cn [College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006 (China); Jiang, Hua [State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Zhejiang Academy of Agricultural Science, Hangzhou 310021 (China); Deng, Xiangxiong; Zhang, Xiaoqin [College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Wang, Hua [State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Zhejiang Academy of Agricultural Science, Hangzhou 310021 (China); Xu, Xiangbin [College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Hu, Jiang; Zeng, Dali [State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006 (China); Guo, Longbiao, E-mail: guolongbiao@caas.cn [State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006 (China); Qian, Qian, E-mail: qianqian188@hotmail.com [College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); State Key Laboratory of Rice Biology, China National Rice Research Institute, Hangzhou 310006 (China)

    2014-09-15

    Graphical abstract: - Highlights: • Cd is the most toxic heavy metal and is a major pollutant in rice grains. • The mechanism of Cd accumulation in rice grains has not been well demonstrated. • Proteomics analysis is carried out and the verification is implemented by QPCR. • Proteins associated with ROS and photosynthesis showed large variation in expression. - Abstract: Rice is one of the most important staple crops. During the growth season, rice plants are inevitably subjected to numerous stresses, among which heavy metal stress represented by cadmium contamination not only hindering the yield of rice but also affecting the food safety by Cd accumulating in rice grains. The mechanism of Cd accumulation in rice grains has not been well elucidated. In this study, we compare the proteomic difference between two genotypes with different Cd accumulation ability in grains. Verification of differentially expressed protein-encoding genes was analyzing by quantitative PCR (QPCR) and reanalysis of microarray expression data. Forty-seven proteins in total were successfully identified through proteomic screening. GO and KEGG enrichment analysis showed Cd accumulation triggered stress-related pathways in the cells, and strongly affecting metabolic pathways. Many proteins associated with nutrient reservoir and starch-related enzyme were identified in this study suggesting that a considerably damage on grain quality was caused. The results also implied stress response was initiated by the abnormal cells and the transmission of signals may mediated by reactive oxygen species (ROS). Our research will provide new insights into Cd accumulation in rice grain under Cd stress.

  14. Quantitative proteomic analysis provides novel insights into cold stress responses in petunia seedlings

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    Wei eZhang

    2016-02-01

    Full Text Available Low temperature is a major adverse environmental factor that impairs petunia growth and development. To better understand the molecular mechanisms of cold stress adaptation of petunia plants, a quantitative proteomic analysis using iTRAQ technology was performed to detect the effects of cold stress on protein expression profiles in petunia seedlings which had been subjected to 2°C for 5d. Of the 2,430 proteins whose levels were quantitated, a total of 117 proteins were discovered to be differentially expressed under low temperature stress in comparison to unstressed controls. As an initial study, 44 proteins including well known and novel cold-responsive proteins were successfully annotated. By integrating the results of two independent Gene Ontology (GO enrichment analyses, seven common GO terms were found of which oxidation-reduction process was the most notable for the cold-responsive proteins. By using the subcellular localization tool Plant-mPLoc predictor, as much as 40.2% of the cold-responsive protein group was found to be located within chloroplasts, suggesting that the chloroplast proteome is particularly affected by cold stress. Gene expression analyses of 11 cold-responsive proteins by real time PCR demonstrated that the mRNA levels were not strongly correlated with the respective protein levels. Further activity assay of anti-oxidative enzymes showed different alterations in cold treated petunia seedlings. Our investigation has highlighted the role of antioxidation mechanisms and also epigenetic factors in the regulation of cold stress responses. Our work has provided novel insights into the plant response to cold stress and should facilitate further studies regarding the molecular mechanisms which determine how plant cells cope with environmental perturbation.

  15. Characterization of the arginolytic microflora provides insights into pH homeostasis in human oral biofilms.

    Science.gov (United States)

    Huang, Xuelian; Schulte, Renee M; Burne, Robert A; Nascimento, Marcelle M

    2015-01-01

    A selected group of oral bacteria commonly associated with dental health is capable of producing alkali via the arginine deiminase system (ADS), which has a profound impact on the pH of human oral biofilms. An increased risk for dental caries has been associated with reduced ADS activity of the bacteria in oral biofilms. Arginolytic bacterial strains from dental plaque samples of caries-free and caries-active adults were isolated and characterized to investigate the basis for differences in plaque ADS activity between individuals. Fifty-six ADS-positive bacterial strains were identified by 16S rRNA gene sequencing, and their ADS activity levels were compared under standard growth conditions. The spectrum of bacterial ADS activity ranged from 45.2 to 688.0 units (mg protein)(-1). Although Streptococcus sanguinis was the most prevalent species, other Streptococcus sp. were also represented. Biochemical assays carried out using 27 ADS-positive strains under conditions known to induce or repress ADS gene expression showed substantial variation in arginolytic activity in response to pH, oxygen and the availability of carbohydrate or arginine. This study reveals that the basis for the wide spectrum of arginolytic expression observed among clinical strains is, at least in part, attributable to differences in the regulation of the ADS within and between species. The results provide insights into the microbiological basis for intersubject differences in ADS activity in oral biofilms and enhance our understanding of dental caries as an ecologically driven disease in which arginine metabolism moderates plaque pH and promotes dental health.

  16. Potential Biomarkers Found by Protein Profiling May Provide Insight for the Macrovascular Pathogenesis of Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    William C. S. Cho

    2006-01-01

    Full Text Available Diabetes mellitus (DM is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100% classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications.

  17. Mitochondrial Genome and Nuclear Markers Provide New Insight into the Evolutionary History of Macaques.

    Science.gov (United States)

    Jiang, Juan; Yu, Jianqiu; Li, Jing; Li, Peng; Fan, Zhenxin; Niu, Lili; Deng, Jiabo; Yue, Bisong; Li, Jing

    2016-01-01

    The evolutionary history of macaques, genus Macaca, has been under debate due to the short times of divergence. In this study, maternal, paternal, and biparental genetic systems were applied to infer phylogenetic relationships among macaques and to trace ancient hybridization events in their evolutionary history. Using a PCR display method, 17 newly phylogenetically informative Alu insertions were identified from M. assamensis. We combined presence/absence analysis of 84 Alu elements with mitochondrial genomes as well as nuclear sequences (five autosomal genes, two Y chromosomal genes, and one X chromosomal fragment) to reconstruct a robust macaque phylogeny. Topologies generated from different inherited markers were similar supporting six well defined species groups and a close relationship of M. assamensis and M. thibetana, but differed in the placing of M. arctoides. Both Alu elements and nuclear genes supported that M. arctoides was close to the sinica group, whereas the mitochondrial data clustered it into the fascicularis/mulatta lineage. Our results reveal that a sex-biased hybridization most likely occurred in the evolutionary history of M. arctoides, and suggest an introgressive pattern of male-mediated gene flow from the ancestors of M. arctoides to the M. mulatta population followed by nuclear swamping. According to the estimation of divergence dates, the hybridization occurred around 0.88~1.77 mya (nuclear data) or 1.38~2.56 mya (mitochondrial data). In general, our study indicates that a combination of various molecular markers could help explain complicated evolutionary relationships. Our results have provided new insights into the evolutionary history of macaques and emphasize that hybridization might play an important role in macaque evolution.

  18. Biomimetics on seed dispersal: survey and insights for space exploration.

    Science.gov (United States)

    Pandolfi, Camilla; Izzo, Dario

    2013-06-01

    Seeds provide the vital genetic link and dispersal agent between successive generations of plants. Without seed dispersal as a means of reproduction, many plants would quickly die out. Because plants lack any sort of mobility and remain in the same spot for their entire lives, they rely on seed dispersal to transport their offspring throughout the environment. This can be accomplished either collectively or individually; in any case as seeds ultimately abdicate their movement, they are at the mercy of environmental factors. Thus, seed dispersal strategies are characterized by robustness, adaptability, intelligence (both behavioral and morphological), and mass and energy efficiency (including the ability to utilize environmental sources of energy available): all qualities that advanced engineering systems aim at in general, and in particular those that need to enable complex endeavors such as space exploration. Plants evolved and adapted their strategy according to their environment, and taken together, they enclose many desirable characteristics that a space mission needs to have. Understanding in detail how plants control the development of seeds, fabricate structural components for their dispersal, build molecular machineries to keep seeds dormant up to the right moment and monitor the environment to release them at the right time could provide several solutions impacting current space mission design practices. It can lead to miniaturization, higher integration and packing efficiency, energy efficiency and higher autonomy and robustness. Consequently, there would appear to be good reasons for considering biomimetic solutions from plant kingdom when designing space missions, especially to other celestial bodies, where solid and liquid surfaces, atmosphere, etc constitute and are obviously parallel with the terrestrial environment where plants evolved. In this paper, we review the current state of biomimetics on seed dispersal to improve space mission design.

  19. Characterisation of full-length cDNA sequences provides insights into the Eimeria tenellatranscriptome

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    Amiruddin Nadzirah

    2012-01-01

    . tenella second generation merozoites and provides new insights into the E. tenella transcriptome. The data generated will be useful for the development and validation of diagnostic and control strategies for coccidiosis and will be of value in annotation of the E. tenella genome sequence.

  20. The perspective of rural physicians providing abortion in Canada: qualitative findings of the BC Abortion Providers Survey (BCAPS.

    Directory of Open Access Journals (Sweden)

    Jennifer Dressler

    Full Text Available BACKGROUND: An increasing proportion of Canadian induced abortions are performed in large urban areas. For unknown reasons the number of rural abortion providers in Canadian provinces, such as British Columbia (BC, has declined substantially. This study explored the experiences of BC rural and urban physicians providing abortion services. METHODS: The mixed methods BC Abortion Providers Survey employed self-administered questionnaires, distributed to all known current and some past BC abortion providers in 2011. The optional semi-structured interviews are the focus of this analysis. Interview questions probed the experiences, facilitators and challenges faced by abortion providers, and their future intentions. Interviews were transcribed and analyzed using cross-case and thematic analysis. RESULTS: Twenty interviews were completed and transcribed, representing 13/27 (48.1% rural abortion providers, and 7/19 (36.8% of urban providers in BC. Emerging themes differed between urban and rural providers. Most urban providers worked within clinics and reported a supportive environment. Rural physicians, all providing surgical abortions within hospitals, reported challenging barriers to provision including operating room scheduling, anesthetist and nursing logistical issues, high demand for services, professional isolation, and scarcity of replacement abortion providers. Many rural providers identified a need to "fly under the radar" in their small community. DISCUSSION: This first study of experiences among rural and urban abortion providers in Canada identifies addressable challenges faced by rural physicians. Rural providers expressed a need for increased support from hospital administration and policy. Further challenges identified include a desire for continuing professional education opportunities, and for available replacement providers.

  1. Multiple Problem-Solving Strategies Provide Insight into Students' Understanding of Open-Ended Linear Programming Problems

    Science.gov (United States)

    Sole, Marla A.

    2016-01-01

    Open-ended questions that can be solved using different strategies help students learn and integrate content, and provide teachers with greater insights into students' unique capabilities and levels of understanding. This article provides a problem that was modified to allow for multiple approaches. Students tended to employ high-powered, complex,…

  2. Quantitative Hydraulic Models Of Early Land Plants Provide Insight Into Middle Paleozoic Terrestrial Paleoenvironmental Conditions

    Science.gov (United States)

    Wilson, J. P.; Fischer, W. W.

    2010-12-01

    Fossil plants provide useful proxies of Earth’s climate because plants are closely connected, through physiology and morphology, to the environments in which they lived. Recent advances in quantitative hydraulic models of plant water transport provide new insight into the history of climate by allowing fossils to speak directly to environmental conditions based on preserved internal anatomy. We report results of a quantitative hydraulic model applied to one of the earliest terrestrial plants preserved in three dimensions, the ~396 million-year-old vascular plant Asteroxylon mackei. This model combines equations describing the rate of fluid flow through plant tissues with detailed observations of plant anatomy; this allows quantitative estimates of two critical aspects of plant function. First and foremost, results from these models quantify the supply of water to evaporative surfaces; second, results describe the ability of plant vascular systems to resist tensile damage from extreme environmental events, such as drought or frost. This approach permits quantitative comparisons of functional aspects of Asteroxylon with other extinct and extant plants, informs the quality of plant-based environmental proxies, and provides concrete data that can be input into climate models. Results indicate that despite their small size, water transport cells in Asteroxylon could supply a large volume of water to the plant's leaves--even greater than cells from some later-evolved seed plants. The smallest Asteroxylon tracheids have conductivities exceeding 0.015 m^2 / MPa * s, whereas Paleozoic conifer tracheids do not reach this threshold until they are three times wider. However, this increase in conductivity came at the cost of little to no adaptations for transport safety, placing the plant’s vegetative organs in jeopardy during drought events. Analysis of the thickness-to-span ratio of Asteroxylon’s tracheids suggests that environmental conditions of reduced relative

  3. Global transcriptional response to mammalian temperature provides new insight into Francisella tularensis pathogenesis

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    Shanks Robert MQ

    2008-10-01

    Full Text Available Abstract Background After infecting a mammalian host, the facultative intracellular bacterium, Francisella tularensis, encounters an elevated environmental temperature. We hypothesized that this temperature change may regulate genes essential for infection. Results Microarray analysis of F. tularensis LVS shifted from 26°C (environmental to 37°C (mammalian showed ~11% of this bacterium's genes were differentially-regulated. Importantly, 40% of the protein-coding genes that were induced at 37°C have been previously implicated in virulence or intracellular growth of Francisella in other studies, associating the bacterial response to this temperature shift with pathogenesis. Forty-four percent of the genes induced at 37°C encode proteins of unknown function, suggesting novel Francisella virulence traits are regulated by mammalian temperature. To explore this possibility, we generated two mutants of loci induced at 37°C [FTL_1581 and FTL_1664 (deoB]. The FTL_1581 mutant was attenuated in a chicken embryo infection model, which was likely attributable to a defect in survival within macrophages. FTL_1581 encodes a novel hypothetical protein that we suggest naming temperature-induced, virulence-associated locus A, tivA. Interestingly, the deoB mutant showed diminished entry into mammalian cells compared to wild-type LVS, including primary human macrophages and dendritic cells, the macrophage-like RAW 264.7 line, and non-phagocytic HEK-293 cells. This is the first study identifying a Francisella gene that contributes to uptake into both phagocytic and non-phagocytic host cells. Conclusion Our results provide new insight into mechanisms of Francisella virulence regulation and pathogenesis. F. tularensis LVS undergoes considerable gene expression changes in response to mammalian body temperature. This temperature shift is important for the regulation of genes that are critical for the pathogenesis of Francisella. Importantly, the compilation of

  4. Quantitative proteomics and bioinformatic analysis provide new insight into protein function during avian eggshell biomineralization.

    Science.gov (United States)

    Marie, Pauline; Labas, Valérie; Brionne, Aurélien; Harichaux, Grégoire; Hennequet-Antier, Christelle; Nys, Yves; Gautron, Joël

    2015-01-15

    are associated with distinct populations of matrix proteins that are secreted into the acellular uterine fluid as modulators of the process. The recent development of high-throughput methods has led to the identification of many proteins in the shell, but little is known concerning their role in shell formation. In order to determine precisely the importance of particular proteins relative to eggshell mineralization, this project used qualitative and quantitative proteomics of the uterine fluid constituents, coupled with bioinformatic analysis, to predict the functional role of proteins secreted at each of the three main stages of shell calcification. Besides its relevance to food production and to hen reproduction, eggshell calcification is furthermore a relevant model for studying calcium carbonate biomineralization on a two-dimensional membrane support. Better understanding of this process will provide insight into the fabrication of ceramics at ambient pressure and temperature. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. An integrated Biophysical CGE model to provide Sustainable Development Goal insights

    Science.gov (United States)

    Sanchez, Marko; Cicowiez, Martin; Howells, Mark; Zepeda, Eduardo

    2016-04-01

    Future projected changes in the energy system will inevitably result in changes to the level of appropriation of environmental resources, particularly land and water, and this will have wider implications for environmental sustainability, and may affect other sectors of the economy. An integrated climate, land, energy and water (CLEW) system will provide useful insights, particularly with regard to the environmental sustainability. However, it will require adequate integration with other tools to detect economic impacts and broaden the scope for policy analysis. A computable general equilibrium (CGE) model is a well suited tool to channel impacts, as detected in a CLEW analysis, onto all sectors of the economy, and evaluate trade-offs and synergies, including those of possible policy responses. This paper will show an application of such integration in a single-country CGE model with the following key characteristics. Climate is partly exogenous (as proxied by temperature and rainfall) and partly endogenous (as proxied by emissions generated by different sectors) and has an impact on endogenous variables such as land productivity and labor productivity. Land is a factor of production used in agricultural and forestry activities which can be of various types if land use alternatives (e.g., deforestation) are to be considered. Energy is an input to the production process of all economic sectors and a consumption good for households. Because it is possible to allow for substitution among different energy sources (e.g. renewable vs non-renewable) in the generation of electricity, the production process of energy products can consider the use of natural resources such as oil and water. Water, data permitting, can be considered as an input into the production process of agricultural sectors, which is particularly relevant in case of irrigation. It can also be considered as a determinant of total factor productivity in hydro-power generation. The integration of a CLEW

  6. Factors influencing healthcare provider respondent fatigue answering a globally administered in-app survey.

    Science.gov (United States)

    O'Reilly-Shah, Vikas N

    2017-01-01

    Respondent fatigue, also known as survey fatigue, is a common problem in the collection of survey data. Factors that are known to influence respondent fatigue include survey length, survey topic, question complexity, and open-ended question type. There is a great deal of interest in understanding the drivers of physician survey responsiveness due to the value of information received from these practitioners. With the recent explosion of mobile smartphone technology, it has been possible to obtain survey data from users of mobile applications (apps) on a question-by-question basis. The author obtained basic demographic survey data as well as survey data related to an anesthesiology-specific drug called sugammadex and leveraged nonresponse rates to examine factors that influenced respondent fatigue. Primary data were collected between December 2015 and February 2017. Surveys and in-app analytics were collected from global users of a mobile anesthesia calculator app. Key independent variables were user country, healthcare provider role, rating of importance of the app to personal practice, length of time in practice, and frequency of app use. Key dependent variable was the metric of respondent fatigue. Provider role and World Bank country income level were predictive of the rate of respondent fatigue for this in-app survey. Importance of the app to the provider and length of time in practice were moderately associated with fatigue. Frequency of app use was not associated. This study focused on a survey with a topic closely related to the subject area of the app. Respondent fatigue rates will likely change dramatically if the topic does not align closely. Although apps may serve as powerful platforms for data collection, responses rates to in-app surveys may differ on the basis of important respondent characteristics. Studies should be carefully designed to mitigate fatigue as well as powered with the understanding of the respondent characteristics that may have higher

  7. Factors influencing healthcare provider respondent fatigue answering a globally administered in-app survey

    Directory of Open Access Journals (Sweden)

    Vikas N. O’Reilly-Shah

    2017-09-01

    Full Text Available Background Respondent fatigue, also known as survey fatigue, is a common problem in the collection of survey data. Factors that are known to influence respondent fatigue include survey length, survey topic, question complexity, and open-ended question type. There is a great deal of interest in understanding the drivers of physician survey responsiveness due to the value of information received from these practitioners. With the recent explosion of mobile smartphone technology, it has been possible to obtain survey data from users of mobile applications (apps on a question-by-question basis. The author obtained basic demographic survey data as well as survey data related to an anesthesiology-specific drug called sugammadex and leveraged nonresponse rates to examine factors that influenced respondent fatigue. Methods Primary data were collected between December 2015 and February 2017. Surveys and in-app analytics were collected from global users of a mobile anesthesia calculator app. Key independent variables were user country, healthcare provider role, rating of importance of the app to personal practice, length of time in practice, and frequency of app use. Key dependent variable was the metric of respondent fatigue. Results Provider role and World Bank country income level were predictive of the rate of respondent fatigue for this in-app survey. Importance of the app to the provider and length of time in practice were moderately associated with fatigue. Frequency of app use was not associated. This study focused on a survey with a topic closely related to the subject area of the app. Respondent fatigue rates will likely change dramatically if the topic does not align closely. Discussion Although apps may serve as powerful platforms for data collection, responses rates to in-app surveys may differ on the basis of important respondent characteristics. Studies should be carefully designed to mitigate fatigue as well as powered with the

  8. Quantitative measures of walking and strength provide insight into brain corticospinal tract pathology in multiple sclerosis.

    Science.gov (United States)

    Fritz, Nora E; Keller, Jennifer; Calabresi, Peter A; Zackowski, Kathleen M

    2017-01-01

    At least 85% of individuals with multiple sclerosis report walking dysfunction as their primary complaint. Walking and strength measures are common clinical measures to mark increasing disability or improvement with rehabilitation. Previous studies have shown an association between strength or walking ability and spinal cord MRI measures, and strength measures with brainstem corticospinal tract magnetization transfer ratio. However, the relationship between walking performance and brain corticospinal tract magnetization transfer imaging measures and the contribution of clinical measurements of walking and strength to the underlying integrity of the corticospinal tract has not been explored in multiple sclerosis. The objectives of this study were explore the relationship of quantitative measures of walking and strength to whole-brain corticospinal tract-specific MRI measures and to determine the contribution of quantitative measures of function in addition to basic clinical measures (age, gender, symptom duration and Expanded Disability Status Scale) to structural imaging measures of the corticospinal tract. We hypothesized that quantitative walking and strength measures would be related to brain corticospinal tract-specific measures, and would provide insight into the heterogeneity of brain pathology. Twenty-nine individuals with relapsing-remitting multiple sclerosis (mean(SD) age 48.7 (11.5) years; symptom duration 11.9(8.7); 17 females; median[range] Expanded Disability Status Scale 4.0 [1.0-6.5]) and 29 age and gender-matched healthy controls (age 50.8(11.6) years; 20 females) participated in clinical tests of strength and walking (Timed Up and Go, Timed 25 Foot Walk, Two Minute Walk Test ) as well as 3 T imaging including diffusion tensor imaging and magnetization transfer imaging. Individuals with multiple sclerosis were weaker (p = 0.0024) and walked slower (p = 0.0013) compared to controls. Quantitative measures of walking and strength were

  9. Surveying rip current survivors: preliminary insights into the experiences of being caught in rip currents

    Science.gov (United States)

    Drozdzewski, D.; Shaw, W.; Dominey-Howes, D.; Brander, R.; Walton, T.; Gero, A.; Sherker, S.; Goff, J.; Edwick, B.

    2012-04-01

    This paper begins a process of addressing a significant gap in knowledge about people's responses to being caught in rip currents. While rip currents are the primary hazard facing recreational ocean swimmers in Australia, debate exists about the best advice to give swimmers caught in rip currents. Such surf rescue advice - on what to do and how to respond when caught in a rip - relies on empirical evidence. However, at present, knowledge about swimmers reactions and responses to rip currents is limited. This gap is a considerable barrier to providing effective advice to beach goers and to understanding how this advice is utilised (or not) when actually caught in the rip current. This paper reports the findings of a pilot study that focussed on garnering a better understanding of swimmers' experiences when caught in rip currents. A large scale questionnaire survey instrument generated data about rip current survivors' demographics, knowledge of beach safety and their reactions and responses when caught in a rip current. A mix of online and paper surveys produced a total of 671 completed surveys. Respondents were predominantly an informed group in terms of rip current knowledge, beach experience and had a high self-rated swimming ability. Preliminary insights from the survey show that most respondents recalled a "swim across the rip/parallel to the beach" message when caught in the rip and most escaped unassisted by acting on this message. However, while nearly a quarter of respondents recalled a message of "not to panic", short answer responses revealed that the onset of panic inhibited some respondents from recalling or enacting any other type of beach safety message when caught in the rip current. Results also showed that despite the research sample being younger, competent and frequent ocean swimmers, they were more likely to swim at unpatrolled beaches and outside of the red and yellow safety flags. Moreover, they were still caught in a rip current and they

  10. Surveying rip current survivors: preliminary insights into the experiences of being caught in rip currents

    Directory of Open Access Journals (Sweden)

    D. Drozdzewski

    2012-04-01

    Full Text Available This paper begins a process of addressing a significant gap in knowledge about people's responses to being caught in rip currents. While rip currents are the primary hazard facing recreational ocean swimmers in Australia, debate exists about the best advice to give swimmers caught in rip currents. Such surf rescue advice – on what to do and how to respond when caught in a rip – relies on empirical evidence. However, at present, knowledge about swimmers reactions and responses to rip currents is limited. This gap is a considerable barrier to providing effective advice to beach goers and to understanding how this advice is utilised (or not when actually caught in the rip current.

    This paper reports the findings of a pilot study that focussed on garnering a better understanding of swimmers' experiences when caught in rip currents. A large scale questionnaire survey instrument generated data about rip current survivors' demographics, knowledge of beach safety and their reactions and responses when caught in a rip current. A mix of online and paper surveys produced a total of 671 completed surveys. Respondents were predominantly an informed group in terms of rip current knowledge, beach experience and had a high self-rated swimming ability. Preliminary insights from the survey show that most respondents recalled a "swim across the rip/parallel to the beach" message when caught in the rip and most escaped unassisted by acting on this message. However, while nearly a quarter of respondents recalled a message of "not to panic", short answer responses revealed that the onset of panic inhibited some respondents from recalling or enacting any other type of beach safety message when caught in the rip current. Results also showed that despite the research sample being younger, competent and frequent ocean swimmers, they were more likely to swim at unpatrolled beaches and outside of the red and yellow safety flags. Moreover, they were still

  11. Drosophila Cappuccino alleles provide insight into formin mechanism and role in oogenesis

    OpenAIRE

    Yoo, Haneul; Roth-Johnson, Elizabeth A.; Bor, Batbileg; Quinlan, Margot E.

    2015-01-01

    During Drosophila development, the formin actin nucleator Cappuccino (Capu) helps build a cytoplasmic actin mesh throughout the oocyte. Loss of Capu leads to female sterility, presumably because polarity determinants fail to localize properly in the absence of the mesh. To gain deeper insight into how Capu builds this actin mesh, we systematically characterized seven capu alleles, which have missense mutations in Capu's formin homology 2 (FH2) domain. We report that all seven alleles have del...

  12. Battling Carpal Tunnel Syndrome through Ergonomics: A Case Study of Texas A&M's Library Provides Insights and Answers.

    Science.gov (United States)

    Thornton, Joyce K.

    1995-01-01

    Current library automation practices and new technologies have forced library managers to seek some means of reducing carpal tunnel syndrome, and a case study of Texas A&M's library provides insights. Highlights include identifying and assessing the injuries, adjusting work surfaces, testing and selecting new keyboards, and developing adjustable…

  13. Multiple kisspeptin receptors in early Osteichthyans provide new insights into the evolution of this receptor family

    DEFF Research Database (Denmark)

    Pasquier, J.; Lafont, A._G.; Jeng, S.-R.

    2012-01-01

    Deorphanization of GPR54 receptor a decade ago led to the characterization of the kisspeptin receptor (Kissr) in mammals and the discovery of its major role in the brain control of reproduction. While a single gene encodes for Kissr in eutherian mammals including human, other vertebrates present...... a variable number of Kissr genes, from none in birds, one or two in teleosts, to three in an amphibian, xenopus. In order to get more insight into the evolution of Kissr gene family, we investigated the presence of Kissr in osteichthyans of key-phylogenetical positions: the coelacanth, a representative...

  14. A survey of scientific literacy to provide a foundation for designing science communication in Japan.

    Science.gov (United States)

    Kawamoto, Shishin; Nakayama, Minoru; Saijo, Miki

    2013-08-01

    There are various definitions and survey methods for scientific literacy. Taking into consideration the contemporary significance of scientific literacy, we have defined it with an emphasis on its social aspects. To acquire the insights needed to design a form of science communication that will enhance the scientific literacy of each individual, we conducted a large-scale random survey within Japan of individuals older than 18 years, using a printed questionnaire. The data thus acquired were analyzed using factor analysis and cluster analysis to create a 3-factor/4-cluster model of people's interest and attitude toward science, technology and society and their resulting tendencies. Differences were found among the four clusters in terms of the three factors: scientific factor, social factor, and science-appreciating factor. We propose a plan for designing a form of science communication that is appropriate to this current status of scientific literacy in Japan.

  15. Spider genomes provide insight into composition and evolution of venom and silk.

    Science.gov (United States)

    Sanggaard, Kristian W; Bechsgaard, Jesper S; Fang, Xiaodong; Duan, Jinjie; Dyrlund, Thomas F; Gupta, Vikas; Jiang, Xuanting; Cheng, Ling; Fan, Dingding; Feng, Yue; Han, Lijuan; Huang, Zhiyong; Wu, Zongze; Liao, Li; Settepani, Virginia; Thøgersen, Ida B; Vanthournout, Bram; Wang, Tobias; Zhu, Yabing; Funch, Peter; Enghild, Jan J; Schauser, Leif; Andersen, Stig U; Villesen, Palle; Schierup, Mikkel H; Bilde, Trine; Wang, Jun

    2014-05-06

    Spiders are ecologically important predators with complex venom and extraordinarily tough silk that enables capture of large prey. Here we present the assembled genome of the social velvet spider and a draft assembly of the tarantula genome that represent two major taxonomic groups of spiders. The spider genomes are large with short exons and long introns, reminiscent of mammalian genomes. Phylogenetic analyses place spiders and ticks as sister groups supporting polyphyly of the Acari. Complex sets of venom and silk genes/proteins are identified. We find that venom genes evolved by sequential duplication, and that the toxic effect of venom is most likely activated by proteases present in the venom. The set of silk genes reveals a highly dynamic gene evolution, new types of silk genes and proteins, and a novel use of aciniform silk. These insights create new opportunities for pharmacological applications of venom and biomaterial applications of silk.

  16. The elite cross-country skier provides unique insights into human exercise physiology.

    Science.gov (United States)

    Holmberg, H-C

    2015-12-01

    Successful cross-country skiing, one of the most demanding of endurance sports, involves considerable physiological challenges posed by the combined upper- and lower-body effort of varying intensity and duration, on hilly terrain, often at moderate altitude and in a cold environment. Over the years, this unique sport has helped physiologists gain novel insights into the limits of human performance and regulatory capacity. There is a long-standing tradition of researchers in this field working together with coaches and athletes to improve training routines, monitor progress, and refine skiing techniques. This review summarizes research on elite cross-country skiers, with special emphasis on the studies initiated by Professor Bengt Saltin. He often employed exercise as a means to learn more about the human body, successfully engaging elite endurance athletes to improve our understanding of the demands, characteristics, and specific effects associated with different types of exercise.

  17. Chemodynamics of the Milky Way and disc formation history: Insight from the RAVE and Gaia-ESO surveys

    Science.gov (United States)

    Kordopatis, G.; Wyse, R. F. G.; Binney, J.

    2016-09-01

    Multi-object spectrographs have opened a new window on the analyses of the chemo-dynamical properties of old Milky Way stars. These analyses allow us to trace back the internal mechanisms and the external factors that have influenced the evolution of our Galaxy, and therefore understand fundamental aspects of galaxy evolution in general. Here, we present recent results from the {RAdial Velocity Experiment} (RAVE) and the {Gaia-ESO survey}. These surveys explore the Milky Way properties in different ways, in terms of sample size and selection, magnitude range, and spectral resolution. We focus here on (i) the first direct detection of evidence for radial migration within the thin disc, providing insight into the history of spiral structure of the Milky Way, and (ii) the chemo-dynamical characterisation of the metal-weak thick and thin discs, for which chemo-dynamical models still have difficulties in reproducing.

  18. Chemodynamics of the Milky Way and disc formation history: insight from the RAVE and Gaia-ESO surveys

    CERN Document Server

    Kordopatis, G; Binney, J

    2016-01-01

    Multi-object spectrographs have opened a new window on the analyses of the chemo-dynamical properties of old Milky Way stars. These analyses allow us to trace back the internal mechanisms and the external factors that have influenced the evolution of our Galaxy, and therefore understand fundamental aspects of galaxy evolution in general. Here, we present recent results from the RAdial Velocity Experiment (RAVE) and the Gaia-ESO survey. These surveys explore the Milky Way properties in different ways, in terms of sample size and selection, magnitude range, and spectral resolution. We focus here on (i) the first direct detection of evidence for radial migration within the thin disc, providing insight into the history of spiral structure of the Milky Way, and (ii) the chemo-dynamical characterisation of the metal-weak thick and thin discs, for which chemo-dynamical models still have difficulties in reproducing.

  19. 42 CFR 431.115 - Disclosure of survey information and provider or contractor evaluation.

    Science.gov (United States)

    2010-10-01

    ... information and provider or contractor evaluation. (a) Basis and purpose. This section implements— (1) Section... 42 Public Health 4 2010-10-01 2010-10-01 false Disclosure of survey information and provider or contractor evaluation. 431.115 Section 431.115 Public Health CENTERS FOR MEDICARE & MEDICAID...

  20. Structure of a bimodular botulinum neurotoxin complex provides insights into its oral toxicity.

    Directory of Open Access Journals (Sweden)

    Kwangkook Lee

    Full Text Available Botulinum neurotoxins (BoNTs are produced by Clostridium botulinum and cause the fatal disease botulism, a flaccid paralysis of the muscle. BoNTs are released together with several auxiliary proteins as progenitor toxin complexes (PTCs to become highly potent oral poisons. Here, we report the structure of a ∼760 kDa 14-subunit large PTC of serotype A (L-PTC/A and reveal insight into its absorption mechanism. Using a combination of X-ray crystallography, electron microscopy, and functional studies, we found that L-PTC/A consists of two structurally and functionally independent sub-complexes. A hetero-dimeric 290 kDa complex protects BoNT, while a hetero-dodecameric 470 kDa complex facilitates its absorption in the harsh environment of the gastrointestinal tract. BoNT absorption is mediated by nine glycan-binding sites on the dodecameric sub-complex that forms multivalent interactions with carbohydrate receptors on intestinal epithelial cells. We identified monosaccharides that blocked oral BoNT intoxication in mice, which suggests a new strategy for the development of preventive countermeasures for BoNTs based on carbohydrate receptor mimicry.

  1. A neurophylogenetic approach provides new insight to the evolution of Scaphopoda.

    Science.gov (United States)

    Sumner-Rooney, Lauren H; Schrödl, Michael; Lodde-Bensch, Eva; Lindberg, David R; Heß, Martin; Brennan, Gerard P; Sigwart, Julia D

    2015-01-01

    The position of scaphopods in molluscan phylogeny remains singularly contentious, with several sister relationships supported by morphological and phylogenomic data: Scaphopoda + Bivalvia (Diasoma), Scaphopoda + Cephalopoda (Variopoda), and Scaphopoda + Gastropoda. Nervous system architecture has contributed significant insights to reconstructing phylogeny in the Mollusca and other invertebrate groups, but a modern neurophylogenetic approach has not been applied to molluscs, hampered by a lack of clearly defined homologous characters that can be unequivocally compared across the radical body plan disparity among the living clades. We present the first three-dimensional reconstruction of the anterior nervous system of a scaphopod, Rhabdus rectius, using histological tomography. We also describe a new putative sensory organ, a paired and pigmented sensory mantle slit. This structure is restricted to our study species and not a general feature of scaphopods, but it forms an integral part of the description of the nervous system in R. rectius. It also highlights the potential utility of neuro-anatomical characters for multiple levels of phylogenetic inference beyond this study. This potential has not previously been exploited for the thorny problem of molluscan phylogeny. The neuroanatomy of scaphopods demonstrates a highly derived architecture that shares a number of key characters with the cephalopod nervous system, and supports a Scaphopoda + Cephalopoda grouping.

  2. Comparative Analysis of Proteomes and Functionomes Provides Insights into Origins of Cellular Diversification

    Directory of Open Access Journals (Sweden)

    Arshan Nasir

    2013-01-01

    Full Text Available Reconstructing the evolutionary history of modern species is a difficult problem complicated by the conceptual and technical limitations of phylogenetic tree building methods. Here, we propose a comparative proteomic and functionomic inferential framework for genome evolution that allows resolving the tripartite division of cells and sketching their history. Evolutionary inferences were derived from the spread of conserved molecular features, such as molecular structures and functions, in the proteomes and functionomes of contemporary organisms. Patterns of use and reuse of these traits yielded significant insights into the origins of cellular diversification. Results uncovered an unprecedented strong evolutionary association between Bacteria and Eukarya while revealing marked evolutionary reductive tendencies in the archaeal genomic repertoires. The effects of nonvertical evolutionary processes (e.g., HGT, convergent evolution were found to be limited while reductive evolution and molecular innovation appeared to be prevalent during the evolution of cells. Our study revealed a strong vertical trace in the history of proteins and associated molecular functions, which was reliably recovered using the comparative genomics approach. The trace supported the existence of a stem line of descent and the very early appearance of Archaea as a diversified superkingdom, but failed to uncover a hidden canonical pattern in which Bacteria was the first superkingdom to deploy superkingdom-specific structures and functions.

  3. Structural studies of Pseudomonas and Chromobacterium ω-aminotransferases provide insights into their differing substrate specificity

    Energy Technology Data Exchange (ETDEWEB)

    Sayer, Christopher; Isupov, Michail N.; Westlake, Aaron; Littlechild, Jennifer A., E-mail: j.a.littlechild@exeter.ac.uk [University of Exeter, Stocker Road, Exeter EX4 4QD (United Kingdom)

    2013-04-01

    The X-ray structures of two ω-aminotransferases from P. aeruginosa and C. violaceum in complex with an inhibitor offer the first detailed insight into the structural basis of the substrate specificity of these industrially important enzymes. The crystal structures and inhibitor complexes of two industrially important ω-aminotransferase enzymes from Pseudomonas aeruginosa and Chromobacterium violaceum have been determined in order to understand the differences in their substrate specificity. The two enzymes share 30% sequence identity and use the same amino acceptor, pyruvate; however, the Pseudomonas enzyme shows activity towards the amino donor β-alanine, whilst the Chromobacterium enzyme does not. Both enzymes show activity towards S-α-methylbenzylamine (MBA), with the Chromobacterium enzyme having a broader substrate range. The crystal structure of the P. aeruginosa enzyme has been solved in the holo form and with the inhibitor gabaculine bound. The C. violaceum enzyme has been solved in the apo and holo forms and with gabaculine bound. The structures of the holo forms of both enzymes are quite similar. There is little conformational difference observed between the inhibitor complex and the holoenzyme for the P. aeruginosa aminotransferase. In comparison, the crystal structure of the C. violaceum gabaculine complex shows significant structural rearrangements from the structures of both the apo and holo forms of the enzyme. It appears that the different rigidity of the protein scaffold contributes to the substrate specificity observed for the two ω-aminotransferases.

  4. Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression

    Science.gov (United States)

    Lim, Chai K.; Bilgin, Ayse; Lovejoy, David B.; Tan, Vanessa; Bustamante, Sonia; Taylor, Bruce V.; Bessede, Alban; Brew, Bruce J.; Guillemin, Gilles J.

    2017-01-01

    Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers. PMID:28155867

  5. What's the use?: analysing student citations to provide new insights into e-book usage

    Directory of Open Access Journals (Sweden)

    Antony Groves

    2014-07-01

    Full Text Available This article reports on a small-scale user-focused piece of research carried out at the University of Sussex. In an attempt to better understand the impact of e-books on student outputs, citation analysis was performed on coursework to identify the e-books that had been used. Of the students surveyed, 11.6% cited an e-book in their work and, for this particular group, EBL was found to be the most popular collection. However, cross reference with the Library discovery tool and Google revealed that e-books available from the web were cited more than those from library collections. Interviews uncovered a spectrum of usage, leading to the conclusion that a comprehensive e-book strategy is required that makes students aware of their benefits, equips them with the skills needed for effective use and increases the number of e-books available.

  6. Phylogenetic analyses provide insights into the historical biogeography and evolution of Brachyrhaphis fishes.

    Science.gov (United States)

    Ingley, Spencer J; Reina, Ruth G; Bermingham, Eldredge; Johnson, Jerald B

    2015-08-01

    The livebearing fish genus Brachyrhaphis (Poeciliidae) has become an increasingly important model in evolution and ecology research, yet the phylogeny of this group is not well understood, nor has it been examined thoroughly using modern phylogenetic methods. Here, we present the first comprehensive phylogenetic analysis of Brachyrhaphis by using four molecular markers (3mtDNA, 1nucDNA) to infer relationships among species in this genus. We tested the validity of this genus as a monophyletic group using extensive outgroup sampling based on recent phylogenetic hypotheses of Poeciliidae. We also tested the validity of recently described species of Brachyrhaphis that are part of the B. episcopi complex in Panama. Finally, we examined the impact of historical events on diversification of Brachyrhaphis, and made predictions regarding the role of different ecological environments on evolutionary diversification where known historical events apparently fail to explain speciation. Based on our results, we reject the monophyly of Brachyrhaphis, and question the validity of two recently described species (B. hessfeldi and B. roswithae). Historical biogeography of Brachyrhaphis generally agrees with patterns found in other freshwater taxa in Lower Central America, which show that geological barriers frequently predict speciation. Specifically, we find evidence in support of an 'island' model of Lower Central American formation, which posits that the nascent isthmus was partitioned by several marine connections before linking North and South America. In some cases where historic events (e.g., vicariance) fail to explain allopatric species breaks in Brachyrhaphis, ecological processes (e.g., divergent predation environments) offer additional insight into our understanding of phylogenetic diversification in this group.

  7. Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution.

    Directory of Open Access Journals (Sweden)

    Henrique F Carvalho

    Full Text Available Metalloproteases have evolved in a vast number of biological systems, being one of the most diverse types of proteases and presenting a wide range of folds and catalytic metal ions. Given the increasing understanding of protein internal dynamics and its role in enzyme function, we are interested in assessing how the structural heterogeneity of metalloproteases translates into their dynamics. Therefore, the dynamical profile of the clan MA type protein thermolysin, derived from an Elastic Network Model of protein structure, was evaluated against those obtained from a set of experimental structures and molecular dynamics simulation trajectories. A close correspondence was obtained between modes derived from the coarse-grained model and the subspace of functionally-relevant motions observed experimentally, the later being shown to be encoded in the internal dynamics of the protein. This prompted the use of dynamics-based comparison methods that employ such coarse-grained models in a representative set of clan members, allowing for its quantitative description in terms of structural and dynamical variability. Although members show structural similarity, they nonetheless present distinct dynamical profiles, with no apparent correlation between structural and dynamical relatedness. However, previously unnoticed dynamical similarity was found between the relevant members Carboxypeptidase Pfu, Leishmanolysin, and Botulinum Neurotoxin Type A, despite sharing no structural similarity. Inspection of the respective alignments shows that dynamical similarity has a functional basis, namely the need for maintaining proper intermolecular interactions with the respective substrates. These results suggest that distinct selective pressure mechanisms act on metalloproteases at structural and dynamical levels through the course of their evolution. This work shows how new insights on metalloprotease function and evolution can be assessed with comparison schemes that

  8. Comparative molecular epidemiology provides new insights into Zucchini yellow mosaic virus occurrence in France.

    Science.gov (United States)

    Lecoq, H; Wipf-Scheibel, C; Nozeran, K; Millot, P; Desbiez, C

    2014-06-24

    Zucchini yellow mosaic virus (ZYMV, genus Potyvirus) causes important crop losses in cucurbits worldwide. In France, ZYMV epidemics are sporadic but occasionally very severe. This contrasts with Watermelon mosaic virus (WMV, genus Potyvirus) which causes regular and early epidemics. Factors influencing ZYMV epidemiology are still poorly understood. In order to gain new insights on the ecology and epidemiology of this virus, a 5-year multilocation trial was conducted in which ZYMV spread and populations were studied in each of the 20 plot/year combinations and compared with WMV. Search for ZYMV alternative hosts was conducted by testing weeds growing naturally around one plot and also by checking ZYMV natural infections in selected ornamental species. Although similar ZYMV populations were observed occasionally in the same plot in two successive years suggesting the occurrence of overwintering hosts nearby, only two Lamium amplexicaule plants were found to be infected by ZYMV of 3459 weed samples that were tested. The scarcity of ZYMV reservoirs contrasts with the frequent detection of WMV in the same samples. Since ZYMV and WMV have many aphid vectors in common and are transmitted with similar efficiencies, the differences observed in ZYMV and WMV reservoir abundances could be a major explanatory factor for the differences observed in the typology of ZYMV and WMV epidemics in France. Other potential ZYMV alternative hosts have been identified in ornamental species including begonia. Although possible in a few cases, exchanges of populations between different plots located from 500 m to 4 km apart seem uncommon. Therefore, the potential dissemination range of ZYMV by its aphid vectors seems to be rather limited in a fragmented landscape. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. KINGFISH -- Key Insights on Nearby Galaxies: A Far-Infrared Survey with Herschel: Survey Description and Image Atlas

    CERN Document Server

    Kennicutt, R C; Aniano, G; Appleton, P; Armus, L; Beirao, P; Bolatto, A D; Brandl, B; Crocker, A; Croxall, K; Dale, D A; Meyer, J Dononvan; Draine, B T; Engelbracht, C W; Galametz, M; Gordon, K D; Groves, B; Hao, C -N; Helou, G; Hinz, J; Hunt, L K; Johnson, B; Koda, J; Krause, O; Leroy, A K; Li, Y; Meidt, S; Montiel, E; Murphy, E J; Rahman, N; Rix, H -W; Roussel, H; Sandstrom, K; Sauvage, M; Schinnerer, E; Skibba, R; Smith, J -D T; Srinivasan, S; Vigroux, L; Walter, F; Wilson, C D; Wolfire, M; Zibetti, S

    2011-01-01

    The KINGFISH project (Key Insights on Nearby Galaxies: a Far-Infrared Survey with Herschel) is an imaging and spectroscopic survey of 61 nearby (d < 30 Mpc) galaxies, chosen to cover a wide range of galaxy properties and local interstellar medium (ISM) environments found in the nearby Universe. Its broad goals are to characterize the ISM of present-day galaxies, the heating and cooling of their gaseous and dust components, and to better understand the physical processes linking star formation and the ISM. KINGFISH is a direct descendant of the Spitzer Infrared Nearby Galaxies Survey (SINGS), which produced complete Spitzer imaging and spectroscopic mapping and a comprehensive set of multi-wavelength ancillary observations for the sample. The Herschel imaging consists of complete maps for the galaxies at 70, 100, 160, 250, 350, and 500 microns. The spectal line imaging of the principal atomic ISM cooling lines ([OI]63um, [OIII]88um, [NII]122,205um, and [CII]158um) covers the subregions in the centers and di...

  10. Barley Brassinosteroid Mutants Provide an Insight into Phytohormonal Homeostasis in Plant Reaction to Drought Stress

    Science.gov (United States)

    Gruszka, Damian; Janeczko, Anna; Dziurka, Michal; Pociecha, Ewa; Oklestkova, Jana; Szarejko, Iwona

    2016-01-01

    Brassinosteroids (BRs) are a class of steroid phytohormones, which regulate various processes of morphogenesis and physiology—from seed development to regulation of flowering and senescence. An accumulating body of evidence indicates that BRs take part in regulation of physiological reactions to various stress conditions, including drought. Many of the physiological functions of BRs are regulated by a complicated, and not fully elucidated network of interactions with metabolic pathways of other phytohormones. Therefore, the aim of this study was to characterize phytohormonal homeostasis in barley (Hordeum vulgare) in reaction to drought and validate role of BRs in regulation of this process. Material of this study included the barley cultivar “Bowman” and five Near-Isogenic Lines (NILs) representing characterized semi-dwarf mutants of several genes encoding enzymes participating in BR biosynthesis and signaling. Analysis of endogenous BRs concentrations in these NILs confirmed that their phenotypes result from abnormalities in BR metabolism. In general, concentrations of 18 compounds, representing various classes of phytohormones, including brassinosteroids, auxins, cytokinins, gibberellins, abscisic acid, salicylic acid and jasmonic acid were analyzed under control and drought conditions in the “Bowman” cultivar and the BR-deficient NILs. Drought induced a significant increase in accumulation of the biologically active form of BRs—castasterone in all analyzed genotypes. Another biologically active form of BRs—24-epi-brassinolide—was identified in one, BR-insensitive NIL under normal condition, but its accumulation was drought-induced in all analyzed genotypes. Analysis of concentration profiles of several compounds representing gibberellins allowed an insight into the BR-dependent regulation of gibberellin biosynthesis. The concentration of the gibberellic acid GA7 was significantly lower in all NILs when compared with the “Bowman” cultivar

  11. Natural history traits associated with detecting mortality within residential bird communities: can citizen science provide insights?

    Science.gov (United States)

    Cooper, Caren Beth; Loyd, Kerrie Anne Therese; Murante, Tessa; Savoca, Matthew; Dickinson, Janis

    2012-07-01

    Cat predation of birds in residential landscapes is ephemeral, unpredictable, and spatially dispersed, and thus requires many person-hours to observe. We sought to identify whether specific behaviors, traits, or feeding ecologies of birds contribute to their probability of cat-caused mortality around residences across temperate North America. In addressing this question, we evaluated citizen science data with respect to peer-reviewed species accounts (Birds of North America, BNA). Using information on cat predation from the BNA, we found that species that glean their prey from the ground or breed in nest boxes were three times more likely to be depredated by cats, while birds that hawk were over two times less likely to become cat prey than would be predicted by random chance. Data from citizen science sources also showed that birds using nest boxes had increased susceptibility to cat predation, as did those that use feeders and that glean from foliage. We caution that observations of predation by citizen science volunteers may be biased towards detection at feeders. Future research should focus on developing volunteer survey techniques for improving estimates of bird mortality rates and sources.

  12. First results from the PARSE.Insight project HEP survey on data preservation, re-use and (open) access

    CERN Document Server

    Holzner, André; Mele, Salvatore

    2009-01-01

    There is growing interest in the issues of preservation and re-use of the records of science, in the “digital era”. The aim of the PARSE.Insight project, partly financed by the European Commission under the Seventh Framework Program, is twofold: to provide an assessment of the current activities, trends and risks in the field of digital preservation of scientific results, from primary data to published articles; to inform the design of the preservation layer of an emerging e-Infrastructure for e-Science. CERN, as a partner of the PARSE.Insight consortium, is performing an in-depth case study on data preservation, re-use and (open) access within the High-Energy Physics (HEP) community. The first results of this large-scale survey of the attitudes and concerns of HEP scientists are presented. The survey reveals the widespread opinion that data preservation is “very important” to “crucial”. At the same time, it also highlights the chronic lack of resources and infrastructure to tackle this issue, as ...

  13. Military Medics' Insight Into Providing Women's Health Care in Deployed Settings.

    Science.gov (United States)

    Wilson, Candy; Corrigan, Robert; Reese, Sharon; Almonte, Angelica; Simpson, Danielle; Wilson, Amber

    2016-11-01

    To gain better understanding of the military medics' (Navy Independent Duty Corpsman, Air Force Independent Duty Medical Technician, and Army Health Care Specialist, experiences providing health care for women in the deployed or ship setting. The researchers used an exploratory, descriptive design informed by ethnography. A total of 86 individuals participated in the focus group and individual interviews. Three themes were identified: Training Fidelity, Advocate Leader, and The Challenges of Providing Patient Care. Experience in austere settings has convinced a number of medics they need additional women's health care topics in every facet of their training. They further suggested such training should be provided in stepwise fashion, beginning with initial, technical training courses and continuing through medical skills sustainment platforms. They were especially interested in basic women's health concerns. Topics suggested included vaginal infections, urinary tract infections, and birth control management. Although the advancement of women in the military continues to make strides-it is clear the availability of quality women's health care that women feel comfortable accessing may be its defining limitation. Medics are an excellent conduit for reinforcing these healthy messages and providing first-line treatment to deployed military women. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  14. The impact of the business cycle on service providers : Insights from international tourism

    NARCIS (Netherlands)

    Dekimpe, Marnik; Peers, Yuri; van Heerde, H.J.

    2016-01-01

    For service providers, it is essential to understand how their business is affected by the macroeconomy. This is especially pressing for the tourism sector, the world’s largest export service, because the number of incoming visitors is likely to be strongly determined by the business cycles in the c

  15. Stable Isotopes Provide Insight into Population Structure and Segregation in Eastern North Atlantic Sperm Whales

    DEFF Research Database (Denmark)

    Borrell, Asuncion; Velasquez Vacca, Adriana; Pinela, Ana M.;

    2013-01-01

    In pelagic species inhabiting large oceans, genetic differentiation tends to be mild and populations devoid of structure. However, large cetaceans have provided many examples of structuring. Here we investigate whether the sperm whale, a pelagic species with large population sizes and reputedly h...

  16. Apollo 17 Lunar Sounder Data provide Insight into Aitken Crater's Subsurface Structure

    Science.gov (United States)

    Cooper, Bonnie L.

    2007-01-01

    In preparation for the forthcoming avalanche of data from Lunar Reconnaissance Orbiter (LRO), we conducted a pilot study to demonstrate integration of multiple geophysical data sets. We applied methods of data integration that are used by the commercial mineral exploration industry to enhance the value of historical data sets and to provide a roadmap for future efforts.

  17. The impact of the business cycle on service providers : Insights from international tourism

    NARCIS (Netherlands)

    Dekimpe, Marnik; Peers, Yuri; van Heerde, H.J.

    2016-01-01

    For service providers, it is essential to understand how their business is affected by the macroeconomy. This is especially pressing for the tourism sector, the world’s largest export service, because the number of incoming visitors is likely to be strongly determined by the business cycles in the c

  18. Human evolutionary history and contemporary evolutionary theory provide insight when assessing cultural group selection.

    Science.gov (United States)

    Fuentes, Agustin; Kissel, Marc

    2016-01-01

    Richerson et al. provide a much needed roadmap for assessing cultural group selection (CGS) theory and for applying it to understanding variation between contemporary human groups. However, the current proposal lacks connection to relevant evidence from the human evolutionary record and requires a better integration with contemporary evolutionary theory. The article also misapplies the F st statistic.

  19. The HapMap Resource is Providing New Insights into Ourselves and its Application to Pharmacogenomics

    OpenAIRE

    2008-01-01

    The exploration of quantitative variation in complex traits such as gene expression and drug response in human populations has become one of the major priorities for medical genetics. The International HapMap Project provides a key resource of genotypic data on human lymphoblastoid cell lines derived from four major world populations of European, African, Chinese and Japanese ancestry for researchers to associate with various phenotypic data to find genes affecting health, disease and respons...

  20. Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

    DEFF Research Database (Denmark)

    You, Xinxin; Bian, Chao; Zan, Qijie

    2014-01-01

    of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision......Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion...

  1. Stable isotopes provide new insights into vestimentiferan physiological ecology at Gulf of Mexico cold seeps.

    Science.gov (United States)

    Becker, Erin Leigh; Macko, Stephen A; Lee, Raymond W; Fisher, Charles R

    2011-02-01

    On the otherwise low-biomass seafloor of the Gulf of Mexico (GoM) continental slope, natural oil and gas seeps are oases of local primary production that support lush animal communities. Hundreds of seep communities have been documented on the continental slope, and nutrition derived from seeps could be an important link in the overall GoM food web. Here, we present a uniquely large and cohesive data set of δ(13)C, δ(15)N, and δ(34)S compositions of the vestimentiferan tubeworms Escarpia laminata and Lamellibrachia sp. 1, which dominate biomass at GoM seeps and provide habitat for hundreds of other species. Our sampling design encompassed an entire region of the GoM lower slope, allowing us for the first time to assess spatial variability in isotope compositions and to robustly address long-standing hypotheses about how vestimentiferans acquire and cycle nutrients over their long lifespan (200+ years). Tissue δ(13)C values provided strong evidence that larger adult vestimentiferans use their buried roots to take up dissolved inorganic carbon from sediment pore water, while very small individuals use their plume to take up carbon dioxide from the seawater. δ(34)S values were extremely variable among individuals of the same species within one location (<1 m(2) area), indicating high variability in the inorganic sulfur pools on a very small spatial scale. This finding supports the hypothesis that vestimentiferans use their roots to cycle sulfate and sulfide between their symbionts and free-living consortia of sulfate-reducing archaea in the sediment. Finally, consistent differences in δ(15)N between two cooccurring vestimentiferan species provided the first strong evidence for partitioning of inorganic resources, which has significant implications for the ecology and evolution of this taxonomic group.

  2. Whole-Genome Enrichment Provides Deep Insights into Vibrio cholerae Metagenome from an African River.

    Science.gov (United States)

    Vezzulli, L; Grande, C; Tassistro, G; Brettar, I; Höfle, M G; Pereira, R P A; Mushi, D; Pallavicini, A; Vassallo, P; Pruzzo, C

    2017-04-01

    The detection and typing of Vibrio cholerae in natural aquatic environments encounter major methodological challenges related to the fact that the bacterium is often present in environmental matrices at very low abundance in nonculturable state. This study applied, for the first time to our knowledge, a whole-genome enrichment (WGE) and next-generation sequencing (NGS) approach for direct genotyping and metagenomic analysis of low abundant V. cholerae DNA (cholerae metagenomic DNA via hybridization. An enriched V. cholerae metagenome library was generated and sequenced on an Illumina MiSeq platform. Up to 1.8 × 10(7) bp (4.5× mean read depth) were found to map against V. cholerae reference genome sequences representing an increase of about 2500 times in target DNA coverage compared to theoretical calculations of performance for shotgun metagenomics. Analysis of metagenomic data revealed the presence of several V. cholerae virulence and virulence associated genes in river water including major virulence regions (e.g. CTX prophage and Vibrio pathogenicity island-1) and genetic markers of epidemic strains (e.g. O1-antigen biosynthesis gene cluster) that were not detectable by standard culture and molecular techniques. Overall, besides providing a powerful tool for direct genotyping of V. cholerae in complex environmental matrices, this study provides a 'proof of concept' on the methodological gap that might currently preclude a more comprehensive understanding of toxigenic V. cholerae emergence from natural aquatic environments.

  3. Lactone-bound structures of cyclohexanone monooxygenase provide insight into the stereochemistry of catalysis.

    Science.gov (United States)

    Yachnin, Brahm J; McEvoy, Michelle B; MacCuish, Roderick J D; Morley, Krista L; Lau, Peter C K; Berghuis, Albert M

    2014-12-19

    The Baeyer-Villiger monooxygenases (BVMOs) are microbial enzymes that catalyze the synthetically useful Baeyer-Villiger oxidation reaction. The available BVMO crystal structures all lack a substrate or product bound in a position that would determine the substrate specificity and stereospecificity of the enzyme. Here, we report two crystal structures of cyclohexanone monooxygenase (CHMO) with its product, ε-caprolactone, bound: the CHMO(Tight) and CHMO(Loose) structures. The CHMO(Tight) structure represents the enzyme state in which substrate acceptance and stereospecificity is determined, providing a foundation for engineering BVMOs with altered substrate spectra and/or stereospecificity. The CHMO(Loose) structure is the first structure where the product is solvent accessible. This structure represents the enzyme state upon binding and release of the substrate and product. In addition, the role of the invariant Arg329 in chaperoning the substrate/product during the catalytic cycle is highlighted. Overall, these data provide a structural framework for the engineering of BVMOs with altered substrate spectra and/or stereospecificity.

  4. The channel catfish genome sequence provides insights into the evolution of scale formation in teleosts

    Science.gov (United States)

    Liu, Zhanjiang; Liu, Shikai; Yao, Jun; Bao, Lisui; Zhang, Jiaren; Li, Yun; Jiang, Chen; Sun, Luyang; Wang, Ruijia; Zhang, Yu; Zhou, Tao; Zeng, Qifan; Fu, Qiang; Gao, Sen; Li, Ning; Koren, Sergey; Jiang, Yanliang; Zimin, Aleksey; Xu, Peng; Phillippy, Adam M.; Geng, Xin; Song, Lin; Sun, Fanyue; Li, Chao; Wang, Xiaozhu; Chen, Ailu; Jin, Yulin; Yuan, Zihao; Yang, Yujia; Tan, Suxu; Peatman, Eric; Lu, Jianguo; Qin, Zhenkui; Dunham, Rex; Li, Zhaoxia; Sonstegard, Tad; Feng, Jianbin; Danzmann, Roy G.; Schroeder, Steven; Scheffler, Brian; Duke, Mary V.; Ballard, Linda; Kucuktas, Huseyin; Kaltenboeck, Ludmilla; Liu, Haixia; Armbruster, Jonathan; Xie, Yangjie; Kirby, Mona L.; Tian, Yi; Flanagan, Mary Elizabeth; Mu, Weijie; Waldbieser, Geoffrey C.

    2016-01-01

    Catfish represent 12% of teleost or 6.3% of all vertebrate species, and are of enormous economic value. Here we report a high-quality reference genome sequence of channel catfish (Ictalurus punctatus), the major aquaculture species in the US. The reference genome sequence was validated by genetic mapping of 54,000 SNPs, and annotated with 26,661 predicted protein-coding genes. Through comparative analysis of genomes and transcriptomes of scaled and scaleless fish and scale regeneration experiments, we address the genomic basis for the most striking physical characteristic of catfish, the evolutionary loss of scales and provide evidence that lack of secretory calcium-binding phosphoproteins accounts for the evolutionary loss of scales in catfish. The channel catfish reference genome sequence, along with two additional genome sequences and transcriptomes of scaled catfishes, provide crucial resources for evolutionary and biological studies. This work also demonstrates the power of comparative subtraction of candidate genes for traits of structural significance. PMID:27249958

  5. Stable isotopes provide new insights into vestimentiferan physiological ecology at Gulf of Mexico cold seeps

    Science.gov (United States)

    Becker, Erin Leigh; Macko, Stephen A.; Lee, Raymond W.; Fisher, Charles R.

    2011-02-01

    On the otherwise low-biomass seafloor of the Gulf of Mexico (GoM) continental slope, natural oil and gas seeps are oases of local primary production that support lush animal communities. Hundreds of seep communities have been documented on the continental slope, and nutrition derived from seeps could be an important link in the overall GoM food web. Here, we present a uniquely large and cohesive data set of δ13C, δ15N, and δ34S compositions of the vestimentiferan tubeworms Escarpia laminata and Lamellibrachia sp. 1, which dominate biomass at GoM seeps and provide habitat for hundreds of other species. Our sampling design encompassed an entire region of the GoM lower slope, allowing us for the first time to assess spatial variability in isotope compositions and to robustly address long-standing hypotheses about how vestimentiferans acquire and cycle nutrients over their long lifespan (200+ years). Tissue δ13C values provided strong evidence that larger adult vestimentiferans use their buried roots to take up dissolved inorganic carbon from sediment pore water, while very small individuals use their plume to take up carbon dioxide from the seawater. δ34S values were extremely variable among individuals of the same species within one location (evolution of this taxonomic group.

  6. The Kids Insight into Dementia Survey (KIDS): development and preliminary psychometric properties.

    Science.gov (United States)

    Baker, Jess R; Low, Lee-Fay; Goodenough, Belinda; Jeon, Yun-Hee; Tsang, Ruby S M; Bryden, Christine; Hutchinson, Karen

    2017-05-08

    Children may have a foundational role in efforts to raise community awareness about dementia. There is some qualitative work with children with a relative with dementia, but little work into the insights of children as general citizens without affected family. One issue is an absence of measurement tools; thus the study aimed to design and pilot a psychometrically sound self-report measure of dementia attitudes for children. Using a multi-staged scale development process, stakeholder and expert input informed a 52-item Kids Insight into Dementia Survey (KIDS). After a pretest of KIDS with 21 Australian schoolchildren aged 10-12 years, exploratory factor analysis and reliability and validity testing were run on a revised KIDS with data from 203 similar-aged schoolchildren. The KIDS was reduced from 52 to 14 items, and a three-factor solution identified: 'Personhood,' 'Stigma,' and 'Dementia Understanding.' A strong positive correlation with an adult measure of dementia attitudes (r = .76) and a moderate positive correlation with a child measure of attitudes towards older adults (r = .47) indicated good concurrent validity. Internal consistency of .83 indicated good reliability. Results support the use of KIDS as a tool to measure children's insight into dementia, and to evaluate dementia education initiatives targeting the youth.

  7. Ghana's National Health Insurance Scheme: insights from members, administrators and health care providers.

    Science.gov (United States)

    Barimah, Kofi Bobi; Mensah, Joseph

    2013-08-01

    The Ghana National Health Insurance Scheme (NHIS) was established as part of a poverty reduction strategy to make health care more affordable to Ghanaians. It is envisaged that it will eventually replace the existing cash-and-carry system. This paper examines the views of NHIS administrators, members/enrollees, and health care providers on how the Scheme operates in practice. It is part of a larger evaluation project on Ghana's NHIS, sponsored by the Bill and Melinda Gates Foundation and the Global Development Network as part of a two-year global research. We rely primarily on qualitative data from focus group discussion in the Brong Ahafo and the Upper East regions respectively. Our findings suggest that the NHIS has improved access to affordable health care services and prescription drugs to many people in Ghana. However, there are concerns about fraud and corruption that must be addressed if the Scheme is to be financially viable.

  8. Molecular developmental mechanism in polypterid fish provides insight into the origin of vertebrate lungs.

    Science.gov (United States)

    Tatsumi, Norifumi; Kobayashi, Ritsuko; Yano, Tohru; Noda, Masatsugu; Fujimura, Koji; Okada, Norihiro; Okabe, Masataka

    2016-07-28

    The lung is an important organ for air breathing in tetrapods and originated well before the terrestrialization of vertebrates. Therefore, to better understand lung evolution, we investigated lung development in the extant basal actinopterygian fish Senegal bichir (Polypterus senegalus). First, we histologically confirmed that lung development in this species is very similar to that of tetrapods. We also found that the mesenchymal expression patterns of three genes that are known to play important roles in early lung development in tetrapods (Fgf10, Tbx4, and Tbx5) were quite similar to those of tetrapods. Moreover, we found a Tbx4 core lung mesenchyme-specific enhancer (C-LME) in the genomes of bichir and coelacanth (Latimeria chalumnae) and experimentally confirmed that these were functional in tetrapods. These findings provide the first molecular evidence that the developmental program for lung was already established in the common ancestor of actinopterygians and sarcopterygians.

  9. Molecular developmental mechanism in polypterid fish provides insight into the origin of vertebrate lungs

    Science.gov (United States)

    Tatsumi, Norifumi; Kobayashi, Ritsuko; Yano, Tohru; Noda, Masatsugu; Fujimura, Koji; Okada, Norihiro; Okabe, Masataka

    2016-01-01

    The lung is an important organ for air breathing in tetrapods and originated well before the terrestrialization of vertebrates. Therefore, to better understand lung evolution, we investigated lung development in the extant basal actinopterygian fish Senegal bichir (Polypterus senegalus). First, we histologically confirmed that lung development in this species is very similar to that of tetrapods. We also found that the mesenchymal expression patterns of three genes that are known to play important roles in early lung development in tetrapods (Fgf10, Tbx4, and Tbx5) were quite similar to those of tetrapods. Moreover, we found a Tbx4 core lung mesenchyme-specific enhancer (C-LME) in the genomes of bichir and coelacanth (Latimeria chalumnae) and experimentally confirmed that these were functional in tetrapods. These findings provide the first molecular evidence that the developmental program for lung was already established in the common ancestor of actinopterygians and sarcopterygians. PMID:27466206

  10. Genetic fingerprinting of plankton community provides new insights into aquatic ecology

    Institute of Scientific and Technical Information of China (English)

    YAN Qingyun; YU Yuhe; FENG Weisong

    2006-01-01

    Over the past two decades, molecular techniques have been widely used in ecological study and molecular ecology has been one of the most important branches of ecology. Meanwhile, genetic fingerprinting analyses have significantly enhanced our knowledge of the diversity and evolutionary relations of the planktonic organisms. Compared with conventional approaches in ecological study ( e. g.morphological classification), genetic fingerprinting techniques are simpler and much more effective. This review provides an overview of the principles, advantages and limitations of the commonly used DNA fingerprinting techniques in plankton research. The aim of this overview is to assess where we have been, where we are now and what the future holds for solving aquatic ecological problems with molecular-level information.

  11. The Opisthorchis viverrini genome provides insights into life in the bile duct.

    Science.gov (United States)

    Young, Neil D; Nagarajan, Niranjan; Lin, Suling Joyce; Korhonen, Pasi K; Jex, Aaron R; Hall, Ross S; Safavi-Hemami, Helena; Kaewkong, Worasak; Bertrand, Denis; Gao, Song; Seet, Qihui; Wongkham, Sopit; Teh, Bin Tean; Wongkham, Chaisiri; Intapan, Pewpan Maleewong; Maleewong, Wanchai; Yang, Xinhua; Hu, Min; Wang, Zuo; Hofmann, Andreas; Sternberg, Paul W; Tan, Patrick; Wang, Jun; Gasser, Robin B

    2014-07-09

    Opisthorchiasis is a neglected, tropical disease caused by the carcinogenic Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is linked to malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Asia. No vaccine is available, and only one drug (praziquantel) is used against the parasite. Little is known about O. viverrini biology and the diseases that it causes. Here we characterize the draft genome (634.5 Mb) and transcriptomes of O. viverrini, elucidate how this fluke survives in the hostile environment within the bile duct and show that metabolic pathways in the parasite are highly adapted to a lipid-rich diet from bile and/or cholangiocytes. We also provide additional evidence that O. viverrini and other flukes secrete proteins that directly modulate host cell proliferation. Our molecular resources now underpin profound explorations of opisthorchiasis/CCA and the design of new interventions.

  12. Molecular taxonomy provides new insights into anopheles species of the neotropical arribalzagia series.

    Directory of Open Access Journals (Sweden)

    Giovan F Gómez

    Full Text Available Phylogenetic analysis of partial mitochondrial cytochrome oxidase c subunit I (COI and nuclear internal transcribed spacer 2 (ITS2 sequences were used to evaluate initial identification and to investigate phylogenetic relationships of seven Anopheles morphospecies of the Arribalzagia Series from Colombia. Phylogenetic trees recovered highly supported clades for An. punctimaculas.s., An. calderoni, An. malefactor s.l., An. neomaculipalpus, An. apicimacula s.l., An. mattogrossensis and An. peryassui. This study provides the first molecular confirmation of An. malefactorfrom Colombia and discovered conflicting patterns of divergence for the molecular markers among specimens from northeast and northern Colombia suggesting the presence of two previously unrecognized Molecular Operational Taxonomic Units (MOTUs. Furthermore, two highly differentiated An. apicimacula MOTUs previously found in Panama were detected. Overall, the combined molecular dataset facilitated the detection of known and new Colombian evolutionary lineages, and constitutes the baseline for future research on their bionomics, ecology and potential role as malaria vectors.

  13. Proteomic analysis of scallop hepatopancreatic extract provides insights into marine polysaccharide digestion

    Science.gov (United States)

    Lyu, Qianqian; Jiao, Wenqian; Zhang, Keke; Bao, Zhenmin; Wang, Shi; Liu, Weizhi

    2016-01-01

    Marine polysaccharides are used in a variety of applications, and the enzymes that degrade these polysaccharides are of increasing interest. The main food source of herbivorous marine mollusks is seaweed, and several polysaccharide-degrading enzymes have been extracted from mollusk digestive glands (hepatopancreases). Here, we used a comprehensive proteomic approach to examine the hepatopancreatic proteins of the Zhikong scallop (Chlamys farreri). We identified 435 proteins, the majority of which were lysosomal enzymes and carbohydrate and protein metabolism enzymes. However, several new enzymes related to polysaccharide metabolism were also identified. Phylogenetic and structural analyses of these enzymes suggest that these polysaccharide-degrading enzymes may have a variety of potential substrate specificities. Taken together, our study characterizes several novel polysaccharide-degrading enzymes in the scallop hepatopancreas and provides an enhanced view of these enzymes and a greater understanding of marine polysaccharide digestion. PMID:27982037

  14. The ASCO Oncology Composite Provider Utilization File: New Data, New Insights.

    Science.gov (United States)

    Barr, Thomas R; Towle, Elaine L; Barr, Thomas R; Towle, Elaine L

    2016-01-01

    As we seek to understand the changing practice environment in oncology, the need for accurate information about demand for services, distribution of the delivery system in this sector of the health economy, and other practice trends is apparent. In this article, we present analysis of the sector using one of the public use files from the Centers for Medicare & Medicaid Services in combination with other publicly available data. Medicare data are particularly useful for this analysis because cancer is associated with aging and Medicare is the primary payer in the United States for patients older than age 65. As a result, nearly all oncologists who serve adult populations are represented in these data. By combining publicly available datasets into what we call the ASCO Provider Utilization File,we can investigate a wide range of supply, demand, and practice issues. We calculate the average work performed per physician, observe regional differences in work production,and quantify the downside risk and upside potential associated with the provision of chemotherapy drugs. Comparing the supply of oncologists by state with physician work relative value units and with estimates of cancer incidence by state reveals intriguing differences in the distribution of physicians and the demand for oncology services. In addition, our analysis demonstrates significant downside practice risk associated with the provision of drug therapy to Medicare beneficiaries. The economic risk associated with the purchase and delivery of chemotherapy is of particular concern as pressure for value increases. This article provides a description of a new dataset and interesting observations from these data.

  15. Functional reconstitution of Haemonchus contortus acetylcholine receptors in Xenopus oocytes provides mechanistic insights into levamisole resistance

    Science.gov (United States)

    Boulin, T; Fauvin, A; Charvet, CL; Cortet, J; Cabaret, J; Bessereau, J-L; Neveu, C

    2011-01-01

    BACKGROUND AND PURPOSE The cholinergic agonist levamisole is widely used to treat parasitic nematode infestations. This anthelmintic drug paralyses worms by activating a class of levamisole-sensitive acetylcholine receptors (L-AChRs) expressed in nematode muscle cells. However, levamisole efficacy has been compromised by the emergence of drug-resistant parasites, especially in gastrointestinal nematodes such as Haemonchus contortus. We report here the first functional reconstitution and pharmacological characterization of H. contortus L-AChRs in a heterologous expression system. EXPERIMENTAL APPROACH In the free-living nematode Caenorhabditis elegans, five AChR subunit and three ancillary protein genes are necessary in vivo and in vitro to synthesize L-AChRs. We have cloned the H. contortus orthologues of these genes and expressed them in Xenopus oocytes. We reconstituted two types of H. contortus L-AChRs with distinct pharmacologies by combining different receptor subunits. KEY RESULTS The Hco-ACR-8 subunit plays a pivotal role in selective sensitivity to levamisole. As observed with C. elegans L-AChRs, expression of H. contortus receptors requires the ancillary proteins Hco-RIC-3, Hco-UNC-50 and Hco-UNC-74. Using this experimental system, we demonstrated that a truncated Hco-UNC-63 L-AChR subunit, which was specifically detected in a levamisole-resistant H. contortus isolate, but not in levamisole-sensitive strains, hampers the normal function of L-AChRs, when co-expressed with its full-length counterpart. CONCLUSIONS AND IMPLICATIONS We provide the first functional evidence for a putative molecular mechanism involved in levamisole resistance in any parasitic nematode. This expression system will provide a means to analyse molecular polymorphisms associated with drug resistance at the electrophysiological level. PMID:21486278

  16. Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation.

    Directory of Open Access Journals (Sweden)

    Jinkui Yang

    2011-09-01

    Full Text Available Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927 was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions.

  17. Spatiotemporal Transcriptome Analysis Provides Insights into Bicolor Tepal Development in Lilium “Tiny Padhye”

    Science.gov (United States)

    Xu, Leifeng; Yang, Panpan; Feng, Yayan; Xu, Hua; Cao, Yuwei; Tang, Yuchao; Yuan, Suxia; Liu, Xinyan; Ming, Jun

    2017-01-01

    The bicolor Asiatic hybrid lily cultivar “Tiny Padhye” is an attractive variety because of its unique color pattern. During its bicolor tepal development, the upper tepals undergo a rapid color change from green to white, while the tepal bases change from green to purple. However, the molecular mechanisms underlying these changes remain largely uncharacterized. To systematically investigate the dynamics of the lily bicolor tepal transcriptome during development, we generated 15 RNA-seq libraries from the upper tepals (S2-U) and basal tepals (S1-D, S2-D, S3-D, and S4-D) of Lilium “Tiny Padhye.” Utilizing the Illumina platform, a total of 295,787 unigenes were obtained from 713.12 million high-quality paired-end reads. A total of 16,182 unigenes were identified as differentially expressed genes during tepal development. Using Kyoto Encyclopedia of Genes and Genomes pathway analysis, candidate genes involved in the anthocyanin biosynthetic pathway (61 unigenes), and chlorophyll metabolic pathway (106 unigenes) were identified. Further analyses showed that most anthocyanin biosynthesis genes were transcribed coordinately in the tepal bases, but not in the upper tepals, suggesting that the bicolor trait of “Tiny Padhye” tepals is caused by the transcriptional regulation of anthocyanin biosynthetic genes. Meanwhile, the high expression level of chlorophyll degradation genes and low expression level of chlorophyll biosynthetic genes resulted in the absence of chlorophylls from “Tiny Padhye” tepals after flowering. Transcription factors putatively involved in the anthocyanin biosynthetic pathway and chlorophyll metabolism in lilies were identified using a weighted gene co-expression network analysis and their possible roles in lily bicolor tepal development were discussed. In conclusion, these extensive transcriptome data provide a platform for elucidating the molecular mechanisms of bicolor tepals in lilies and provide a basis for similar research in other

  18. Ancient DNA provides new insight into the maternal lineages and domestication of Chinese donkeys.

    Science.gov (United States)

    Han, Lu; Zhu, Songbiao; Ning, Chao; Cai, Dawei; Wang, Kai; Chen, Quanjia; Hu, Songmei; Yang, Junkai; Shao, Jing; Zhu, Hong; Zhou, Hui

    2014-11-30

    The donkey (Equus asinus) is an important domestic animal that provides a reliable source of protein and method of transportation for many human populations. However, the process of domestication and the dispersal routes of the Chinese donkey are still unclear, as donkey remains are sparse in the archaeological record and often confused with horse remains. To explore the maternal origins and dispersal route of Chinese donkeys, both mitochondrial DNA D-loop and cytochrome b gene fragments of 21 suspected donkey remains from four archaeological sites in China were amplified and sequenced. Molecular methods of species identification show that 17 specimens were donkeys and three samples had the maternal genetic signature of horses. One sample that dates to about 20,000 years before present failed to amplify. In this study, the phylogenetic analysis reveals that ancient Chinese donkeys have high mitochondrial DNA diversity and two distinct mitochondrial maternal lineages, known as the Somali and Nubian lineages. These results indicate that the maternal origin of Chinese domestic donkeys was probably related to the African wild ass, which includes the Nubian wild ass (Equus africanus africanus) and the Somali wild ass (Equus africanus somaliensis). Combined with historical records, the results of this study implied that domestic donkeys spread into west and north China before the emergence of the Han dynasty. The number of Chinese domestic donkeys had increased primarily to meet demand for the expansion of trade, and they were likely used as commodities or for shipping goods along the Silk Road during the Tang Dynasty, when the Silk Road reached its golden age. This study is the first to provide valuable ancient animal DNA evidence for early trade between African and Asian populations. The ancient DNA analysis of Chinese donkeys also sheds light on the dynamic process of the maternal origin, domestication, and dispersal route of ancient Chinese donkeys.

  19. Medicinal Cannabis: A Survey Among Health Care Providers in Washington State

    Science.gov (United States)

    Carlini, Beatriz H; Garrett, Sharon B; Carter, Gregory T

    2017-02-01

    Washington State allows marijuana use for medical (since 1998) and recreational (since 2012) purposes. The benefits of medicinal cannabis (MC) can be maximized if clinicians educate patients about dosing, routes of administration, side effects, and plant composition. However, little is known about clinicians' knowledge and practices in Washington State. An anonymous online survey assessed providers' MC knowledge, beliefs, clinical practices, and training needs. The survey was disseminated through health care providers' professional organizations in Washington State. Descriptive analysis compared providers who had and had not authorized MC for patients. Survey results informed the approach and content of an online training on best clinical practices of MC. Four hundred ninety-four health care providers responded to the survey. Approximately two-third were women, aged 30 to 60 years, and working in family or internal medicine. More than half of the respondents were legally allowed to write MC authorizations per Washington State law, and 27% of those had issued written MC authorizations. Overall, respondents reported low knowledge and comfort level related to recommending MC. Respondents rated MC knowledge as important and supported inclusion of MC training in medical/health provider curriculum. Most Washington State providers have not received education on scientific basis of MC or training on best clinical practices of MC. Clinicians who had issued MC authorizations were more likely to have received MC training than those who had not issued MC authorization. The potential of MCs to benefit some patients is hindered by the lack of comfort of clinicians to recommend it. Training opportunities are badly needed to address these issues.

  20. Dust devil track survey at Elysium Planitia, Mars: Implications for the InSight landing sites

    Science.gov (United States)

    Reiss, Dennis; Lorenz, Ralph D.

    2016-03-01

    The InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) robotic lander is scheduled to land in Elysium Planitia on Mars in September 2016. InSight will perform the first comprehensive surface-based geophysical investigation including seismic measurements. Knowledge about encounter rates of dust devils with the InSight lander are important for two main reasons: (1) dust devils will affect the scientific measurements, i.e., wind-induced seismic noise, and (2) the power-supply of the InSight lander and instruments is provided by solar arrays and previous landers and rovers on Mars were affected by a steady decline in electrical power output due to atmospheric dust deposition on the solar panels. Long term science operations were only made possible by dust clearing events of the solar arrays caused by wind gusts and dust devils. In this study we analyzed dust devil tracks (DDTs) at the final InSight landing site region in Elysium Planitia. Formation of DDTs is caused by the removal of a layer of dust by passing dust devils, hence in principle the same process as clearing of dust from solar panels. We mapped the number, size (width and length), and orientation of DDTs in repeat observations using High Resolution Imaging Science Experiment (HiRISE) images covering the exact same surface area acquired within a relatively short time span (solar panel clearing recurrence interval estimate of ∼11 Mars years using the mean annual DDT formation rate, and the mean DDT width and length from all measured DDTs. Due to several uncertainties this solar panel clearing recurrence interval for the InSight landing should be seen as an upper limit estimate.

  1. The amphioxus genome provides unique insight into the evolution of immunity.

    Science.gov (United States)

    Dishaw, Larry J; Haire, Robert N; Litman, Gary W

    2012-03-01

    Immune systems evolve as essential strategies to maintain homeostasis with the environment, prevent microbial assault and recycle damaged host tissues. The immune system is composed of two components, innate and adaptive immunity. The former is common to all animals while the latter consists of a vertebrate-specific system that relies on somatically derived lymphocytes and is associated with near limitless genetic diversity as well as long-term memory. Deuterostome invertebrates provide a view of immune repertoires in phyla that immediately predate the origins of vertebrates. Genomic studies in amphioxus, a cephalochordate, have revealed homologs of genes encoding most innate immune receptors found in vertebrates; however, many of the gene families have undergone dramatic expansions, greatly increasing the innate immune repertoire. In addition, domain-swapping accounts for the innovation of new predicted pathways of receptor function. In both amphioxus and Ciona, a urochordate, the VCBPs (variable region containing chitin-binding proteins), which consist of immunoglobulin V (variable) and chitin binding domains, mediate recognition through the V domains. The V domains of VCBPs in amphioxus exhibit high levels of allelic complexity that presumably relate to functional specificity. Various features of the amphioxus immune repertoire reflect novel selective pressures, which likely have resulted in innovative strategies. Functional genomic studies underscore the value of amphioxus as a model for studying innate immunity and may help reveal how unique relationships between innate immune receptors and both pathogens and symbionts factored in the evolution of adaptive immune systems.

  2. Transcriptome Analysis of Thapsia laciniata Rouy Provides Insights into Terpenoid Biosynthesis and Diversity in Apiaceae

    Directory of Open Access Journals (Sweden)

    Henrik Toft Simonsen

    2013-04-01

    Full Text Available Thapsia laciniata Rouy (Apiaceae produces irregular and regular sesquiterpenoids with thapsane and guaiene carbon skeletons, as found in other Apiaceae species. A transcriptomic analysis utilizing Illumina next-generation sequencing enabled the identification of novel genes involved in the biosynthesis of terpenoids in Thapsia. From 66.78 million HQ paired-end reads obtained from T. laciniata roots, 64.58 million were assembled into 76,565 contigs (N50: 1261 bp. Seventeen contigs were annotated as terpene synthases and five of these were predicted to be sesquiterpene synthases. Of the 67 contigs annotated as cytochromes P450, 18 of these are part of the CYP71 clade that primarily performs hydroxylations of specialized metabolites. Three contigs annotated as aldehyde dehydrogenases grouped phylogenetically with the characterized ALDH1 from Artemisia annua and three contigs annotated as alcohol dehydrogenases grouped with the recently described ADH1 from A. annua. ALDH1 and ADH1 were characterized as part of the artemisinin biosynthesis. We have produced a comprehensive EST dataset for T. laciniata roots, which contains a large sample of the T. laciniata transcriptome. These transcriptome data provide the foundation for future research into the molecular basis for terpenoid biosynthesis in Thapsia and on the evolution of terpenoids in Apiaceae.

  3. Interaction studies between periplasmic cytochromes provide insights into extracellular electron transfer pathways of Geobacter sulfurreducens.

    Science.gov (United States)

    Fernandes, Ana P; Nunes, Tiago C; Paquete, Catarina M; Salgueiro, Carlos A

    2017-02-20

    Geobacter bacteria usually prevail among other microorganisms in soils and sediments where Fe(III) reduction has a central role. This reduction is achieved by extracellular electron transfer (EET), where the electrons are exported from the interior of the cell to the surrounding environment. Periplasmic cytochromes play an important role in establishing an interface between inner and outer membrane electron transfer components. In addition, periplasmic cytochromes, in particular nanowire cytochromes that contain at least 12 haem groups, have been proposed to play a role in electron storage in conditions of an environmental lack of electron acceptors. Up to date, no redox partners have been identified in Geobacter sulfurreducens, and concomitantly, the EET and electron storage mechanisms remain unclear. In this work, NMR chemical shift perturbation measurements were used to probe for an interaction between the most abundant periplasmic cytochrome PpcA and the dodecahaem cytochrome GSU1996, one of the proposed nanowire cytochromes in G. sulfurreducens The perturbations on the haem methyl signals of GSU1996 and PpcA showed that the proteins form a transient redox complex in an interface that involves haem groups from two different domains located at the C-terminal of GSU1996. Overall, the present study provides for the first time a clear evidence for an interaction between periplasmic cytochromes that might be relevant for the EET and electron storage pathways in G. sulfurreducens. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  4. European sea bass genome and its variation provide insights into adaptation to euryhalinity and speciation

    Science.gov (United States)

    Tine, Mbaye; Kuhl, Heiner; Gagnaire, Pierre-Alexandre; Louro, Bruno; Desmarais, Erick; Martins, Rute S.T.; Hecht, Jochen; Knaust, Florian; Belkhir, Khalid; Klages, Sven; Dieterich, Roland; Stueber, Kurt; Piferrer, Francesc; Guinand, Bruno; Bierne, Nicolas; Volckaert, Filip A. M.; Bargelloni, Luca; Power, Deborah M.; Bonhomme, François; Canario, Adelino V. M.; Reinhardt, Richard

    2014-01-01

    The European sea bass (Dicentrarchus labrax) is a temperate-zone euryhaline teleost of prime importance for aquaculture and fisheries. This species is subdivided into two naturally hybridizing lineages, one inhabiting the north-eastern Atlantic Ocean and the other the Mediterranean and Black seas. Here we provide a high-quality chromosome-scale assembly of its genome that shows a high degree of synteny with the more highly derived teleosts. We find expansions of gene families specifically associated with ion and water regulation, highlighting adaptation to variation in salinity. We further generate a genome-wide variation map through RAD-sequencing of Atlantic and Mediterranean populations. We show that variation in local recombination rates strongly influences the genomic landscape of diversity within and differentiation between lineages. Comparing predictions of alternative demographic models to the joint allele-frequency spectrum indicates that genomic islands of differentiation between sea bass lineages were generated by varying rates of introgression across the genome following a period of geographical isolation. PMID:25534655

  5. Stable Isotopes Provide Insight into Population Structure and Segregation in Eastern North Atlantic Sperm Whales

    Science.gov (United States)

    Borrell, Asunción; Velásquez Vacca, Adriana; Pinela, Ana M.; Kinze, Carl; Lockyer, Christina H.; Vighi, Morgana; Aguilar, Alex

    2013-01-01

    In pelagic species inhabiting large oceans, genetic differentiation tends to be mild and populations devoid of structure. However, large cetaceans have provided many examples of structuring. Here we investigate whether the sperm whale, a pelagic species with large population sizes and reputedly highly mobile, shows indication of structuring in the eastern North Atlantic, an ocean basin in which a single population is believed to occur. To do so, we examined stable isotope values in sequential growth layer groups of teeth from individuals sampled in Denmark and NW Spain. In each layer we measured oxygen- isotope ratios (δ18O) in the inorganic component (hydroxyapatite), and nitrogen and carbon isotope ratios (δ15N: δ13C) in the organic component (primarily collagenous). We found significant differences between Denmark and NW Spain in δ15N and δ18O values in the layer deposited at age 3, considered to be the one best representing the baseline of the breeding ground, in δ15N, δ13C and δ18O values in the period up to age 20, and in the ontogenetic variation of δ15N and δ18O values. These differences evidence that diet composition, use of habitat and/or migratory destinations are dissimilar between whales from the two regions and suggest that the North Atlantic population of sperm whales is more structured than traditionally accepted. PMID:24324782

  6. Directed evolution of a model primordial enzyme provides insights into the development of the genetic code.

    Directory of Open Access Journals (Sweden)

    Manuel M Müller

    Full Text Available The contemporary proteinogenic repertoire contains 20 amino acids with diverse functional groups and side chain geometries. Primordial proteins, in contrast, were presumably constructed from a subset of these building blocks. Subsequent expansion of the proteinogenic alphabet would have enhanced their capabilities, fostering the metabolic prowess and organismal fitness of early living systems. While the addition of amino acids bearing innovative functional groups directly enhances the chemical repertoire of proteomes, the inclusion of chemically redundant monomers is difficult to rationalize. Here, we studied how a simplified chorismate mutase evolves upon expanding its amino acid alphabet from nine to potentially 20 letters. Continuous evolution provided an enhanced enzyme variant that has only two point mutations, both of which extend the alphabet and jointly improve protein stability by >4 kcal/mol and catalytic activity tenfold. The same, seemingly innocuous substitutions (Ile→Thr, Leu→Val occurred in several independent evolutionary trajectories. The increase in fitness they confer indicates that building blocks with very similar side chain structures are highly beneficial for fine-tuning protein structure and function.

  7. Ancient DNA from Nubian and Somali wild ass provides insights into donkey ancestry and domestication.

    Science.gov (United States)

    Kimura, Birgitta; Marshall, Fiona B; Chen, Shanyuan; Rosenbom, Sónia; Moehlman, Patricia D; Tuross, Noreen; Sabin, Richard C; Peters, Joris; Barich, Barbara; Yohannes, Hagos; Kebede, Fanuel; Teclai, Redae; Beja-Pereira, Albano; Mulligan, Connie J

    2011-01-07

    Genetic data from extant donkeys (Equus asinus) have revealed two distinct mitochondrial DNA haplogroups, suggestive of two separate domestication events in northeast Africa about 5000 years ago. Without distinct phylogeographic structure in domestic donkey haplogroups and with little information on the genetic makeup of the ancestral African wild ass, however, it has been difficult to identify wild ancestors and geographical origins for the domestic mitochondrial clades. Our analysis of ancient archaeological and historic museum samples provides the first genetic information on the historic Nubian wild ass (Equus africanus africanus), Somali wild ass (Equus africanus somaliensis) and ancient donkey. The results demonstrate that the Nubian wild ass was an ancestor of the first donkey haplogroup. In contrast, the Somali wild ass has considerable mitochondrial divergence from the Nubian wild ass and domestic donkeys. These findings resolve the long-standing issue of the role of the Nubian wild ass in the domestication of the donkey, but raise new questions regarding the second ancestor for the donkey. Our results illustrate the complexity of animal domestication, and have conservation implications for critically endangered Nubian and Somali wild ass.

  8. Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.

    Science.gov (United States)

    Tachibana, Shin-Ichiro; Sullivan, Steven A; Kawai, Satoru; Nakamura, Shota; Kim, Hyunjae R; Goto, Naohisa; Arisue, Nobuko; Palacpac, Nirianne M Q; Honma, Hajime; Yagi, Masanori; Tougan, Takahiro; Katakai, Yuko; Kaneko, Osamu; Mita, Toshihiro; Kita, Kiyoshi; Yasutomi, Yasuhiro; Sutton, Patrick L; Shakhbatyan, Rimma; Horii, Toshihiro; Yasunaga, Teruo; Barnwell, John W; Escalante, Ananias A; Carlton, Jane M; Tanabe, Kazuyuki

    2012-09-01

    P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax.

  9. Neristatin 1 provides critical insight into bryostatin 1 structure-function relationships.

    Science.gov (United States)

    Kedei, Noemi; Kraft, Matthew B; Keck, Gary E; Herald, Cherry L; Melody, Noeleen; Pettit, George R; Blumberg, Peter M

    2015-04-24

    Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain.

  10. Neristatin 1 Provides Critical Insight into Bryostatin 1 Structure–Function Relationships

    Science.gov (United States)

    2015-01-01

    Bryostatin 1, a complex macrocyclic lactone isolated from Bugula neritina, has been the subject of multiple clinical trials for cancer. Although it functions as an activator of protein kinase C (PKC) in vitro, bryostatin 1 paradoxically antagonizes most responses to the prototypical PKC activator, the phorbol esters. The bottom half of the bryostatin 1 structure has been shown to be sufficient to confer binding to PKC. In contrast, we have previously shown that the top half of the bryostatin 1 structure is necessary for its unique biological behavior to antagonize phorbol ester responses. Neristatin 1 comprises a top half similar to that of bryostatin 1 together with a distinct bottom half that confers PKC binding. We report here that neristatin 1 is bryostatin 1-like, not phorbol ester-like, in its biological activity on U937 promyelocytic leukemia cells. We conclude that the top half of the bryostatin 1 structure is largely sufficient for bryostatin 1-like activity, provided the molecule also possesses an appropriate PKC binding domain. PMID:25808573

  11. Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling

    Directory of Open Access Journals (Sweden)

    Tzviya Zeev-Ben-Mordehai

    2015-12-01

    Full Text Available Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, the conserved herpesvirus proteins pUL31 and pUL34 form the heterodimeric nuclear egress complex (NEC, which, in turn, mediates the formation of tight-fitting membrane vesicles around capsids at the inner nuclear membrane. Here, we present the crystal structure of the pseudorabies virus NEC. The structure revealed that a zinc finger motif in pUL31 and an extensive interaction network between the two proteins stabilize the complex. Comprehensive mutational analyses, characterized both in situ and in vitro, indicated that the interaction network is not redundant but rather complementary. Fitting of the NEC crystal structure into the recently determined cryoEM-derived hexagonal lattice, formed in situ by pUL31 and pUL34, provided details on the molecular basis of NEC coat formation and inner nuclear membrane remodeling.

  12. A 4000-species dataset provides new insight into the evolution of ferns.

    Science.gov (United States)

    Testo, Weston; Sundue, Michael

    2016-12-01

    Ferns are the second-most diverse lineage of vascular plants on Earth, yet the best-sampled time-calibrated phylogeny of the group to date includes fewer than 5% of global diversity and was published seven years ago. We present a time-calibrated phylogeny that includes nearly half of extant fern diversity. Our results are evaluated in the context of previous studies and the fossil record, and we develop new hypotheses about the radiation of leptosporangiate ferns. We used sequence data from six chloroplast regions for nearly 4000 species of ferns to generate the most comprehensive phylogeny of the group ever published. We calibrate the phylogeny with twenty-six fossils and use an array of phylogenetic methods to resolve phylogenetic relationships, estimate divergence times, and infer speciation, extinction, and net diversification rates. We infer a mid-late Silurian origin for ferns (including horsetails) and an early Carboniferous origin for leptosporangiate ferns. Most derived fern families appeared in the Cretaceous and persisted for millions of years before rapidly diversifying in the Cenozoic. We find no evidence of differential rates of diversification among terrestrial and epiphytic species. Our findings challenge previous hypotheses on the evolutionary history of ferns and present a new paradigm for their Cenozoic radiation. We estimate earlier divergences for most fern lineages than were reported in previous studies and provide evidence of extended persistence of major fern lineages prior to rapid diversification in the last fifty million years.

  13. Comparative exome sequencing of metastatic lesions provides insights into the mutational progression of melanoma

    Directory of Open Access Journals (Sweden)

    Gartner Jared J

    2012-09-01

    Full Text Available Abstract Background Metastasis is characterized by spreading of neoplastic cells to an organ other than where they originated and is the predominant cause of death among cancer patients. This holds true for melanoma, whose incidence is increasing more rapidly than any other cancer and once disseminated has few therapeutic options. Here we performed whole exome sequencing of two sets of matched normal and metastatic tumor DNAs. Results Using stringent criteria, we evaluated the similarities and differences between the lesions. We find that in both cases, 96% of the single nucleotide variants are shared between the two metastases indicating that clonal populations gave rise to the distant metastases. Analysis of copy number variation patterns of both metastatic sets revealed a trend similar to that seen with our single nucleotide variants. Analysis of pathway enrichment on tumor sets shows commonly mutated pathways enriched between individual sets of metastases and all metastases combined. Conclusions These data provide a proof-of-concept suggesting that individual metastases may have sufficient similarity for successful targeting of driver mutations.

  14. Genome of an arbuscular mycorrhizal fungus provides insight into the oldest plant symbiosis

    Science.gov (United States)

    Tisserant, Emilie; Malbreil, Mathilde; Kuo, Alan; Kohler, Annegret; Symeonidi, Aikaterini; Balestrini, Raffaella; Charron, Philippe; Duensing, Nina; Frei dit Frey, Nicolas; Gianinazzi-Pearson, Vivienne; Gilbert, Luz B.; Handa, Yoshihiro; Herr, Joshua R.; Hijri, Mohamed; Koul, Raman; Kawaguchi, Masayoshi; Krajinski, Franziska; Lammers, Peter J.; Masclaux, Frederic G.; Murat, Claude; Morin, Emmanuelle; Ndikumana, Steve; Pagni, Marco; Petitpierre, Denis; Requena, Natalia; Rosikiewicz, Pawel; Riley, Rohan; Saito, Katsuharu; San Clemente, Hélène; Shapiro, Harris; van Tuinen, Diederik; Bécard, Guillaume; Bonfante, Paola; Paszkowski, Uta; Shachar-Hill, Yair Y.; Tuskan, Gerald A.; Young, J. Peter W.; Sanders, Ian R.; Henrissat, Bernard; Rensing, Stefan A.; Grigoriev, Igor V.; Corradi, Nicolas; Roux, Christophe; Martin, Francis

    2013-01-01

    The mutualistic symbiosis involving Glomeromycota, a distinctive phylum of early diverging Fungi, is widely hypothesized to have promoted the evolution of land plants during the middle Paleozoic. These arbuscular mycorrhizal fungi (AMF) perform vital functions in the phosphorus cycle that are fundamental to sustainable crop plant productivity. The unusual biological features of AMF have long fascinated evolutionary biologists. The coenocytic hyphae host a community of hundreds of nuclei and reproduce clonally through large multinucleated spores. It has been suggested that the AMF maintain a stable assemblage of several different genomes during the life cycle, but this genomic organization has been questioned. Here we introduce the 153-Mb haploid genome of Rhizophagus irregularis and its repertoire of 28,232 genes. The observed low level of genome polymorphism (0.43 SNP per kb) is not consistent with the occurrence of multiple, highly diverged genomes. The expansion of mating-related genes suggests the existence of cryptic sex-related processes. A comparison of gene categories confirms that R. irregularis is close to the Mucoromycotina. The AMF obligate biotrophy is not explained by genome erosion or any related loss of metabolic complexity in central metabolism, but is marked by a lack of genes encoding plant cell wall-degrading enzymes and of genes involved in toxin and thiamine synthesis. A battery of mycorrhiza-induced secreted proteins is expressed in symbiotic tissues. The present comprehensive repertoire of R. irregularis genes provides a basis for future research on symbiosis-related mechanisms in Glomeromycota. PMID:24277808

  15. Intraspecific Variation in Mitogenomes of Five Crassostrea Species Provides Insight into Oyster Diversification and Speciation.

    Science.gov (United States)

    Ren, Jianfeng; Hou, Zhanhui; Wang, Haiyan; Sun, Ming-An; Liu, Xiao; Liu, Bin; Guo, Ximing

    2016-04-01

    A large number of Crassostrea oysters are found in Asia-Pacific. While analyses of interspecific variation have helped to establish historical relationships among these species, studies on intraspecific variation are necessary to understand their recent evolutionary history and current forces driving population biology. We resequenced 18 and analyzed 31 mitogenomes of five Crassostrea species from China: Crassostrea gigas, Crassostrea angulata, Crassostrea sikamea, Crassostrea ariakensis, and Crassostrea hongkongensis. Our analysis finds abundant insertions, deletions, and single-nucleotide polymorphisms in all species. Intraspecific variation varies greatly among species with polymorphic sites ranging from 54 to 293 and nucleotide diversity ranging from 0.00106 to 0.00683. In all measurements, C. hongkongensis that has the narrowest geographic distribution exhibits the least sequence diversity; C. ariakensis that has the widest distribution shows the highest diversity, and species with intermediate distribution show intermediate levels of diversity. Low sequence diversity in C. hongkongensis may reflect recent bottlenecks that are probably exacerbated by human transplantation. High diversity in C. ariakensis is likely due to divergence of northern and southern China populations that have been separated without gene flow. The significant differences in mitogenome diversity suggest that the five sister species of Crassostrea have experienced different evolutionary forces since their divergence. The recent divergence of two C. ariakensis populations and the C. gigas/angulata species complex provides evidence for continued diversification and speciation of Crassostrea species along China's coast, which are shaped by unknown mechanisms in a north-south divide.

  16. Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia

    Science.gov (United States)

    Legge, Sophie E; Hamshere, Marian L; Ripke, Stephan; Pardinas, Antonio F; Goldstein, Jacqueline I; Rees, Elliott; Richards, Alexander L; Leonenko, Ganna; Jorskog, L Fredrik; Chambert, Kimberly D; Collier, David A; Genovese, Giulio; Giegling, Ina; Holmans, Peter; Jonasdottir, Adalbjorg; Kirov, George; McCarroll, Steven A; MacCabe, James H; Mantripragada, Kiran; Moran, Jennifer L; Neale, Benjamin M; Stefansson, Hreinn; Rujescu, Dan; Daly, Mark J; Sullivan, Patrick F; Owen, Michael J; O’Donovan, Michael C; Walters, James T R

    2016-01-01

    The antipsychotic clozapine is uniquely effective in the management of schizophrenia, but its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown although genetic factors play an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed HLA alleles, exome array, and copy number variation analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (OR=4.32, P=1.79×10-8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P = 0.015, positive predictive value = 35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect. PMID:27400856

  17. Crystal structure of class III chitinase from pomegranate provides the insight into its metal storage capacity.

    Science.gov (United States)

    Masuda, Taro; Zhao, Guanghua; Mikami, Bunzo

    2015-01-01

    Chitinase hydrolyzes the β-1,4-glycosidic bond in chitin. In higher plants, this enzyme has been regarded as a pathogenesis-related protein. Recently, we identified a class III chitinase, which functions as a calcium storage protein in pomegranate (Punica granatum) seed (PSC, pomegranate seed chitinase). Here, we solved a crystal structure of PSC at 1.6 Å resolution. Although its overall structure, including the structure of catalytic site and non-proline cis-peptides, was closely similar to those of other class III chitinases, PSC had some unique structural characteristics. First, there were some metal-binding sites with coordinated water molecules on the surface of PSC. Second, many unconserved aspartate residues were present in the PSC sequence which rendered the surface of PSC negatively charged. This acidic electrostatic property is in contrast to that of hevamine, well-characterized plant class III chitinase, which has rather a positively charged surface. Thus, the crystal structure provides a clue for metal association property of PSC.

  18. Weird mammals provide insights into the evolution of mammalian sex chromosomes and dosage compensation

    Indian Academy of Sciences (India)

    Jennifer A. Marshall Graves

    2015-12-01

    The deep divergence of mammalian groups 166 and 190 million years ago (MYA) provide genetic variation to explore the evolution of DNA sequence, gene arrangement and regulation of gene expression in mammals. With encouragement from the founder of the field, Mary Lyon, techniques in cytogenetics and molecular biology were progressively adapted to characterize the sex chromosomes of kangaroos and other marsupials, platypus and echidna—and weird rodent species. Comparative gene mapping reveals the process of sex chromosome evolution from their inception 190 MYA (they are autosomal in platypus) to their inevitable end (the Y has disappeared in two rodent lineages). Our X and Y are relatively young, getting their start with the evolution of the sex-determining gene, which triggered progressive degradation of the Y chromosome. Even more recently, sex chromosomes of placental mammals fused with an autosomal region which now makes up most of the Y. Exploration of gene activity patterns over four decades showed that dosage compensation via X-chromosome inactivation is unique to therian mammals, and that this whole chromosome control process is different in marsupials and absent in monotremes and reptiles, and birds. These differences can be exploited to deduce how mammalian sex chromosomes and epigenetic silencing evolved.

  19. Bioinformatics analyses provide insight into distant homology of the Keap1-Nrf2 pathway.

    Science.gov (United States)

    Gacesa, Ranko; Dunlap, Walter C; Long, Paul F

    2015-11-01

    An essential requirement for the evolution of early eukaryotic life was the development of effective means to protect against metabolic oxidative stress and exposure to environmental toxicants. In present-day mammals, the master transcription factor Nrf2 regulates basal level homeostasis and inducible expression of numerous detoxifying and antioxidant genes. To examine early evolution of the Keap1-Nrf2 pathway, we present bioinformatics analyses of distant homology of mammalian Keap1 and Nrf2 proteins across the Kingdoms of Life. Software written for this analysis is made freely available on-line. Furthermore, utilizing protein modeling and virtual screening methods, we demonstrate potential for Nrf2 activation by competitive inhibition of its binding to Keap1, specifically by UV-protective fungal mycosporines and marine mycosporine-like amino acids (MAAs). We contend that coevolution of Nrf2-activating secondary metabolites by fungi and other extant microbiota may provide prospective compound leads for the design of new therapeutics to target activation of the human Keap1-Nrf2 pathway for treating degenerative diseases of ageing.

  20. Metabolomic Analysis Provides Insights on Paraquat-Induced Parkinson-Like Symptoms in Drosophila melanogaster.

    Science.gov (United States)

    Shukla, Arvind Kumar; Ratnasekhar, Ch; Pragya, Prakash; Chaouhan, Hitesh Singh; Patel, Devendra Kumar; Chowdhuri, Debapratim Kar; Mudiam, Mohana Krishna Reddy

    2016-01-01

    Paraquat (PQ) exposure causes degeneration of the dopaminergic neurons in an exposed organism while altered metabolism has a role in various neurodegenerative disorders. Therefore, the study presented here was conceived to depict the role of altered metabolism in PQ-induced Parkinson-like symptoms and to explore Drosophila as a potential model organism for such studies. Metabolic profile was generated in control and in flies that were fed PQ (5, 10, and 20 mM) in the diet for 12 and 24 h concurrent with assessment of indices of oxidative stress, dopaminergic neurodegeneration, and behavioral alteration. PQ was found to significantly alter 24 metabolites belonging to different biological pathways along with significant alterations in the above indices. In addition, PQ attenuated brain dopamine content in the exposed organism. The study demonstrates that PQ-induced alteration in the metabolites leads to oxidative stress and neurodegeneration in the exposed organism along with movement disorder, a phenotype typical of Parkinson-like symptoms. The study is relevant in the context of Drosophila and humans because similar alteration in the metabolic pathways has been observed in both PQ-exposed Drosophila and in postmortem samples of patients with Parkinsonism. Furthermore, this study provides advocacy towards the applicability of Drosophila as an alternate model organism for pre-screening of environmental chemicals for their neurodegenerative potential with altered metabolism.

  1. Genome of an arbuscular mycorrhizal fungus provides insight into the oldest plant symbiosis.

    Science.gov (United States)

    Tisserant, Emilie; Malbreil, Mathilde; Kuo, Alan; Kohler, Annegret; Symeonidi, Aikaterini; Balestrini, Raffaella; Charron, Philippe; Duensing, Nina; Frei dit Frey, Nicolas; Gianinazzi-Pearson, Vivienne; Gilbert, Luz B; Handa, Yoshihiro; Herr, Joshua R; Hijri, Mohamed; Koul, Raman; Kawaguchi, Masayoshi; Krajinski, Franziska; Lammers, Peter J; Masclaux, Frederic G; Murat, Claude; Morin, Emmanuelle; Ndikumana, Steve; Pagni, Marco; Petitpierre, Denis; Requena, Natalia; Rosikiewicz, Pawel; Riley, Rohan; Saito, Katsuharu; San Clemente, Hélène; Shapiro, Harris; van Tuinen, Diederik; Bécard, Guillaume; Bonfante, Paola; Paszkowski, Uta; Shachar-Hill, Yair Y; Tuskan, Gerald A; Young, J Peter W; Young, Peter W; Sanders, Ian R; Henrissat, Bernard; Rensing, Stefan A; Grigoriev, Igor V; Corradi, Nicolas; Roux, Christophe; Martin, Francis

    2013-12-10

    The mutualistic symbiosis involving Glomeromycota, a distinctive phylum of early diverging Fungi, is widely hypothesized to have promoted the evolution of land plants during the middle Paleozoic. These arbuscular mycorrhizal fungi (AMF) perform vital functions in the phosphorus cycle that are fundamental to sustainable crop plant productivity. The unusual biological features of AMF have long fascinated evolutionary biologists. The coenocytic hyphae host a community of hundreds of nuclei and reproduce clonally through large multinucleated spores. It has been suggested that the AMF maintain a stable assemblage of several different genomes during the life cycle, but this genomic organization has been questioned. Here we introduce the 153-Mb haploid genome of Rhizophagus irregularis and its repertoire of 28,232 genes. The observed low level of genome polymorphism (0.43 SNP per kb) is not consistent with the occurrence of multiple, highly diverged genomes. The expansion of mating-related genes suggests the existence of cryptic sex-related processes. A comparison of gene categories confirms that R. irregularis is close to the Mucoromycotina. The AMF obligate biotrophy is not explained by genome erosion or any related loss of metabolic complexity in central metabolism, but is marked by a lack of genes encoding plant cell wall-degrading enzymes and of genes involved in toxin and thiamine synthesis. A battery of mycorrhiza-induced secreted proteins is expressed in symbiotic tissues. The present comprehensive repertoire of R. irregularis genes provides a basis for future research on symbiosis-related mechanisms in Glomeromycota.

  2. Analyses of pig genomes provide insight into porcine demography and evolution

    Science.gov (United States)

    Groenen, Martien A. M.; Archibald, Alan L.; Uenishi, Hirohide; Tuggle, Christopher K.; Takeuchi, Yasuhiro; Rothschild, Max F.; Rogel-Gaillard, Claire; Park, Chankyu; Milan, Denis; Megens, Hendrik-Jan; Li, Shengting; Larkin, Denis M.; Kim, Heebal; Frantz, Laurent A. F.; Caccamo, Mario; Ahn, Hyeonju; Aken, Bronwen L.; Anselmo, Anna; Anthon, Christian; Auvil, Loretta; Badaoui, Bouabid; Beattie, Craig W.; Bendixen, Christian; Berman, Daniel; Blecha, Frank; Blomberg, Jonas; Bolund, Lars; Bosse, Mirte; Botti, Sara; Bujie, Zhan; Bystrom, Megan; Capitanu, Boris; Silva, Denise Carvalho; Chardon, Patrick; Chen, Celine; Cheng, Ryan; Choi, Sang-Haeng; Chow, William; Clark, Richard C.; Clee, Christopher; Crooijmans, Richard P. M. A.; Dawson, Harry D.; Dehais, Patrice; De Sapio, Fioravante; Dibbits, Bert; Drou, Nizar; Du, Zhi-Qiang; Eversole, Kellye; Fadista, João; Fairley, Susan; Faraut, Thomas; Faulkner, Geoffrey J.; Fowler, Katie E.; Fredholm, Merete; Fritz, Eric; Gilbert, James G. R.; Giuffra, Elisabetta; Gorodkin, Jan; Griffin, Darren K.; Harrow, Jennifer L.; Hayward, Alexander; Howe, Kerstin; Hu, Zhi-Liang; Humphray, Sean J.; Hunt, Toby; Hornshøj, Henrik; Jeon, Jin-Tae; Jern, Patric; Jones, Matthew; Jurka, Jerzy; Kanamori, Hiroyuki; Kapetanovic, Ronan; Kim, Jaebum; Kim, Jae-Hwan; Kim, Kyu-Won; Kim, Tae-Hun; Larson, Greger; Lee, Kyooyeol; Lee, Kyung-Tai; Leggett, Richard; Lewin, Harris A.; Li, Yingrui; Liu, Wansheng; Loveland, Jane E.; Lu, Yao; Lunney, Joan K.; Ma, Jian; Madsen, Ole; Mann, Katherine; Matthews, Lucy; McLaren, Stuart; Morozumi, Takeya; Murtaugh, Michael P.; Narayan, Jitendra; Nguyen, Dinh Truong; Ni, Peixiang; Oh, Song-Jung; Onteru, Suneel; Panitz, Frank; Park, Eung-Woo; Park, Hong-Seog; Pascal, Geraldine; Paudel, Yogesh; Perez-Enciso, Miguel; Ramirez-Gonzalez, Ricardo; Reecy, James M.; Zas, Sandra Rodriguez; Rohrer, Gary A.; Rund, Lauretta; Sang, Yongming; Schachtschneider, Kyle; Schraiber, Joshua G.; Schwartz, John; Scobie, Linda; Scott, Carol; Searle, Stephen; Servin, Bertrand; Southey, Bruce R.; Sperber, Goran; Stadler, Peter; Sweedler, Jonathan V.; Tafer, Hakim; Thomsen, Bo; Wali, Rashmi; Wang, Jian; Wang, Jun; White, Simon; Xu, Xun; Yerle, Martine; Zhang, Guojie; Zhang, Jianguo; Zhang, Jie; Zhao, Shuhong; Rogers, Jane; Churcher, Carol; Schook, Lawrence B.

    2013-01-01

    For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ~1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model. PMID:23151582

  3. In situ biodeposition measurements on a Modiolus modiolus (horse mussel) reef provide insights into ecosystem services

    Science.gov (United States)

    Kent, Flora E. A.; Last, Kim S.; Harries, Daniel B.; Sanderson, William G.

    2017-01-01

    Horse mussel (Modiolus modiolus) shellfish reefs are a threatened and declining habitat in the North East Atlantic and support high levels of biodiversity. Shellfish can influence the surrounding water column and modify the quality of material that reaches the seabed by filtering water, actively depositing particles and changing the benthic boundary layer due to surface roughness. In the present study M. modiolus biodeposition was measured in a field location for the first time. The results show that M. modiolus enhance sedimentation and contribute to the downward flux of material to the seabed. Approximately 30% of the total sediment deposition was attributed to active filter feeding and overall, the presence of horse mussels enhanced deposition two fold. The results are discussed in terms of the potential for horse mussel reefs to provide ecosystem services to society, through functions such as benthopelagic coupling and sediment stabilisation. Highlighting the societal benefits supplied by marine habitats can help prioritise conservation efforts and feed into the sustainable management of coastal water bodies.

  4. Geographic variation in the structure of oak hybrid zones provides insights into the dynamics of speciation.

    Science.gov (United States)

    Zeng, Yan-Fei; Liao, Wan-Jin; Petit, Rémy J; Zhang, Da-Yong

    2011-12-01

    Studying geographic variation in the rate of hybridization between closely related species could provide a useful window on the evolution of reproductive isolation. Reinforcement theory predicts greater prezygotic isolation in areas of prolonged contact between recently diverged species than in areas of recent contact, which implies that old contact zones would be dominated by parental phenotypes with few hybrids (bimodal hybrid zones), whereas recent contact zones would be characterized by hybrid swarms (unimodal hybrid zones). Here, we investigate how the hybrid zones of two closely related Chinese oaks, Quercus mongolica and Q. liaotungensis, are structured geographically using both nuclear and chloroplast markers. We found that populations of Q. liaotungensis located around the Changbai Mountains in Northeast China, an inferred glacial refugium, were introgressed by genes from Q. mongolica, suggesting historical contact between the two species in this region. However, these introgressed populations form sharp bimodal hybrid zones with Q. mongolica. In contrast, populations of Q. liaotungensis located in North China, which show no sign of ancient introgression with Q. mongolica, form unimodal hybrid zones with Q. mongolica. These results are consistent with the hypothesis that selection against hybrids has had sufficient time to reinforce the reproductive barriers between Q. liaotungensis and Q. mongolica in Northeast China but not in North China.

  5. A Near-Atomic Structure of the Dark Apoptosome Provides Insight into Assembly and Activation.

    Science.gov (United States)

    Cheng, Tat Cheung; Akey, Ildikó V; Yuan, Shujun; Yu, Zhiheng; Ludtke, Steven J; Akey, Christopher W

    2017-01-03

    In Drosophila, the Apaf-1-related killer (Dark) forms an apoptosome that activates procaspases. To investigate function, we have determined a near-atomic structure of Dark double rings using cryo-electron microscopy. We then built a nearly complete model of the apoptosome that includes 7- and 8-blade β-propellers. We find that the preference for dATP during Dark assembly may be governed by Ser325, which is in close proximity to the 2' carbon of the deoxyribose ring. Interestingly, β-propellers in V-shaped domains of the Dark apoptosome are more widely separated, relative to these features in the Apaf-1 apoptosome. This wider spacing may be responsible for the lack of cytochrome c binding to β-propellers in the Dark apoptosome. Our structure also highlights the roles of two loss-of-function mutations that may block Dark assembly. Finally, the improved model provides a framework to understand apical procaspase activation in the intrinsic cell death pathway.

  6. Comparative proteomic analyses provide new insights into low phosphorus stress responses in maize leaves.

    Directory of Open Access Journals (Sweden)

    Kewei Zhang

    Full Text Available Phosphorus deficiency limits plant growth and development. To better understand the mechanisms behind how maize responds to phosphate stress, we compared the proteome analysis results of two groups of maize leaves that were treated separately with 1,000 µM (control, +P and 5 µM of KH2PO4 (intervention group, -P for 25 days. In total, 1,342 protein spots were detected on 2-DE maps and 15.43% had changed (P<0.05; ≥1.5-fold significantly in quantity between the +P and -P groups. These proteins are involved in several major metabolic pathways, including photosynthesis, carbohydrate metabolism, energy metabolism, secondary metabolism, signal transduction, protein synthesis, cell rescue and cell defense and virulence. The results showed that the reduction in photosynthesis under low phosphorus treatment was due to the down-regulation of the proteins involved in CO2 enrichment, the Calvin cycle and the electron transport system. Electron transport and photosynthesis restrictions resulted in a large accumulation of peroxides. Maize has developed many different reactive oxygen species (ROS scavenging mechanisms to cope with low phosphorus stress, including up-regulating its antioxidant content and antioxidase activity. After being subjected to phosphorus stress over a long period, maize may increase its internal phosphorus utilization efficiency by altering photorespiration, starch synthesis and lipid composition. These results provide important information about how maize responds to low phosphorus stress.

  7. In vivo cell biology in zebrafish - providing insights into vertebrate development and disease.

    Science.gov (United States)

    Vacaru, Ana M; Unlu, Gokhan; Spitzner, Marie; Mione, Marina; Knapik, Ela W; Sadler, Kirsten C

    2014-02-01

    Over the past decades, studies using zebrafish have significantly advanced our understanding of the cellular basis for development and human diseases. Zebrafish have rapidly developing transparent embryos that allow comprehensive imaging of embryogenesis combined with powerful genetic approaches. However, forward genetic screens in zebrafish have generated unanticipated findings that are mirrored by human genetic studies: disruption of genes implicated in basic cellular processes, such as protein secretion or cytoskeletal dynamics, causes discrete developmental or disease phenotypes. This is surprising because many processes that were assumed to be fundamental to the function and survival of all cell types appear instead to be regulated by cell-specific mechanisms. Such discoveries are facilitated by experiments in whole animals, where zebrafish provides an ideal model for visualization and manipulation of organelles and cellular processes in a live vertebrate. Here, we review well-characterized mutants and newly developed tools that underscore this notion. We focus on the secretory pathway and microtubule-based trafficking as illustrative examples of how studying cell biology in vivo using zebrafish has broadened our understanding of the role fundamental cellular processes play in embryogenesis and disease.

  8. Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor

    Energy Technology Data Exchange (ETDEWEB)

    Szallasi, A.; Blumberg, P.M. (National Institutes of Health, Bethesda, MD (USA))

    1990-01-01

    Capsaicin, the pungent constituent of chili peppers, represents the paradigm for the capsaicinoids or vanilloids, a family of compounds shown to stimulate and then desensitize specific subpopulations of sensory receptors, including C-polymodal nociceptors, A-delta mechanoheat nociceptors and warm receptors of the skin, as well as enteroceptors of thin afferent fibers. An exciting recent advance in the field has been the finding that resiniferatoxin (RTX), a naturally occurring diterpene containing a homovanillic acid ester, a key structural motif of capsaicin, functions as an ultrapotent capsaicin analog. For most of the responses characteristic of capsaicin, RTX is 100-10,000 fold more potent. Structure/activity analysis indicates, however, that RTX and related homovanillyl-diterpene esters display distinct spectra of activity. Specific ({sup 3}H)RTX binding provides the first direct proof for the existence of vanilloid receptors. We expect that the RTX class of vanilloids will promote rapid progress in understanding of vanilloid structure/activity requirements and mechanism.

  9. Heterochronic truncation of odontogenesis in theropod dinosaurs provides insight into the macroevolution of avian beaks.

    Science.gov (United States)

    Wang, Shuo; Stiegler, Josef; Wu, Ping; Chuong, Cheng-Ming; Hu, Dongyu; Balanoff, Amy; Zhou, Yachun; Xu, Xing

    2017-09-25

    Beaks are innovative structures characterizing numerous tetrapod lineages, including birds, but little is known about how developmental processes influenced the macroevolution of these important structures. Here we provide evidence of ontogenetic vestigialization of alveoli in two lineages of theropod dinosaurs and show that these are transitional phenotypes in the evolution of beaks. One of the smallest known caenagnathid oviraptorosaurs and a small specimen of the Early Cretaceous bird Sapeornis both possess shallow, empty vestiges of dentary alveoli. In both individuals, the system of vestiges connects via foramina with a dorsally closed canal homologous to alveoli. Similar morphologies are present in Limusaurus, a beaked theropod that becomes edentulous during ontogeny; and an analysis of neontological and paleontological evidence shows that ontogenetic reduction of the dentition is a relatively common phenomenon in vertebrate evolution. Based on these lines of evidence, we propose that progressively earlier postnatal and embryonic truncation of odontogenesis corresponds with expansion of rostral keratin associated with the caruncle, and these progenesis and peramorphosis heterochronies combine to drive the evolution of edentulous beaks in nonavian theropods and birds. Following initial apomorphic expansion of rostral keratinized epithelia in perinatal toothed theropods, beaks appear to inhibit odontogenesis as they grow postnatally, resulting in a sequence of common morphologies. This sequence is shifted earlier in development through phylogeny until dentition is absent at hatching, and odontogenesis is inhibited by beak formation in ovo.

  10. Genome-Wide Analysis of Gene Expression Provides New Insights into Cold Responses in Thellungiella salsuginea

    Directory of Open Access Journals (Sweden)

    Jiangshan Wang

    2017-05-01

    Full Text Available Low temperature is one of the major environmental stresses that affects plant growth and development, and leads to decrease in crop yield and quality. Thellungiella salsuginea (salt cress exhibits high tolerance to chilling, is an appropriate model to investigate the molecular mechanisms of cold tolerance. Here, we compared transcription changes in the roots and leaves of T. salsuginea under cold stress using RNA-seq. We identified 2,782 and 1,430 differentially expressed genes (DEGs in leaves and roots upon cold treatment, respectively. The expression levels of some genes were validated by quantitative real-time-PCR (qRT-PCR. Among these DEGs, 159 (11.1% genes in roots and 232 (8.3% genes in leaves were annotated as various types of transcription factors. We found that five aquaporin genes (three TIPs, one PIPs, and one NIPs responded to cold treatment. In addition, the expression of COR47, ICE1, and CBF1 genes of DREB1/CBF-dependent cold signaling pathway genes altered in response to low temperature. KEGG pathway analysis indicated that these cold regulated genes were enriched in metabolism, photosynthesis, circadian rhythm, and transcriptional regulation. Our findings provided a complete picture of the regulatory network of cold stress response in T. salsuginea. These cold-responsive genes could be targeted for detail functional study and utilization in crop cold tolerance improvement.

  11. Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology

    Science.gov (United States)

    Dey, Aditi; Castleton, Anna Z.; Schwab, Claire; Samuel, Edward; Sivakumaran, Janani; Beaton, Brendan; Zareian, Nahid; Zhang, Christie Yu; Rai, Lena; Enver, Tariq; Moorman, Anthony V.; Fielding, Adele K.

    2014-01-01

    The distinct nature of acute lymphoblastic leukemia (ALL) in adults, evidenced by inferior treatment outcome and different genetic landscape, mandates specific studies of disease-initiating mechanisms. In this study, we used NOD/LtSz-scid IL2Rγ nullc (NSG) mouse xenotransplantation approaches to elucidate leukemia-initiating cell (LIC) biology in primary adult precursor B (pre-B) ALL to optimize disease modeling. In contrast with xenografting studies of pediatric ALL, we found that modification of the NSG host environment using preconditioning total body irradiation (TBI) was indispensable for efficient engraftment of adult non-t(4;11) pre-B ALL, whereas t(4;11) pre-B ALL was successfully reconstituted without this adaptation. Furthermore, TBI-based xenotransplantation of non-t(4;11) pre-B ALL enabled detection of a high frequency of LICs (<1:6900) and permitted frank leukemic engraftment from a remission sample containing drug-resistant minimal residual disease. Investigation of TBI-sensitive stromal-derived factor-1/chemokine receptor type 4 signaling revealed greater functional dependence of non-t(4;11) pre-B ALL on this niche-based interaction, providing a possible basis for the differential engraftment behavior. Thus, our studies establish the optimal conditions for experimental modeling of human adult pre-B ALL and demonstrate the critical protumorogenic role of microenvironment-derived SDF-1 in regulating adult pre-B LIC activity that may present a therapeutic opportunity. PMID:24825861

  12. Pathway analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Hariklia Eleftherohorinou

    Full Text Available Although the introduction of genome-wide association studies (GWAS have greatly increased the number of genes associated with common diseases, only a small proportion of the predicted genetic contribution has so far been elucidated. Studying the cumulative variation of polymorphisms in multiple genes acting in functional pathways may provide a complementary approach to the more common single SNP association approach in understanding genetic determinants of common disease. We developed a novel pathway-based method to assess the combined contribution of multiple genetic variants acting within canonical biological pathways and applied it to data from 14,000 UK individuals with 7 common diseases. We tested inflammatory pathways for association with Crohn's disease (CD, rheumatoid arthritis (RA and type 1 diabetes (T1D with 4 non-inflammatory diseases as controls. Using a variable selection algorithm, we identified variants responsible for the pathway association and evaluated their use for disease prediction using a 10 fold cross-validation framework in order to calculate out-of-sample area under the Receiver Operating Curve (AUC. The generalisability of these predictive models was tested on an independent birth cohort from Northern Finland. Multiple canonical inflammatory pathways showed highly significant associations (p 10(-3-10(-20 with CD, T1D and RA. Variable selection identified on average a set of 205 SNPs (149 genes for T1D, 350 SNPs (189 genes for RA and 493 SNPs (277 genes for CD. The pattern of polymorphisms at these SNPS were found to be highly predictive of T1D (91% AUC and RA (85% AUC, and weakly predictive of CD (60% AUC. The predictive ability of the T1D model (without any parameter refitting had good predictive ability (79% AUC in the Finnish cohort. Our analysis suggests that genetic contribution to common inflammatory diseases operates through multiple genes interacting in functional pathways.

  13. Quantitative analysis of glycerol in dicarboxylic acid-rich cutins provides insights into Arabidopsis cutin structure.

    Science.gov (United States)

    Yang, Weili; Pollard, Mike; Li-Beisson, Yonghua; Ohlrogge, John

    2016-10-01

    Cutin is an extracellular lipid polymer that contributes to protective cuticle barrier functions against biotic and abiotic stresses in land plants. Glycerol has been reported as a component of cutin, contributing up to 14% by weight of total released monomers. Previous studies using partial hydrolysis of cuticle-enriched preparations established the presence of oligomers with glycerol-aliphatic ester links. Furthermore, glycerol-3-phosphate 2-O-acyltransferases (sn-2-GPATs) are essential for cutin biosynthesis. However, precise roles of glycerol in cutin assembly and structure remain uncertain. Here, a stable isotope-dilution assay was developed for the quantitative analysis of glycerol by GC/MS of triacetin with simultaneous determination of aliphatic monomers. To provide clues about the role of glycerol in dicarboxylic acid (DCA)-rich cutins, this methodology was applied to compare wild-type (WT) Arabidopsis cutin with a series of mutants that are defective in cutin synthesis. The molar ratio of glycerol to total DCAs in WT cutins was 2:1. Even when allowing for a small additional contribution from hydroxy fatty acids, this is a substantially higher glycerol to aliphatic monomer ratio than previously reported for any cutin. Glycerol content was strongly reduced in both stem and leaf cutin from all Arabidopsis mutants analyzed (gpat4/gpat8, att1-2 and lacs2-3). In addition, the molar reduction of glycerol was proportional to the molar reduction of total DCAs. These results suggest "glycerol-DCA-glycerol" may be the dominant motif in DCA-rich cutins. The ramifications and caveats for this hypothesis are presented.

  14. Echidna venom gland transcriptome provides insights into the evolution of monotreme venom.

    Directory of Open Access Journals (Sweden)

    Emily S W Wong

    Full Text Available Monotremes (echidna and platypus are egg-laying mammals. One of their most unique characteristic is that males have venom/crural glands that are seasonally active. Male platypuses produce venom during the breeding season, delivered via spurs, to aid in competition against other males. Echidnas are not able to erect their spurs, but a milky secretion is produced by the gland during the breeding season. The function and molecular composition of echidna venom is as yet unknown. Hence, we compared the deeply sequenced transcriptome of an in-season echidna crural gland to that of a platypus and searched for putative venom genes to provide clues into the function of echidna venom and the evolutionary history of monotreme venom. We found that the echidna venom gland transcriptome was markedly different from the platypus with no correlation between the top 50 most highly expressed genes. Four peptides found in the venom of the platypus were detected in the echidna transcriptome. However, these genes were not highly expressed in echidna, suggesting that they are the remnants of the evolutionary history of the ancestral venom gland. Gene ontology terms associated with the top 100 most highly expressed genes in echidna, showed functional terms associated with steroidal and fatty acid production, suggesting that echidna "venom" may play a role in scent communication during the breeding season. The loss of the ability to erect the spur and other unknown evolutionary forces acting in the echidna lineage resulted in the gradual decay of venom components and the evolution of a new role for the crural gland.

  15. Echidna venom gland transcriptome provides insights into the evolution of monotreme venom.

    Science.gov (United States)

    Wong, Emily S W; Nicol, Stewart; Warren, Wesley C; Belov, Katherine

    2013-01-01

    Monotremes (echidna and platypus) are egg-laying mammals. One of their most unique characteristic is that males have venom/crural glands that are seasonally active. Male platypuses produce venom during the breeding season, delivered via spurs, to aid in competition against other males. Echidnas are not able to erect their spurs, but a milky secretion is produced by the gland during the breeding season. The function and molecular composition of echidna venom is as yet unknown. Hence, we compared the deeply sequenced transcriptome of an in-season echidna crural gland to that of a platypus and searched for putative venom genes to provide clues into the function of echidna venom and the evolutionary history of monotreme venom. We found that the echidna venom gland transcriptome was markedly different from the platypus with no correlation between the top 50 most highly expressed genes. Four peptides found in the venom of the platypus were detected in the echidna transcriptome. However, these genes were not highly expressed in echidna, suggesting that they are the remnants of the evolutionary history of the ancestral venom gland. Gene ontology terms associated with the top 100 most highly expressed genes in echidna, showed functional terms associated with steroidal and fatty acid production, suggesting that echidna "venom" may play a role in scent communication during the breeding season. The loss of the ability to erect the spur and other unknown evolutionary forces acting in the echidna lineage resulted in the gradual decay of venom components and the evolution of a new role for the crural gland.

  16. Transcriptome analysis of Nautilus and pygmy squid developing eye provides insights in lens and eye evolution.

    Science.gov (United States)

    Sousounis, Konstantinos; Ogura, Atsushi; Tsonis, Panagiotis A

    2013-01-01

    Coleoid cephalopods like squids have a camera-type eye similar to vertebrates. On the other hand, Nautilus (Nautiloids) has a pinhole eye that lacks lens and cornea. Since pygmy squid and Nautilus are closely related species they are excellent model organisms to study eye evolution. Having being able to collect Nautilus embryos, we employed next-generation RNA sequencing using Nautilus and pygmy squid developing eyes. Their transcriptomes were compared and analyzed. Enrichment analysis of Gene Ontology revealed that contigs related to nucleic acid binding were largely up-regulated in squid, while the ones related to metabolic processes and extracellular matrix-related genes were up-regulated in Nautilus. These differences are most likely correlated with the complexity of tissue organization in these species. Moreover, when the analysis focused on the eye-related contigs several interesting patterns emerged. First, contigs from both species related to eye tissue differentiation and morphogenesis as well as to cilia showed best hits with their Human counterparts, while contigs related to rabdomeric photoreceptors showed the best hit with their Drosophila counterparts. This bolsters the idea that eye morphogenesis genes have been generally conserved in evolution, and compliments other studies showing that genes involved in photoreceptor differentiation clearly follow the diversification of invertebrate (rabdomeric) and vertebrate (ciliated) photoreceptors. Interestingly some contigs showed as good a hit with Drosophila and Human homologues in Nautilus and squid samples. One of them, capt/CAP1, is known to be preferentially expressed in Drosophila developing eye and in vertebrate lens. Importantly our analysis also provided evidence of gene duplication and diversification of their function in both species. One of these genes is the Neurofibromatosis 1 (NF1/Nf1), which in mice has been implicated in lens formation, suggesting a hitherto unsuspected role in the evolution

  17. Wing shape of four new bee fossils (Hymenoptera: Anthophila) provides insights to bee evolution.

    Science.gov (United States)

    Dehon, Manuel; Michez, Denis; Nel, André; Engel, Michael S; De Meulemeester, Thibaut

    2014-01-01

    Bees (Anthophila) are one of the major groups of angiosperm-pollinating insects and accordingly are widely studied in both basic and applied research, for which it is essential to have a clear understanding of their phylogeny, and evolutionary history. Direct evidence of bee evolutionary history has been hindered by a dearth of available fossils needed to determine the timing and tempo of their diversification, as well as episodes of extinction. Here we describe four new compression fossils of bees from three different deposits (Miocene of la Cerdanya, Spain; Oligocene of Céreste, France; and Eocene of the Green River Formation, U.S.A.). We assess the similarity of the forewing shape of the new fossils with extant and fossil taxa using geometric morphometrics analyses. Predictive discriminant analyses show that three fossils share similar forewing shapes with the Apidae [one of uncertain tribal placement and perhaps near Euglossini, one definitive bumble bee (Bombini), and one digger bee (Anthophorini)], while one fossil is more similar to the Andrenidae. The corbiculate fossils are described as Euglossopteryx biesmeijeri De Meulemeester, Michez, & Engel, gen. nov. sp. nov. (type species of Euglossopteryx Dehon & Engel, n. gen.) and Bombus cerdanyensis Dehon, De Meulemeester, & Engel, sp. nov. They provide new information on the distribution and timing of particular corbiculate groups, most notably the extension into North America of possible Eocene-Oligocene cooling-induced extinctions. Protohabropoda pauli De Meulemeester & Michez, gen. nov. sp. nov. (type species of Protohabropoda Dehon & Engel, n. gen.) reinforces previous hypotheses of anthophorine evolution in terms of ecological shifts by the Oligocene from tropical to mesic or xeric habitats. Lastly, a new fossil of the Andreninae, Andrena antoinei Michez & De Meulemeester, sp. nov., further documents the presence of the today widespread genus Andrena Fabricius in the Late Oligocene of France.

  18. Inferences from the historical distribution of wild and domesticated maize provide ecological and evolutionary insight.

    Directory of Open Access Journals (Sweden)

    Matthew B Hufford

    Full Text Available BACKGROUND: The species Zea mays includes both domesticated maize (ssp. mays and its closest wild relatives known as the teosintes. While genetic and archaeological studies have provided a well-established history of Z. mays evolution, there is currently minimal description of its current and past distribution. Here, we implemented species distribution modeling using paleoclimatic models of the last interglacial (LI; ∼135,000 BP and the last glacial maximum (LGM; ∼21,000 BP to hindcast the distribution of Zea mays subspecies over time and to revisit current knowledge of its phylogeography and evolutionary history. METHODOLOGY/PRINCIPAL FINDINGS: Using a large occurrence data set and the distribution modeling MaxEnt algorithm, we obtained robust present and past species distributions of the two widely distributed teosinte subspecies (ssps. parviglumis and mexicana revealing almost perfect complementarity, stable through time, of their occupied distributions. We also investigated the present distributions of primitive maize landraces, which overlapped but were broader than those of the teosintes. Our data reinforced the idea that little historical gene flow has occurred between teosinte subspecies, but maize has served as a genetic bridge between them. We observed an expansion of teosinte habitat from the LI, consistent with population genetic data. Finally, we identified locations potentially serving as refugia for the teosintes throughout epochs of climate change and sites that should be targeted in future collections. CONCLUSION/SIGNIFICANCE: The restricted and highly contrasting ecological niches of the wild teosintes differ substantially from domesticated maize. Variables determining the distributions of these taxa can inform future considerations of local adaptation and the impacts of climate change. Our assessment of the changing distributions of Zea mays taxa over time offers a unique glimpse into the history of maize, highlighting a

  19. Whole Transcriptome Analysis Provides Insights into Molecular Mechanisms for Molting in Litopenaeus vannamei.

    Science.gov (United States)

    Gao, Yi; Zhang, Xiaojun; Wei, Jiankai; Sun, Xiaoqing; Yuan, Jianbo; Li, Fuhua; Xiang, Jianhai

    2015-01-01

    Molting is one of the most important biological processes in shrimp growth and development. All shrimp undergo cyclic molting periodically to shed and replace their exoskeletons. This process is essential for growth, metamorphosis, and reproduction in shrimp. However, the molecular mechanisms underlying shrimp molting remain poorly understood. In this study, we investigated global expression changes in the transcriptomes of the Pacific white shrimp, Litopenaeus vannamei, the most commonly cultured shrimp species worldwide. The transcriptome of whole L. vannamei was investigated by RNA-sequencing (RNA-seq) throughout the molting cycle, including the inter-molt (C), pre-molt (D0, D1, D2, D3, D4), and post-molt (P1 and P2) stages, and 93,756 unigenes were identified. Among these genes, we identified 5,117 genes differentially expressed (log2ratio ≥1 and FDR ≤0.001) in adjacent molt stages. The results were compared against the National Center for Biotechnology Information (NCBI) non-redundant protein/nucleotide sequence database, Swiss-Prot, PFAM database, the Gene Ontology database, and the Kyoto Encyclopedia of Genes and Genomes database in order to annotate gene descriptions, associate them with gene ontology terms, and assign them to pathways. The expression patterns for genes involved in several molecular events critical for molting, such as hormone regulation, triggering events, implementation phases, skelemin, immune responses were characterized and considered as mechanisms underlying molting in L. vannamei. Comparisons with transcriptomic analyses in other arthropods were also performed. The characterization of major transcriptional changes in genes involved in the molting cycle provides candidates for future investigation of the molecular mechanisms. The data generated in this study will serve as an important transcriptomic resource for the shrimp research community to facilitate gene and genome annotation and to characterize key molecular processes

  20. The Genome of Laccaria Bi color Provides Insights into Mycorrhizal Symbiosis

    Energy Technology Data Exchange (ETDEWEB)

    Martin, F [UMR, France; Aerts, A. [U.S. Department of Energy, Joint Genome Institute; Ahren, D [Lund University, Sweden; Brun, A [UMR, France; Duchaussoy, F [UMR, France; Gibon, J [UMR, France; Kohler, A [UMR, France; Lindquist, E [U.S. Department of Energy, Joint Genome Institute; Pereda, V [UMR, France; Salamov, A. [U.S. Department of Energy, Joint Genome Institute; Shapiro, HJ [U.S. Department of Energy, Joint Genome Institute; Wuyts, J [UMR, France; Blaudez, D [UMR, France; Buee, M [UMR, France; Brokstein, P [U.S. Department of Energy, Joint Genome Institute; Canbeck, B [Lund University, Sweden; Cohen, D [UMR, France; Courty, PE [UMR, France; Coutinho, PM [Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS and Unive; Danchin, E [Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS and Unive; Delaruelle, C [UMR, France; Detter, J C [U.S. Department of Energy, Joint Genome Institute; Deveau, A [UMR, France; DiFazio, Stephen P [West Virginia University; Duplessis, S [UMR, France; Fraissinet-Tachet, L [Universite de Lyon, France; Lucic, E [UMR, France; Frey-Klett, P [UMR, France; Fourrey, C [UMR, France; Feussner, I [Georg-August Universitat Gottingen Germany; Gay, G [Universite de Lyon, France; Grimwood, Jane [Stanford University; Hoegger, P J [Georg-August Universitat Gottingen Germany; Jain, P [University of Alabama, Huntsville; Kilaru, S [Georg-August Universitat Gottingen Germany; Labbe, J [UMR, France; Lin, Y C [Ghent University, Belgium; Legue, V [UMR, France; Le Tacon, F [UMR, France; Marmeisse, R [Universite de Lyon, France; Melayah, D [Universite de Lyon, France; Montanini, B [UMR, France; Muratet, M [University of Alabama, Huntsville; Nehls, U [Eberhard-Karls-Universitat, Tubingen, Germany; Niculita-Hirzel, H [University of Lausanne, Switzerland; Oudot-Le Secq, M P [UMR, France; Peter, M [UMR, France; Quesneville, H [Unite de Recherches en Genomique-Info,Evry Cedex; Rajashekar, B [Lund University, Sweden; Reich, M [UMR, France; Rouhler, N [UMR, France; Schmutz, Jeremy [Stanford University; Yin, Tongming [ORNL; Chalot, M [UMR, France; Henrissat, B [Architecture et Fonction des Macromolecules Biologiques, UMR 6098 CNRS and Unive; Kues, U [Georg-August Universitat Gottingen Germany; Lucas, S [U.S. Department of Energy, Joint Genome Institute; Van de Peer, Y [Ghent University, Belgium; Podila, G [University of Alabama, Huntsville; Polle, A [Georg-August Universitat Gottingen Germany; Pukkila, P J [University of North Carolina, Chapel Hill; Richardson, P M [U.S. Department of Energy, Joint Genome Institute; Rouze, P [Ghent University, Belgium; Sanders, I R [University of Lausanne, Switzerland; Stajich, J E [University of California, Berkeley; Tunlid, A [Lund University, Sweden; Tuskan, Gerald A [ORNL; Grigoriev, I. [U.S. Department of Energy, Joint Genome Institute

    2008-01-01

    Mycorrhizal symbioses the union of roots and soil fungi are universal in terrestrial ecosystems and may have been fundamental to land colonization by plants1,2. Boreal, temperate and montane forests all depend on ectomycorrhizae1. Identification of the primary factors that regulate symbiotic development and metabolic activity will therefore open the door to understanding the role of ectomycorrhizae in plant development and physiology, allowing the full ecological significance of this symbiosis to be explored. Here we report the genome sequence of the ectomycorrhizal basidiomycete Laccaria bicolor (Fig. 1) and highlight gene sets involved in rhizosphere colonization and symbiosis. This 65-megabase genome assembly contains 20,000 predicted protein-encoding genes and a very large number of transposons and repeated sequences. We detected unexpected genomic features, most notably a battery of effector-type small secreted proteins (SSPs) with unknown function, several of which are only expressed in symbiotic tissues. The most highly expressed SSP accumulates in the proliferating hyphae colonizing the host root. The ectomycorrhizae-specific SSPs probably have a decisive role in the establishment of the symbiosis. The unexpected observation that the genome of L. bicolor lacks carbohydrate-active enzymes involved in degradation of plant cell walls, but maintains the ability to degrade non-plant cell wall polysaccharides, reveals the dual saprotrophic and biotrophic lifestyle of the mycorrhizal fungus that enables it to grow within both soil and living plant roots. The predicted gene inventory of the L. bicolor genome, therefore, points to previously unknown mechanisms of symbiosis operating in biotrophic mycorrhizal fungi. The availability of this genome provides an unparalleled opportunity to develop a deeper understanding of the processes by which symbionts interact with plants within their ecosystem to perform vital functions in the carbon and

  1. Temporal-Spatial Transcriptome Analyses Provide Insights into the Development of Petaloid Androecium in Canna indica

    Directory of Open Access Journals (Sweden)

    Xueyi Tian

    2016-08-01

    Full Text Available Canna indica (Zingiberales is one of the most important ornamental species characterized with beautiful petaloid staminodes, which are considered to evolve from stamens. However, the genetic basis for the development of petaloid staminodes remains unclear largely because the genomic sequences are not available. By using RNA-Seq, we sequenced the transcripts in the flower of Canna indica, and quantified the temporal gene expressions in flower primordium and differentiated flower, as well as the spatial gene expressions in petal and petaloid staminode. In total, 118,869 unigenes were assembled, among which 67,299 unigenes were annotated. Quantification analysis identified the differentially expressed genes in the temporal and spatial two comparisons, based on which, Gene Ontology enrichment analysis highlighted the representative terms in each sample, such as specification of organ number in flower primordium, growth in differentiated flower, secondary cell wall biogenesis in petal and cell division in petaloid staminode. Among the 51 analyzed MADS-box unigenes, 37 were up-regulated in differentiated flower compared with those in flower primordium. A-class unigenes were expressed higher in petal than in petaloid staminode, and C-class unigenes were expressed oppositely, whereas B-class unigenes demonstrated close expression levels in these two organs, indicating that petaloid staminode retains stamen identity to some degree. In situ hybridization provided more detailed expression patterns of these unigenes, and revealed the extended expression of B-class to the carpel at later stages when the style turned flat. These results constitute a preliminary basis for the study of flower development in Canna indica and can be applied in further study of the evolution of Zingiberales.

  2. SSR marker variations in Brassica species provide insight into the origin and evolution of Brassica amphidiploids.

    Science.gov (United States)

    Thakur, Ajay Kumar; Singh, Kunwar Harendra; Singh, Lal; Nanjundan, Joghee; Khan, Yasin Jeshima; Singh, Dhiraj

    2018-01-01

    Oilseed Brassica represents an important group of oilseed crops with a long history of evolution and cultivation. To understand the origin and evolution of Brassica amphidiploids, simple sequence repeat (SSR) markers were used to unravel genetic variations in three diploids and three amphidiploid Brassica species of U's triangle along with Eruca sativa as an outlier. Of 124 Brassica-derived SSR loci assayed, 100% cross-transferability was obtained for B. juncea and three subspecies of B. rapa, while lowest cross-transferability (91.93%) was obtained for Eruca sativa. The average % age of cross-transferability across all the seven species was 98.15%. The number of alleles detected at each locus ranged from one to six with an average of 3.41 alleles per primer pair. Neighbor-Joining-based dendrogram divided all the 40 accessions into two main groups composed of B. juncea/B. nigra/B. rapa and B. carinata/B. napus/B. oleracea. C-genome of oilseed Brassica species remained relatively more conserved than A- and B-genome. A- genome present in B. juncea and B. napus seems distinct from each other and hence provides great opportunity for generating diversity through synthesizing amphidiploids from different sources of A- genome. B. juncea had least intra-specific distance indicating narrow genetic base. B. rapa appears to be more primitive species from which other two diploid species might have evolved. The SSR marker set developed in this study will assist in DNA fingerprinting of various Brassica species cultivars, evaluating the genetic diversity in Brassica germplasm, genome mapping and construction of linkage maps, gene tagging and various other genomics-related studies in Brassica species. Further, the evolutionary relationship established among various Brassica species would assist in formulating suitable breeding strategies for widening the genetic base of Brassica amphidiploids by exploiting the genetic diversity present in diploid progenitor gene pools.

  3. Hierarchical partitioning of metazoan protein conservation profiles provides new functional insights.

    Directory of Open Access Journals (Sweden)

    Jonathan Witztum

    Full Text Available The availability of many complete, annotated proteomes enables the systematic study of the relationships between protein conservation and functionality. We explore this question based solely on the presence or absence of protein homologues (a.k.a. conservation profiles. We study 18 metazoans, from two distinct points of view: the human's and the fly's. Using the GOrilla gene ontology (GO analysis tool, we explore functional enrichment of the "universal proteins", those with homologues in all 17 other species, and of the "non-universal proteins". A large number of GO terms are strongly enriched in both human and fly universal proteins. Most of these functions are known to be essential. A smaller number of GO terms, exhibiting markedly different properties, are enriched in both human and fly non-universal proteins. We further explore the non-universal proteins, whose conservation profiles are consistent with the "tree of life" (TOL consistent, as well as the TOL inconsistent proteins. Finally, we applied Quantum Clustering to the conservation profiles of the TOL consistent proteins. Each cluster is strongly associated with one or a small number of specific monophyletic clades in the tree of life. The proteins in many of these clusters exhibit strong functional enrichment associated with the "life style" of the related clades. Most previous approaches for studying function and conservation are "bottom up", studying protein families one by one, and separately assessing the conservation of each. By way of contrast, our approach is "top down". We globally partition the set of all proteins hierarchically, as described above, and then identify protein families enriched within different subdivisions. While supporting previous findings, our approach also provides a tool for discovering novel relations between protein conservation profiles, functionality, and evolutionary history as represented by the tree of life.

  4. Wing shape of four new bee fossils (Hymenoptera: Anthophila provides insights to bee evolution.

    Directory of Open Access Journals (Sweden)

    Manuel Dehon

    Full Text Available Bees (Anthophila are one of the major groups of angiosperm-pollinating insects and accordingly are widely studied in both basic and applied research, for which it is essential to have a clear understanding of their phylogeny, and evolutionary history. Direct evidence of bee evolutionary history has been hindered by a dearth of available fossils needed to determine the timing and tempo of their diversification, as well as episodes of extinction. Here we describe four new compression fossils of bees from three different deposits (Miocene of la Cerdanya, Spain; Oligocene of Céreste, France; and Eocene of the Green River Formation, U.S.A.. We assess the similarity of the forewing shape of the new fossils with extant and fossil taxa using geometric morphometrics analyses. Predictive discriminant analyses show that three fossils share similar forewing shapes with the Apidae [one of uncertain tribal placement and perhaps near Euglossini, one definitive bumble bee (Bombini, and one digger bee (Anthophorini], while one fossil is more similar to the Andrenidae. The corbiculate fossils are described as Euglossopteryx biesmeijeri De Meulemeester, Michez, & Engel, gen. nov. sp. nov. (type species of Euglossopteryx Dehon & Engel, n. gen. and Bombus cerdanyensis Dehon, De Meulemeester, & Engel, sp. nov. They provide new information on the distribution and timing of particular corbiculate groups, most notably the extension into North America of possible Eocene-Oligocene cooling-induced extinctions. Protohabropoda pauli De Meulemeester & Michez, gen. nov. sp. nov. (type species of Protohabropoda Dehon & Engel, n. gen. reinforces previous hypotheses of anthophorine evolution in terms of ecological shifts by the Oligocene from tropical to mesic or xeric habitats. Lastly, a new fossil of the Andreninae, Andrena antoinei Michez & De Meulemeester, sp. nov., further documents the presence of the today widespread genus Andrena Fabricius in the Late Oligocene of France.

  5. The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise Transcription until Infection.

    Directory of Open Access Journals (Sweden)

    David Roquis

    Full Text Available Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC. It allows them to rapidly engage specific developmental pathways. We reasoned that non-vertebrate metazoans that encounter a similar developmental constraint (i.e. to quickly start development into a new phenotype might use a similar system. Schistosomes are parasitic platyhelminthes that are characterized by passage through two hosts: a mollusk as intermediate host and humans or rodents as definitive host. During its development, the parasite undergoes drastic changes, most notable immediately after infection of the definitive host, i.e. during the transition from the free-swimming cercariae into adult worms.We used Chromatin Immunoprecipitation followed by massive parallel sequencing (ChIP-Seq to analyze genome-wide chromatin structure of S. mansoni on the level of histone modifications (H3K4me3, H3K27me3, H3K9me3, and H3K9ac in cercariae, schistosomula and adults (available at http://genome.univ-perp.fr. We saw striking differences in chromatin structure between the developmental stages, but most importantly we found that cercariae possess a specific combination of marks at the transcription start sites (TSS that has similarities to a structure found in ESC. We demonstrate that in cercariae no transcription occurs, and we provide evidences that cercariae do not possess large numbers of canonical stem cells.We describe here a broad view on the epigenome of a metazoan parasite. Most notably, we find bivalent histone H3 methylation in cercariae. Methylation of H3K27 is removed during transformation into schistosomula (and stays absent in adults and transcription is activated. In addition, shifts of H3K9 methylation and acetylation occur towards upstream and downstream of the transcriptional start site (TSS. We conclude

  6. Comprehensive transcriptome analysis provides new insights into nutritional strategies and phylogenetic relationships of chrysophytes

    Directory of Open Access Journals (Sweden)

    Daniela Beisser

    2017-01-01

    based on ribosomal RNA and orthologous genes. Finally, we make functionally annotated reference transcriptomes of each strain available to the community, significantly enhancing publicly available data on Chrysophyceae. Conclusions Our study is the first comprehensive transcriptomic characterisation of a diverse set of Chrysophyceaen strains. In addition, we showcase the possibility of inferring phylogenies from assembled transcriptomes using an alignment-free approach. The raw and functionally annotated data we provide will prove beneficial for further examination of the diversity within this taxon. Our molecular characterisation of different trophic modes presents a first such example.

  7. Galaxy Evolution Insights from Spectral Modeling of Large Data Sets from the Sloan Digital Sky Survey

    Energy Technology Data Exchange (ETDEWEB)

    Hoversten, Erik A. [Johns Hopkins Univ., Baltimore, MD (United States)

    2007-10-01

    This thesis centers on the use of spectral modeling techniques on data from the Sloan Digital Sky Survey (SDSS) to gain new insights into current questions in galaxy evolution. The SDSS provides a large, uniform, high quality data set which can be exploited in a number of ways. One avenue pursued here is to use the large sample size to measure precisely the mean properties of galaxies of increasingly narrow parameter ranges. The other route taken is to look for rare objects which open up for exploration new areas in galaxy parameter space. The crux of this thesis is revisiting the classical Kennicutt method for inferring the stellar initial mass function (IMF) from the integrated light properties of galaxies. A large data set (~ 105 galaxies) from the SDSS DR4 is combined with more in-depth modeling and quantitative statistical analysis to search for systematic IMF variations as a function of galaxy luminosity. Galaxy Hα equivalent widths are compared to a broadband color index to constrain the IMF. It is found that for the sample as a whole the best fitting IMF power law slope above 0.5 M is Γ = 1.5 ± 0.1 with the error dominated by systematics. Galaxies brighter than around Mr,0.1 = -20 (including galaxies like the Milky Way which has Mr,0.1 ~ -21) are well fit by a universal Γ ~ 1.4 IMF, similar to the classical Salpeter slope, and smooth, exponential star formation histories (SFH). Fainter galaxies prefer steeper IMFs and the quality of the fits reveal that for these galaxies a universal IMF with smooth SFHs is actually a poor assumption. Related projects are also pursued. A targeted photometric search is conducted for strongly lensed Lyman break galaxies (LBG) similar to MS1512-cB58. The evolution of the photometric selection technique is described as are the results of spectroscopic follow-up of the best targets. The serendipitous discovery of two interesting blue compact dwarf galaxies is reported. These

  8. Understanding the cost of dermatologic care: A survey study of dermatology providers, residents, and patients.

    Science.gov (United States)

    Steen, Aaron J; Mann, Julianne A; Carlberg, Valerie M; Kimball, Alexa B; Musty, Michael J; Simpson, Eric L

    2017-04-01

    The American Academy of Dermatology recommends dermatologists understand the costs of dermatologic care. This study sought to measure dermatology providers' understanding of the cost of dermatologic care and how those costs are communicated to patients. We also aimed to understand the perspectives of patients and dermatological trainees on how cost information enters into the care they receive or provide. Surveys were systematically developed and distributed to 3 study populations: dermatology providers, residents, and patients. Response rates were over 95% in all 3 populations. Dermatology providers and residents consistently underestimated the costs of commonly recommended dermatologic medications but accurately predicted the cost of common dermatologic procedures. Dermatology patients preferred to know the cost of procedures and medications, even when covered by insurance. In this population, the costs of dermatologic medications frequently interfered with patients' ability to properly adhere to prescribed regimens. The surveyed population was limited to the northwestern United States and findings may not be generalizable. Cost estimations were based on average reimbursement rates, which vary by insurer. Improving dermatology providers' awareness and communication of the costs of dermatologic care might enhance medical decision-making, improve adherence and outcomes, and potentially reduce overall health care expenditures. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  9. Mechanisms of cell death in canine parvovirus-infected cells provide intuitive insights to developing nanotools for medicine.

    Science.gov (United States)

    Nykky, Jonna; Tuusa, Jenni E; Kirjavainen, Sanna; Vuento, Matti; Gilbert, Leona

    2010-08-09

    Viruses have great potential as nanotools in medicine for gene transfer, targeted gene delivery, and oncolytic cancer virotherapy. Here we have studied cell death mechanisms of canine parvovirus (CPV) to increase the knowledge on the CPV life cycle in order to facilitate the development of better parvovirus vectors. Morphological studies of CPV-infected Norden laboratory feline kidney (NLFK) cells and canine fibroma cells (A72) displayed characteristic apoptotic events. Apoptosis was further confirmed by activation of caspases and cellular DNA damage. However, results from annexin V-propidium iodide (PI) labeling and membrane polarization assays indicated disruption of the plasma membrane uncommon to apoptosis. These results provide evidence that secondary necrosis followed apoptosis. In addition, two human cancer cell lines were found to be infected by CPV. This necrotic event over apoptotic cell death and infection in human cells provide insightful information when developing CPV as a nanotool for cancer treatments.

  10. Smartphone use habits of anesthesia providers during anesthetized patient care: a survey from Turkey.

    Science.gov (United States)

    Pınar, Hüseyin Ulaş; Karaca, Omer; Doğan, Rafi; Konuk, Ümmü Mine

    2016-10-06

    Smartphones are used in many areas of anesthesia practice. However, recent editorial articles have expressed concerns about smartphone uses in the operating room for non-medical purposes. We performed a survey to learn about the smartphone use habits and views of Turkish anesthesia providers. A questionnaire consisting of 14 questions about smartphone use habits during anesthesia care was sent anesthesia providers. In November-December 2015, a total of 955 participants answered our survey with 93.7 % of respondents responding that they used smartphones during the anesthetized patient care. Phone calls (65.4 %), messaging (46.4 %), social media (35.3 %), and surfing the internet (33.7 %) were the most common purposes. However, 96.7 % of respondents indicated that smartphones were either never or seldom used during critical stages of anesthesia. Most respondents (87.3 %) stated that they were never distracted because of smartphone use; however, 41 % had witnessed their collagues in such a situation at least once. According to the results of the survey, smartphones are used in the operating room often for non-medical purposes. Distraction remains a concern but evidence-based data on whether restrictions to smartphone use are required are not yet available.

  11. Systematic large-scale study of the inheritance mode of Mendelian disorders provides new insight into human diseasome.

    Science.gov (United States)

    Hao, Dapeng; Wang, Guangyu; Yin, Zuojing; Li, Chuanxing; Cui, Yan; Zhou, Meng

    2014-11-01

    One important piece of information about the human Mendelian disorders is the mode of inheritance. Recent studies of human genetic diseases on a large scale have provided many novel insights into the underlying molecular mechanisms. However, most successful analyses ignored the mode of inheritance of diseases, which severely limits our understanding of human disease mechanisms relating to the mode of inheritance at the large scale. Therefore, we here conducted a systematic large-scale study of the inheritance mode of Mendelian disorders, to bring new insight into human diseases. Our analyses include the comparison between dominant and recessive disease genes on both genomic and proteomic characteristics, Mendelian mutations, protein network properties and disease connections on both the genetic and the population levels. We found that dominant disease genes are more functionally central, topological central and more sensitive to disease outcome. On the basis of these findings, we suggested that dominant diseases should have higher genetic heterogeneity and should have more comprehensive connections with each other compared with recessive diseases, a prediction we confirm by disease network and disease comorbidity.

  12. Can high resolution 3D topographic surveys provide reliable grain size estimates in gravel bed rivers?

    Science.gov (United States)

    Pearson, E.; Smith, M. W.; Klaar, M. J.; Brown, L. E.

    2017-09-01

    High resolution topographic surveys such as those provided by Structure-from-Motion (SfM) contain a wealth of information that is not always exploited in the generation of Digital Elevation Models (DEMs). In particular, several authors have related sub-metre scale topographic variability (or 'surface roughness') to sediment grain size by deriving empirical relationships between the two. In fluvial applications, such relationships permit rapid analysis of the spatial distribution of grain size over entire river reaches, providing improved data to drive three-dimensional hydraulic models, allowing rapid geomorphic monitoring of sub-reach river restoration projects, and enabling more robust characterisation of riverbed habitats. However, comparison of previously published roughness-grain-size relationships shows substantial variability between field sites. Using a combination of over 300 laboratory and field-based SfM surveys, we demonstrate the influence of inherent survey error, irregularity of natural gravels, particle shape, grain packing structure, sorting, and form roughness on roughness-grain-size relationships. Roughness analysis from SfM datasets can accurately predict the diameter of smooth hemispheres, though natural, irregular gravels result in a higher roughness value for a given diameter and different grain shapes yield different relationships. A suite of empirical relationships is presented as a decision tree which improves predictions of grain size. By accounting for differences in patch facies, large improvements in D50 prediction are possible. SfM is capable of providing accurate grain size estimates, although further refinement is needed for poorly sorted gravel patches, for which c-axis percentiles are better predicted than b-axis percentiles.

  13. An Extended, Boolean Model of the Septation Initiation Network in S.Pombe Provides Insights into Its Regulation.

    Science.gov (United States)

    Chasapi, Anastasia; Wachowicz, Paulina; Niknejad, Anne; Collin, Philippe; Krapp, Andrea; Cano, Elena; Simanis, Viesturs; Xenarios, Ioannis

    2015-01-01

    Cytokinesis in fission yeast is controlled by the Septation Initiation Network (SIN), a protein kinase signaling network using the spindle pole body as scaffold. In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach. In this paper, we report the construction of an extended, Boolean model of the SIN, comprising most SIN components and regulators as individual, experimentally testable nodes. The model uses CDK activity levels as control nodes for the simulation of SIN related events in different stages of the cell cycle. The model was optimized using single knock-out experiments of known phenotypic effect as a training set, and was able to correctly predict a double knock-out test set. Moreover, the model has made in silico predictions that have been validated in vivo, providing new insights into the regulation and hierarchical organization of the SIN.

  14. Comprehensive mapping of the Helicobacter pylori NikR regulon provides new insights in bacterial nickel responses

    Science.gov (United States)

    Vannini, Andrea; Pinatel, Eva; Costantini, Paolo Emidio; Pelliciari, Simone; Roncarati, Davide; Puccio, Simone; De Bellis, Gianluca; Peano, Clelia; Danielli, Alberto

    2017-01-01

    Nickel homeostasis is important for pathogenic and ureolytic bacteria, which use this metal ion as enzymatic cofactor. For example, in the human pathogen Helicobacter pylori an optimal balance between nickel uptake and incorporation in metallo-enzymes is fundamental for colonization of the host. Nickel is also used as cofactor to modulate DNA binding of the NikR regulator, which controls transcription of genes involved in nickel trafficking or infection in many bacteria. Accordingly, there is much interest in a systematic characterization of NikR regulation. Herein we use H. pylori as a model to integrate RNA-seq and ChIP-seq data demonstrating that NikR not only regulates metal-ion transporters but also virulence factors, non-coding RNAs, as well as toxin-antitoxin systems in response to nickel stimulation. Altogether, results provide new insights into the pathobiology of H. pylori and contribute to understand the responses to nickel in other bacteria. PMID:28393877

  15. Temporal and spatial regulation of mRNA export: Single particle RNA-imaging provides new tools and insights.

    Science.gov (United States)

    Heinrich, Stephanie; Derrer, Carina Patrizia; Lari, Azra; Weis, Karsten; Montpetit, Ben

    2017-02-01

    The transport of messenger RNAs (mRNAs) from the nucleus to cytoplasm is an essential step in the gene expression program of all eukaryotes. Recent technological advances in the areas of RNA-labeling, microscopy, and sequencing are leading to novel insights about mRNA biogenesis and export. This includes quantitative single molecule imaging (SMI) of RNA molecules in live cells, which is providing knowledge of the spatial and temporal dynamics of the export process. As this information becomes available, it leads to new questions, the reinterpretation of previous findings, and revised models of mRNA export. In this review, we will briefly highlight some of these recent findings and discuss how live cell SMI approaches may be used to further our current understanding of mRNA export and gene expression. © 2017 WILEY Periodicals, Inc.

  16. Cross-Sectional Survey of Physicians on Providing Volunteer Care for In-Flight Medical Events.

    Science.gov (United States)

    Chatfield, Eric; Bond, William F; McCay, Bradley; Thibeault, Claude; Alves, Paulo M; Squillante, Marc; Timpe, Joshua; Cook, Courtney J; Bertino, Raymond E

    2017-09-01

    Airline carriers have equipment, procedures, and protocols in place to handle in-flight medical events (IFMEs). Community physicians may be asked for aid during IFMEs. Cross-Sectional Survey of Physicians on Providing Volunteer Care for In-Flight Medical Events surveyed self-assessed awareness and knowledge, perceived barriers, and suggestions for improving responses to IFMEs. We composed a survey regarding clinicians' self-assessed understanding of in-flight resources, procedures, flight environmental issues, and Good Samaritan protections. The survey was distributed primarily via electronic mail to medical staff list serves to a total of approximately 1300 physicians representing 2 health networks that serve urban, suburban, and rural areas in both inpatient and outpatient settings. Total number of responses was 418. Physician response rate was 29.2% (379/1300). In 3% (39/1300), the responder either failed to indicate their background or was another type of health care professional (e.g., dentist, medical student, physician assistant). Of the physicians, 37.5% (142/379) were primary care and 42% (177/418) of responders reported at least one experience of being asked to volunteer. When asked how well they understand the protocols with which medical events are handled, 64% (262/412) responded "not at all" and 23% (94/412) reported "a little" knowledge. Only 56% (223/397) answered that 75% or more of U.S. flights have ground medical support available. There were 73% (298/411) who believed airlines were required to have medical supplies, but 54% (222/410) reported no knowledge of supplies available. A total of 69% (279/403) believed or were sure that the U.S. has a Good Samaritan law that applies to IFMEs. Many physicians lack basic knowledge about IFMEs. Responders may assist more effectively if better informed about protocols and the availability of ground medical support. Education and timely information support are recommended.Chatfield E, Bond WF, McCay B

  17. The integrins of the urochordate Ciona intestinalis provide novel insights into the molecular evolution of the vertebrate integrin family

    Directory of Open Access Journals (Sweden)

    Robertson David L

    2005-05-01

    Full Text Available Abstract Background Integrins are a functionally significant family of metazoan cell surface adhesion receptors. The receptors are dimers composed of an alpha and a beta chain. Vertebrate genomes encode an expanded set of integrin alpha and beta chains in comparison with protostomes such as drosophila or the nematode worm. The publication of the genome of a basal chordate, Ciona intestinalis, provides a unique opportunity to gain further insight into how and when the expanded integrin supergene family found in vertebrates evolved. Results The Ciona genome encodes eleven α and five β chain genes that are highly homologous to their vertebrate homologues. Eight of the α chains contain an A-domain that lacks the short alpha helical region present in the collagen-binding vertebrate alpha chains. Phylogenetic analyses indicate the eight A-domain containing α chains cluster to form an ascidian-specific clade that is related to but, distinct from, the vertebrate A-domain clade. Two Ciona α chains cluster in laminin-binding clade and the remaining chain clusters in the clade that binds the RGD tripeptide sequence. Of the five Ciona β chains, three form an ascidian-specific clade, one clusters in the vertebrate β1 clade and the remaining Ciona chain is the orthologue of the vertebrate β4 chain. Conclusion The Ciona repertoire of integrin genes provides new insight into the basic set of these receptors available at the beginning of vertebrate evolution. The ascidian and vertebrate α chain A-domain clades originated from a common precursor but radiated separately in each lineage. It would appear that the acquisition of collagen binding capabilities occurred in the chordate lineage after the divergence of ascidians.

  18. Innovative treatment modalities for urinary incontinence: a European survey identifying experience and attitude of healthcare providers.

    Science.gov (United States)

    Kastelein, Arnoud W; Dicker, Maarten F A; Opmeer, Brent C; Angles, Sonia S; Raatikainen, Kaisa E; Alonso, Joan F; Tăut, Diana; Airaksinen, Olavi; Cardozo, Linda D; Roovers, Jan-Paul W R

    2017-04-21

    Urinary incontinence is a common condition in women, with a reported prevalence ranging from 25% to 51%. Of these women, an estimated 38% suffer from stress urinary incontinence (SUI). A European research consortium is investigating an innovative system based on information and communication technology for the conservative treatment of women with SUI. When introducing a new intervention, implementation barriers arise and need to be identified. Therefore, we investigated healthcare providers' experience with and attitude towards innovative care options. We performed an online survey to assess (1) the characteristics and practice of healthcare providers, (2) current protocols for SUI, (3) current use of biofeedback, and (4) knowledge about serious gaming. The survey was sent to members of professional societies in Europe (EUGA), UK (BSUG) and The Netherlands (DPFS). Of 341 questionnaires analyzed (response rate between 18% and 30%), 64% of the respondents had access to a protocol for the treatment of SUI, and 31% used biofeedback when treating patients with SUI. However, 92% considered that biofeedback has a clear or probable added value, and 97% of those who did not use biofeedback would change their practice if research evidence supported its use. Finally, 89% of respondents indicated that they had no experience of serious gaming, but 92% considered that it could be useful. Although inexperienced, European urogynecologists and physical therapists welcome innovative treatment options for the conservative treatment of SUI such as portable wireless biofeedback and serious gaming. Scientific evidence is considered a prerequisite to incorporate such innovations into clinical practice.

  19. Novel information on the epitope of an inverse agonist monoclonal antibody provides insight into the structure of the TSH receptor.

    Directory of Open Access Journals (Sweden)

    Chun-Rong Chen

    Full Text Available The TSH receptor (TSHR comprises an extracellular leucine-rich domain (LRD linked by a hinge region to the transmembrane domain (TMD. Insight into the orientation of these components to each other is required for understanding how ligands activate the receptor. We previously identified residue E251 at the LRD-hinge junction as contributing to coupling TSH binding with receptor activation. However, a single residue cannot stabilize the LRD-hinge unit. Therefore, based on the LRD crystal structure we selected for study four other potential LRD-hinge interface charged residues. Alanine substitutions of individual residues K244, E247, K250 and R255 (as well as previously known E251A did not affect TSH binding or function. However, the cumulative mutation of these residues in varying permutations, primarily K250A and R255A when associated with E251A, partially uncoupled TSH binding and function. These data suggest that these three residues, spatially very close to each other at the LRD base, interact with the hinge region. Unexpectedly and most important, monoclonal antibody CS-17, a TSHR inverse agonist whose epitope straddles the LRD-hinge, was found to interact with residues K244 and E247 at the base of the convex LRD surface. These observations, together with the functional data, exclude residues K244 and E247 from the TSHR LRD-hinge interface. Further, for CS-17 accessibility to K244 and E247, the concave surface of the TSHR LRD must be tilted forwards towards the hinge region and plasma membrane. Overall, these data provide insight into the mechanism by which ligands either activate the TSHR or suppress its constitutive activity.

  20. High-density interspecific genetic linkage mapping provides insights into genomic incompatibility between channel catfish and blue catfish.

    Science.gov (United States)

    Liu, S; Li, Y; Qin, Z; Geng, X; Bao, L; Kaltenboeck, L; Kucuktas, H; Dunham, R; Liu, Z

    2016-02-01

    Catfish is the leading aquaculture species in the United States. The interspecific hybrid catfish produced by mating female channel catfish with male blue catfish outperform both of their parent species in a number of traits. However, mass production of the hybrids has been difficult because of reproductive isolation. Investigations of genome structure and organization of the hybrids provide insights into the genetic basis for maintenance of species divergence in the face of gene flow, thereby helping develop strategies for introgression and efficient production of the hybrids for aquaculture. In this study, we constructed a high-density genetic linkage map using the hybrid catfish system with the catfish 250K SNP array. A total of 26,238 SNPs were mapped to 29 linkage groups, with 12,776 unique marker positions. The linkage map spans approximately 3240 cM with an average intermarker distance of 0.25 cM. A fraction of markers (986 of 12,776) exhibited significant deviation from the expected Mendelian ratio of segregation, and they were clustered in major genomic blocks across 15 LGs, most notably LG9 and LG15. The distorted markers exhibited significant bias for maternal alleles among the backcross progenies, suggesting strong selection against the blue catfish alleles. The clustering of distorted markers within genomic blocks should lend insights into speciation as marked by incompatibilities between the two species. Such findings should also have profound implications for understanding the genomic evolution of closely related species as well as the introgression of hybrid production programs in aquaculture.

  1. The Structure of Allophanate Hydrolase from Granulibacter bethesdensis Provides Insights into Substrate Specificity in the Amidase Signature Family

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yi [Marquette Univ., Milwaukee, WI (United States); Maurice, Martin [Marquette Univ., Milwaukee, WI (United States)

    2013-01-02

    Allophanate hydrolase (AH) catalyzes the hydrolysis of allophanate, an intermediate in atrazine degradation and urea catabolism pathways, to NH3 and CO2. AH belongs to the amidase signature family, which is characterized by a conserved block of 130 amino acids rich in Gly and Ser and a Ser-cis-Ser-Lys catalytic triad. In this study, the first structures of AH fromGranulibacter bethesdensis were determined, with and without the substrate analogue malonate, to 2.2 and 2.8 Å, respectively. The structures confirm the identity of the catalytic triad residues and reveal an altered dimerization interface that is not conserved in the amidase signature family. The structures also provide insights into previously unrecognized substrate specificity determinants in AH. Two residues, Tyr299 and Arg307, are within hydrogen bonding distance of a carboxylate moiety of malonate. Both Tyr299 and Arg307 were mutated, and the resulting modified enzymes revealed >3 order of magnitude reductions in both catalytic efficiency and substrate stringency. It is proposed that Tyr299 and Arg307 serve to anchor and orient the substrate for attack by the catalytic nucleophile, Ser172. The structure further suggests the presence of a unique C-terminal domain in AH. While this domain is conserved, it does not contribute to catalysis or to the structural integrity of the core domain, suggesting that it may play a role in mediating transient and specific interactions with the urea carboxylase component of urea amidolyase. Analysis of the AH active site architecture offers new insights into common determinants of catalysis and specificity among divergent members of the amidase signature family.

  2. Pathologic examination of the placenta and its clinical utility: a survey of obstetrics and gynecology providers.

    Science.gov (United States)

    Odibo, Imelda; Gehlot, Ashita; Ounpraseuth, Songthip T; Magann, Everett F

    2016-01-01

    To determine provider awareness of the College of American Pathologists (CAP) recommended guidelines for examination of placenta and evaluate the Obstetrician -Gynecologist's perception of the clinical utility of placenta pathology reports. An anonymous survey of Obstetrician Gynecologists who attended the national conference of The Central Association of Obstetricians and Gynecologists (CAOG) in 2013 assessing their knowledge of the CAP guidelines and utilization of information obtained from pathology reports. Chi-square or Fisher's exact test were used to evaluate association between specialists and non-specialist providers as related to survey questions and multivariable logistic regression used to explore factors associated with utilization and awareness of the guidelines. A total of 218 providers attended the conference and 111 surveys were completed. Only 36% of participants were aware of the CAP guidelines for pathologic examination of the placenta. The odds that a physician with more than 15 years of experience will send a placenta for examination was 0.210 times that of physicians with less than 15 years of experience (CI 0.084, 0.521). The odds for awareness of the CAP guideline among subspecialists who participated in the study were 3.630 times the odds for non-specialist (CI 1.44, 9.147). In addition, the odds of sending a placenta for those physicians in a community hospital are 0.300 times that of physicians in a University hospital (CI 0.110, 0.820). The presence of a pathologist skilled in obstetrics and gynecology did not seem to affect awareness of the CAP guidelines, perception of the usefulness of the guidelines and likelihood of sending a placenta for examination. Only 21% of participants reported understanding the nomenclature used in pathology reports "all the time". Participants ranked the explanation of adverse pregnancy outcome as the most useful clinical application of placenta pathologic examination and most advocated for continued

  3. Does fish origin matter to European consumers? Insights from a consumer survey in Belgium, Norway and Spain

    NARCIS (Netherlands)

    Vanhonacker, F.; Altintzoglou, T.; Luten, J.B.; Verbeke, W.

    2011-01-01

    Purpose – This study aims to gain insights into the relevance and market potential of fish origin (farmed or wild) among consumers in Belgium, Norway and Spain. Design/methodology/approach – Cross-sectional data were collected through a consumer survey (n=1,319), conducted in November-December 2007

  4. Does fish origin matter to European consumers? Insights from a consumer survey in Belgium, Norway and Spain

    NARCIS (Netherlands)

    Vanhonacker, F.; Altintzoglou, T.; Luten, J.B.; Verbeke, W.

    2011-01-01

    Purpose – This study aims to gain insights into the relevance and market potential of fish origin (farmed or wild) among consumers in Belgium, Norway and Spain. Design/methodology/approach – Cross-sectional data were collected through a consumer survey (n=1,319), conducted in November-December 2007

  5. Literature Survey on Technical Issues and Insights of Multi-Unit PSA

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Sejin; Park, Soyoung; Heo, Gyunyoung [Kyung Hee Univ., Yongin (Korea, Republic of)

    2016-10-15

    The need consider the risk impact in case of multi-unit in a single site increased after the accident at Fukushima Daiichi in March 2011. This means that we have to consider the single-unit initiators impacting the other units and the simultaneous accidents of the multi-unit on the same site. Particularly, this kind of technical concern is serious in case of the Republic of Korea where multi-units had to be located in high-density population area due to geographical features. The Nuclear Safety and Security Commission (NSSC) in the Republic of Korea has been trying to identify the state of the art of international and domestic regulations and techniques on multi-unit risk assessment and planning the road map for the safety researches. However, we have to say that finding a common accepted methodology along with safety criteria for multi-unit PSA was not an easy task up to now. This paper summarizes and analyzes related international and domestic journals' papers, conferences' papers and reports about the multi-unit PSA classifying categories with themes to understand the technical tendency of multi-unit PSA. In addition, some insights that were obtained from this classification have been arranged too. This paper investigated the technical trend of the multi-unit PSA as collecting of the international and domestic journals' papers, conferences papers and reports, and analyzing them. Upon the literature survey, a few statistics, technical issues, and insights were summarized. Both of the fundamental and practical researches need to find a globally accepted methodology to calculate and determine quantitative objectives for a multi-unit PSA. We want to expect that this paper can be shared to understand the current status of multi-unit PSA.

  6. Physical mapping and BAC-end sequence analysis provide initial insights into the flax (Linum usitatissimum L. genome

    Directory of Open Access Journals (Sweden)

    Cloutier Sylvie

    2011-05-01

    Full Text Available Abstract Background Flax (Linum usitatissimum L. is an important source of oil rich in omega-3 fatty acids, which have proven health benefits and utility as an industrial raw material. Flax seeds also contain lignans which are associated with reducing the risk of certain types of cancer. Its bast fibres have broad industrial applications. However, genomic tools needed for molecular breeding were non existent. Hence a project, Total Utilization Flax GENomics (TUFGEN was initiated. We report here the first genome-wide physical map of flax and the generation and analysis of BAC-end sequences (BES from 43,776 clones, providing initial insights into the genome. Results The physical map consists of 416 contigs spanning ~368 Mb, assembled from 32,025 fingerprints, representing roughly 54.5% to 99.4% of the estimated haploid genome (370-675 Mb. The N50 size of the contigs was estimated to be ~1,494 kb. The longest contig was ~5,562 kb comprising 437 clones. There were 96 contigs containing more than 100 clones. Approximately 54.6 Mb representing 8-14.8% of the genome was obtained from 80,337 BES. Annotation revealed that a large part of the genome consists of ribosomal DNA (~13.8%, followed by known transposable elements at 6.1%. Furthermore, ~7.4% of sequence was identified to harbour novel repeat elements. Homology searches against flax-ESTs and NCBI-ESTs suggested that ~5.6% of the transcriptome is unique to flax. A total of 4064 putative genomic SSRs were identified and are being developed as novel markers for their use in molecular breeding. Conclusion The first genome-wide physical map of flax constructed with BAC clones provides a framework for accessing target loci with economic importance for marker development and positional cloning. Analysis of the BES has provided insights into the uniqueness of the flax genome. Compared to other plant genomes, the proportion of rDNA was found to be very high whereas the proportion of known transposable

  7. National survey of comprehensive pharmacy services provided in cancer clinical trials.

    Science.gov (United States)

    Khandoobhai, Anand; Poi, Ming; Kelley, Katherine; Mirtallo, Jay; Lopez, Ben; Griffith, Niesha

    2017-06-01

    Pharmacy services provided in clinical trials at National Cancer Institute (NCI)-designated centers were assessed. This was a cross-sectional survey of 61 NCI-designated cancer centers. Directors of pharmacy were contacted and data were collected electronically via Qualtrics over 2 months. Trial participants were asked to estimate the frequency that their sites performed 26 services and the perceived importance of these services. Services were examined with respect to the difference between their reported performance and their reported importance. Eight of the 26 services showed a difference of at least 40% between the proportion of respondents performing the activities "often" or "almost always" and the proportion considering them "important" or "very important." Demographic information was collected, as well as perceived barriers. Survey response rate was 59% (36 out of 61). The majority of services for clinical trials (19 out of 26) were viewed as important for pharmacists to perform; however, less than half (10 out of 26) were performed more than 50% of the time. Eight services had a gap of more than 40% when comparing the importance versus extent of implementation. Some of the largest gaps were reported in investigator-initiated trials development, medication reconciliation, therapeutic drug monitoring, and oral chemotherapy adherence assessment. Future studies can assist with cost justification by demonstrating the regulatory, safety, and financial benefits of pharmacist involvement in cancer trials. A survey of pharmacy directors at cancer centers revealed gaps between what respondents considered important pharmacist services in the provision of cancer clinical trials and the actual performance of those services in their institution. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  8. Mechanisms of cell death in canine parvovirus-infected cells provide intuitive insights to developing nanotools for medicine

    Directory of Open Access Journals (Sweden)

    Jonna Nykky

    2010-06-01

    Full Text Available Jonna Nykky, Jenni E Tuusa, Sanna Kirjavainen, Matti Vuento, Leona GilbertNanoscience Center and Department of Biological and Environmental Science, University of Jyväskylä, FinlandAbstract: Viruses have great potential as nanotools in medicine for gene transfer, targeted gene delivery, and oncolytic cancer virotherapy. Here we have studied cell death mechanisms of canine parvovirus (CPV to increase the knowledge on the CPV life cycle in order to facilitate the development of better parvovirus vectors. Morphological studies of CPV-infected Norden laboratory feline kidney (NLFK cells and canine fibroma cells (A72 displayed characteristic apoptotic events. Apoptosis was further confirmed by activation of caspases and cellular DNA damage. However, results from annexin V-propidium iodide (PI labeling and membrane polarization assays indicated disruption of the plasma membrane uncommon to apoptosis. These results provide evidence that secondary necrosis followed apoptosis. In addition, two human cancer cell lines were found to be infected by CPV. This necrotic event over apoptotic cell death and infection in human cells provide insightful information when developing CPV as a nanotool for cancer treatments.Keywords: canine parvovirus, apoptosis, necrosis, nanoparticle, virotherapy

  9. NEW INSIGHT INTO THE SOLAR SYSTEM’S TRANSITION DISK PHASE PROVIDED BY THE METAL-RICH CARBONACEOUS CHONDRITE ISHEYEVO

    Energy Technology Data Exchange (ETDEWEB)

    Morris, Melissa A. [State University of New York, Cortland, NY 13045 (United States); Garvie, Laurence A. J. [Center for Meteorite Studies, Arizona State University, Tempe, AZ 85287 (United States); Knauth, L. Paul, E-mail: melissa.morris@cortland.edu [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287 (United States)

    2015-03-10

    Many aspects of planet formation are controlled by the amount of gas remaining in the natal protoplanetary disks (PPDs). Infrared observations show that PPDs undergo a transition stage at several megayears, during which gas densities are reduced. Our Solar System would have experienced such a stage. However, there is currently no data that provides insight into this crucial time in our PPD’s evolution. We show that the Isheyevo meteorite contains the first definitive evidence for a transition disk stage in our Solar System. Isheyevo belongs to a class of metal-rich meteorites whose components have been dated at almost 5 Myr after formation of Ca, Al-rich inclusions, and exhibits unique sedimentary layers that imply formation through gentle sedimentation. We show that such layering can occur via the gentle sweep-up of material found in the impact plume resulting from the collision of two planetesimals. Such sweep-up requires gas densities consistent with observed transition disks (10{sup −12}–10{sup −11} g cm{sup −3}). As such, Isheyevo presents the first evidence of our own transition disk and provides new constraints on the evolution of our solar nebula.

  10. Taxonomic and functional diversity provides insight into microbial pathways and stress responses in the saline Qinghai Lake, China.

    Science.gov (United States)

    Huang, Qiuyuan; Briggs, Brandon R; Dong, Hailiang; Jiang, Hongchen; Wu, Geng; Edwardson, Christian; De Vlaminck, Iwijn; Quake, Stephen

    2014-01-01

    Microbe-mediated biogeochemical cycles contribute to the global climate system and have sensitive responses and feedbacks to environmental stress caused by climate change. Yet, little is known about the effects of microbial biodiversity (i.e., taxonmic and functional diversity) on biogeochemical cycles in ecosytems that are highly sensitive to climate change. One such sensitive ecosystem is Qinghai Lake, a high-elevation (3196 m) saline (1.4%) lake located on the Tibetan Plateau, China. This study provides baseline information on the microbial taxonomic and functional diversity as well as the associated stress response genes. Illumina metagenomic and metatranscriptomic datasets were generated from lake water samples collected at two sites (B and E). Autotrophic Cyanobacteria dominated the DNA samples, while heterotrophic Proteobacteria dominated the RNA samples at both sites. Photoheterotrophic Loktanella was also present at both sites. Photosystem II was the most active pathway at site B; while, oxidative phosphorylation was most active at site E. Organisms that expressed photosystem II or oxidative phosphorylation also expressed genes involved in photoprotection and oxidative stress, respectively. Assimilatory pathways associated with the nitrogen cycle were dominant at both sites. Results also indicate a positive relationship between functional diversity and the number of stress response genes. This study provides insight into the stress resilience of microbial metabolic pathways supported by greater taxonomic diversity, which may affect the microbial community response to climate change.

  11. Variation in breeding phenology provides insights into drivers of long-term population change in harbour seals.

    Science.gov (United States)

    Cordes, Line S; Thompson, Paul M

    2013-08-07

    Phenological trends provide important indicators of environmental change and population dynamics. However, the use of untested population-level measures can lead to incorrect conclusions about phenological trends, particularly when changes in population structure or density are ignored. We used individual-based estimates of birth date and lactation duration of harbour seals (Phoca vitulina) to investigate energetic consequences of changes in pupping phenology. Using generalized linear mixed models, we first demonstrate annual variation in pupping phenology. Second, we show a negative relationship between lactation duration and the timing of pupping, indicating that females who pup early nurse their pups longer, thereby highlighting lactation duration as a useful proxy of female condition and resource availability. Third, individual-based data were used to derive a population-level proxy that demonstrated an advance in pupping date over the last 25 years, co-incident with a reduction in population abundance that resulted from fisheries-related shootings. These findings demonstrate that phenological studies examining the impacts of climate change on mammal populations must carefully control for changes in population density and highlight how joint investigations of phenological and demographic change provide insights into the drivers of population declines.

  12. Multilocus sequence analysis provides insights into molecular epidemiology of Chlamydia pecorum infections in Australian sheep, cattle, and koalas.

    Science.gov (United States)

    Jelocnik, Martina; Frentiu, Francesca D; Timms, Peter; Polkinghorne, Adam

    2013-08-01

    Chlamydia pecorum is a significant pathogen of domestic livestock and wildlife. We have developed a C. pecorum-specific multilocus sequence analysis (MLSA) scheme to examine the genetic diversity of and relationships between Australian sheep, cattle, and koala isolates. An MLSA of seven concatenated housekeeping gene fragments was performed using 35 isolates, including 18 livestock isolates (11 Australian sheep, one Australian cow, and six U.S. livestock isolates) and 17 Australian koala isolates. Phylogenetic analyses showed that the koala isolates formed a distinct clade, with limited clustering with C. pecorum isolates from Australian sheep. We identified 11 MLSA sequence types (STs) among Australian C. pecorum isolates, 10 of them novel, with koala and sheep sharing at least one identical ST (designated ST2013Aa). ST23, previously identified in global C. pecorum livestock isolates, was observed here in a subset of Australian bovine and sheep isolates. Most notably, ST23 was found in association with multiple disease states and hosts, providing insights into the transmission of this pathogen between livestock hosts. The complexity of the epidemiology of this disease was further highlighted by the observation that at least two examples of sheep were infected with different C. pecorum STs in the eyes and gastrointestinal tract. We have demonstrated the feasibility of our MLSA scheme for understanding the host relationship that exists between Australian C. pecorum strains and provide the first molecular epidemiological data on infections in Australian livestock hosts.

  13. Cadastral Surveys, Published in Not Provided, 1:1200 (1in=100ft) scale, Southwest Gas Corporation.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Cadastral Surveys dataset, published at 1:1200 (1in=100ft) scale as of Not Provided. Data by this publisher are often provided in State Plane coordinate system;...

  14. Getting satisfaction: drivers of surgical Hospital Consumer Assessment of Health care Providers and Systems survey scores.

    Science.gov (United States)

    Iannuzzi, James C; Kahn, Steven A; Zhang, Linlin; Gestring, Mark L; Noyes, Katia; Monson, John R T

    2015-07-01

    Hospital consumer assessment of health care providers and systems (HCAHPS) survey scores formally recognize that patients are central to health care, shifting quality metrics from the physician to patient perspective. This study describes clinical predictors of patient satisfaction in surgical patients. Analysis of a single institution's Surgical Department HCAHPS responses was performed from March 2011-October 2012. The end points were top box satisfaction on two global domains. Multivariable regression was used to determine satisfaction predictors including HCAHPS domains, demographics, and clinical variables such as comorbidities, intensive care unit stay, emergency case, discharge day, floor transfers, complications, and ancillary procedures. In total, 978 surveys were evaluated representing admissions to Acute care and/or Trauma (n = 177, 18.1%), Thoracic (n = 169, 17.3%), Colorectal (n = 107, 10.9%), Transplant (n = 95, 9.7%), Vascular (n = 92, 9.4%), Oncology (n = 88, 9.0%), Plastic (n = 49, 5.0%), and Cardiac (n = 201, 20.6%) divisions. Overall, 658 patients (67.3%) had high satisfaction and 733 (74.9%) gave definite hospital recommendations. Hospital satisfaction was positively associated with an intensive care unit admission (odds ratio [OR] = 1.64, confidence interval [CI]: 1.20-2.23, P = 0.002) and satisfaction with provider and pain domains. Factors associated with decreased satisfaction were race (non-black minority compared with whites; OR = 0.41, CI: 0.21-0.83, P = 0.012), self-reported poor health (OR = 0.43, CI: 0.27-0.68, P nurse-patient interactions. These results help inform future quality improvement and resource allocation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Electrospray ionization ion mobility mass spectrometry provides novel insights into the pattern and activity of fetal hippocampus gangliosides.

    Science.gov (United States)

    Sarbu, Mirela; Vukelić, Željka; Clemmer, David E; Zamfir, Alina D

    2017-08-01

    Gangliosides (GGs), a particular class of glycosphingolipids ubiquitously found in tissues and body fluids, exhibit the highest expression in the central nervous system, especially in brain. GGs are involved in crucial processes, such as neurogenesis, synaptogenesis, synaptic transmission, cell adhesion, growth and proliferation. For these reasons, efforts are constantly invested into development and refinement of specific methods for GG analysis. We have recently shown that ion mobility separation (IMS) mass spectrometry (MS) has the capability to provide consistent compositional and structural information on GGs at high sensitivity, resolution and mass accuracy. In the present paper, we have implemented IMS MS for the first time in the study of a highly complex native GG mixture extracted and purified from human fetal hippocampus. As compared to previous studies, where no separation techniques prior to MS were applied, IMS MS technique has not just generated valuable novel information on the GG pattern characteristic for hippocampus in early developmental stage, but also provided data related to the GG molecular involvement in the synaptic functions by the discovery of 25 novel structures modified by CH3COO(-). The detection and identification in fetal hippocampus of a much larger number of GG species than ever reported before was possible due to the ion mobility separation according to the charge state, the carbohydrate chain length and the degree of sialylation. By applying IMS in conjunction with collision induced dissociation (CID) tandem MS (MS/MS), novel GG species modified by CH3COO(-) attachment, discovered here for the first time, were sequenced and structurally investigated in details. The present findings, based on IMS MS, provide a more reliable insight into the expression and role of gangliosides in human hippocampus, with a particular emphasis on their cholinergic activity at this level. Copyright © 2017 Elsevier B.V. and Société Française de

  16. HIV knowledge and attitudes among providers in aging: results from a national survey.

    Science.gov (United States)

    Hughes, Anne K

    2011-09-01

    Within 5 years, half the U.S. HIV-infected population will be over age 50, and providers caring for older adults must deal with this reality. This study assessed attitudes toward people with HIV/AIDS and knowledge of HIV/AIDS among physicians with a geriatrics specialty, and nurses and social workers who specialize in gerontology. A survey mailed in 2008 to a random sample of U.S. providers yielded a 60% response rate. Main outcome measures included: Knowledge of HIV/AIDS, attitudes toward people with HIV/AIDS, and knowledge of issues related to HIV in older adults. General knowledge of HIV/AIDS was good with scores of 89%, 84%, and 81% for physicians, nurses, and social workers, respectively; groups differed significantly (F(2, 483)=18.626, page 50 varied widely; few answered correctly, with no significant differences by professional group (F(2,319)=2.82, p=0.06). These findings highlight the need for further education among providers who specialize in aging.

  17. Unanswered clinical questions: a survey of specialists and primary care providers*

    Science.gov (United States)

    Gunn, Bridget; Shenoy, Anant M.; Blanchard, Rebecca

    2017-01-01

    Objective With the myriad of cases presented to clinicians every day at our integrated academic health system, clinical questions are bound to arise. Clinicians need to recognize these knowledge gaps and act on them. However, for many reasons, clinicians might not seek answers to these questions. Our goal was to investigate the rationale and process behind these unanswered clinical questions. Subsequently, we explored the use of biomedical information resources among specialists and primary care providers and identified ways to promote more informed clinical decision making. Methods We conducted a survey to assess how practitioners identify and respond to information gaps, their background knowledge of search tools and strategies, and their usage of and comfort level with technology. Results Most of the 292 respondents encountered clinical questions at least a few times per week. While the vast majority often or always pursued answers, time was the biggest barrier for not following through on questions. Most respondents did not have any formal training in searching databases, were unaware of many digital resources, and indicated a need for resources and services that could be provided at the point of care. Conclusions While the reasons for unanswered clinical questions varied, thoughtful review of the responses suggested that a combination of educational strategies, embedded librarian services, and technology applications could help providers pursue answers to their clinical questions, enhance patient safety, and contribute to patient-based, self-directed learning. PMID:28096740

  18. Who continues to stock oral artemisinin monotherapy? Results of a provider survey in Myanmar.

    Science.gov (United States)

    Thein, Si Thu; Sudhinaraset, May; Khin, Hnin Su Su; McFarland, Willi; Aung, Tin

    2016-06-22

    Artemisinin-based combination therapy (ACT) is a key strategy for global malaria elimination efforts. However, the development of artemisinin-resistant malaria parasites threatens progress and continued usage of oral artemisinin monotherapies (AMT) predisposes the selection of drug resistant strains. This is particularly a problem along the Myanmar/Thailand border. The artemisinin monotherapy replacement programme (AMTR) was established in 2012 to remove oral AMT from stocks in Myanmar, specifically by replacing oral AMT with quality-assured ACT and conducting behavioural change communication activities to the outlets dispensing anti-malarial medications. This study attempts to quantify the characteristics of outlet providers who continue to stock oral AMT despite these concerted efforts. A cross-sectional survey of all types of private sector outlets that were stocking anti-malarial drugs in 13 townships of Eastern Myanmar was implemented from July to August 2014. A total of 573 outlets were included. Bivariate and multivariable logistic regressions were conducted to assess outlet and provider-level characteristics associated with stocking oral AMT. In total, 2939 outlets in Eastern Myanmar were screened for presence of any anti-malarial drugs in August 2014. The study found that 573 (19.5 %) had some kind of oral anti-malarial drug in stock at the time of survey and among them, 96 (16.8 %) stocked oral AMT. In bivariate analyses, compared to health care facilities, itinerant drug vendors, retailers and health workers were less likely to stock oral AMT (33.3 vs 12.9, 10.0, 8.1 %, OR = 0.30, 0.22, 0.18, respectively). Providers who cut blister pack or sell partial courses (40.6 vs 11.7 %, OR 5.18, CI 3.18-8.44) and those who based their stock decision on consumer demand (32.8 vs 12.1 %, OR 3.54, CI 2.21-5.63) were more likely to stock oAMT. Multivariate logistic regressions produced similar significant associations. Private healthcare facilities and drug

  19. De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses

    Science.gov (United States)

    Meena, Seema; Kumar, Sarma R.; Venkata Rao, D. K.; Dwivedi, Varun; Shilpashree, H. B.; Rastogi, Shubhra; Shasany, Ajit K.; Nagegowda, Dinesh A.

    2016-01-01

    Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition. PMID:27516768

  20. Structure of the CED-4-CED-9 Complex Provides Insights into Programmed Cell Death in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Yan,N.; Chai, J.; Lee, E.; Gu, L.; Liu, Q.; He, J.; Wu, J.; Kokel, D.; Li, H.; et al.

    2005-01-01

    Interplay among four genes-egl-1, ced-9, ced-4 and ced-3-controls the onset of programmed cell death in the nematode Caenorhabditis elegans. Activation of the cell-killing protease CED-3 requires CED-4. However, CED-4 is constitutively inhibited by CED-9 until its release by EGL-1. Here we report the crystal structure of the CED-4-CED-9 complex at 2.6 Angstrom resolution, and a complete reconstitution of the CED-3 activation pathway using homogeneous proteins of CED-4, CED-9 and EGL-1. One molecule of CED-9 binds to an asymmetric dimer of CED-4, but specifically recognizes only one of the two CED-4 molecules. This specific interaction prevents CED-4 from activating CED-3. EGL-1 binding induces pronounced conformational changes in CED-9 that result in the dissociation of the CED-4 dimer from CED-9. The released CED-4 dimer further dimerizes to form a tetramer, which facilitates the autoactivation of CED-3. Together, our studies provide important insights into the regulation of cell death activation in C. elegans.

  1. Novel UDP-GalNAc Derivative Structures Provide Insight into the Donor Specificity of Human Blood Group Glycosyltransferase.

    Science.gov (United States)

    Wagner, Gerd K; Pesnot, Thomas; Palcic, Monica M; Jørgensen, Rene

    2015-12-25

    Two closely related glycosyltransferases are responsible for the final step of the biosynthesis of ABO(H) human blood group A and B antigens. The two enzymes differ by only four amino acid residues, which determine whether the enzymes transfer GalNAc from UDP-GalNAc or Gal from UDP-Gal to the H-antigen acceptor. The enzymes belong to the class of GT-A folded enzymes, grouped as GT6 in the CAZy database, and are characterized by a single domain with a metal dependent retaining reaction mechanism. However, the exact role of the four amino acid residues in the specificity of the enzymes is still unresolved. In this study, we report the first structural information of a dual specificity cis-AB blood group glycosyltransferase in complex with a synthetic UDP-GalNAc derivative. Interestingly, the GalNAc moiety adopts an unusual yet catalytically productive conformation in the binding pocket, which is different from the "tucked under" conformation previously observed for the UDP-Gal donor. In addition, we show that this UDP-GalNAc derivative in complex with the H-antigen acceptor provokes the same unusual binding pocket closure as seen for the corresponding UDP-Gal derivative. Despite this, the two derivatives show vastly different kinetic properties. Our results provide a important structural insight into the donor substrate specificity and utilization in blood group biosynthesis, which can very likely be exploited for the development of new glycosyltransferase inhibitors and probes.

  2. High Content Analysis Provides Mechanistic Insights on the Pathways of Toxicity Induced by Amine-Modified Polystyrene Nanoparticles

    Science.gov (United States)

    Anguissola, Sergio; Garry, David; Salvati, Anna; O'Brien, Peter J.; Dawson, Kenneth A.

    2014-01-01

    The fast-paced development of nanotechnology needs the support of effective safety testing. We have developed a screening platform measuring simultaneously several cellular parameters for exposure to various concentrations of nanoparticles (NPs). Cell lines representative of different organ cell types, including lung, endothelium, liver, kidney, macrophages, glia, and neuronal cells were exposed to 50 nm amine-modified polystyrene (PS-NH2) NPs previously reported to induce apoptosis and to 50 nm sulphonated and carboxyl-modified polystyrene NPs that were reported to be silent. All cell lines apart from Raw 264.7 executed apoptosis in response to PS-NH2 NPs, showing specific sequences of EC50 thresholds; lysosomal acidification was the most sensitive parameter. Loss of mitochondrial membrane potential and plasma membrane integrity measured by High Content Analysis resulted comparably sensitive to the equivalent OECD-recommended assays, allowing increased output. Analysis of the acidic compartments revealed good cerrelation between size/fluorescence intensity and dose of PS-NH2 NPs applied; moreover steatosis and phospholipidosis were observed, consistent with the lysosomal alterations revealed by Lysotracker green; similar responses were observed when comparing astrocytoma cells with primary astrocytes. We have established a platform providing mechanistic insights on the response to exposure to nanoparticles. Such platform holds great potential for in vitro screening of nanomaterials in highthroughput format. PMID:25238162

  3. The gene expression data of Mycobacterium tuberculosis based on Affymetrix gene chips provide insight into regulatory and hypothetical genes

    Directory of Open Access Journals (Sweden)

    Fu-Liu Casey S

    2007-05-01

    Full Text Available Abstract Background Tuberculosis remains a leading infectious disease with global public health threat. Its control and management have been complicated by multi-drug resistance and latent infection, which prompts scientists to find new and more effective drugs. With the completion of the genome sequence of the etiologic bacterium, Mycobacterium tuberculosis, it is now feasible to search for new drug targets by sieving through a large number of gene products and conduct genome-scale experiments based on microarray technology. However, the full potential of genome-wide microarray analysis in configuring interrelationships among all genes in M. tuberculosis has yet to be realized. To date, it is only possible to assign a function to 52% of proteins predicted in the genome. Results We conducted a functional-genomics study using the high-resolution Affymetrix oligonucleotide GeneChip. Approximately one-half of the genes were found to be always expressed, including more than 100 predicted conserved hypotheticals, in the genome of M. tuberculosis during the log phase of in vitro growth. The gene expression profiles were analyzed and visualized through cluster analysis to epitomize the full details of genomic behavior. Broad patterns derived from genome-wide expression experiments in this study have provided insight into the interrelationships among genes in the basic cellular processes of M. tuberculosis. Conclusion Our results have confirmed several known gene clusters in energy production, information pathways, and lipid metabolism, and also hinted at potential roles of hypothetical and regulatory proteins.

  4. De novo Sequencing and Analysis of Lemongrass Transcriptome Provides First Insights into the Essential Oil Biosynthesis of Aromatic Grasses

    Directory of Open Access Journals (Sweden)

    Seema Meena

    2016-07-01

    Full Text Available Aromatic grasses of the genus Cymbopogon (Poaceae family represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavour, fragrance, cosmetic and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step towards understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases (TPS, pyrophosphatases (PPase, alcohol dehydrogenases (ADH, aldo-keto reductases (AKR, carotenoid cleavage dioxygenases (CCD, alcohol acetyltransferases (AAT and aldehyde dehydrogenases (ALDH, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes and acetates. Molecular modeling and docking further supported the role of identified enzymes in aroma formation in Cymbopogon. Also, simple sequence repeats (SSRs were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition.

  5. Comparative physiological and transcriptomic analyses provide integrated insight into osmotic, cold, and salt stress tolerance mechanisms in banana

    Science.gov (United States)

    Hu, Wei; Ding, Zehong; Tie, Weiwei; Yan, Yan; Liu, Yang; Wu, Chunlai; Liu, Juhua; Wang, Jiashui; Peng, Ming; Xu, Biyu; Jin, Zhiqiang

    2017-01-01

    The growth, development, and production of banana plants are constrained by multiple abiotic stressors. However, it remains elusive for the tolerance mechanisms of banana responding to multiple abiotic stresses. In this study, we found that Fen Jiao (FJ) was more tolerant to osmotic, cold, and salt stresses than BaXi Jiao (BX) by phenotypic and physiological analyses. Comparative transcriptomic analyses highlighted stress tolerance genes that either specifically regulated in FJ or changed more than twofold in FJ relative to BX after treatments. In total, 933, 1644, and 133 stress tolerance genes were identified after osmotic, cold, and salt treatments, respectively. Further integrated analyses found that 30 tolerance genes, including transcription factor, heat shock protein, and E3 ubiquitin protein ligase, could be commonly regulated by osmotic, cold, and salt stresses. Finally, ABA and ROS signaling networks were found to be more active in FJ than in BX under osmotic, cold, and salt treatments, which may contribute to the strong stress tolerances of FJ. Together, this study provides new insights into the tolerance mechanism of banana responding to multiple stresses, thus leading to potential applications in the genetic improvement of multiple abiotic stress tolerances in banana. PMID:28223714

  6. Comparative genomic analysis of the genus Nocardiopsis provides new insights into its genetic mechanisms of environmental adaptability.

    Directory of Open Access Journals (Sweden)

    Hong-Wei Li

    Full Text Available The genus Nocardiopsis, a widespread group in phylum Actinobacteria, has received much attention owing to its ecological versatility, pathogenicity, and ability to produce a rich array of bioactive metabolites. Its high environmental adaptability might be attributable to its genome dynamics, which can be estimated through comparative genomic analysis targeting microorganisms with close phylogenetic relationships but different phenotypes. To shed light on speciation, gene content evolution, and environmental adaptation in these unique actinobacteria, we sequenced draft genomes for 16 representative species of the genus and compared them with that of the type species N. dassonvillei subsp. dassonvillei DSM 43111(T. The core genome of 1,993 orthologous and paralogous gene clusters was identified, and the pan-genomic reservoir was found not only to accommodate more than 22,000 genes, but also to be open. The top ten paralogous genes in terms of copy number could be referred to three functional categories: transcription regulators, transporters, and synthases related to bioactive metabolites. Based on phylogenomic reconstruction, we inferred past evolutionary events, such as gene gains and losses, and identified a list of clade-specific genes implicated in environmental adaptation. These results provided insights into the genetic causes of environmental adaptability in this cosmopolitan actinobacterial group and the contributions made by its inherent features, including genome dynamics and the constituents of core and accessory proteins.

  7. Structure of the Tuberous Sclerosis Complex 2 (TSC2) N Terminus Provides Insight into Complex Assembly and Tuberous Sclerosis Pathogenesis.

    Science.gov (United States)

    Zech, Reinhard; Kiontke, Stephan; Mueller, Uwe; Oeckinghaus, Andrea; Kümmel, Daniel

    2016-09-16

    Tuberous sclerosis complex (TSC) is caused by mutations in the TSC1 and TSC2 tumor suppressor genes. The gene products hamartin and tuberin form the TSC complex that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of rapamycin complex 1 (mTORC1). Tuberin contains a RapGAP homology domain responsible for inactivation of Rheb, but functions of other protein domains remain elusive. Here we show that the TSC2 N terminus interacts with the TSC1 C terminus to mediate complex formation. The structure of the TSC2 N-terminal domain from Chaetomium thermophilum and a homology model of the human tuberin N terminus are presented. We characterize the molecular requirements for TSC1-TSC2 interactions and analyze pathological point mutations in tuberin. Many mutations are structural and produce improperly folded protein, explaining their effect in pathology, but we identify one point mutant that abrogates complex formation without affecting protein structure. We provide the first structural information on TSC2/tuberin with novel insight into the molecular function.

  8. Serial explant culture provides novel insights into the potential location and phenotype of corneal endothelial progenitor cells.

    Science.gov (United States)

    Walshe, Jennifer; Harkin, Damien G

    2014-10-01

    The routine cultivation of human corneal endothelial cells, with the view to treating patients with endothelial dysfunction, remains a challenging task. While progress in this field has been buoyed by the proposed existence of progenitor cells for the corneal endothelium at the corneal limbus, strategies for exploiting this concept remain unclear. In the course of evaluating methods for growing corneal endothelial cells, we have noted a case where remarkable growth was achieved using a serial explant culture technique. Over the course of 7 months, a single explant of corneal endothelium, acquired from cadaveric human tissue, was sequentially seeded into 7 culture plates and on each occasion produced a confluent cell monolayer. Sample cultures were confirmed as endothelial in origin by positive staining for glypican-4. On each occasion, small cells, closest to the tissue explant, developed into a highly compact layer with an almost homogenous structure. This layer was resistant to removal with trypsin and produced continuous cell outgrowth during multiple culture periods. The small cells gave rise to larger cells with phase-bright cell boundaries and prominent immunostaining for both nestin and telomerase. Nestin and telomerase were also strongly expressed in small cells immediately adjacent to the wound site, following transfer of the explant to another culture plate. These findings are consistent with the theory that progenitor cells for the corneal endothelium reside within the limbus and provide new insights into expected expression patterns for nestin and telomerase within the differentiation pathway.

  9. Scrutiny of Mycobacterium tuberculosis 19 kDa antigen proteoforms provides new insights in the lipoglycoprotein biogenesis paradigm

    Science.gov (United States)

    Parra, Julien; Marcoux, Julien; Poncin, Isabelle; Canaan, Stéphane; Herrmann, Jean Louis; Nigou, Jérôme; Burlet-Schiltz, Odile; Rivière, Michel

    2017-01-01

    Post-translational modifications (PTMs) are essential processes conditioning the biophysical properties and biological activities of the vast majority of mature proteins. However, occurrence of several distinct PTMs on a same protein dramatically increases its molecular diversity. The comprehensive understanding of the functionalities resulting from any particular PTM association requires a highly challenging full structural description of the PTM combinations. Here, we report the in-depth exploration of the natural structural diversity of the M. tuberculosis (Mtb) virulence associated 19 kDa lipoglycoprotein antigen (LpqH) using intact protein high-resolution mass spectrometry (HR-MS) coupled to liquid chromatography. Combined top-down and bottom-up HR-MS analyses of the purified Mtb LpqH protein allow, for the first time, to uncover a complex repertoire of about 130 molecular species resulting from the intrinsically heterogeneous combination of lipidation and glycosylation together with some truncations. Direct view on the co-occurring PTMs stoichiometry reveals the presence of functionally distinct LpqH lipidation states and indicates that glycosylation is independent from lipidation. This work allowed the identification of a novel unsuspected phosphorylated form of the unprocessed preprolipoglycoprotein totally absent from the current lipoglycoprotein biogenesis pathway and providing new insights into the biogenesis and functional determinants of the mycobacterial lipoglycoprotein interacting with the host immune PRRs. PMID:28272507

  10. Differential Proteomic Profiles of Pleurotus ostreatus in Response to Lignocellulosic Components Provide Insights into Divergent Adaptive Mechanisms.

    Science.gov (United States)

    Xiao, Qiuyun; Ma, Fuying; Li, Yan; Yu, Hongbo; Li, Chengyun; Zhang, Xiaoyu

    2017-01-01

    Pleurotus ostreatus is a white rot fungus that grows on lignocellulosic biomass by metabolizing the main constituents. Extracellular enzymes play a key role in this process. During the hydrolysis of lignocellulose, potentially toxic molecules are released from lignin, and the molecules are derived from hemicellulose or cellulose that trigger various responses in fungus, thereby influencing mycelial growth. In order to characterize the mechanism underlying the response of P. ostreatus to lignin, we conducted a comparative proteomic analysis of P. ostreatus grown on different lignocellulose substrates. In this work, the mycelium proteome of P. ostreatus grown in liquid minimal medium with lignin, xylan, and carboxymethyl cellulose (CMC) was analyzed using the complementary two-dimensional gel electrophoresis (2-DE) approach; 115 proteins were identified, most of which were classified into five types according to their function. Proteins with an antioxidant function that play a role in the stress response were upregulated in response to lignin. Most proteins involving in carbohydrate and energy metabolism were less abundant in lignin. Xylan and CMC may enhanced the process of carbohydrate metabolism by regulating the level of expression of various carbohydrate metabolism-related proteins. The change of protein expression level was related to the adaptability of P. ostreatus to lignocellulose. These findings provide novel insights into the mechanisms underlying the response of white-rot fungus to lignocellulose.

  11. Structure of Utp21 tandem WD domain provides insight into the organization of the UTPB complex involved in ribosome synthesis.

    Directory of Open Access Journals (Sweden)

    Cheng Zhang

    Full Text Available Assembly of the eukaryotic ribosome requires a large number of trans-acting proteins and small nucleolar RNAs that transiently associate with the precursor rRNA to facilitate its modification, processing and binding with ribosomal proteins. UTPB is a large evolutionarily conserved complex in the 90S small subunit processome that mediates early processing of 18S rRNA. UTPB consists of six proteins Utp1/Pwp1, Utp6, Utp12/Dip2, Utp13, Utp18 and Utp21 and has abundant WD domains. Here, we determined the crystal structure of the tandem WD domain of yeast Utp21 at 2.1 Å resolution, revealing two open-clamshell-shaped β-propellers. The bottom faces of both WD domains harbor several conserved patches that potentially function as molecular binding sites. We show that residues 100-190 of Utp18 bind to the tandem WD domain of Utp21. Structural mapping of previous crosslinking data shows that the WD domains of Utp18 and Utp1 are organized on two opposite sides of the Utp21 WD domains. This study reports the first structure of a UTPB component and provides insight into the structural organization of the UTPB complex.

  12. Neuroanatomy of the vestimentiferan tubeworm Lamellibrachia satsuma provides insights into the evolution of the polychaete nervous system.

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    Norio Miyamoto

    Full Text Available Vestimentiferan tubeworms are marine invertebrates that inhabit chemosynthetic environments, and although recent molecular phylogenetic analyses have suggested that vestimentiferan tubeworms are derived from polychaete annelids, they show some morphological features that are different from other polychaetes. For example, vestimentiferans lack a digestive tract and have less body segments and comparative neuroanatomy can provide essential insight into the vestimentiferan body plan and its evolution. In the present study, we investigated the adult nervous system in the vestimentiferan Lamellibrachia satsuma using antibodies against synapsin, serotonin, FMRMamide and acetylated α-tubulin. We also examined the expressions of neural marker genes, elav and synaptotagmin to reveal the distribution of neuronal cell bodies. Brain anatomy shows simple organization in Lamellibrachia compared to other polychaetes. This simplification is probably due to the loss of the digestive tract, passing through the body between the brain and the subesophageal ganglion. In contrast, the ventral nerve cord shows a repeated organizational structure as in the other polychaetes, despite the absence of the multiple segmentation of the trunk. These results suggest that the brain anatomy is variable depending on the function and the condition of surrounding tissues, and that the formation of the rope ladder-like nervous system of the ventral nerve cord is independent from segmentation in polychaetes.

  13. Genome of Diaporthe sp. provides insights into the potential inter-phylum transfer of a fungal sesquiterpenoid biosynthetic pathway.

    Science.gov (United States)

    de Sena Filho, Jose Guedes; Quin, Maureen B; Spakowicz, Daniel J; Shaw, Jeffrey J; Kucera, Kaury; Dunican, Brian; Strobel, Scott A; Schmidt-Dannert, Claudia

    2016-08-01

    Fungi have highly active secondary metabolic pathways which enable them to produce a wealth of sesquiterpenoids that are bioactive. One example is Δ6-protoilludene, the precursor to the cytotoxic illudins, which are pharmaceutically relevant as anticancer therapeutics. To date, this valuable sesquiterpene has only been identified in members of the fungal division Basidiomycota. To explore the untapped potential of fungi belonging to the division Ascomycota in producing Δ6-protoilludene, we isolated a fungal endophyte Diaporthe sp. BR109 and show that it produces a diversity of terpenoids including Δ6-protoilludene. Using a genome sequencing and mining approach 17 putative novel sesquiterpene synthases were identified in Diaporthe sp. BR109. A phylogenetic approach was used to predict which gene encodes Δ6-protoilludene synthase, which was then confirmed experimentally. These analyses reveal that the sesquiterpene synthase and its putative sesquiterpene scaffold modifying cytochrome P450(s) may have been acquired by inter-phylum horizontal gene transfer from Basidiomycota to Ascomycota. Bioinformatic analyses indicate that inter-phylum transfer of these minimal sequiterpenoid secondary metabolic pathways may have occurred in other fungi. This work provides insights into the evolution of fungal sesquiterpenoid secondary metabolic pathways in the production of pharmaceutically relevant bioactive natural products.

  14. High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticles.

    Science.gov (United States)

    Anguissola, Sergio; Garry, David; Salvati, Anna; O'Brien, Peter J; Dawson, Kenneth A

    2014-01-01

    The fast-paced development of nanotechnology needs the support of effective safety testing. We have developed a screening platform measuring simultaneously several cellular parameters for exposure to various concentrations of nanoparticles (NPs). Cell lines representative of different organ cell types, including lung, endothelium, liver, kidney, macrophages, glia, and neuronal cells were exposed to 50 nm amine-modified polystyrene (PS-NH2) NPs previously reported to induce apoptosis and to 50 nm sulphonated and carboxyl-modified polystyrene NPs that were reported to be silent. All cell lines apart from Raw 264.7 executed apoptosis in response to PS-NH2 NPs, showing specific sequences of EC50 thresholds; lysosomal acidification was the most sensitive parameter. Loss of mitochondrial membrane potential and plasma membrane integrity measured by High Content Analysis resulted comparably sensitive to the equivalent OECD-recommended assays, allowing increased output. Analysis of the acidic compartments revealed good cerrelation between size/fluorescence intensity and dose of PS-NH2 NPs applied; moreover steatosis and phospholipidosis were observed, consistent with the lysosomal alterations revealed by Lysotracker green; similar responses were observed when comparing astrocytoma cells with primary astrocytes. We have established a platform providing mechanistic insights on the response to exposure to nanoparticles. Such platform holds great potential for in vitro screening of nanomaterials in highthroughput format.

  15. Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.

    Science.gov (United States)

    Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

    2011-03-23

    Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not "equally sensitive" to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

  16. Supplementary Material for: Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

    KAUST Repository

    Phelan, Jody

    2016-01-01

    Abstract Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel

  17. Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance

    KAUST Repository

    Phelan, Jody

    2016-03-23

    Background Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. Methods To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. Results The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. Conclusions Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance

  18. Whole Genome Sequencing of Mycobacterium africanum Strains from Mali Provides Insights into the Mechanisms of Geographic Restriction.

    Directory of Open Access Journals (Sweden)

    Kathryn Winglee

    2016-01-01

    Full Text Available Mycobacterium africanum, made up of lineages 5 and 6 within the Mycobacterium tuberculosis complex (MTC, causes up to half of all tuberculosis cases in West Africa, but is rarely found outside of this region. The reasons for this geographical restriction remain unknown. Possible reasons include a geographically restricted animal reservoir, a unique preference for hosts of West African ethnicity, and an inability to compete with other lineages outside of West Africa. These latter two hypotheses could be caused by loss of fitness or altered interactions with the host immune system.We sequenced 92 MTC clinical isolates from Mali, including two lineage 5 and 24 lineage 6 strains. Our genome sequencing assembly, alignment, phylogeny and average nucleotide identity analyses enabled us to identify features that typify lineages 5 and 6 and made clear that these lineages do not constitute a distinct species within the MTC. We found that in Mali, lineage 6 and lineage 4 strains have similar levels of diversity and evolve drug resistance through similar mechanisms. In the process, we identified a putative novel streptomycin resistance mutation. In addition, we found evidence of person-to-person transmission of lineage 6 isolates and showed that lineage 6 is not enriched for mutations in virulence-associated genes.This is the largest collection of lineage 5 and 6 whole genome sequences to date, and our assembly and alignment data provide valuable insights into what distinguishes these lineages from other MTC lineages. Lineages 5 and 6 do not appear to be geographically restricted due to an inability to transmit between West African hosts or to an elevated number of mutations in virulence-associated genes. However, lineage-specific mutations, such as mutations in cell wall structure, secretion systems and cofactor biosynthesis, provide alternative mechanisms that may lead to host specificity.

  19. Whole Genome Sequencing of Mycobacterium africanum Strains from Mali Provides Insights into the Mechanisms of Geographic Restriction

    Science.gov (United States)

    Maiga, Mamoudou; Abeel, Thomas; Shea, Terrance; Desjardins, Christopher A.; Diarra, Bassirou; Baya, Bocar; Sanogo, Moumine; Diallo, Souleymane; Earl, Ashlee M.; Bishai, William R.

    2016-01-01

    Background Mycobacterium africanum, made up of lineages 5 and 6 within the Mycobacterium tuberculosis complex (MTC), causes up to half of all tuberculosis cases in West Africa, but is rarely found outside of this region. The reasons for this geographical restriction remain unknown. Possible reasons include a geographically restricted animal reservoir, a unique preference for hosts of West African ethnicity, and an inability to compete with other lineages outside of West Africa. These latter two hypotheses could be caused by loss of fitness or altered interactions with the host immune system. Methodology/Principal Findings We sequenced 92 MTC clinical isolates from Mali, including two lineage 5 and 24 lineage 6 strains. Our genome sequencing assembly, alignment, phylogeny and average nucleotide identity analyses enabled us to identify features that typify lineages 5 and 6 and made clear that these lineages do not constitute a distinct species within the MTC. We found that in Mali, lineage 6 and lineage 4 strains have similar levels of diversity and evolve drug resistance through similar mechanisms. In the process, we identified a putative novel streptomycin resistance mutation. In addition, we found evidence of person-to-person transmission of lineage 6 isolates and showed that lineage 6 is not enriched for mutations in virulence-associated genes. Conclusions This is the largest collection of lineage 5 and 6 whole genome sequences to date, and our assembly and alignment data provide valuable insights into what distinguishes these lineages from other MTC lineages. Lineages 5 and 6 do not appear to be geographically restricted due to an inability to transmit between West African hosts or to an elevated number of mutations in virulence-associated genes. However, lineage-specific mutations, such as mutations in cell wall structure, secretion systems and cofactor biosynthesis, provide alternative mechanisms that may lead to host specificity. PMID:26751217

  20. Analysis of BAC end sequences in oak, a keystone forest tree species, providing insight into the composition of its genome

    Directory of Open Access Journals (Sweden)

    Le Provost Grégoire

    2011-06-01

    Full Text Available Abstract Background One of the key goals of oak genomics research is to identify genes of adaptive significance. This information may help to improve the conservation of adaptive genetic variation and the management of forests to increase their health and productivity. Deep-coverage large-insert genomic libraries are a crucial tool for attaining this objective. We report herein the construction of a BAC library for Quercus robur, its characterization and an analysis of BAC end sequences. Results The EcoRI library generated consisted of 92,160 clones, 7% of which had no insert. Levels of chloroplast and mitochondrial contamination were below 3% and 1%, respectively. Mean clone insert size was estimated at 135 kb. The library represents 12 haploid genome equivalents and, the likelihood of finding a particular oak sequence of interest is greater than 99%. Genome coverage was confirmed by PCR screening of the library with 60 unique genetic loci sampled from the genetic linkage map. In total, about 20,000 high-quality BAC end sequences (BESs were generated by sequencing 15,000 clones. Roughly 5.88% of the combined BAC end sequence length corresponded to known retroelements while ab initio repeat detection methods identified 41 additional repeats. Collectively, characterized and novel repeats account for roughly 8.94% of the genome. Further analysis of the BESs revealed 1,823 putative genes suggesting at least 29,340 genes in the oak genome. BESs were aligned with the genome sequences of Arabidopsis thaliana, Vitis vinifera and Populus trichocarpa. One putative collinear microsyntenic region encoding an alcohol acyl transferase protein was observed between oak and chromosome 2 of V. vinifera. Conclusions This BAC library provides a new resource for genomic studies, including SSR marker development, physical mapping, comparative genomics and genome sequencing. BES analysis provided insight into the structure of the oak genome. These sequences will be

  1. Trauma-informed care for children in the ambulance: international survey among pre-hospital providers.

    Science.gov (United States)

    Alisic, Eva; Tyler, Mark P; Giummarra, Melita J; Kassam-Adams, Rahim; Gouweloos, Juul; Landolt, Markus A; Kassam-Adams, Nancy

    2017-01-01

    Background: Pre-hospital providers, such as paramedics and emergency medical technicians, are in a position to provide key emotional support to injured children and their families. Objective: Our goal was to examine (a) pre-hospital providers' knowledge of traumatic stress in children, attitudes towards psychosocial aspects of care, and confidence in providing psychosocial care, (b) variations in knowledge, attitudes, and confidence according to demographic and professional characteristics, and (c) training preferences of pre-hospital providers regarding psychosocial care to support paediatric patients and their families. Method: We conducted a cross-sectional, online survey among an international sample of 812 pre-hospital providers from high-income countries. The questionnaire was adapted from a measure for a similar study among Emergency Department staff, and involved 62 items in 7 main categories (e.g. personal and work characteristics, knowledge of paediatric traumatic stress, and confidence regarding 18 elements of psychosocial care). The main analyses comprised descriptive statistics and multiple regression analyses. Results: On average, respondents answered 2.7 (SD = 1.59) out of seven knowledge questions correctly. Respondents with higher knowledge scores were more often female, parent of a child under 17, and reported that at least 10% of their patients were children. A majority of participants (83.5%) saw all 18 aspects of psychosocial care as part of their job. Providers felt moderately confident (M = 3.2, SD = 0.45) regarding their skills in psychosocial care, which was predicted by gender (female), having more experience, having a larger proportion of child patients, and having received training in psychosocial care in the past five years. Most respondents (89.7%) wanted to gain more knowledge and skills regarding psychosocial care for injured children. In terms of training format, they preferred an interactive website or a one-off group

  2. Education in naturopathy and western herbal medicine in Australia: results of a survey of education providers.

    Science.gov (United States)

    McCabe, Pauline

    2008-08-01

    Questions about the risks and regulatory requirements of naturopathy and western herbal medicine (WHM) in Australia prompted research by the Department of Human Services Victoria. This article offers findings from a survey of education providers, which was one of several studies carried out for the report. (The full report can be found at http://www.health.vic.gov.au/pracreg/naturopathy.htm.) Questionnaires were sent to 43 Australian providers of naturopathy and WHM education. Unsustainable variation was found in award types, contact hours, clinical education, length of courses, and course content. Naturopaths and WHM practitioners are primary contact health professionals but educational standards vary widely, with some practitioners not likely to be adequately prepared. The degree of risk in their practice, and the need for better integration of complementary care with mainstream healthcare, require education at least to the level of a bachelor degree. Courses should be subject to independent external accreditation. However, attempts to determine appropriate minimum educational standards are unlikely to succeed without the support of a regulatory system that can mandate those minimum requirements.

  3. Trauma-informed care for children in the ambulance: international survey among pre-hospital providers

    Science.gov (United States)

    Alisic, Eva; Tyler, Mark P.; Giummarra, Melita J.; Kassam-Adams, Rahim; Gouweloos, Juul; Landolt, Markus A.; Kassam-Adams, Nancy

    2017-01-01

    ABSTRACT Background: Pre-hospital providers, such as paramedics and emergency medical technicians, are in a position to provide key emotional support to injured children and their families. Objective: Our goal was to examine (a) pre-hospital providers’ knowledge of traumatic stress in children, attitudes towards psychosocial aspects of care, and confidence in providing psychosocial care, (b) variations in knowledge, attitudes, and confidence according to demographic and professional characteristics, and (c) training preferences of pre-hospital providers regarding psychosocial care to support paediatric patients and their families. Method: We conducted a cross-sectional, online survey among an international sample of 812 pre-hospital providers from high-income countries. The questionnaire was adapted from a measure for a similar study among Emergency Department staff, and involved 62 items in 7 main categories (e.g. personal and work characteristics, knowledge of paediatric traumatic stress, and confidence regarding 18 elements of psychosocial care). The main analyses comprised descriptive statistics and multiple regression analyses. Results: On average, respondents answered 2.7 (SD = 1.59) out of seven knowledge questions correctly. Respondents with higher knowledge scores were more often female, parent of a child under 17, and reported that at least 10% of their patients were children. A majority of participants (83.5%) saw all 18 aspects of psychosocial care as part of their job. Providers felt moderately confident (M = 3.2, SD = 0.45) regarding their skills in psychosocial care, which was predicted by gender (female), having more experience, having a larger proportion of child patients, and having received training in psychosocial care in the past five years. Most respondents (89.7%) wanted to gain more knowledge and skills regarding psychosocial care for injured children. In terms of training format, they preferred an interactive website or a one

  4. Information and Communication Technologies and Continuing Health Professional Education in Canada. A Survey of Providers Final Report.

    Science.gov (United States)

    Memorial Univ., St. John's (Newfoundland).

    The use of information and communication technologies (ICT) in continuing health professional education (CHPE) was examined in a national survey of Canadian CHPE providers. Of the 3,044 surveys distributed to schools of medicine, nursing, and pharmacy, national/provincial health professional associations, nonprofit health advocacy organizations,…

  5. Substrate specificity provides insights into the sugar donor recognition mechanism of O-GlcNAc transferase (OGT.

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    Xiaofeng Ma

    Full Text Available O-Linked β-N-acetylglucosaminyl transferase (OGT plays an important role in the glycosylation of proteins, which is involved in various cellular events. In human, three isoforms of OGT (short OGT [sOGT]; mitochondrial OGT [mOGT]; and nucleocytoplasmic OGT [ncOGT] share the same catalytic domain, implying that they might adopt a similar catalytic mechanism, including sugar donor recognition. In this work, the sugar-nucleotide tolerance of sOGT was investigated. Among a series of uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc analogs tested using the casein kinase II (CKII peptide as the sugar acceptor, four compounds could be used by sOGT, including UDP-6-deoxy-GlcNAc, UDP-GlcNPr, UDP-6-deoxy-GalNAc and UDP-4-deoxy-GlcNAc. Determined values of Km showed that the substitution of the N-acyl group, deoxy modification of C6/C4-OH or epimerization of C4-OH of the GlcNAc in UDP-GlcNAc decreased its affinity to sOGT. A molecular docking study combined with site-directed mutagenesis indicated that the backbone carbonyl oxygen of Leu653 and the hydroxyl group of Thr560 in sOGT contributed to the recognition of the sugar moiety via hydrogen bonds. The close vicinity between Met501 and the N-acyl group of GlcNPr, as well as the hydrophobic environment near Met501, were responsible for the selective binding of UDP-GlcNPr. These findings illustrate the interaction of OGT and sugar nucleotide donor, providing insights into the OGT catalytic mechanism.

  6. A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria

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    Yunpeng Yang

    2017-01-01

    Full Text Available Catabolite control protein A (CcpA is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR and carbon catabolite activation (CCA, two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt consensus site that is called a catabolite response element (cre within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named crevar, has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA. It was found that the length of the intervening spacer of crevar can affect CcpA binding affinity, and moreover, the core palindromic sequence of crevar is the key structure for regulation. Such a variable architecture of crevar shows potential importance for CcpA’s diverse and fine regulation. A total of 103 potential crevar sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs, and 30 sites were confirmed to be bound by CcpA. These 30 crevar sites are associated with 27 genes involved in many important pathways. Also of significance, the crevar sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria.

  7. A Genomic Island in Salmonella enterica ssp. salamae provides new insights on the genealogy of the locus of enterocyte effacement.

    Science.gov (United States)

    Chandry, P Scott; Gladman, Simon; Moore, Sean C; Seemann, Torsten; Crandall, Keith A; Fegan, Narelle

    2012-01-01

    The genomic island encoding the locus of enterocyte effacement (LEE) is an important virulence factor of the human pathogenic Escherichia coli. LEE typically encodes a type III secretion system (T3SS) and secreted effectors capable of forming attaching and effacing lesions. Although prominent in the pathogenic E. coli such as serotype O157:H7, LEE has also been detected in Citrobacter rodentium, E. albertii, and although not confirmed, it is likely to also be in Shigella boydii. Previous phylogenetic analysis of LEE indicated the genomic island was evolving through stepwise acquisition of various components. This study describes a new LEE region from two strains of Salmonella enterica subspecies salamae serovar Sofia along with a phylogenetic analysis of LEE that provides new insights into the likely evolution of this genomic island. The Salmonella LEE contains 36 of the 41 genes typically observed in LEE within a genomic island of 49, 371 bp that encodes a total of 54 genes. A phylogenetic analysis was performed on the entire T3SS and four T3SS genes (escF, escJ, escN, and escV) to elucidate the genealogy of LEE. Phylogenetic analysis inferred that the previously known LEE islands are members of a single lineage distinct from the new Salmonella LEE lineage. The previously known lineage of LEE diverged between islands found in Citrobacter and those in Escherichia and Shigella. Although recombination and horizontal gene transfer are important factors in the genealogy of most genomic islands, the phylogeny of the T3SS of LEE can be interpreted with a bifurcating tree. It seems likely that the LEE island entered the Enterobacteriaceae through horizontal gene transfer as a single unit, rather than as separate subsections, which was then subjected to the forces of both mutational change and recombination.

  8. Comparative transcriptional profiling provides insights into the evolution and development of the zygomorphic flower of Vicia sativa (Papilionoideae.

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    Zhipeng Liu

    Full Text Available BACKGROUND: Vicia sativa (the common vetch possesses a predominant zygomorphic flower and belongs to the subfamily Papilionoideae, which is related to Arabidopsis thaliana in the eurosid II clade of the core eudicots. Each vetch flower consists of 21 concentrically arranged organs: the outermost five sepals, then five petals and ten stamens, and a single carpel in the center. METHODOLOGY/PRINCIPAL FINDINGS: We explored the floral transcriptome to examine a genome-scale genetic model of the zygomorphic flower of vetch. mRNA was obtained from an equal mixture of six floral organs, leaves and roots. De novo assembly of the vetch transcriptome using Illumina paired-end technology produced 71,553 unigenes with an average length of 511 bp. We then compared the expression changes in the 71,553 unigenes in the eight independent organs through RNA-Seq Quantification analysis. We predominantly analyzed gene expression patterns specific to each floral organ and combinations of floral organs that corresponded to the traditional ABC model domains. Comparative analyses were performed in the floral transcriptomes of vetch and Arabidopsis, and genomes of vetch and Medicago truncatula. CONCLUSIONS/SIGNIFICANCE: Our comparative analysis of vetch and Arabidopsis showed that the vetch flowers conform to a strict ABC model. We analyzed the evolution and expression of the TCP gene family in vetch at a whole-genome level, and several unigenes specific to three different vetch petals, which might offer some clues toward elucidating the molecular mechanisms underlying floral zygomorphy. Our results provide the first insights into the genome-scale molecular regulatory network that controls the evolution and development of the zygomorphic flower in Papilionoideae.

  9. Mutant analysis in Arabidopsis provides insight into the molecular mode of action of the auxinic herbicide dicamba.

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    Cynthia Gleason

    Full Text Available Herbicides that mimic the natural auxin indole-3-acetic acid are widely used in weed control. One common auxin-like herbicide is dicamba, but despite its wide use, plant gene responses to dicamba have never been extensively studied. To further understand dicamba's mode of action, we utilized Arabidopsis auxin-insensitive mutants and compared their sensitivity to dicamba and the widely-studied auxinic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D. The mutant axr4-2, which has disrupted auxin transport into cells, was resistant to 2,4-D but susceptible to dicamba. By comparing dicamba resistance in auxin signalling F-box receptor mutants (tir1-1, afb1, afb2, afb3, and afb5, only tir1-1 and afb5 were resistant to dicamba, and this resistance was additive in the double tir1-1/afb5 mutant. Interestingly, tir1-1 but not afb5 was resistant to 2,4-D. Whole genome analysis of dicamba-induced gene expression showed that 10 hours after application, dicamba stimulated many stress-responsive and signalling genes, including those involved in biosynthesis or signalling of auxin, ethylene, and abscisic acid (ABA, with TIR1 and AFB5 required for the dicamba-responsiveness of some genes. Research into dicamba-regulated gene expression and the selectivity of auxin receptors has provided molecular insight into dicamba-regulated signalling and could help in the development of novel herbicide resistance in crop plants.

  10. Meta-coexpression conservation analysis of microarray data: a "subset" approach provides insight into brain-derived neurotrophic factor regulation

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    Timmusk Tõnis

    2009-09-01

    Full Text Available Abstract Background Alterations in brain-derived neurotrophic factor (BDNF gene expression contribute to serious pathologies such as depression, epilepsy, cancer, Alzheimer's, Huntington and Parkinson's disease. Therefore, exploring the mechanisms of BDNF regulation represents a great clinical importance. Studying BDNF expression remains difficult due to its multiple neural activity-dependent and tissue-specific promoters. Thus, microarray data could provide insight into the regulation of this complex gene. Conventional microarray co-expression analysis is usually carried out by merging the datasets or by confirming the re-occurrence of significant correlations across datasets. However, co-expression patterns can be different under various conditions that are represented by subsets in a dataset. Therefore, assessing co-expression by measuring correlation coefficient across merged samples of a dataset or by merging datasets might not capture all correlation patterns. Results In our study, we performed meta-coexpression analysis of publicly available microarray data using BDNF as a "guide-gene" introducing a "subset" approach. The key steps of the analysis included: dividing datasets into subsets with biologically meaningful sample content (e.g. tissue, gender or disease state subsets; analyzing co-expression with the BDNF gene in each subset separately; and confirming co- expression links across subsets. Finally, we analyzed conservation in co-expression with BDNF between human, mouse and rat, and sought for conserved over-represented TFBSs in BDNF and BDNF-correlated genes. Correlated genes discovered in this study regulate nervous system development, and are associated with various types of cancer and neurological disorders. Also, several transcription factor identified here have been reported to regulate BDNF expression in vitro and in vivo. Conclusion The study demonstrates the potential of the "subset" approach in co-expression conservation

  11. Crystal structure of peroxide stress regulator from Streptococcus pyogenes provides functional insights into the mechanism of oxidative stress sensing.

    Science.gov (United States)

    Makthal, Nishanth; Rastegari, Sheila; Sanson, Misu; Ma, Zhen; Olsen, Randall J; Helmann, John D; Musser, James M; Kumaraswami, Muthiah

    2013-06-21

    Regulation of oxidative stress responses by the peroxide stress regulator (PerR) is critical for the in vivo fitness and virulence of group A Streptococcus. To elucidate the molecular mechanism of DNA binding, peroxide sensing, and gene regulation by PerR, we performed biochemical and structural characterization of PerR. Sequence-specific DNA binding by PerR does not require regulatory metal occupancy. However, metal binding promotes higher affinity PerR-DNA interactions. PerR metallated with iron directly senses peroxide stress and dissociates from operator sequences. The crystal structure revealed that PerR exists as a homodimer with two metal-binding sites per subunit as follows: a structural zinc site and a regulatory metal site that is occupied in the crystals by nickel. The regulatory metal-binding site in PerR involves a previously unobserved HXH motif located in its unique N-terminal extension. Mutational analysis of the regulatory site showed that the PerR metal ligands are involved in regulatory metal binding, and integrity of this site is critical for group A Streptococcus virulence. Interestingly, the metal-binding HXH motif is not present in the structurally characterized members of ferric uptake regulator (Fur) family but is fully conserved among PerR from the genus Streptococcus. Thus, it is likely that the PerR orthologs from streptococci share a common mechanism of metal binding, peroxide sensing, and gene regulation that is different from that of well characterized PerR from Bacillus subtilis. Together, our findings provide key insights into the peroxide sensing and regulation of the oxidative stress-adaptive responses by the streptococcal subfamily of PerR.

  12. Comparative genomics reveals two novel RNAi factors in Trypanosoma brucei and provides insight into the core machinery.

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    Rebecca L Barnes

    Full Text Available The introduction ten years ago of RNA interference (RNAi as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1 protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5. TbRIF4 is a 3'-5' exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites.

  13. A comparison of the seasonal movements of tiger sharks and green turtles provides insight into their predator-prey relationship.

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    Richard Fitzpatrick

    Full Text Available During the reproductive season, sea turtles use a restricted area in the vicinity of their nesting beaches, making them vulnerable to predation. At Raine Island (Australia, the highest density green turtle Chelonia mydas rookery in the world, tiger sharks Galeocerdo cuvier have been observed to feed on green turtles, and it has been suggested that they may specialise on such air-breathing prey. However there is little information with which to examine this hypothesis. We compared the spatial and temporal components of movement behaviour of these two potentially interacting species in order to provide insight into the predator-prey relationship. Specifically, we tested the hypothesis that tiger shark movements are more concentrated at Raine Island during the green turtle nesting season than outside the turtle nesting season when turtles are not concentrated at Raine Island. Turtles showed area-restricted search behaviour around Raine Island for ∼3-4 months during the nesting period (November-February. This was followed by direct movement (transit to putative foraging grounds mostly in the Torres Straight where they switched to area-restricted search mode again, and remained resident for the remainder of the deployment (53-304 days. In contrast, tiger sharks displayed high spatial and temporal variation in movement behaviour which was not closely linked to the movement behaviour of green turtles or recognised turtle foraging grounds. On average, tiger sharks were concentrated around Raine Island throughout the year. While information on diet is required to determine whether tiger sharks are turtle specialists our results support the hypothesis that they target this predictable and plentiful prey during turtle nesting season, but they might not focus on this less predictable food source outside the nesting season.

  14. A Genomic Island in Salmonella enterica ssp. salamae provides new insights on the genealogy of the locus of enterocyte effacement.

    Directory of Open Access Journals (Sweden)

    P Scott Chandry

    Full Text Available The genomic island encoding the locus of enterocyte effacement (LEE is an important virulence factor of the human pathogenic Escherichia coli. LEE typically encodes a type III secretion system (T3SS and secreted effectors capable of forming attaching and effacing lesions. Although prominent in the pathogenic E. coli such as serotype O157:H7, LEE has also been detected in Citrobacter rodentium, E. albertii, and although not confirmed, it is likely to also be in Shigella boydii. Previous phylogenetic analysis of LEE indicated the genomic island was evolving through stepwise acquisition of various components. This study describes a new LEE region from two strains of Salmonella enterica subspecies salamae serovar Sofia along with a phylogenetic analysis of LEE that provides new insights into the likely evolution of this genomic island. The Salmonella LEE contains 36 of the 41 genes typically observed in LEE within a genomic island of 49, 371 bp that encodes a total of 54 genes. A phylogenetic analysis was performed on the entire T3SS and four T3SS genes (escF, escJ, escN, and escV to elucidate the genealogy of LEE. Phylogenetic analysis inferred that the previously known LEE islands are members of a single lineage distinct from the new Salmonella LEE lineage. The previously known lineage of LEE diverged between islands found in Citrobacter and those in Escherichia and Shigella. Although recombination and horizontal gene transfer are important factors in the genealogy of most genomic islands, the phylogeny of the T3SS of LEE can be interpreted with a bifurcating tree. It seems likely that the LEE island entered the Enterobacteriaceae through horizontal gene transfer as a single unit, rather than as separate subsections, which was then subjected to the forces of both mutational change and recombination.

  15. Comprehensive Transcriptome Analyses of the Fructose-Fed Syrian Golden Hamster Liver Provides Novel Insights into Lipid Metabolism.

    Science.gov (United States)

    Li, Ziyang; Xiong, Chaoliang; Mo, Suo; Tian, Haiying; Yu, Mengqian; Mao, Tingting; Chen, Qian; Luo, Haitao; Li, Quanzhen; Lu, Jianxin; Zhao, Yi; Li, Wei

    2016-01-01

    Dyslipidemia has been widely proven to contribute to cardiovascular diseases and other metabolic disorders, especially in insulin resistance and type 2 diabetes. The overproduction of VLDL is a significant characteristic of dyslipidemia, indicating the dysfunction of hepatic lipid metabolism, from triglyceride synthesis to transport. The fructose-fed Syrian golden hamster is an established animal model for the study of VLDL assembly with insulin resistance, however, it remains unknown how VLDL production is regulated at the transcriptional level due to the absence of a complete hamster genome. Here, we performed deep sequencing and constructed an mRNA-miRNA-lncRNA interaction network of Syrian golden hamster liver in order to reveal the global transcription profile and find potential RNA molecular regulation of VLDL production. We identified 4,450 novel multi-exon hamster lncRNAs and 755 miRNAs expressed in liver. Additionally, 146 differentially expressed coding genes, 27 differentially expressed lncRNA genes, as well as 16 differentially expressed miRNAs were identified. We then constructed an mRNA-miRNA-lncRNA interaction network that may potentially regulate VLDL production, and interestingly found several microRNA-centered regulatory networks. In order to verify our interpretation, miR-486 was selected for further experiments. Overexpression or down-regulation of miR-486 in fructose-fed hamsters resulted in altered hepatic expression of proteins involved in VLDL production, and in modulated levels of circulating VLDL. Our findings implicated that miR-486 is a potential regulator of circulating VLDL levels. These results provide new insights and a valuable resource for further study of the molecular mechanisms of VLDL secretion.

  16. Recommended survey designs for occupancy modelling using motion-activated cameras: insights from empirical wildlife data.

    Science.gov (United States)

    Shannon, Graeme; Lewis, Jesse S; Gerber, Brian D

    2014-01-01

    Motion-activated cameras are a versatile tool that wildlife biologists can use for sampling wild animal populations to estimate species occurrence. Occupancy modelling provides a flexible framework for the analysis of these data; explicitly recognizing that given a species occupies an area the probability of detecting it is often less than one. Despite the number of studies using camera data in an occupancy framework, there is only limited guidance from the scientific literature about survey design trade-offs when using motion-activated cameras. A fuller understanding of these trade-offs will allow researchers to maximise available resources and determine whether the objectives of a monitoring program or research study are achievable. We use an empirical dataset collected from 40 cameras deployed across 160 km(2) of the Western Slope of Colorado, USA to explore how survey effort (number of cameras deployed and the length of sampling period) affects the accuracy and precision (i.e., error) of the occupancy estimate for ten mammal and three virtual species. We do this using a simulation approach where species occupancy and detection parameters were informed by empirical data from motion-activated cameras. A total of 54 survey designs were considered by varying combinations of sites (10-120 cameras) and occasions (20-120 survey days). Our findings demonstrate that increasing total sampling effort generally decreases error associated with the occupancy estimate, but changing the number of sites or sampling duration can have very different results, depending on whether a species is spatially common or rare (occupancy = ψ) and easy or hard to detect when available (detection probability = p). For rare species with a low probability of detection (i.e., raccoon and spotted skunk) the required survey effort includes maximizing the number of sites and the number of survey days, often to a level that may be logistically unrealistic for many studies. For common species with

  17. New insights into the North Taranaki Basin from New Zealand's first broadband 3D survey

    Science.gov (United States)

    Uzcategui, Marjosbet; Francis, Malcolm; Kong, Wai Tin Vincent; Patenall, Richard; Fell, Dominic; Paxton, Andrea; Allen, Tristan

    2016-06-01

    The Taranaki Basin is the only hydrocarbon producing basin in New Zealand. The North Taranaki Basin has widespread two-dimensional (2D) seismic coverage and numerous wells that have not encountered commercial accumulations. This is attributed to the structural complexity in the central graben and the absence of necessary information to help understand the basin's evolution. An active petroleum system has been confirmed by hydrocarbon shows and non-commercial oil and gas discoveries (Karewa-1 and Kora-1). A broadband long offset three-dimensional (3D) seismic survey was acquired and processed by Schlumberger in 2013 to evaluate the hydrocarbon potential of the North Taranaki Basin. Innovative acquisition techniques were combined with advanced processing and imaging methods. Raypath distortions and depth uncertainty were significantly reduced by processing through tilted transverse isotropy (TTI) anisotropic Kirchhoff prestack depth migration with a geologically constrained velocity model. The survey provided the necessary information to understand the petroleum system and provide evidence for material hydrocarbon accumulations. In this investigation, we assessed the hydrocarbon potential of the North Taranaki Basin using the newly acquired data. 3D seismic interpretation and amplitude-versus-offset (AVO) analysis support the renewed potential of the basin and demonstrate effectiveness of these technologies that together can achieve encouraging results for hydrocarbon exploration.

  18. The providers of health services in Lebanon: a survey of physicians

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    Osseiran Arabia

    2006-02-01

    Full Text Available Abstract Background Emerging from civil distress carries with it major challenges to reforming a health system. One such challenge is to ensure an adequate supply of competent human resources. The objective of this study was to assess the supply of physicians in Lebanon in 1998, with an assessment of their practice patterns and capacity building. Methods Lists of members of physician's associations were examined to determine the number of physicians in Lebanon and their geographical distribution. A self-administered survey targeted 388 physicians (5% randomly stratified by the five regions of Lebanon. Some 377 providers reported information on their demographic profile, practice patterns and development. Further, information on continuing education activities was acquired. Results In Lebanon, the overall physician-to-population ratio was 248 per 100, 000, characterized by an evident maldistribution at the intracountry regional level. Physicians worked 38 hours per week examining on average 21 patients per day, with an average time of 30 minutes spent per visit. They also reported spending 11% of their time waiting for patients. Respondents reported a very wide range of income, with 90% earning less than USD 2,000 per month. Moreover, the continuing education profile revealed a total of 43.7 hours per year, similar to that required for board certification in many developed countries. Conference attendance was the dominant continuing education activity (95% of respondents and consumed most of the time allotted for continuing education, reported at 32 hours per year. Discussion and conclusion Various economic indicators point to an oversupply of physicians in Lebanon and a poor allocation of their time for capacity building. Therefore, it is crucial for decision-makers to closely monitor the increasing supply of providers and institute appropriate intervention strategies, taking into consideration appropriate provision of good-quality services and

  19. Genomics and Comparative Genomic Analyses Provide Insight into the Taxonomy and Pathogenic Potential of Novel Emmonsia Pathogens

    Science.gov (United States)

    Yang, Ying; Ye, Qiang; Li, Kang; Li, Zongwei; Bo, Xiaochen; Li, Zhen; Xu, Yingchun; Wang, Shengqi; Wang, Peng; Chen, Huipeng; Wang, Junzhi

    2017-01-01

    adaptations of new Emmonsia, but this question warrants further investigation. Overall, our analyses provide a framework from which to further study the evolutionary dynamics of Emmonsia strains and identity the underlying molecular mechanisms that determine the infectious and pathogenic potency of these fungal pathogens, and also provide insight into potential targets for therapeutic intervention of emmonsiosis and further research.

  20. RNA-Seq Analysis Provides the First Insights into the Phylogenetic Relationship and Interspecific Variation between Agropyron cristatum and Wheat

    Directory of Open Access Journals (Sweden)

    Shenghui Zhou

    2017-09-01

    Full Text Available Agropyron cristatum, which is a wild grass of the tribe Triticeae, grows widely in harsh environments and provides many desirable genetic resources for wheat improvement. However, unclear interspecific phylogeny and genome-wide variation has limited the utilization of A. cristatum in the production of superior wheat varieties. In this study, by sequencing the transcriptome of the representative tetraploid A. cristatum Z559 and the common wheat variety Fukuhokomugi (Fukuho, which are often used as parents in a wide cross, their phylogenetic relationship and interspecific variation were dissected. First, 214,854 transcript sequences were assembled, and 3,457 orthologous genes related to traits of interest were identified in A. cristatum. Second, a total of 72 putative orthologous gene clusters were used to construct phylogenetic relationships among A. cristatum, Triticeae and other genomes. A clear division between A. cristatum and the other Triticeae species was revealed. Third, the sequence similarity of most genes related to traits of interest is greater than 95% between A. cristatum and wheat. Therefore, using the 5% mismatch parameter for A. cristatum, we mapped the transcriptome sequencing data to wheat reference sequences to discover the variations between A. cristatum and wheat and 862,340 high-quality variants were identified. Additionally, compared with the wheat A and B genomes, the P and D genomes displayed an obviously larger variant density and a longer evolutionary distance, suggesting that A. cristatum is more distantly related to the wheat D genome. Finally, by using Kompetitive Allele Specific PCR array (KASPar technology, 37 of 53 (69.8% SNPs were shown to be genuine in Z559, Fukuho, and additional lines with seven different P chromosomes, and function of the genes in which these SNPs are located were also determined. This study provides not only the first insights into the phylogenetic relationships between the P genome and

  1. Comprehensive Profiling of Proteome Changes Provide Insights of Industrial Penicillium chrysogenum During Pilot and Industrial Penicillin G Fermentation.

    Science.gov (United States)

    Cheng, Jing-Sheng; Zhao, Yan; Qiao, Bin; Lu, Hua; Chen, Yao; Yuan, Ying-Jin

    2016-07-01

    197 and 198) and CoA ligase at 80 h during the industrial process were around 2-fold of that during the pilot process, indicating that the industrial process with a higher penicillin production per cell might provide available environments to induce over-expression of IPN acyltransferase and accelerate penicillin formation. These results provide new insights into the globally potential responses of P. chrysogenum to variations of environments in different fermentation scales so as to consequently regulate the penicillin production.

  2. A genome survey of Moniliophthora perniciosa gives new insights into Witches' Broom Disease of cacao

    Directory of Open Access Journals (Sweden)

    Bailey Bryan A

    2008-11-01

    Full Text Available Abstract Background The basidiomycete fungus Moniliophthora perniciosa is the causal agent of Witches' Broom Disease (WBD in cacao (Theobroma cacao. It is a hemibiotrophic pathogen that colonizes the apoplast of cacao's meristematic tissues as a biotrophic pathogen, switching to a saprotrophic lifestyle during later stages of infection. M. perniciosa, together with the related species M. roreri, are pathogens of aerial parts of the plant, an uncommon characteristic in the order Agaricales. A genome survey (1.9× coverage of M. perniciosa was analyzed to evaluate the overall gene content of this phytopathogen. Results Genes encoding proteins involved in retrotransposition, reactive oxygen species (ROS resistance, drug efflux transport and cell wall degradation were identified. The great number of genes encoding cytochrome P450 monooxygenases (1.15% of gene models indicates that M. perniciosa has a great potential for detoxification, production of toxins and hormones; which may confer a high adaptive ability to the fungus. We have also discovered new genes encoding putative secreted polypeptides rich in cysteine, as well as genes related to methylotrophy and plant hormone biosynthesis (gibberellin and auxin. Analysis of gene families indicated that M. perniciosa have similar amounts of carboxylesterases and repertoires of plant cell wall degrading enzymes as other hemibiotrophic fungi. In addition, an approach for normalization of gene family data using incomplete genome data was developed and applied in M. perniciosa genome survey. Conclusion This genome survey gives an overview of the M. perniciosa genome, and reveals that a significant portion is involved in stress adaptation and plant necrosis, two necessary characteristics for a hemibiotrophic fungus to fulfill its infection cycle. Our analysis provides new evidence revealing potential adaptive traits that may play major roles in the mechanisms of pathogenicity in the M. perniciosa

  3. A GTPase chimera illustrates an uncoupled nucleotide affinity and release rate, Providing insight into the activation mechanism

    DEFF Research Database (Denmark)

    Guilfoyle, Amy P.; Deshpande, Chandrika N.; Font Sadurni, Josep

    2014-01-01

    for GDP release, or, alternatively, the movement is a consequence of release. To gain additional insight into the sequence of events leading to GDP release, we have created a chimeric protein comprised of Escherichia coli NFeoB and the G5 loop from the human Giα1 protein. The protein chimera retains...

  4. Novel murine infection models provide deep insights into the "menage a trois" of Campylobacter jejuni, microbiota and host innate immunity.

    Directory of Open Access Journals (Sweden)

    Stefan Bereswill

    gnotobiotic and "humanized" mice represent excellent novel C. jejuni-infection and -inflammation models and provide deep insights into the immunological and molecular interplays between C. jejuni, microbiota and innate immunity in human campylobacteriosis.

  5. National Archive of Marine Seismic Surveys (NAMSS): U.S. Geological Survey Program to Provide new Access to Proprietary Data

    Science.gov (United States)

    Childs, J. R.; Hart, P. E.

    2004-12-01

    Marine seismic reflection profile data originally acquired for purposes of offshore oil and gas exploration and development within the United States Exclusive Economic Zone represent a national scientific resource of inestimable value. Although the commercial value of these data has diminished due to technological advances and offshore development moratoria, the value to current and future scientific endeavors continues to be very high. Recently, commercial owners (including WesternGeco and ChevronTexaco) of large data holdings offshore the eastern, western, and Alaskan coasts of the United States have offered to transfer over 200,000 line kilometers of two-dimensional data (vintage 1970 to 1985) to the public domain. Recognizing the value of these data, the U.S. Geological Survey in co-operation with the Institute for Crustal Studies at UCSB, the Incorporated Research Institutions for Seismology, and the American Geological Institute) is promoting efforts to safeguard on behalf of the research community and the nation any data that may otherwise be lost, and to ensure free and open access to that data. To achieve these goals, the USGS has developed a National Archive of Marine Seismic Surveys (NAMSS). Work is underway to organize and reformat digital data currently stored on obsolete media, primarily nine-track tapes. The NAMSS web site below has further information on the project, including trackline maps of surveys that will soon be publicly available. The ultimate objective is the establishment of a data repository accessible through an on-line database, with graphical and text-based search and retrieval interface.

  6. Knowledge, attitude, willingness and readiness of primary health care providers to provide oral health services to children in Niagara, Ontario: a cross-sectional survey

    Science.gov (United States)

    Singhal, Sonica; Figueiredo, Rafael; Dupuis, Sandy; Skellet, Rachel; Wincott, Tara; Dyer, Carolyn; Feller, Andrea; Quiñonez, Carlos

    2017-01-01

    Background: Most children are exposed to medical, but not dental, care at an early age, making primary health care providers an important player in the reduction of tooth decay. The goal of this research was to understand the feasibility of using primary health care providers in promoting oral health by assessing their knowledge, attitude, willingness and readiness in this regard. Methods: Using the Dillman method, a mail-in cross-sectional survey was conducted among all family physicians and pediatricians in the Niagara region of Ontario who have primary contact with children. A descriptive analysis was performed. Results: Close to 70% (181/265) of providers responded. More than 90% know that untreated tooth decay could affect the general health of a child. More than 80% examine the oral cavity for more than 50% of their child patients. However, more than 50% are not aware that white spots or lines on the tooth surface are the first signs of tooth decay. Lack of clinical time was the top reason for not performing oral disease prevention measures. Interpretation: Overall, survey responses show a positive attitude and willingness to engage in the oral health of children. To capitalize on this, there is a need to identify mechanisms of providing preventive oral health care services by primary health care providers; including improving their knowledge of oral health and addressing other potential barriers.

  7. The science of trail surveys: Recreation ecology provides new tools for managing wilderness trails

    Science.gov (United States)

    Marion, Jeffrey L.; Wimpey, Jeremy F.; Park, Logan O.

    2011-01-01

    Recreation ecology examines the effects of recreation on protected area ecosystems. One core focus of recreation ecology research is trail science, including the development of efficient protocols to assess and monitor the type and severity of resource impacts, analyses to improve knowledge of factors that influence trail conditions, and studies to assist land managers in improving trail design, maintenance, and visitor management. This article reviews alternative trail survey methodologies most useful for the management of wilderness and backcountry trail networks. Illustrations and implications from survey data for trail planning, design, and management are included.

  8. Investigation of bacterial communities within the digestive organs of the hydrothermal vent shrimp Rimicaris exoculata provide insights into holobiont geographic clustering

    Science.gov (United States)

    Durand, Lucile; Cambon-Bonavita, Marie-Anne; Arnaud-Haond, Sophie

    2017-01-01

    Prokaryotic communities forming symbiotic relationships with the vent shrimp, Rimicaris exoculata, are well studied components of hydrothermal ecosystems at the Mid-Atlantic Ridge (MAR). Despite the tight link between host and symbiont, the observed lack of spatial genetic structure seen in R. exoculata contrasts with the geographic differentiation detected in specific bacterial ectosymbionts. The geographic clustering of bacterial lineages within a seemingly panmictic host suggests either the presence of finer scale restriction to gene flow not yet detected in the host, horizontal transmission (environmental selection) of its endosymbionts as a consequence of unique vent geochemistry, or vertically transmitted endosymbionts that exhibit genetic differentiation. To identify which hypothesis best fits, we tested whether bacterial assemblages exhibit differentiation across sites or host populations by performing a 16S rRNA metabarcoding survey on R. exoculata digestive prokaryote samples (n = 31) taken from three geochemically distinct vents across MAR: Rainbow, Trans-Atlantic Geotraverse (TAG) and Logatchev. Analysis of communities across two organs (digestive tract, stomach), three molt colors (white, red, black) and three life stages (eggs, juveniles, adults) also provided insights into symbiont transmission mode. Examining both whole communities and operational taxonomic units (OTUs) confirmed the presence of three main epibionts: Epsilonproteobacteria, Mollicutes and Deferribacteres. With these findings, we identified a clear pattern of geographic segregation by vent in OTUs assigned to Epsilonproteobacteria. Additionally, we detected evidence for differentiation among all communities associated to vents and life stages. Overall, results suggest a combination of environmental selection and vertical inheritance of some of the symbiotic lineages. PMID:28296889

  9. A survey of midwives' views on providing aspects of antenatal care in Estonia

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V; Rull, Kristiina; Wyn Huws, Dyfed

    2007-01-01

    OBJECTIVE: to survey the views of midwives in Estonia about who they considered should have responsibility for carrying out certain aspects of antenatal care (ANC) in Estonia. DESIGN, SETTING AND STUDY POPULATION: in collaboration with key stakeholder organisations, the authors developed eight...

  10. Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

    NARCIS (Netherlands)

    Strawbridge, Rona J.; Dupuis, Josee; Prokopenko, Inga; Barker, Adam; Ahlqvist, Emma; Rybin, Denis; Petrie, John R.; Travers, Mary E.; Bouatia-Naji, Nabila; Dimas, Antigone S.; Nica, Alexandra; Wheeler, Eleanor; Chen, Han; Voight, Benjamin F.; Taneera, Jalal; Kanoni, Stavroula; Peden, John F.; Turrini, Fabiola; Gustafsson, Stefan; Zabena, Carina; Almgren, Peter; Barker, David J. P.; Barnes, Daniel; Dennison, Elaine M.; Eriksson, Johan G.; Eriksson, Per; Eury, Elodie; Folkersen, Lasse; Fox, Caroline S.; Frayling, Timothy M.; Goel, Anuj; Gu, Harvest F.; Horikoshi, Momoko; Isomaa, Bo; Jackson, Anne U.; Jameson, Karen A.; Kajantie, Eero; Kerr-Conte, Julie; Kuulasmaa, Teemu; Kuusisto, Johanna; Loos, Ruth J. F.; Luan, Jian'an; Makrilakis, Konstantinos; Manning, Alisa K.; Teresa Martinez-Larrad, Maria; Narisu, Narisu; Mannila, Maria Nastase; Ohrvik, John; Osmond, Clive; Pascoe, Laura; Payne, Felicity; Sayer, Avan A.; Sennblad, Bengt; Silveira, Angela; Stancakova, Alena; Stirrups, Kathy; Swift, Amy J.; Syvanen, Ann-Christine; Tuomi, Tiinamaija; van 't Hooft, Ferdinand M.; Walker, Mark; Weedon, Michael N.; Xie, Weijia; Zethelius, Bjorn; Ongen, Halit; Malarstig, Anders; Hopewell, Jemma C.; Saleheen, Danish; Chambers, John; Parish, Sarah; Danesh, John; Kooner, Jaspal; Ostenson, Claes-Goran; Lind, Lars; Cooper, Cyrus C.; Serrano-Rios, Manuel; Ferrannini, Ele; Forsen, Tom J.; Clarke, Robert; Franzosi, Maria Grazia; Seedorf, Udo; Watkins, Hugh; Froguel, Philippe; Johnson, Paul; Deloukas, Panos; Collins, Francis S.; Laakso, Markku; Dermitzakis, Emmanouil T.; Boehnke, Michael; McCarthy, Mark I.; Wareham, Nicholas J.; Groop, Leif; Pattou, Francois; Gloyn, Anna L.; Dedoussis, George V.; Lyssenko, Valeriya; Meigs, James B.; Barroso, Ines; Watanabe, Richard M.; Ingelsson, Erik; Langenberg, Claudia; Hamsten, Anders; Florez, Jose C.

    2011-01-01

    OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about

  11. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

    NARCIS (Netherlands)

    Strawbridge, R.J.; Dupuis, J.; Prokopenko, I.; Barker, A.; Ahlqvist, E.; Rybin, D.; Petrie, J.R.; Travers, M.E.; Bouatia-Naji, N.; Dimas, A.S.; Nica, A.; Wheeler, E.; Chen, H.; Voight, B.F.; Taneera, J.; Kanoni, S.; Peden, J.F.; Turrini, F.; Gustafsson, S.; Zabena, C.; Almgren, P.; Barker, D.J.; Barnes, D.; Dennison, E.M.; Eriksson, J.G.; Eriksson, P.; Eury, E.; Folkersen, L.; Fox, C.S.; Frayling, T.M.; Goel, A.; Gu, H.F.; Horikoshi, M.; Isomaa, B.; Jackson, A.U.; Jameson, K.A.; Kajantie, E.; Kerr-Conte, J.; Kuulasmaa, T.; Kuusisto, J.; Loos, R.J.; Luan, J.; Makrilakis, K.; Manning, A.K.; Martinez-Larrad, M.T.; Narisu, N.; Nastase Mannila, M.; Ohrvik, J.; Osmond, C.; Pascoe, L.; Payne, F.; Sayer, A.A.; Sennblad, B.; Silveira, A.; Stancakova, A.; Stirrups, K.; Swift, A.J.; Syvanen, A.C.; Tuomi, T.; Hooft, F. van 't; Walker, M.; Weedon, M.N.; Xie, W.; Zethelius, B.; Ongen, H.; Malarstig, A.; Hopewell, J.C.; Saleheen, D.; Chambers, J.; Parish, S.; Danesh, J.; Kooner, J.; Ostenson, C.G.; Lind, L.; Cooper, C.C.; Serrano-Rios, M.; Ferrannini, E.; Forsen, T.J.; Clarke, R.; Franzosi, M.G.; Seedorf, U.; Watkins, H.; Froguel, P.; Johnson, P.; Deloukas, P.; Collins, F.S.; Laakso, M.; Dermitzakis, E.T.; Boehnke, M.; McCarthy, M.I.; Wareham, N.J.; Groop, L.; Pattou, F.; Gloyn, A.L.; Dedoussis, G.V.; Lyssenko, V.; Meigs, J.B.; Barroso, I.; Watanabe, R.M.; Heijer, M. den; Kiemeney, L.A.L.M.

    2011-01-01

    OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about

  12. Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

    NARCIS (Netherlands)

    Strawbridge, Rona J.; Dupuis, Josee; Prokopenko, Inga; Barker, Adam; Ahlqvist, Emma; Rybin, Denis; Petrie, John R.; Travers, Mary E.; Bouatia-Naji, Nabila; Dimas, Antigone S.; Nica, Alexandra; Wheeler, Eleanor; Chen, Han; Voight, Benjamin F.; Taneera, Jalal; Kanoni, Stavroula; Peden, John F.; Turrini, Fabiola; Gustafsson, Stefan; Zabena, Carina; Almgren, Peter; Barker, David J. P.; Barnes, Daniel; Dennison, Elaine M.; Eriksson, Johan G.; Eriksson, Per; Eury, Elodie; Folkersen, Lasse; Fox, Caroline S.; Frayling, Timothy M.; Goel, Anuj; Gu, Harvest F.; Horikoshi, Momoko; Isomaa, Bo; Jackson, Anne U.; Jameson, Karen A.; Kajantie, Eero; Kerr-Conte, Julie; Kuulasmaa, Teemu; Kuusisto, Johanna; Loos, Ruth J. F.; Luan, Jian'an; Makrilakis, Konstantinos; Manning, Alisa K.; Teresa Martinez-Larrad, Maria; Narisu, Narisu; Mannila, Maria Nastase; Ohrvik, John; Osmond, Clive; Pascoe, Laura; Payne, Felicity; Sayer, Avan A.; Sennblad, Bengt; Silveira, Angela; Stancakova, Alena; Stirrups, Kathy; Swift, Amy J.; Syvanen, Ann-Christine; Tuomi, Tiinamaija; van 't Hooft, Ferdinand M.; Walker, Mark; Weedon, Michael N.; Xie, Weijia; Zethelius, Bjorn; Ongen, Halit; Malarstig, Anders; Hopewell, Jemma C.; Saleheen, Danish; Chambers, John; Parish, Sarah; Danesh, John; Kooner, Jaspal; Ostenson, Claes-Goran; Lind, Lars; Cooper, Cyrus C.; Serrano-Rios, Manuel; Ferrannini, Ele; Forsen, Tom J.; Clarke, Robert; Franzosi, Maria Grazia; Seedorf, Udo; Watkins, Hugh; Froguel, Philippe; Johnson, Paul; Deloukas, Panos; Collins, Francis S.; Laakso, Markku; Dermitzakis, Emmanouil T.; Boehnke, Michael; McCarthy, Mark I.; Wareham, Nicholas J.; Groop, Leif; Pattou, Francois; Gloyn, Anna L.; Dedoussis, George V.; Lyssenko, Valeriya; Meigs, James B.; Barroso, Ines; Watanabe, Richard M.; Ingelsson, Erik; Langenberg, Claudia; Hamsten, Anders; Florez, Jose C.

    2011-01-01

    OBJECTIVE-Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired beta-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about

  13. Understanding and improving patient experience: a national survey of training courses provided by higher education providers and healthcare organizations in England.

    Science.gov (United States)

    Robert, Glenn; Waite, Richard; Cornwell, Jocelyn; Morrow, Elizabeth; Maben, Jill

    2014-01-01

    Understanding and improving 'patient experience' is essential to delivering high quality healthcare. However, little is known about the provision of education and training to healthcare staff in this increasingly important area. This study aims to ascertain the extent and nature of such provision in England and to identify how it might be developed in the future. An on-line survey was designed to explore training provision relating to patient experiences. To ensure that respondents thought about patient experience in the same way we defined patient experience training as that which aims to teach staff: 'How to measure or monitor the experience, preferences and priorities of patients and use that knowledge to improve their experience'. Survey questions (n=15) were devised to cover nine consistently reported key aspects of patient experience; identified from the research literature and recommendations put forward by professional bodies. The survey was administered to (i) all 180 providers of Higher Education (HE) to student/qualified doctors, nurses and allied health professionals, and (ii) all 390 National Health Service (NHS) trusts in England. In addition, we added a single question to the NHS 2010 Staff Survey (n=306,000) relating to the training staff had received to deliver a good patient experience. Two hundred and sixty-five individuals responded to the on-line survey representing a total of 159 different organizations from the HE and healthcare sectors. Respondents most commonly identified 'relationships' as an 'essential' aspect of patient experience education and training. The biggest perceived gaps in current provision related to the 'physical' and 'measurement' aspects of our conceptualization of patient experience. Of the 148,657 staff who responded to the Staff Survey 41% said they had not received patient experience training and 22% said it was not applicable to them. While some relevant education courses are in place in England, the results suggest

  14. Energy Density, Nutrient Adequacy, and Cost per Serving Can Provide Insight into Food Choices in the Lower Mississippi Delta

    Science.gov (United States)

    Connell, Carol L.; Zoellner, Jamie M.; Yadrick, M. Kathleen; Chekuri, Srinivasa C.; Crook, Lashaundrea B.; Bogle, Margaret L.

    2012-01-01

    Objective: To compare differences across food groups for food cost, energy, and nutrient profiles of 100 items from a cross-sectional survey of 225 stores in 18 counties across the Lower Mississippi Delta of Arkansas, Louisiana, and Mississippi. Methods: Energy, nutrient, and cost profiles for food items were calculated by using Naturally Nutrient…

  15. Energy density, nutrient adequacy, and cost per serving can provide insight into food choices in the lower Mississippi delta.

    Science.gov (United States)

    Compare differences across food groups for food cost, energy and nutrient profiles of 100 items from a cross-sectional survey of 225 stores in a representative sample of 18 counties across the [Blinded for Review]. Energy, nutrient, and cost profiles for food items were calculated using Naturally Nu...

  16. Energy Density, Nutrient Adequacy, and Cost per Serving Can Provide Insight into Food Choices in the Lower Mississippi Delta

    Science.gov (United States)

    Connell, Carol L.; Zoellner, Jamie M.; Yadrick, M. Kathleen; Chekuri, Srinivasa C.; Crook, Lashaundrea B.; Bogle, Margaret L.

    2012-01-01

    Objective: To compare differences across food groups for food cost, energy, and nutrient profiles of 100 items from a cross-sectional survey of 225 stores in 18 counties across the Lower Mississippi Delta of Arkansas, Louisiana, and Mississippi. Methods: Energy, nutrient, and cost profiles for food items were calculated by using Naturally Nutrient…

  17. The updating of clinical practice guidelines: insights from an international survey

    Directory of Open Access Journals (Sweden)

    Solà Ivan

    2011-09-01

    Full Text Available Abstract Background Clinical practice guidelines (CPGs have become increasingly popular, and the methodology to develop guidelines has evolved enormously. However, little attention has been given to the updating process, in contrast to the appraisal of the available literature. We conducted an international survey to identify current practices in CPG updating and explored the need to standardize and improve the methods. Methods We developed a questionnaire (28 items based on a review of the existing literature about guideline updating and expert comments. We carried out the survey between March and July 2009, and it was sent by email to 106 institutions: 69 members of the Guidelines International Network who declared that they developed CPGs; 30 institutions included in the U.S. National Guideline Clearinghouse database that published more than 20 CPGs; and 7 institutions selected by an expert committee. Results Forty-four institutions answered the questionnaire (42% response rate. In the final analysis, 39 completed questionnaires were included. Thirty-six institutions (92% reported that they update their guidelines. Thirty-one institutions (86% have a formal procedure for updating their guidelines, and 19 (53% have a formal procedure for deciding when a guideline becomes out of date. Institutions describe the process as moderately rigorous (36% or acknowledge that it could certainly be more rigorous (36%. Twenty-two institutions (61% alert guideline users on their website when a guideline is older than three to five years or when there is a risk of being outdated. Twenty-five institutions (64% support the concept of "living guidelines," which are continuously monitored and updated. Eighteen institutions (46% have plans to design a protocol to improve their guideline-updating process, and 21 (54% are willing to share resources with other organizations. Conclusions Our study is the first to describe the process of updating CPGs among prominent

  18. Provision of contraceptive services to homeless women: results of a survey of health care for the homeless providers.

    Science.gov (United States)

    Saver, Barry G; Weinreb, Linda; Gelberg, Lillian; Zerger, Suzanne

    2012-01-01

    Homeless women have both a higher rate of pregnancy and a higher proportion of unintended pregnancies than other American women. The authors sought to learn about contraception services offered by providers of health care to homeless women and barriers to provision of long-acting, reversible contraception in these settings. A survey of the 31 member organizations in the national Health Care for the Homeless Practice-Based Research Network was conducted, inquiring about services provided and barriers to service provision. Among the 20 responding organizations (65% response rate), 17 directly provided contraceptive services; two referred patients elsewhere, and one provided no contraceptive services. All 17 that provided such services provided condoms; 15 provided oral contraceptives; 14 provided injectable contraception; 6 provided intrauterine devices, and 2 provided contraceptive implants. Barriers to providing the last two methods included lack of provider training, lack of resources for placement, costs, and concerns about complications. The present survey results suggested very limited access for homeless women across the country to the two most effective means of long-acting, reversible contraception. Modest investments of resources could reduce a number of barriers to providing these services.

  19. Integration of complex data sources to provide biologic insight into pulmonary vascular disease (2015 Grover Conference Series)

    Science.gov (United States)

    Chan, Stephen Y.

    2016-01-01

    Abstract The application of complex data sources to pulmonary vascular diseases is an emerging and promising area of investigation. The use of -omics platforms, in silico modeling of gene networks, and linkage of large human cohorts with DNA biobanks are beginning to bear biologic insight into pulmonary hypertension. These approaches to high-throughput molecular phenotyping offer the possibility of discovering new therapeutic targets and identifying variability in response to therapy that can be leveraged to improve clinical care. Optimizing the methods for analyzing complex data sources and accruing large, well-phenotyped human cohorts linked to biologic data remain significant challenges. Here, we discuss two specific types of complex data sources—gene regulatory networks and DNA-linked electronic medical record cohorts—that illustrate the promise, challenges, and current limitations of these approaches to understanding and managing pulmonary vascular disease. PMID:27683602

  20. Spatially extensive microbial biogeography of the Indian Ocean provides insights into the unique community structure of a pristine coral atoll

    DEFF Research Database (Denmark)

    Jeffries, Thomas C; Ostrowski, Martin; Williams, Rohan B

    2015-01-01

    Microorganisms act both as drivers and indicators of perturbations in the marine environment. In an effort to establish baselines to predict the response of marine habitats to environmental change, here we report a broad survey of microbial diversity across the Indian Ocean, including the first...... patterns in microbial community composition across the Indian Ocean. Samples from within the Salomon Islands lagoon contained a community which was different even from adjacent samples despite constant water exchange, driven by the dominance of the photosynthetic cyanobacterium Synechococcus. In the lagoon...

  1. Survey Research in the Forest Science Journals - Insights from Journal Editors

    Directory of Open Access Journals (Sweden)

    Mirjana Stevanov

    2015-06-01

    Full Text Available Background and Purpose: Survey research is one of the most commonly applied approaches in the social sciences. In the forest research it has been used for more than five decades. In spite of that or the fact that the amount of survey-based articles in the forest science journals has increased during the last decade, their share in all articles published in 20 forest science journals (9,372 articles, 2005-2014 is quite modest (3.2%. In our paper we look at the opinions and attitudes of forest science journal editors towards survey research, as their perspective might enlarge our understanding of the use of this approach in the field of forestry. Materials and Methods: We selected 20 forest science journals - 15 from the SCI list and five non-SCI journals and contacted editors of these journals with the self-administered e-mail questionnaire. Data were collected in October 2014 and analyzed by descriptive statistics. The overall response rate was 75%. The assumptions for the study were based on the evidence addressing opinions and attitudes of journal editors from other research fields (finance since no similar study was found in the field of forestry. Results: The majority of editors reported the same review process for survey-based articles as for all others. In two journals, articles with the survey-based content are screened more rigorously and in two journals their publishing is generally discouraged. 40% of journal editors hold the view that no difference should be made between survey research and other types of original research, and another 40% think that survey research should in the first place play a complementary role. As the main strength of survey research editors see the possibility to obtain data unavailable from other sources. They perceive adverse selection and the difficulty to generalize results as the main weaknesses. Conclusions: Editors of forest science journals have similar opinion on survey research as those from the

  2. The Work Experience Survey (WES) Manual: A Structured Interview for Identifying Barriers to Career Maintenance. A Service Provider's Guide.

    Science.gov (United States)

    Roessler, Richard T.; And Others

    This manual provides information on and instructions for administering the Work Experience Survey (WES), a 30- to 60-minute structured interview methodology to help individuals with disabilities direct their own accommodation planning. Section 1 describes the WES, which consists of six sections: (1) background information on the respondent, (2) an…

  3. Multi-unit Providers Survey. For-profits report decline in acute-care hospitals ... newcomers to top 10.

    Science.gov (United States)

    Bellandi, D; Kirchheimer, B

    1999-05-24

    For-profit hospital systems cleaned house last year. After years of adding hospitals, investor-owned operators shed facilities in 1998, recording the first decline in the number of acute-care hospitals they've owned or managed since 1991, according to our 23rd annual Multi-unit Providers Survey.

  4. Living with fibromyalgia: results from the functioning with fibro survey highlight patients' experiences and relationships with health care providers

    Directory of Open Access Journals (Sweden)

    Golden A

    2015-11-01

    Full Text Available Angela Golden,1 Yvonne D'Arcy,2 Elizabeth T Masters,3 Andrew Clair3 1NP from Home, LLC, Munds Park, AZ, 2Pain Management and Palliative Care, Suburban Hospital-Johns Hopkins Medicine, Bethesda, MD, 3Pfizer, New York, NY, USA Abstract: Fibromyalgia (FM is a chronic disorder characterized by widespread pain, which can limit patients' physical function and daily activities. FM can be challenging to treat, and the treatment approach could benefit from a greater understanding of patients' perspectives on their condition and their care. Patients with FM participated in an online survey conducted in the USA that sought to identify the symptoms that had the greatest impact on patients' daily lives. The purpose of the survey was to facilitate efforts toward improving care of patients by nurse practitioners, primary care providers, and specialists, in addition to contributing to the development of new outcome measures in both clinical trials and general practice. A total of 1,228 patients with FM completed the survey, responding to specific questions pertaining to symptoms, impact of symptoms, management of FM, and the relationship with health care providers. Chronic pain was identified as the key FM symptom, affecting personal and professional relationships, and restricting physical activity, work, and social commitments. Patients felt that the severity of their condition was underestimated by family, friends, and health care providers. The results of this survey highlight the need for nurse practitioners, primary care providers, and specialists to provide understanding and support to patients as they work together to enable effective diagnosis and management of FM. Keywords: fibromyalgia, pain, survey, impact, support

  5. Genome-wide profiling of AP-1-regulated transcription provides insights into the invasiveness of triple-negative breast cancer.

    Science.gov (United States)

    Zhao, Chunyan; Qiao, Yichun; Jonsson, Philip; Wang, Jian; Xu, Li; Rouhi, Pegah; Sinha, Indranil; Cao, Yihai; Williams, Cecilia; Dahlman-Wright, Karin

    2014-07-15

    Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell-cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties.

  6. Analysis of Transcriptome Changes Induced by Ptr ToxA in Wheat Provides Insights into the Mechanisms of Plant Susceptibility

    Institute of Scientific and Technical Information of China (English)

    Iovanna Pandelova; Melania E Betts; Viola A. Manning; Larry J. Wilhelm; Todd C. Mockler; Lynda M. Ciuffetti

    2009-01-01

    To obtain greater insight into the molecular events underlying plant disease susceptibility, we studied tran-scriptome changes induced by a host-selective toxin of Pyrenophora tritici-repentis, Ptr ToxA (ToxA), on its host plant, wheat. Transcriptional profiling of ToxA-treated leaves of a ToxA-sensitive wheat cultivar was performed using the GeneChip~(R) Wheat Genome Array. An improved and up-to-date annotation of the wheat microarray was generated and a new tool for array data analysis (BRAT) was developed, and both are available for public use via a web-based in-terface. Our data indicate that massive transcriptional reprogramming occurs due to ToxA treatment, including cellular responses typically associated with defense. In addition, this study supports previous results indicating that ToxA-induced cell death is triggered by impairment of the photosynthetic machinery and accumulation of reactive oxygen species. Based on results of this study, we propose that ToxA acts as both an elicitor and a virulence factor.

  7. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

    Science.gov (United States)

    Mahajan, Anubha; Go, Min Jin; Zhang, Weihua; Below, Jennifer E; Gaulton, Kyle J; Ferreira, Teresa; Horikoshi, Momoko; Johnson, Andrew D; Ng, Maggie C Y; Prokopenko, Inga; Saleheen, Danish; Wang, Xu; Zeggini, Eleftheria; Abecasis, Goncalo R; Adair, Linda S; Almgren, Peter; Atalay, Mustafa; Aung, Tin; Baldassarre, Damiano; Balkau, Beverley; Bao, Yuqian; Barnett, Anthony H; Barroso, Ines; Basit, Abdul; Been, Latonya F; Beilby, John; Bell, Graeme I; Benediktsson, Rafn; Bergman, Richard N; Boehm, Bernhard O; Boerwinkle, Eric; Bonnycastle, Lori L; Burtt, Noël; Cai, Qiuyin; Campbell, Harry; Carey, Jason; Cauchi, Stephane; Caulfield, Mark; Chan, Juliana C N; Chang, Li-Ching; Chang, Tien-Jyun; Chang, Yi-Cheng; Charpentier, Guillaume; Chen, Chien-Hsiun; Chen, Han; Chen, Yuan-Tsong; Chia, Kee-Seng; Chidambaram, Manickam; Chines, Peter S; Cho, Nam H; Cho, Young Min; Chuang, Lee-Ming; Collins, Francis S; Cornelis, Marylin C; Couper, David J; Crenshaw, Andrew T; van Dam, Rob M; Danesh, John; Das, Debashish; de Faire, Ulf; Dedoussis, George; Deloukas, Panos; Dimas, Antigone S; Dina, Christian; Doney, Alex S; Donnelly, Peter J; Dorkhan, Mozhgan; van Duijn, Cornelia; Dupuis, Josée; Edkins, Sarah; Elliott, Paul; Emilsson, Valur; Erbel, Raimund; Eriksson, Johan G; Escobedo, Jorge; Esko, Tonu; Eury, Elodie; Florez, Jose C; Fontanillas, Pierre; Forouhi, Nita G; Forsen, Tom; Fox, Caroline; Fraser, Ross M; Frayling, Timothy M; Froguel, Philippe; Frossard, Philippe; Gao, Yutang; Gertow, Karl; Gieger, Christian; Gigante, Bruna; Grallert, Harald; Grant, George B; Grrop, Leif C; Groves, Chrisropher J; Grundberg, Elin; Guiducci, Candace; Hamsten, Anders; Han, Bok-Ghee; Hara, Kazuo; Hassanali, Neelam; Hattersley, Andrew T; Hayward, Caroline; Hedman, Asa K; Herder, Christian; Hofman, Albert; Holmen, Oddgeir L; Hovingh, Kees; Hreidarsson, Astradur B; Hu, Cheng; Hu, Frank B; Hui, Jennie; Humphries, Steve E; Hunt, Sarah E; Hunter, David J; Hveem, Kristian; Hydrie, Zafar I; Ikegami, Hiroshi; Illig, Thomas; Ingelsson, Erik; Islam, Muhammed; Isomaa, Bo; Jackson, Anne U; Jafar, Tazeen; James, Alan; Jia, Weiping; Jöckel, Karl-Heinz; Jonsson, Anna; Jowett, Jeremy B M; Kadowaki, Takashi; Kang, Hyun Min; Kanoni, Stavroula; Kao, Wen Hong L; Kathiresan, Sekar; Kato, Norihiro; Katulanda, Prasad; Keinanen-Kiukaanniemi, Kirkka M; Kelly, Ann M; Khan, Hassan; Khaw, Kay-Tee; Khor, Chiea-Chuen; Kim, Hyung-Lae; Kim, Sangsoo; Kim, Young Jin; Kinnunen, Leena; Klopp, Norman; Kong, Augustine; Korpi-Hyövälti, Eeva; Kowlessur, Sudhir; Kraft, Peter; Kravic, Jasmina; Kristensen, Malene M; Krithika, S; Kumar, Ashish; Kumate, Jesus; Kuusisto, Johanna; Kwak, Soo Heon; Laakso, Markku; Lagou, Vasiliki; Lakka, Timo A; Langenberg, Claudia; Langford, Cordelia; Lawrence, Robert; Leander, Karin; Lee, Jen-Mai; Lee, Nanette R; Li, Man; Li, Xinzhong; Li, Yun; Liang, Junbin; Liju, Samuel; Lim, Wei-Yen; Lind, Lars; Lindgren, Cecilia M; Lindholm, Eero; Liu, Ching-Ti; Liu, Jian Jun; Lobbens, Stéphane; Long, Jirong; Loos, Ruth J F; Lu, Wei; Luan, Jian'an; Lyssenko, Valeriya; Ma, Ronald C W; Maeda, Shiro; Mägi, Reedik; Männisto, Satu; Matthews, David R; Meigs, James B; Melander, Olle; Metspalu, Andres; Meyer, Julia; Mirza, Ghazala; Mihailov, Evelin; Moebus, Susanne; Mohan, Viswanathan; Mohlke, Karen L; Morris, Andrew D; Mühleisen, Thomas W; Müller-Nurasyid, Martina; Musk, Bill; Nakamura, Jiro; Nakashima, Eitaro; Navarro, Pau; Ng, Peng-Keat; Nica, Alexandra C; Nilsson, Peter M; Njølstad, Inger; Nöthen, Markus M; Ohnaka, Keizo; Ong, Twee Hee; Owen, Katharine R; Palmer, Colin N A; Pankow, James S; Park, Kyong Soo; Parkin, Melissa; Pechlivanis, Sonali; Pedersen, Nancy L; Peltonen, Leena; Perry, John R B; Peters, Annette; Pinidiyapathirage, Janini M; Platou, Carl G; Potter, Simon; Price, Jackie F; Qi, Lu; Radha, Venkatesan; Rallidis, Loukianos; Rasheed, Asif; Rathman, Wolfgang; Rauramaa, Rainer; Raychaudhuri, Soumya; Rayner, N William; Rees, Simon D; Rehnberg, Emil; Ripatti, Samuli; Robertson, Neil; Roden, Michael; Rossin, Elizabeth J; Rudan, Igor; Rybin, Denis; Saaristo, Timo E; Salomaa, Veikko; Saltevo, Juha; Samuel, Maria; Sanghera, Dharambir K; Saramies, Jouko; Scott, James; Scott, Laura J; Scott, Robert A; Segrè, Ayellet V; Sehmi, Joban; Sennblad, Bengt; Shah, Nabi; Shah, Sonia; Shera, A Samad; Shu, Xiao Ou; Shuldiner, Alan R; Sigurđsson, Gunnar; Sijbrands, Eric; Silveira, Angela; Sim, Xueling; Sivapalaratnam, Suthesh; Small, Kerrin S; So, Wing Yee; Stančáková, Alena; Stefansson, Kari; Steinbach, Gerald; Steinthorsdottir, Valgerdur; Stirrups, Kathleen; Strawbridge, Rona J; Stringham, Heather M; Sun, Qi; Suo, Chen; Syvänen, Ann-Christine; Takayanagi, Ryoichi; Takeuchi, Fumihiko; Tay, Wan Ting; Teslovich, Tanya M; Thorand, Barbara; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Trakalo, Joseph; Tremoli, Elena; Trip, Mieke D; Tsai, Fuu Jen; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Uitterlinden, Andre G; Valladares-Salgado, Adan; Vedantam, Sailaja; Veglia, Fabrizio; Voight, Benjamin F; Wang, Congrong; Wareham, Nicholas J; Wennauer, Roman; Wickremasinghe, Ananda R; Wilsgaard, Tom; Wilson, James F; Wiltshire, Steven; Winckler, Wendy; Wong, Tien Yin; Wood, Andrew R; Wu, Jer-Yuarn; Wu, Ying; Yamamoto, Ken; Yamauchi, Toshimasa; Yang, Mingyu; Yengo, Loic; Yokota, Mitsuhiro; Young, Robin; Zabaneh, Delilah; Zhang, Fan; Zhang, Rong; Zheng, Wei; Zimmet, Paul Z; Altshuler, David; Bowden, Donald W; Cho, Yoon Shin; Cox, Nancy J; Cruz, Miguel; Hanis, Craig L; Kooner, Jaspal; Lee, Jong-Young; Seielstad, Mark; Teo, Yik Ying; Boehnke, Michael; Parra, Esteban J; Chambers, Jonh C; Tai, E Shyong; McCarthy, Mark I; Morris, Andrew P

    2014-03-01

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

  8. Quality of reproductive healthcare for adolescents: A nationally representative survey of providers in Mexico

    Science.gov (United States)

    De Castro, Filipa; Barrientos-Gutiérrez, Tonatiuh; Leyva-López, Ahideé

    2017-01-01

    Objective Adolescents need sexual and reproductive health services but little is known about quality-of-care in lower- and middle-income countries where most of the world’s adolescents reside. Quality-of-care has important implications as lower quality may be linked to higher unplanned pregnancy and sexually transmitted infection rates. This study sought to generate evidence about quality-of-care in public sexual and reproductive health services for adolescents. Methods This cross-sectional study had a complex, probabilistic, stratified sampling design, representative at the national, regional and rural/urban level in Mexico, collecting provider questionnaires at 505 primary care units in 2012. A sexual and reproductive quality-of-healthcare index was defined and multinomial logistic regression was utilized in 2015. Results At the national level 13.9% (95%CI: 6.9–26.0) of healthcare units provide low quality, 68.6% (95%CI: 58.4–77.3) medium quality and 17.5% (95%CI: 11.9–25.0) high quality reproductive healthcare services to adolescents. Urban or metropolitan primary care units were at least 10 times more likely to provide high quality care than those in rural areas. Units with a space specifically for counseling adolescents were at least 8 times more likely to provide high quality care. Ministry of Health clinics provided the lowest quality of service, while those from Social Security for the Underserved provided the best. Conclusions The study indicates higher quality sexual and reproductive healthcare services are needed. In Mexico and other middle- to low-income countries where quality-of-care has been shown to be a problem, incorporating adolescent-friendly, gender-equity and rights-based perspectives could contribute to improvement. Setting and disseminating standards for care in guidelines and providing tools such as algorithms could help healthcare personnel provide higher quality care. PMID:28273129

  9. Quality of reproductive healthcare for adolescents: A nationally representative survey of providers in Mexico.

    Science.gov (United States)

    Villalobos, Aremis; Allen-Leigh, Betania; Salazar-Alberto, Javier; De Castro, Filipa; Barrientos-Gutiérrez, Tonatiuh; Leyva-López, Ahideé; Rojas-Martínez, Rosalba

    2017-01-01

    Adolescents need sexual and reproductive health services but little is known about quality-of-care in lower- and middle-income countries where most of the world's adolescents reside. Quality-of-care has important implications as lower quality may be linked to higher unplanned pregnancy and sexually transmitted infection rates. This study sought to generate evidence about quality-of-care in public sexual and reproductive health services for adolescents. This cross-sectional study had a complex, probabilistic, stratified sampling design, representative at the national, regional and rural/urban level in Mexico, collecting provider questionnaires at 505 primary care units in 2012. A sexual and reproductive quality-of-healthcare index was defined and multinomial logistic regression was utilized in 2015. At the national level 13.9% (95%CI: 6.9-26.0) of healthcare units provide low quality, 68.6% (95%CI: 58.4-77.3) medium quality and 17.5% (95%CI: 11.9-25.0) high quality reproductive healthcare services to adolescents. Urban or metropolitan primary care units were at least 10 times more likely to provide high quality care than those in rural areas. Units with a space specifically for counseling adolescents were at least 8 times more likely to provide high quality care. Ministry of Health clinics provided the lowest quality of service, while those from Social Security for the Underserved provided the best. The study indicates higher quality sexual and reproductive healthcare services are needed. In Mexico and other middle- to low-income countries where quality-of-care has been shown to be a problem, incorporating adolescent-friendly, gender-equity and rights-based perspectives could contribute to improvement. Setting and disseminating standards for care in guidelines and providing tools such as algorithms could help healthcare personnel provide higher quality care.

  10. Probability of solar panel clearing events at the Insight landing sites (Mars) from a dust devil track survey

    Science.gov (United States)

    Reiss, D.; Lorenz, R. D.

    2015-10-01

    The InSight robotic lander is scheduled to land on Mars in September 2016. InSight was designed to perform the first comprehensive surface-based geophysical investigation of Mars [1]. Passage of vortices may have a number of influences on the geophysical measurements to be made by InSight. Seismic data could be influenced by dust devils and vortices via several mechanisms such as loading of the elastic ground by a surface pressure field which causes a local tilt [e.g. 2]. In addition, the power supply of the InSight instruments is provided by solar arrays. Solar-powered missions on Mars like the Sojourner rover in 1997 were affected by a decline in electrical power output by 0.2-0.3 %per day caused by steadily dust deposition on its horizontal solar panel [3]. The solar-powered Mars Exploration Rovers (MERs) Spirit and Opportunity experienced similar dust deposition rates [4] which led to steady power decrease over time endangering longer rover operation times. The much longer operation times of the rovers were made possible by unanticipated 'dust clearing events' of the solar arrays by wind gust or dust devils [5]. Recent studies imply that dust devils are primarily responsible for those recurrent 'dust clearing events' [6]. In this study we investigate the potential frequency of intense dust devil occurrences at the InSight landing site regions, which are able to remove dust from its solar panels. We analyzed newly formed dust devil tracks within a given time span using multi-temporal HiRISE image data covering the same surface area. Based on these measurements we will give encounter rate predictions of intense (high tangential speed and high pressure drop) dust devils with the InSight lander.

  11. Stakeholder analysis combined with social network analysis provides fine-grained insights into water infrastructure planning processes.

    Science.gov (United States)

    Lienert, Judit; Schnetzer, Florian; Ingold, Karin

    2013-08-15

    Environmental policy and decision-making are characterized by complex interactions between different actors and sectors. As a rule, a stakeholder analysis is performed to understand those involved, but it has been criticized for lacking quality and consistency. This lack is remedied here by a formal social network analysis that investigates collaborative and multi-level governance settings in a rigorous way. We examine the added value of combining both elements. Our case study examines infrastructure planning in the Swiss water sector. Water supply and wastewater infrastructures are planned far into the future, usually on the basis of projections of past boundary conditions. They affect many actors, including the population, and are expensive. In view of increasing future dynamics and climate change, a more participatory and long-term planning approach is required. Our specific aims are to investigate fragmentation in water infrastructure planning, to understand how actors from different decision levels and sectors are represented, and which interests they follow. We conducted 27 semi-structured interviews with local stakeholders, but also cantonal and national actors. The network analysis confirmed our hypothesis of strong fragmentation: we found little collaboration between the water supply and wastewater sector (confirming horizontal fragmentation), and few ties between local, cantonal, and national actors (confirming vertical fragmentation). Infrastructure planning is clearly dominated by engineers and local authorities. Little importance is placed on longer-term strategic objectives and integrated catchment planning, but this was perceived as more important in a second analysis going beyond typical questions of stakeholder analysis. We conclude that linking a stakeholder analysis, comprising rarely asked questions, with a rigorous social network analysis is very fruitful and generates complementary results. This combination gave us deeper insight into the

  12. Genome Sequence of the Fish Pathogen Yersinia ruckeri SC09 Provides Insights into Niche Adaptation and Pathogenic Mechanism.

    Science.gov (United States)

    Liu, Tao; Wang, Kai-Yu; Wang, Jun; Chen, De-Fang; Huang, Xiao-Li; Ouyang, Ping; Geng, Yi; He, Yang; Zhou, Yi; Min, Jie

    2016-04-14

    Yersinia ruckeri is the etiologic agent of enteric red mouth disease (ERM), a severe fish disease prevailing in worldwide aquaculture industries. Here we report for the first time the complete genome of Y. ruckeri (Yersinia ruckeri) SC09, a highly virulent strain isolated from Ictalurus punctatus with severe septicemia. SC09 possesses a single chromosome of 3,923,491 base pairs, which contains 3651 predicted protein coding sequences (CDS), 19 rRNA genes, and 79 tRNA genes. Among the CDS, we have identified a Ysa locus containing genes encoding all the components of a type III secretion system (T3SS). Comparative analysis suggest that SC09-Ysa share extensive similarity in sequence, gene content, and gene arrangement with Salmonella enterica pathogenicity island 1 (SPI1) and chromosome-encoded T3SS from Yersinia enterocolitica biotype 1B. Furthermore, phylogenetic analysis shown that SC09-Ysa and SPI1-T3SS belong on the same branch of the phylogenetic tree. These results suggest that SC09-Ysa and SPI1-T3SS appear to mediate biological function to adapt to specific hosts with a similar niche, and both of them are likely to facilitate the development of an intracellular niche. In addition, our analysis also indicated that a substantial part of the SC09 genome might contribute to adaption in the intestinal microenvironment, including a number of proteins associated with aerobic or anaerobic respiration, signal transduction, and various stress reactions. Genomic analysis of the bacterium offered insights into the pathogenic mechanism associated with intracellular infection and intestinal survivability, which constitutes an important first step in understanding the pathogenesis of Y. ruckeri.

  13. Insertion sequence element single nucleotide polymorphism typing provides insights into the population structure and evolution of Mycobacterium ulcerans across Africa.

    Science.gov (United States)

    Vandelannoote, Koen; Jordaens, Kurt; Bomans, Pieter; Leirs, Herwig; Durnez, Lies; Affolabi, Dissou; Sopoh, Ghislain; Aguiar, Julia; Phanzu, Delphin Mavinga; Kibadi, Kapay; Eyangoh, Sara; Manou, Louis Bayonne; Phillips, Richard Odame; Adjei, Ohene; Ablordey, Anthony; Rigouts, Leen; Portaels, Françoise; Eddyani, Miriam; de Jong, Bouke C

    2014-02-01

    Buruli ulcer is an indolent, slowly progressing necrotizing disease of the skin caused by infection with Mycobacterium ulcerans. In the present study, we applied a redesigned technique to a vast panel of M. ulcerans disease isolates and clinical samples originating from multiple African disease foci in order to (i) gain fundamental insights into the population structure and evolutionary history of the pathogen and (ii) disentangle the phylogeographic relationships within the genetically conserved cluster of African M. ulcerans. Our analyses identified 23 different African insertion sequence element single nucleotide polymorphism (ISE-SNP) types that dominate in different areas where Buruli ulcer is endemic. These ISE-SNP types appear to be the initial stages of clonal diversification from a common, possibly ancestral ISE-SNP type. ISE-SNP types were found unevenly distributed over the greater West African hydrological drainage basins. Our findings suggest that geographical barriers bordering the basins to some extent prevented bacterial gene flow between basins and that this resulted in independent focal transmission clusters associated with the hydrological drainage areas. Different phylogenetic methods yielded two well-supported sister clades within the African ISE-SNP types. The ISE-SNP types from the "pan-African clade" were found to be widespread throughout Africa, while the ISE-SNP types of the "Gabonese/Cameroonian clade" were much rarer and found in a more restricted area, which suggested that the latter clade evolved more recently. Additionally, the Gabonese/Cameroonian clade was found to form a strongly supported monophyletic group with Papua New Guinean ISE-SNP type 8, which is unrelated to other Southeast Asian ISE-SNP types.

  14. Structural and mutational analysis of Escherichia coli AlkB provides insight into substrate specificity and DNA damage searching.

    Directory of Open Access Journals (Sweden)

    Paul J Holland

    Full Text Available BACKGROUND: In Escherichia coli, cytotoxic DNA methyl lesions on the N1 position of purines and N3 position of pyrimidines are primarily repaired by the 2-oxoglutarate (2-OG iron(II dependent dioxygenase, AlkB. AlkB repairs 1-methyladenine (1-meA and 3-methylcytosine (3-meC lesions, but it also repairs 1-methylguanine (1-meG and 3-methylthymine (3-meT at a much less efficient rate. How the AlkB enzyme is able to locate and identify methylated bases in ssDNA has remained an open question. METHODOLOGY/PRINCIPAL FINDINGS: We determined the crystal structures of the E. coli AlkB protein holoenzyme and the AlkB-ssDNA complex containing a 1-meG lesion. We coupled this to site-directed mutagenesis of amino acids in and around the active site, and tested the effects of these mutations on the ability of the protein to bind both damaged and undamaged DNA, as well as catalyze repair of a methylated substrate. CONCLUSIONS/SIGNIFICANCE: A comparison of our substrate-bound AlkB-ssDNA complex with our unliganded holoenzyme reveals conformational changes of residues within the active site that are important for binding damaged bases. Site-directed mutagenesis of these residues reveals novel insight into their roles in DNA damage recognition and repair. Our data support a model that the AlkB protein utilizes at least two distinct conformations in searching and binding methylated bases within DNA: a "searching" mode and "repair" mode. Moreover, we are able to functionally separate these modes through mutagenesis of residues that affect one or the other binding state. Finally, our mutagenesis experiments show that amino acid D135 of AlkB participates in both substrate specificity and catalysis.

  15. Colorectal cancer screening practices of primary care providers: results of a national survey in Malaysia.

    Science.gov (United States)

    Norwati, Daud; Harmy, Mohamed Yusoff; Norhayati, Mohd Noor; Amry, Abdul Rahim

    2014-01-01

    The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics.

  16. Line Transect and Triangulation Surveys Provide Reliable Estimates of the Density of Kloss' Gibbons (Hylobates klossii) on Siberut Island, Indonesia.

    Science.gov (United States)

    Höing, Andrea; Quinten, Marcel C; Indrawati, Yohana Maria; Cheyne, Susan M; Waltert, Matthias

    2013-02-01

    Estimating population densities of key species is crucial for many conservation programs. Density estimates provide baseline data and enable monitoring of population size. Several different survey methods are available, and the choice of method depends on the species and study aims. Few studies have compared the accuracy and efficiency of different survey methods for large mammals, particularly for primates. Here we compare estimates of density and abundance of Kloss' gibbons (Hylobates klossii) using two of the most common survey methods: line transect distance sampling and triangulation. Line transect surveys (survey effort: 155.5 km) produced a total of 101 auditory and visual encounters and a density estimate of 5.5 gibbon clusters (groups or subgroups of primate social units)/km(2). Triangulation conducted from 12 listening posts during the same period revealed a similar density estimate of 5.0 clusters/km(2). Coefficients of variation of cluster density estimates were slightly higher from triangulation (0.24) than from line transects (0.17), resulting in a lack of precision in detecting changes in cluster densities of triangulation and triangulation method also may be appropriate.

  17. Unanswered clinical questions: a survey of specialists and primary care providers

    Directory of Open Access Journals (Sweden)

    Ellen Brassil, MSLS, MAT, AHIP

    2017-01-01

    Conclusions: While the reasons for unanswered clinical questions varied, thoughtful review of the responses suggested that a combination of educational strategies, embedded librarian services, and technology applications could help providers pursue answers to their clinical questions, enhance patient safety, and contribute to patient-based, self-directed learning.

  18. Pilot Survey of Physician Assistants Regarding Lesbian, Gay, Bisexual, and Transgender Providers Suggests Role for Workplace Nondiscrimination Policies.

    Science.gov (United States)

    Ewton, Tiffany A; Lingas, Elena O

    2015-12-01

    Lesbian, gay, bisexual, and transgender (LGBT) medical providers in the United States have historically faced discrimination from their peers. To assess current workplace culture and attitudes, and to evaluate awareness of workplace and professional policies regarding LGBT discrimination, we sent a cross-sectional survey to 163 PAs (Physician Assistants). Respondents had an overall positive attitude towards LGBT providers, yet the majority was not aware of relevant policy statements (>60%). A significant association existed between policy awareness and LGBT inclusivity (PLGBT providers, non-discriminatory work environments for LGBT physician assistants may relate to greater awareness of specific workplace policy standards.

  19. Global Connectedness and Global Migration: Insights from the International Changing Academic Profession Survey

    Science.gov (United States)

    McGinn, Michelle K.; Ratkovic, Snežana; Wolhunter, Charl C.

    2013-01-01

    The Changing Academic Profession (CAP) international survey was designed in part to consider the effects of globalization on the work context and activities of academics in 19 countries or regions around the world. This paper draws from a subset of these data to explore the extent to which academics are globally connected in their research and…

  20. Domestic Violence in India: Insights from the 2005-2006 National Family Health Survey

    Science.gov (United States)

    Kimuna, Sitawa R.; Djamba, Yanyi K.; Ciciurkaite, Gabriele; Cherukuri, Suvarna

    2013-01-01

    This article assesses the prevalence and risk factors of domestic violence in India. The study uses the 2005-2006 India National Family Health Survey-III (NFHS-III) and focuses on the 69,484 ever-married women ages 15 to 49 from all regions, who were administered the domestic violence module. The results show that 31% of respondents experienced…

  1. Variation in Management of Fever and Neutropenia Among Pediatric Patients With Cancer: A Survey of Providers in Michigan.

    Science.gov (United States)

    Mueller, Emily L; Walkovich, Kelly J; Yanik, Gregory A; Clark, Sarah J

    2015-01-01

    Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An online survey of 90 pediatric cancer providers in Michigan was performed in Spring 2014. The survey frame was pediatric patients with cancer receiving treatment, with a Port-a-cath, who were clinically stable. Criteria for "Decreased" and "Increased" risk groups were defined by respondents. Survey questions addressed FN definitions, risk groups conceptualization, routine clinical practice, and management guidelines, in the context of risk groups and distance to treating institution. Fifty providers responded (56%); the majority defined a febrile event as temperature >38.3°C and/or 2 events >38.0°C within a 24-hour period. Neutropenia was defined as current or anticipated absolute neutrophil count (ANC) 2 hours away. Respondents were significantly more likely to have a "Decreased Risk" patient travel over 2 hours if they rated the local ED as "Poor to Fair" on ability to access Port-a-caths (P = .048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL; 40% preferred discharge on oral antibiotics when the ANC febrile pediatric patients with cancer is significantly influenced by the providers' perceptions of local EDs. Future investigation of local hospitals' ability to provide urgent evaluation, combined with parental perspectives, could lead to improvements in timely and effective management.

  2. Self-reported preparedness of New Zealand acute care providers to mass emergencies before the Canterbury Earthquakes: a national survey.

    Science.gov (United States)

    Al-Shaqsi, Sultan; Gauld, Robin; McBride, David; Al-Kashmiri, Ammar; Al-Harthy, Abdullah

    2015-02-01

    Disasters occur more frequently. Acute care providers are the first to respond to mass emergencies from the healthcare sector. The preparedness of acute care providers in New Zealand to respond to mass emergencies has not been previously studied. To assess the self-reported training and experience of New Zealand acute care providers to respond to mass emergencies and the factors associated with strong preparedness. A cross-sectional national survey of 1500 acute care providers in New Zealand carried out between 2009 and 2010. The survey assessed experience, training and self-reported preparedness. It also determined the factors associated with strong perceived preparedness. The response rate to this survey was 60.7%. Nurses had a higher response rate than doctors or paramedics. Only 29.2% of acute care providers reported responding to a previous mass emergency event. There were 53.5% of acute care providers who reported having formal training in how to deal with mass emergencies, whereas 58.1% of participants reported that they were aware of their role during a healthcare mass emergency response. The factors associated with self-reported strong preparedness to deal with mass emergencies included: being a paramedic, previous training, participation in a drill, willingness to report to work during an infection or man-made emergency, ability to triage and general awareness of the role during a mass emergency. Almost half of New Zealand acute healthcare providers have no training in dealing with mass emergency events. Training and general awareness of the role during a mass emergency response were the main factors associated with strong self-reported preparedness of acute care providers. The apparent efficacy of training allied to lack of availability means that it should be a national priority. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  3. Neotenic Phenotype and Sex Ratios Provide Insight into Developmental Pathways in Reticulitermes flavipes (Isoptera: Rhinotermitidae

    Directory of Open Access Journals (Sweden)

    Brian T. Forschler

    2012-06-01

    Full Text Available Several thousand Reticulitermes flavipes (Kollar including worker, nymph, soldier, neotenic and alate castes were collected from three pine logs brought into the laboratory on dates five years apart. The neotenics, all nymphoid, were divided into three groups based on the extent of cuticle pigmentation and termed regular neotenics (RN, black-headed neotenics (BHN or black neotenics (BN. All castes, from Log A, in 2008, provided a neutral sex ratio except BHN (N = 378 and BN (N = 51 which were exclusively male while the soldiers (N = 466 were female-biased. This information suggests that there is a sex-linked bifurcation along the path for termite development with a male-biased neotenic or female-biased soldier as the choice. In contrast, termites collected in 2004 from Log B provided sex ratios that included a female biased RN (N = 1017, a neutral soldier (N = 258 and male biased BHN (N = 99 and workers (N = 54. Log C, collected in 2009, provided female biased soldiers (N = 32, RNs (N = 18 and BHNs (N = 4 and only male BN (N = 5. Eight laboratory cultures, ranging in age from five to 14 years old, also were sampled and all castes sexed. The census included a 14-year old queen-right colony, an 8-year old polyandrous colony and six colonies provided nymphs and male-biased worker populations. Together these data indicate a flexible caste determination system providing a unique opportunity for a better understanding of the flexible developmental options available in R. flavipes that we discuss relative to the literature on Reticulitermes ontogeny.

  4. A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence.

    Directory of Open Access Journals (Sweden)

    Tannistha Nandi

    2010-04-01

    Full Text Available Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence". To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp, a tropical soil microbe and causative agent of the human and animal disease melioidosis. We found evidence for the existence of several new genes in the Bp reference genome, identifying 282 novel genes supported by at least two independent lines of supporting evidence (mRNA transcripts, database homologs, and presence of ribosomal binding sites and 81 novel genes supported by all three lines. Within the Bp core genome, 211 genes exhibited significant levels of positive selection (4.5%, distributed across many cellular pathways including carbohydrate and secondary metabolism. Functional experiments revealed that certain positively selected genes might enhance mammalian virulence by interacting with host cellular pathways or utilizing host nutrients. Evolutionary modifications improving Bp environmental fitness may thus have indirectly facilitated the ability of Bp to colonize and survive in mammalian hosts. These findings improve our understanding of the pathogenesis of melioidosis, and establish Bp as a model system for studying the genetics of accidental virulence.

  5. Synchrotron imaging of dentition provides insights into the biology of Hesperornis and Ichthyornis, the “last” toothed birds

    OpenAIRE

    Dumont, Maïtena; Tafforeau, Paul; Bertin, Thomas; Bhullar, Bhart-Anjan; Field, Daniel; Schulp, Anne; Strilisky, Brandon; Thivichon-Prince, Béatrice; Viriot, Laurent; Louchart, Antoine

    2016-01-01

    Background The dentitions of extinct organisms can provide pivotal information regarding their phylogenetic position, as well as paleobiology, diet, development, and growth. Extant birds are edentulous (toothless), but their closest relatives among stem birds, the Cretaceous Hesperornithiformes and Ichthyornithiformes, retained teeth. Despite their significant phylogenetic position immediately outside the avian crown group, the dentitions of these taxa have never been studied in detail. To ob...

  6. Systems biology provides new insights into the molecular mechanisms that control the fate of embryonic stem cells.

    Science.gov (United States)

    Mallanna, Sunil K; Rizzino, Angie

    2012-01-01

    During the last 5 years there has been enormous progress in developing a deeper understanding of the molecular mechanisms that control the self-renewal and pluripotency of embryonic stem cells (ESC). Early progress resulted from studying individual transcription factors and signaling pathways. Unexpectedly, these studies demonstrated that small changes in the levels of master regulators, such as Oct4 and Sox2, promote the differentiation of ESC. More recently, impressive progress has been made using technologies that provide a global view of the signaling pathways and the gene regulatory networks that control the fate of ESC. This review provides an overview of the progress made using several different high-throughput technologies and focuses on proteomic studies, which provide the first glimpse of the protein-protein interaction networks used by ESC. The latter studies indicate that transcription factors required for the self-renewal of ESC are part of a large, highly integrated protein-protein interaction landscape, which helps explain why the levels of master regulators need to be regulated precisely in ESC.

  7. Facial Diagnosis of Mild and Variant CdLS: Insights From a Dysmorphologist Survey

    Science.gov (United States)

    Rohatgi, Sarika; Clark, Dinah; Kline, Antonie D.; Jackson, Laird G.; Pie, Juan; Siu, Victoria; Ramos, Feliciano J.; Krantz, Ian D.; Deardorff, Matthew A.

    2014-01-01

    Cornelia de Lange syndrome (CdLS) is a dominant disorder with classic severe forms and milder atypical variants. Central to making the diagnosis is identification of diagnostic facial features. With the recognition that patients with SMC1A and SMC3 mutations have milder, atypical features, we surveyed 65 dysmorphologists using facial photographs from 32 CdLS patients with the goals of (1) Illustrating examples of milder patients with SMC1A mutations and (2) Obtaining objective data to determine which facial features were useful and misleading in making a diagnosis of CdLS. Clinicians were surveyed whether the patient had CdLS or another diagnosis, the certainty of response and the clinical features used to support each response. Using only facial photographs, an average of 24 cases (75%) were accurately diagnosed per clinician. Correct diagnoses were made in 90% of classic CdLS and 87% of non-CdLS cases, however, only 54% of mild or variant CdLS were correctly diagnosed by respondents. We confirmed that CdLS is most accurately diagnosed in childhood and the diagnosis becomes increasingly difficult with age. This survey demonstrated that emphasis is placed on the eyebrows, nasal features, prominent upper lip and micrognathia. In addition, the presence of fuller, atypical eyebrows, a prominent nasal bridge and significant prognathism with age dissuaded survey takers from arriving at a diagnosis of CdLS in individuals with mild NIPBL and SMC1A mutations. This work underscores the difficulty in diagnosing patients with mild and variant CdLS and serves to objectively classify both useful and misleading features in the diagnosis of CdLS. PMID:20583156

  8. A Survey on Agricultural Trade Policies in Bangladesh: theoretical Insights and empirical Evidence

    Directory of Open Access Journals (Sweden)

    D. Talukder

    2014-06-01

    Full Text Available The purpose of this paper is to review the theoretical insights and empirical evidence on agricultural trade policies and their impacts on the Bangladesh’s economy, with a view to presenting both, the positive and negative effects of trade liberalization. Theoretically, while advocates of trade liberalization argue that free trade is an engine of growth and protection leads to wasteful use of resources, critics argue that openness has its costs and sometimes it could be detrimental to the economic development. The empirical evidence in Bangladesh was consistent with the ongoing debate on the effects of trade liberalization on economic development. The evidence remained mixed and loaded with criticisms on the grounds of choice of liberalization determinants, model specifications and methodology, as well as other measurement shortcomings. The review suggests that the literature is inconclusive and outcomes are largely case-specific

  9. Chromosome-level genome map provides insights into diverse defense mechanisms in the medicinal fungus Ganoderma sinense.

    Science.gov (United States)

    Zhu, Yingjie; Xu, Jiang; Sun, Chao; Zhou, Shiguo; Xu, Haibin; Nelson, David R; Qian, Jun; Song, Jingyuan; Luo, Hongmei; Xiang, Li; Li, Ying; Xu, Zhichao; Ji, Aijia; Wang, Lizhi; Lu, Shanfa; Hayward, Alice; Sun, Wei; Li, Xiwen; Schwartz, David C; Wang, Yitao; Chen, Shilin

    2015-06-05

    Fungi have evolved powerful genomic and chemical defense systems to protect themselves against genetic destabilization and other organisms. However, the precise molecular basis involved in fungal defense remain largely unknown in Basidiomycetes. Here the complete genome sequence, as well as DNA methylation patterns and small RNA transcriptomes, was analyzed to provide a holistic overview of secondary metabolism and defense processes in the model medicinal fungus, Ganoderma sinense. We reported the 48.96 Mb genome sequence of G. sinense, consisting of 12 chromosomes and encoding 15,688 genes. More than thirty gene clusters involved in the biosynthesis of secondary metabolites, as well as a large array of genes responsible for their transport and regulation were highlighted. In addition, components of genome defense mechanisms, namely repeat-induced point mutation (RIP), DNA methylation and small RNA-mediated gene silencing, were revealed in G. sinense. Systematic bioinformatic investigation of the genome and methylome suggested that RIP and DNA methylation combinatorially maintain G. sinense genome stability by inactivating invasive genetic material and transposable elements. The elucidation of the G. sinense genome and epigenome provides an unparalleled opportunity to advance our understanding of secondary metabolism and fungal defense mechanisms.

  10. Phylogeny and ancient DNA of Sus provides insights into neolithic expansion in Island Southeast Asia and Oceania

    Science.gov (United States)

    Larson, Greger; Cucchi, Thomas; Fujita, Masakatsu; Matisoo-Smith, Elizabeth; Robins, Judith; Anderson, Atholl; Rolett, Barry; Spriggs, Matthew; Dolman, Gaynor; Kim, Tae-Hun; Thuy, Nguyen Thi Dieu; Randi, Ettore; Doherty, Moira; Due, Rokus Awe; Bollt, Robert; Djubiantono, Tony; Griffin, Bion; Intoh, Michiko; Keane, Emile; Kirch, Patrick; Li, Kuang-Ti; Morwood, Michael; Pedriña, Lolita M.; Piper, Philip J.; Rabett, Ryan J.; Shooter, Peter; Van den Bergh, Gert; West, Eric; Wickler, Stephen; Yuan, Jing; Cooper, Alan; Dobney, Keith

    2007-01-01

    Human settlement of Oceania marked the culmination of a global colonization process that began when humans first left Africa at least 90,000 years ago. The precise origins and dispersal routes of the Austronesian peoples and the associated Lapita culture remain contentious, and numerous disparate models of dispersal (based primarily on linguistic, genetic, and archeological data) have been proposed. Here, through the use of mtDNA from 781 modern and ancient Sus specimens, we provide evidence for an early human-mediated translocation of the Sulawesi warty pig (Sus celebensis) to Flores and Timor and two later separate human-mediated dispersals of domestic pig (Sus scrofa) through Island Southeast Asia into Oceania. Of the later dispersal routes, one is unequivocally associated with the Neolithic (Lapita) and later Polynesian migrations and links modern and archeological Javan, Sumatran, Wallacean, and Oceanic pigs with mainland Southeast Asian S. scrofa. Archeological and genetic evidence shows these pigs were certainly introduced to islands east of the Wallace Line, including New Guinea, and that so-called “wild” pigs within this region are most likely feral descendants of domestic pigs introduced by early agriculturalists. The other later pig dispersal links mainland East Asian pigs to western Micronesia, Taiwan, and the Philippines. These results provide important data with which to test current models for human dispersal in the region. PMID:17360400

  11. Structural analysis of the human SYCE2-TEX12 complex provides molecular insights into synaptonemal complex assembly.

    Science.gov (United States)

    Davies, Owen R; Maman, Joseph D; Pellegrini, Luca

    2012-07-01

    The successful completion of meiosis is essential for all sexually reproducing organisms. The synaptonemal complex (SC) is a large proteinaceous structure that holds together homologous chromosomes during meiosis, providing the structural framework for meiotic recombination and crossover formation. Errors in SC formation are associated with infertility, recurrent miscarriage and aneuploidy. The current lack of molecular information about the dynamic process of SC assembly severely restricts our understanding of its function in meiosis. Here, we provide the first biochemical and structural analysis of an SC protein component and propose a structural basis for its function in SC assembly. We show that human SC proteins SYCE2 and TEX12 form a highly stable, constitutive complex, and define the regions responsible for their homotypic and heterotypic interactions. Biophysical analysis reveals that the SYCE2-TEX12 complex is an equimolar hetero-octamer, formed from the association of an SYCE2 tetramer and two TEX12 dimers. Electron microscopy shows that biochemically reconstituted SYCE2-TEX12 complexes assemble spontaneously into filamentous structures that resemble the known physical features of the SC central element (CE). Our findings can be combined with existing biological data in a model of chromosome synapsis driven by growth of SYCE2-TEX12 higher-order structures within the CE of the SC.

  12. Global mass spectrometry and transcriptomics array based drug profiling provides novel insight into glucosamine induced endoplasmic reticulum stress

    DEFF Research Database (Denmark)

    Carvalho, Ana Sofia; Ribeiro, Helena; Voabil, Paula;

    2014-01-01

    We investigated the molecular effects of glucosamine supplements, a popular and safe alternative to nonsteroidal anti-inflammatory drugs, for decreasing pain, inflammation, and maintaining healthy joints. Numerous studies have reported an array of molecular effects after glucosamine treatment. We...... questioned whether the differences in the effects observed in previous studies were associated with the focus on a specific subproteome or with the use of specific cell lines or tissues. To address this question, global mass spectrometry- and transcription array-based glucosamine drug profiling was performed...... mainly observed glucosamine induced O-GlcNAcylation/O-GalNAcylation (O-HexNAcylation); however, we also observed global and local changes in acetylation, methylation, and phosphorylation. For example, our data provides two additional examples of "yin-yang" between phosphorylation and O...

  13. Quality management and safety culture in medicine - Do standard quality reports provide insights into the human factor of patient safety?

    Science.gov (United States)

    Wischet, Werner; Schusterschitz, Claudia

    2009-12-15

    In 1999 the Institute of Medicine (IOM) published the landmark report "To err is human: building a safer healthcare system" highlighting critical deficiencies within the area of patient safety. As a consequence, safety culture evolved as a core component of quality management in medicine. Purpose of the investigation at hand was to find out to what extent this is reflected in standard quality reports issued by German hospitals providing maximum medical care. Reports issued for the year 2006 were analysed with respect to the appearance of indicators for the presence of a safety culture. Results suggest that despite the huge awareness for patient safety caused by the IOM report, the topic of safety culture does not get the anticipated attention within the quality reports. This may indicate that the current requirements for the quality reports do not facilitate transparency when it comes to the human factor of patient safety.

  14. A novel human-infection-derived bacterium provides insights into the evolutionary origins of mutualistic insect-bacterial symbioses.

    Science.gov (United States)

    Clayton, Adam L; Oakeson, Kelly F; Gutin, Maria; Pontes, Arthur; Dunn, Diane M; von Niederhausern, Andrew C; Weiss, Robert B; Fisher, Mark; Dale, Colin

    2012-01-01

    Despite extensive study, little is known about the origins of the mutualistic bacterial endosymbionts that inhabit approximately 10% of the world's insects. In this study, we characterized a novel opportunistic human pathogen, designated "strain HS," and found that it is a close relative of the insect endosymbiont Sodalis glossinidius. Our results indicate that ancestral relatives of strain HS have served as progenitors for the independent descent of Sodalis-allied endosymbionts found in several insect hosts. Comparative analyses indicate that the gene inventories of the insect endosymbionts were independently derived from a common ancestral template through a combination of irreversible degenerative changes. Our results provide compelling support for the notion that mutualists evolve from pathogenic progenitors. They also elucidate the role of degenerative evolutionary processes in shaping the gene inventories of symbiotic bacteria at a very early stage in these mutualistic associations.

  15. A novel human-infection-derived bacterium provides insights into the evolutionary origins of mutualistic insect-bacterial symbioses.

    Directory of Open Access Journals (Sweden)

    Adam L Clayton

    Full Text Available Despite extensive study, little is known about the origins of the mutualistic bacterial endosymbionts that inhabit approximately 10% of the world's insects. In this study, we characterized a novel opportunistic human pathogen, designated "strain HS," and found that it is a close relative of the insect endosymbiont Sodalis glossinidius. Our results indicate that ancestral relatives of strain HS have served as progenitors for the independent descent of Sodalis-allied endosymbionts found in several insect hosts. Comparative analyses indicate that the gene inventories of the insect endosymbionts were independently derived from a common ancestral template through a combination of irreversible degenerative changes. Our results provide compelling support for the notion that mutualists evolve from pathogenic progenitors. They also elucidate the role of degenerative evolutionary processes in shaping the gene inventories of symbiotic bacteria at a very early stage in these mutualistic associations.

  16. Teff, an Orphan Cereal in the Chloridoideae, Provides Insights into the Evolution of Storage Proteins in Grasses.

    Science.gov (United States)

    Zhang, Wei; Xu, Jianhong; Bennetzen, Jeffrey L; Messing, Joachim

    2016-06-13

    Seed storage proteins (SSP) in cereals provide essential nutrition for humans and animals. Genes encoding these proteins have undergone rapid evolution in different grass species. To better understand the degree of divergence, we analyzed this gene family in the subfamily Chloridoideae, where the genome of teff (Eragrostis tef) has been sequenced. We find gene duplications, deletions, and rapid mutations in protein-coding sequences. The main SSPs in teff, like other grasses, are prolamins, here called eragrostins. Teff has γ- and δ-prolamins, but has no β-prolamins. One δ-type prolamin (δ1) in teff has higher methionine (33%) levels than in maize (23-25%). The other δ-type prolamin (δ2) has reduced methionine residues (<10%) and is phylogenetically closer to α prolamins. Prolamin δ2 in teff represents an intermediate between δ and α types that appears to have been lost in maize and other Panicoideae, and was replaced by the expansion of α-prolamins. Teff also has considerably larger numbers of α-prolamin genes, which we further divide into five sub-groups, where α2 and α5 represent the most abundant α-prolamins both in number and in expression. In addition, indolines that determine kernel softness are present in teff and the panicoid cereal called foxtail millet (Setaria italica) but not in sorghum or maize, indicating that these genes were only recently lost in some members of the Panicoideae Moreover, this study provides not only information on the evolution of SSPs in the grass family but also the importance of α-globulins in protein aggregation and germplasm divergence.

  17. Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.

    Directory of Open Access Journals (Sweden)

    Mandy Muller

    Full Text Available Human Papillomaviruses (HPV cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV. To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes.

  18. Building-block architecture of botulinum toxin complex: Conformational changes provide insights into the hemagglutination ability of the complex

    Directory of Open Access Journals (Sweden)

    Tomonori Suzuki

    2017-03-01

    Full Text Available Clostridium botulinum produces the botulinum neurotoxin (BoNT. Previously, we provided evidence for the “building-block” model of botulinum toxin complex (TC. In this model, a single BoNT is associated with a single nontoxic nonhemagglutinin (NTNHA, yielding M-TC; three HA-70 molecules are attached and form M-TC/HA-70, and one to three “arms” of the HA-33/HA-17 trimer (two HA-33 and one HA-17 further bind to M-TC/HA-70 via HA-17 and HA-70 binding, yielding one-, two-, and three-arm L-TC. Of all TCs, only the three-arm L-TC caused hemagglutination. In this study, we determined the solution structures for the botulinum TCs using small-angle X-ray scattering (SAXS. The mature three-arm L-TC exhibited the shape of a “bird spreading its wings”, in contrast to the model having three “arms”, as revealed by transmission electron microscopy. SAXS images indicated that one of the three arms of the HA-33/HA-17 trimer bound to both HA-70 and BoNT. Taken together, these findings regarding the conformational changes in the building-block architecture of TC may explain why only three-arm L-TC exhibited hemagglutination.

  19. Transcriptome of the Australian Mollusc Dicathais orbita Provides Insights into the Biosynthesis of Indoles and Choline Esters

    Directory of Open Access Journals (Sweden)

    Abdul Baten

    2016-07-01

    Full Text Available Dicathais orbita is a mollusc of the Muricidae family and is well known for the production of the expensive dye Tyrian purple and its brominated precursors that have anticancer properties, in addition to choline esters with muscle-relaxing properties. However, the biosynthetic pathways that produce these secondary metabolites in D. orbita are not known. Illumina HiSeq 2000 transcriptome sequencing of hypobranchial glands, prostate glands, albumen glands, capsule glands, and mantle and foot tissues of D. orbita generated over 201 million high quality reads that were de novo assembled into 219,437 contigs. Annotation with reference to the Nr, Swiss-Prot and Kyoto Encyclopedia of Genes and Genomes (KEGG databases identified candidate-coding regions in 76,152 of these contigs, with transcripts for many enzymes in various metabolic pathways associated with secondary metabolite biosynthesis represented. This study revealed that D. orbita expresses a number of genes associated with indole, sulfur and histidine metabolism pathways that are relevant to Tyrian purple precursor biosynthesis, and many of which were not found in the fully annotated genomes of three other molluscs in the KEGG database. However, there were no matches to known bromoperoxidase enzymes within the D. orbita transcripts. These transcriptome data provide a significant molecular resource for gastropod research in general and Tyrian purple producing Muricidae in particular.

  20. The transcriptomes of the crucian carp complex (Carassius auratus) provide insights into the distinction between unisexual triploids and sexual diploids.

    Science.gov (United States)

    Li, Chun-Yan; Li, Jiong-Tang; Kuang, You-Yi; Xu, Ru; Zhao, Zi-Xia; Hou, Guang-Yuan; Liang, Hong-Wei; Sun, Xiao-Wen

    2014-05-27

    Both sexual reproduction and unisexual reproduction are adaptive strategies for species survival and evolution. Unisexual animals have originated largely by hybridization, which tends to elevate their heterozygosity. However, the extent of genetic diversity resulting from hybridization and the genomic differences that determine the type of reproduction are poorly understood. In Carassius auratus, sexual diploids and unisexual triploids coexist. These two forms are similar morphologically but differ markedly in their modes of reproduction. Investigation of their genomic differences will be useful to study genome diversity and the development of reproductive mode. We generated transcriptomes for the unisexual and sexual populations. Genes were identified using homology searches and an ab initio method. Estimation of the synonymous substitution rate in the orthologous pairs indicated that the hybridization of gibel carp occurred 2.2 million years ago. Microsatellite genotyping in each individual from the gibel carp population indicated that most gibel carp genes were not tri-allelic. Molecular function and pathway comparisons suggested few gene expansions between them, except for the progesterone-mediated oocyte maturation pathway, which is enriched in gibel carp. Differential expression analysis identified highly expressed genes in gibel carp. The transcriptomes provide information on genetic diversity and genomic differences, which should assist future studies in functional genomics.

  1. The Transcriptomes of the Crucian Carp Complex (Carassius auratus Provide Insights into the Distinction between Unisexual Triploids and Sexual Diploids

    Directory of Open Access Journals (Sweden)

    Chun-Yan Li

    2014-05-01

    Full Text Available Both sexual reproduction and unisexual reproduction are adaptive strategies for species survival and evolution. Unisexual animals have originated largely by hybridization, which tends to elevate their heterozygosity. However, the extent of genetic diversity resulting from hybridization and the genomic differences that determine the type of reproduction are poorly understood. In Carassius auratus, sexual diploids and unisexual triploids coexist. These two forms are similar morphologically but differ markedly in their modes of reproduction. Investigation of their genomic differences will be useful to study genome diversity and the development of reproductive mode. We generated transcriptomes for the unisexual and sexual populations. Genes were identified using homology searches and an ab initio method. Estimation of the synonymous substitution rate in the orthologous pairs indicated that the hybridization of gibel carp occurred 2.2 million years ago. Microsatellite genotyping in each individual from the gibel carp population indicated that most gibel carp genes were not tri-allelic. Molecular function and pathway comparisons suggested few gene expansions between them, except for the progesterone-mediated oocyte maturation pathway, which is enriched in gibel carp. Differential expression analysis identified highly expressed genes in gibel carp. The transcriptomes provide information on genetic diversity and genomic differences, which should assist future studies in functional genomics.

  2. Phloem sap proteome studied by iTRAQ provides integrated insight into salinity response mechanisms in cucumber plants.

    Science.gov (United States)

    Fan, Huaifu; Xu, Yanli; Du, Changxia; Wu, Xue

    2015-07-01

    Cucumber is an economically important crop as well as a model system for plant vascular biology. Salinity is one of the major environmental factors limiting plant growth. Here, we used an iTRAQ-based quantitative proteomics approach for comparative analysis of protein abundances in cucumber phloem sap in response to salt. A total of 745 distinct proteins were identified and 111 proteins were differentially expressed upon salinity in sensitive and tolerant cultivars, of which 69 and 65 proteins changed significantly in sensitive and tolerant cultivars, respectively. A bioinformatics analysis indicated that cucumber phloem employed a combination of induced metabolism, protein turnover, common stress response, energy and transport, signal transduction and regulation of transcription, and development proteins as protection mechanisms against salinity. The proteins that were mapped to the carbon fixation pathway decreased in abundance in sensitive cultivars and had no change in tolerant cultivars under salt stress, suggesting that this pathway may promote salt tolerance by stabilizing carbon fixation and maintaining the essential energy and carbohydrates in tolerant cultivars. This study leads to a better understanding of the salinity mechanism in cucumber phloem and provides a list of potential gene targets for the further engineering of salt tolerance in plants.

  3. Phenology of Lithothamnion glaciale in mixed fjord conditions: mesocosm experiments provide insight to maerl physiology and distribution in southwestern Greenland.

    Science.gov (United States)

    Schoenrock, Kathryn; Baquet, Marion; Kamenos, Nicholas

    2017-04-01

    Maerl are free living coralline algae that are often bedded in the subtidal forming important marine habitats in many regions of the world. Greenland is known to have at least three species of maerl along the coast and extending into some fjord systems. In the Godthåbsfjord region, Lithothamnion glaciale is never found dominating shallow maerl beds as it is further north (Disko bay) and in other regions of the Arctic. To investigate reasons for this maerl physiology was measured in situ over two field seasons and over the year in a mesocosm experiment which manipulated temperature and salinity to represent marine and fjord systems. The results of these measurements show that calcification and photosynthesis (DO production) in L. glaciale as well as another maerl species, Clathromorphum compactum, operate at very low rates and are influenced negatively by low salinity but positively by low temperature throughout the year. Photosynthesis and calcification are not often correlated in these species which is an unusual finding as these two metabolic processes are thought to be coupled. Findings provide natural history background for ecotypes from the Godthåbsfjord region and a baseline for future research in biogeochemistry and ecology.

  4. Proteomic Analysis Provides New Insights in Phosphorus Homeostasis Subjected to Pi (Inorganic Phosphate) Starvation in Tomato Plants (Solanum lycopersicum L.).

    Science.gov (United States)

    Muneer, Sowbiya; Jeong, Byoung Ryong

    2015-01-01

    Phosphorus is a major nutrient acquired by plants via high-affinity inorganic phosphate (Pi) transporters. To determine the adaptation and homeostasis strategy to Pi starvation, we compared the proteome analysis of tomato leaves that were treated with and without Pi (as KH2PO4) for 10 days. Among 600 reproducible proteins on 2-DE gels 46 of them were differentially expressed. These proteins were involved in major metabolic pathways, including photosynthesis, transcriptional/translational regulations, carbohydrate/energy metabolism, protein synthesis, defense response, and other secondary metabolism. The results also showed that the reduction in photosynthetic pigments lowered P content under -Pi treatments. Furthermore, high-affinity Pi transporters (lePT1 and lePT2) expressed in higher amounts under -Pi treatments. Also, the accumulation of Pi transporters was observed highly in the epidermis and palisade parenchyma under +Pi treatments compared to -Pi treatments. Our data suggested that tomato plants developed reactive oxygen species (ROS) scavenging mechanisms to cope with low Pi content, including the up-regulation of proteins mostly involved in important metabolic pathways. Moreover, Pi-starved tomato plants increased their internal Pi utilization efficiency by increasing the Pi transporter genes and their rational localization. These results thus provide imperative information about how tomato plants respond to Pi starvation and its homeostasis.

  5. Crystal structure of I-DmoI in complex with its target DNA provides new insights into meganuclease engineering.

    Science.gov (United States)

    Marcaida, María José; Prieto, Jesús; Redondo, Pilar; Nadra, Alejandro D; Alibés, Andreu; Serrano, Luis; Grizot, Sylvestre; Duchateau, Philippe; Pâques, Frédéric; Blanco, Francisco J; Montoya, Guillermo

    2008-11-04

    Homing endonucleases, also known as meganucleases, are sequence-specific enzymes with large DNA recognition sites. These enzymes can be used to induce efficient homologous gene targeting in cells and plants, opening perspectives for genome engineering with applications in a wide series of fields, ranging from biotechnology to gene therapy. Here, we report the crystal structures at 2.0 and 2.1 A resolution of the I-DmoI meganuclease in complex with its substrate DNA before and after cleavage, providing snapshots of the catalytic process. Our study suggests that I-DmoI requires only 2 cations instead of 3 for DNA cleavage. The structure sheds light onto the basis of DNA binding, indicating key residues responsible for nonpalindromic target DNA recognition. In silico and in vivo analysis of the I-DmoI DNA cleavage specificity suggests that despite the relatively few protein-base contacts, I-DmoI is highly specific when compared with other meganucleases. Our data open the door toward the generation of custom endonucleases for targeted genome engineering using the monomeric I-DmoI scaffold.

  6. Structure of putrescine aminotransferase from Escherichia coli provides insights into the substrate specificity among class III aminotransferases.

    Directory of Open Access Journals (Sweden)

    Hyung Jin Cha

    Full Text Available YgjG is a putrescine aminotransferase enzyme that transfers amino groups from compounds with terminal primary amines to compounds with an aldehyde group using pyridoxal-5'-phosphate (PLP as a cofactor. Previous biochemical data show that the enzyme prefers primary diamines, such as putrescine, over ornithine as a substrate. To better understand the enzyme's substrate specificity, crystal structures of YgjG from Escherichia coli were determined at 2.3 and 2.1 Å resolutions for the free and putrescine-bound enzymes, respectively. Sequence and structural analyses revealed that YgjG forms a dimer that adopts a class III PLP-dependent aminotransferase fold. A structural comparison between YgjG and other class III aminotransferases revealed that their structures are similar. However, YgjG has an additional N-terminal helical structure that partially contributes to a dimeric interaction with the other subunit via a helix-helix interaction. Interestingly, the YgjG substrate-binding site entrance size and charge distribution are smaller and more hydrophobic than other class III aminotransferases, which suggest that YgjG has a unique substrate binding site that could accommodate primary aliphatic diamine substrates, including putrescine. The YgjG crystal structures provide structural clues to putrescine aminotransferase substrate specificity and binding.

  7. Tobacco and alcohol sponsorship of sporting events provide insights about how food and beverage sponsorship may affect children's health.

    Science.gov (United States)

    Kelly, Bridget; Baur, Louise A; Bauman, Adrian E; King, Lesley

    2011-08-01

    Determining children's exposure to food and beverage company sponsorship, and the effect of this exposure, is important in establishing the extent to which there may be health and societal consequences. This paper aimed to provide preliminary evidence on the scope and potential effects on children of unhealthy food and beverage sponsorship. A review of published literature and media and marketing reports was conducted to determine the types of food and beverage sponsorship campaigns that children are exposed to, and the effect of corporate sponsorship (including tobacco and alcohol) on children and adolescents. A large range of food and beverage sponsorship activities, in Australia and internationally, were identified for both school and sport settings. In particular, food and beverage companies have attempted to develop a marketing presence at all levels of professional and community sport. No information was identified measuring the effect of food and beverage company sponsorship on children and adolescents. However, empirical evidence from consumer studies relating to tobacco and alcohol sponsorship has repeatedly demonstrated that sponsorship has an impact on children's product recall and product-related attitudes and behavioural intentions. While there is no available research on the direct effect of food and beverage sponsorship, the demonstrated effects of tobacco and alcohol sponsorship on children's product awareness, preferences and consumption are likely to be applicable to food companies.

  8. The structure of arabidopsis thaliana OST1 provides insights into the kinase regulation mechanism in response to osmotic stress

    KAUST Repository

    Yunta, Cristina

    2011-11-01

    SnRK [SNF1 (sucrose non-fermenting-1)-related protein kinase] 2.6 [open stomata 1 (OST1)] is well characterized at molecular and physiological levels to control stomata closure in response to water-deficit stress. OST1 is a member of a family of 10 protein kinases from Arabidopsis thaliana (SnRK2) that integrates abscisic acid (ABA)-dependent and ABA-independent signals to coordinate the cell response to osmotic stress. A subgroup of protein phosphatases type 2C binds OST1 and keeps the kinase dephosphorylated and inactive. Activation of OST1 relies on the ABA-dependent inhibition of the protein phosphatases type 2C and the subsequent self-phosphorylation of the kinase. The OST1 ABA-independent activation depends on a short sequence motif that is conserved among all the members of the SnRK2 family. However, little is known about the molecular mechanism underlying this regulation. The crystallographic structure of OST1 shows that ABA-independent regulation motif stabilizes the conformation of the kinase catalytically essential α C helix, and it provides the basis of the ABA-independent regulation mechanism for the SnRK2 family of protein kinases. © 2011 Elsevier Ltd. All rights reserved.

  9. Experimental induction of reading difficulties in normal readers provides novel insights into the neurofunctional mechanisms of visual word recognition.

    Science.gov (United States)

    Heim, Stefan; Weidner, Ralph; von Overheidt, Ann-Christin; Tholen, Nicole; Grande, Marion; Amunts, Katrin

    2014-03-01

    Phonological and visual dysfunctions may result in reading deficits like those encountered in developmental dyslexia. Here, we use a novel approach to induce similar reading difficulties in normal readers in an event-related fMRI study, thus systematically investigating which brain regions relate to different pathways relating to orthographic-phonological (e.g. grapheme-to-phoneme conversion, GPC) vs. visual processing. Based upon a previous behavioural study (Tholen et al. 2011), the retrieval of phonemes from graphemes was manipulated by lowering the identifiability of letters in familiar vs. unfamiliar shapes. Visual word and letter processing was impeded by presenting the letters of a word in a moving, non-stationary manner. FMRI revealed that the visual condition activated cytoarchitectonically defined area hOC5 in the magnocellular pathway and area 7A in the right mesial parietal cortex. In contrast, the grapheme manipulation revealed different effects localised predominantly in bilateral inferior frontal gyrus (left cytoarchitectonic area 44; right area 45) and inferior parietal lobule (including areas PF/PFm), regions that have been demonstrated to show abnormal activation in dyslexic as compared to normal readers. This pattern of activation bears close resemblance to recent findings in dyslexic samples both behaviourally and with respect to the neurofunctional activation patterns. The novel paradigm may thus prove useful in future studies to understand reading problems related to distinct pathways, potentially providing a link also to the understanding of real reading impairments in dyslexia.

  10. Exploration of insights, opportunities and caveats provided by the X-ray structures of hSERT.

    Science.gov (United States)

    Topiol, Sid; Bang-Andersen, Benny; Sanchez, Connie; Bøgesø, Klaus P

    2016-10-15

    The recently reported X-ray structures of the human serotonin (5-HT) transporter SERT with bound inhibitors open new opportunities for drug discovery at SERT, selectivity design with respect to other neurotransmitter sodium transporters, and enhanced understanding of the molecular events involved in SERT action. Through computational and structural analyses, we explore the binding and migration of 5-HT at SERT. Consistent with earlier studies of leucine migration at the bacterial homolog of SERT, LeuT, we find multiple potential 'stopover' sites for 5-HT binding at SERT including the two (transmembrane S1 and extracellular vestibule S2) seen in the binding of the SSRI (S)-citalopram (S-Cit) to SERT, as well as other sites. Docking studies reveal the possibility of both hetero- (S-Cit+5-HT) and homo-dimeric (5-HT+5-HT) co-binding at both these sites which may explain earlier published allosteric activity observations and provide novel design strategies. Comparisons with substrate bound X-ray structures of the dopamine transporter reveal a number of potential sources of selectivity, some of which may be 'artificial' including target based, species related, experimental design related, and ligand dependent examples including substrate versus inhibitor related features.

  11. Structure of putrescine aminotransferase from Escherichia coli provides insights into the substrate specificity among class III aminotransferases.

    Science.gov (United States)

    Cha, Hyung Jin; Jeong, Jae-Hee; Rojviriya, Catleya; Kim, Yeon-Gil

    2014-01-01

    YgjG is a putrescine aminotransferase enzyme that transfers amino groups from compounds with terminal primary amines to compounds with an aldehyde group using pyridoxal-5'-phosphate (PLP) as a cofactor. Previous biochemical data show that the enzyme prefers primary diamines, such as putrescine, over ornithine as a substrate. To better understand the enzyme's substrate specificity, crystal structures of YgjG from Escherichia coli were determined at 2.3 and 2.1 Å resolutions for the free and putrescine-bound enzymes, respectively. Sequence and structural analyses revealed that YgjG forms a dimer that adopts a class III PLP-dependent aminotransferase fold. A structural comparison between YgjG and other class III aminotransferases revealed that their structures are similar. However, YgjG has an additional N-terminal helical structure that partially contributes to a dimeric interaction with the other subunit via a helix-helix interaction. Interestingly, the YgjG substrate-binding site entrance size and charge distribution are smaller and more hydrophobic than other class III aminotransferases, which suggest that YgjG has a unique substrate binding site that could accommodate primary aliphatic diamine substrates, including putrescine. The YgjG crystal structures provide structural clues to putrescine aminotransferase substrate specificity and binding.

  12. A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms.

    Science.gov (United States)

    Cruzeiro, Catarina; Lopes-Marques, Mónica; Ruivo, Raquel; Rodrigues-Oliveira, Nádia; Santos, Miguel M; Rocha, Maria João; Rocha, Eduardo; Castro, L Filipe C

    2016-05-01

    The origin and diversification of the metazoan endocrine systems represents a fundamental research issue in biology. Nuclear receptors are critical components of these systems. A particular group named VDR/PXR/CAR (NR1I/J) is central in the mediation of detoxification responses. While orthologues have been thoroughly characterized in vertebrates, a sparse representation is currently available for invertebrates. Here, we provide the first isolation and characterization of a lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J), in the estuarine bivalve the peppery furrow shell (Scrobicularia plana). Using a reporter gene assay, we evaluated the xenobiotic receptor plasticity comparing the human PXR with the S. plana NR1Jβ. Our results show that the molluscan receptor responds to a natural toxin (okadaic acid) in a similar fashion to that reported for other invertebrates. In contrast, the pesticide esfenvalerate displayed a unique response, since it down regulated transactivation at higher concentrations, while for triclosan no response was observed. Additionally, we uncovered lineage specific gene duplications and gene loss in the gene group encoding NRs in protostomes with likely impacts on the complexity of detoxification mechanisms across different phyla. Our findings pave the way for the development of multi-specific sensor tools to screen xenobiotic compounds acting via the NR1I/J group.

  13. The Structure of a Sugar Transporter of the Glucose EIIC Superfamily Provides Insight into the Elevator Mechanism of Membrane Transport.

    Science.gov (United States)

    McCoy, Jason G; Ren, Zhenning; Stanevich, Vitali; Lee, Jumin; Mitra, Sharmistha; Levin, Elena J; Poget, Sebastien; Quick, Matthias; Im, Wonpil; Zhou, Ming

    2016-06-07

    The phosphoenolpyruvate:carbohydrate phosphotransferase systems are found in bacteria, where they play central roles in sugar uptake and regulation of cellular uptake processes. Little is known about how the membrane-embedded components (EIICs) selectively mediate the passage of carbohydrates across the membrane. Here we report the functional characterization and 2.55-Å resolution structure of a maltose transporter, bcMalT, belonging to the glucose superfamily of EIIC transporters. bcMalT crystallized in an outward-facing occluded conformation, in contrast to the structure of another glucose superfamily EIIC, bcChbC, which crystallized in an inward-facing occluded conformation. The structures differ in the position of a structurally conserved substrate-binding domain that is suggested to play a central role in sugar transport. In addition, molecular dynamics simulations suggest a potential pathway for substrate entry from the periplasm into the bcMalT substrate-binding site. These results provide a mechanistic framework for understanding substrate recognition and translocation for the glucose superfamily EIIC transporters.

  14. Whole Genome Sequencing of the Asian Arowana (Scleropages formosus) Provides Insights into the Evolution of Ray-Finned Fishes.

    Science.gov (United States)

    Austin, Christopher M; Tan, Mun Hua; Croft, Larry J; Hammer, Michael P; Gan, Han Ming

    2015-10-06

    The Asian arowana (Scleropages formosus) is of commercial importance, conservation concern, and is a representative of one of the oldest lineages of ray-finned fish, the Osteoglossomorpha. To add to genomic knowledge of this species and the evolution of teleosts, the genome of a Malaysian specimen of arowana was sequenced. A draft genome is presented consisting of 42,110 scaffolds with a total size of 708 Mb (2.85% gaps) representing 93.95% of core eukaryotic genes. Using a k-mer-based method, a genome size of 900 Mb was also estimated. We present an update on the phylogenomics of fishes based on a total of 27 species (23 fish species and 4 tetrapods) using 177 orthologous proteins (71,360 amino acid sites), which supports established relationships except that arowana is placed as the sister lineage to all teleost clades (Bayesian posterior probability 1.00, bootstrap replicate 93%), that evolved after the teleost genome duplication event rather than the eels (Elopomorpha). Evolutionary rates are highly heterogeneous across the tree with fishes represented by both slowly and rapidly evolving lineages. A total of 94 putative pigment genes were identified, providing the impetus for development of molecular markers associated with the spectacular colored phenotypes found within this species.

  15. Comparative Proteomic Analysis of the Graft Unions in Hickory (Carya cathayensis Provides Insights into Response Mechanisms to Grafting Process

    Directory of Open Access Journals (Sweden)

    Daoliang Yan

    2017-04-01

    Full Text Available Hickory (Carya cathayensis, a tree with high nutritional and economic value, is widely cultivated in China. Grafting greatly reduces the juvenile phase length and makes the large scale cultivation of hickory possible. To reveal the response mechanisms of this species to grafting, we employed a proteomics-based approach to identify differentially expressed proteins in the graft unions during the grafting process. Our study identified 3723 proteins, of which 2518 were quantified. A total of 710 differentially expressed proteins (DEPs were quantified and these were involved in various molecular functional and biological processes. Among these DEPs, 341 were up-regulated and 369 were down-regulated at 7 days after grafting compared with the control. Four auxin-related proteins were down-regulated, which was in agreement with the transcription levels of their encoding genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG analysis showed that the ‘Flavonoid biosynthesis’ pathway and ‘starch and sucrose metabolism’ were both significantly up-regulated. Interestingly, five flavonoid biosynthesis-related proteins, a flavanone 3-hyfroxylase, a cinnamate 4-hydroxylase, a dihydroflavonol-4-reductase, a chalcone synthase, and a chalcone isomerase, were significantly up-regulated. Further experiments verified a significant increase in the total flavonoid contents in scions, which suggests that graft union formation may activate flavonoid biosynthesis to increase the content of a series of downstream secondary metabolites. This comprehensive analysis provides fundamental information on the candidate proteins and secondary metabolism pathways involved in the grafting process for hickory.

  16. Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif

    Science.gov (United States)

    Smith, Jennifer J.; Hill, Justine M.; Little, Michelle J.; Nicholson, Graham M.; King, Glenn F.; Alewood, Paul F.

    2011-01-01

    The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails. Over a decade ago it was proposed that the ICK motif is an elaboration of an ancestral two-disulfide fold coined the disulfide-directed β-hairpin (DDH). Here we report the isolation, characterization, and structure of a novel toxin [U1-liotoxin-Lw1a (U1-LITX-Lw1a)] from the venom of the scorpion Liocheles waigiensis that is the first example of a native peptide that adopts the DDH fold. U1-LITX-Lw1a not only represents the discovery of a missing link in venom protein evolution, it is the first member of a fourth structural fold to be adopted by scorpion-venom peptides. Additionally, we show that U1-LITX-Lw1a has potent insecticidal activity across a broad range of insect pest species, thereby providing a unique structural scaffold for bioinsecticide development. PMID:21670253

  17. Unique scorpion toxin with a putative ancestral fold provides insight into evolution of the inhibitor cystine knot motif.

    Science.gov (United States)

    Smith, Jennifer J; Hill, Justine M; Little, Michelle J; Nicholson, Graham M; King, Glenn F; Alewood, Paul F

    2011-06-28

    The three-disulfide inhibitor cystine knot (ICK) motif is a fold common to venom peptides from spiders, scorpions, and aquatic cone snails. Over a decade ago it was proposed that the ICK motif is an elaboration of an ancestral two-disulfide fold coined the disulfide-directed β-hairpin (DDH). Here we report the isolation, characterization, and structure of a novel toxin [U(1)-liotoxin-Lw1a (U(1)-LITX-Lw1a)] from the venom of the scorpion Liocheles waigiensis that is the first example of a native peptide that adopts the DDH fold. U(1)-LITX-Lw1a not only represents the discovery of a missing link in venom protein evolution, it is the first member of a fourth structural fold to be adopted by scorpion-venom peptides. Additionally, we show that U(1)-LITX-Lw1a has potent insecticidal activity across a broad range of insect pest species, thereby providing a unique structural scaffold for bioinsecticide development.

  18. Will China's Cooperative Medical System fail again? Insight from farmer satisfaction survey.

    Science.gov (United States)

    Chen, Dong; Tang, Kam Ki; Zhao, Lifeng; Zhang, Yuhong

    2015-06-01

    This paper studied the sustainability of China's New Rural Cooperative Medical System (NCMS) by evaluating the satisfaction rate of its participants-the farmers. The study related the overall satisfaction of the farmers to their satisfaction with the four different aspects of the program. It also identified which personal and program attributes affect the farmers' satisfaction rate. Survey data of 1278 households from 66 counties in Shandong Province of China were collected in 2011 using a multi-stage stratified cluster-sampling method. To overcome the nepotistic barriers in rural China, field surveys in each township were conducted by university students from the same place. Data were analyzed using multiple regressions and structural equation modeling method. The results showed that 86% of the farmers were either satisfied or very satisfied with the NCMS and 82% indicated their intention to continue participating in the program. Aside from its financial benefits, both the publicity and reimbursement procedure of the program were found to be significant factors in influencing the satisfaction of the farmers. Majority of the participants held positive opinions toward the NCMS, contradicting the negative assessments made by many previous studies. Given the high proportion of farmers willing to continue with the program, it is likely to be sustainable in the near future. Greater publicity and education efforts should be made to make the farmers better informed about the program, and measures should be taken to improve its reimbursement procedure and the setting of the premium level.

  19. Transcriptome changes in Eriocheir sinensis megalopae after desalination provide insights into osmoregulation and stress adaption in larvae.

    Directory of Open Access Journals (Sweden)

    Min Hui

    Full Text Available Eriocheir sinensis, an extremely invasive alien crab species, has important economic value in China. It encounters different salinities during its life cycle, and at the megalopal stage it faces a turning point regarding the salinity in its environment. We applied RNA sequencing to E. sinensis megalopae before (MB and after (MA desalination, resulting in the discovery of 21,042 unigenes and 908 differentially expressed genes (DEGs, 4.32% of the unigenes. The DEGs primarily belonged to the Gene Ontology groups "Energy metabolism," "Oxidoreductase activity," "Translation," "Transport," "Metabolism," and "Stress response." In total, 33 DEGs related to transport processes were found, including 12 proton pump genes, three ATP-binding cassettes (ABCs, 13 solute carrier (SLC family members, two sweet sugar transporter (ST family members and three other substance transporters. Mitochondrial genes as well as genes involved in the tricarboxylic acid cycle, glycolytic pathway, or β-oxidation pathway, which can generate energy in the form of ATP, were typically up-regulated in MA. 11 unigenes related to amino acid metabolism and a large number of genes related to protein synthesis were differentially expressed in MB and MA, indicating that E. sinensis possibly adjusts its concentration of free amino acid osmolytes for hyper-osmoregulation. Additionally, 33 salinity and oxidative stress induced genes were found to be differentially expressed, such as the LEA2, HSPs, GST and coagulation factor genes. Notably, LEA2 is an extremely hydrophilic protein that responds to desiccation and reported for the first time in crabs. Therefore, we suppose that when the environment is hypo-osmotic, the megalopae might compensate for ion loss via hyper-osmoregulation by consuming more energy, accompanied by a series of stress induced adaptions. This study provides the first genome-wide transcriptome analysis of E. sinensis megalopae for studying its osmoregulation and stress

  20. A mollusk VDR/PXR/CAR-like (NR1J) nuclear receptor provides insight into ancient detoxification mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Cruzeiro, Catarina, E-mail: catarinarcruzeiro@hotmail.com [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Lopes-Marques, Mónica, E-mail: monicaslm@hotmail.com [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Ruivo, Raquel, E-mail: ruivo.raquel@gmail.com [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Rodrigues-Oliveira, Nádia, E-mail: nadia.oliveira@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Santos, Miguel M., E-mail: santos@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); FCUP - Faculty of Sciences, Department of Biology, U. Porto (Portugal); Rocha, Maria João, E-mail: mjsrocha@netcabo.pt [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Rocha, Eduardo, E-mail: erocha@icbas.up.pt [ICBAS - Institute of Biomedical Sciences Abel Salazar, U. Porto - University of Porto (Portugal); CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); Castro, L. Filipe C., E-mail: filipe.castro@ciimar.up.pt [CIIMAR/CIMAR - Interdisciplinary Center of Marine and Environmental Research, U. Porto (Portugal); FCUP - Faculty of Sciences, Department of Biology, U. Porto (Portugal)

    2016-05-15

    Highlights: • A nuclear receptor orthologue of the NR1J group is isolated from a mollusc. • The molluscan NR1J transactivates gene expression upon exposure to okadaic acid but not a pesticide, esfenvarelate and triclosan. • Lineage specific gene duplications and gene loss have occurred in the NR1J of protostomes with likely impacts on detoxification mechanisms. - Abstract: The origin and diversification of the metazoan endocrine systems represents a fundamental research issue in biology. Nuclear receptors are critical components of these systems. A particular group named VDR/PXR/CAR (NR1I/J) is central in the mediation of detoxification responses. While orthologues have been thoroughly characterized in vertebrates, a sparse representation is currently available for invertebrates. Here, we provide the first isolation and characterization of a lophotrochozoan protostome VDR/PXR/CAR nuclear receptor (NR1J), in the estuarine bivalve the peppery furrow shell (Scrobicularia plana). Using a reporter gene assay, we evaluated the xenobiotic receptor plasticity comparing the human PXR with the S. plana NR1Jβ. Our results show that the molluscan receptor responds to a natural toxin (okadaic acid) in a similar fashion to that reported for other invertebrates. In contrast, the pesticide esfenvalerate displayed a unique response, since it down regulated transactivation at higher concentrations, while for triclosan no response was observed. Additionally, we uncovered lineage specific gene duplications and gene loss in the gene group encoding NRs in protostomes with likely impacts on the complexity of detoxification mechanisms across different phyla. Our findings pave the way for the development of multi-specific sensor tools to screen xenobiotic compounds acting via the NR1I/J group.

  1. Live imaging provides new insights on dynamic F-actin filopodia and differential endocytosis during myoblast fusion in Drosophila.

    Science.gov (United States)

    Haralalka, Shruti; Shelton, Claude; Cartwright, Heather N; Guo, Fengli; Trimble, Rhonda; Kumar, Ram P; Abmayr, Susan M

    2014-01-01

    The process of myogenesis includes the recognition, adhesion, and fusion of committed myoblasts into multinucleate syncytia. In the larval body wall muscles of Drosophila, this elaborate process is initiated by Founder Cells and Fusion-Competent Myoblasts (FCMs), and cell adhesion molecules Kin-of-IrreC (Kirre) and Sticks-and-stones (Sns) on their respective surfaces. The FCMs appear to provide the driving force for fusion, via the assembly of protrusions associated with branched F-actin and the WASp, SCAR and Arp2/3 pathways. In the present study, we utilize the dorsal pharyngeal musculature that forms in the Drosophila embryo as a model to explore myoblast fusion and visualize the fusion process in live embryos. These muscles rely on the same cell types and genes as the body wall muscles, but are amenable to live imaging since they do not undergo extensive morphogenetic movement during formation. Time-lapse imaging with F-actin and membrane markers revealed dynamic FCM-associated actin-enriched protrusions that rapidly extend and retract into the myotube from different sites within the actin focus. Ultrastructural analysis of this actin-enriched area showed that they have two morphologically distinct structures: wider invasions and/or narrow filopodia that contain long linear filaments. Consistent with this, formin Diaphanous (Dia) and branched actin nucleator, Arp3, are found decorating the filopodia or enriched at the actin focus, respectively, indicating that linear actin is present along with branched actin at sites of fusion in the FCM. Gain-of-function Dia and loss-of-function Arp3 both lead to fusion defects, a decrease of F-actin foci and prominent filopodia from the FCMs. We also observed differential endocytosis of cell surface components at sites of fusion, with actin reorganizing factors, WASp and SCAR, and Kirre remaining on the myotube surface and Sns preferentially taken up with other membrane proteins into early endosomes and lysosomes in the

  2. Global mass spectrometry and transcriptomics array based drug profiling provides novel insight into glucosamine induced endoplasmic reticulum stress.

    Science.gov (United States)

    Carvalho, Ana Sofia; Ribeiro, Helena; Voabil, Paula; Penque, Deborah; Jensen, Ole N; Molina, Henrik; Matthiesen, Rune

    2014-12-01

    We investigated the molecular effects of glucosamine supplements, a popular and safe alternative to nonsteroidal anti-inflammatory drugs, for decreasing pain, inflammation, and maintaining healthy joints. Numerous studies have reported an array of molecular effects after glucosamine treatment. We questioned whether the differences in the effects observed in previous studies were associated with the focus on a specific subproteome or with the use of specific cell lines or tissues. To address this question, global mass spectrometry- and transcription array-based glucosamine drug profiling was performed on malignant cell lines from different stages of lymphocyte development. We combined global label-free MS-based protein quantitation with an open search for modifications to obtain the best possible proteome coverage. Our data were largely consistent with previous studies in a variety of cellular models. We mainly observed glucosamine induced O-GlcNAcylation/O-GalNAcylation (O-HexNAcylation); however, we also observed global and local changes in acetylation, methylation, and phosphorylation. For example, our data provides two additional examples of "yin-yang" between phosphorylation and O-HexNAcylation. Furthermore, we mapped novel O-HexNAc sites on GLU2B and calnexin. GLU2B and calnexin are known to be located in the endoplasmic reticulum (ER) and involved in protein folding and quality control. The O-HexNAc sites were regulated by glucosamine treatment and correlated with the up-regulation of the ER stress marker GRP78. The occupancy of O-HexNAc on GLU2B and calnexin sites differed between the cytosolic and nuclear fractions with a higher occupancy in the cytosolic fraction. Based on our data we propose the hypothesis that O-HexNAc either inactivates calnexin and/or targets it to the cytosolic fraction. Further, we hypothesize that O-HexNAcylation induced by glucosamine treatment enhances protein trafficking.

  3. Structure of the extracellular portion of CD46 provides insights into its interactions with complement proteins and pathogens.

    Directory of Open Access Journals (Sweden)

    B David Persson

    2010-09-01

    Full Text Available The human membrane cofactor protein (MCP, CD46 is a central component of the innate immune system. CD46 protects autologous cells from complement attack by binding to complement proteins C3b and C4b and serving as a cofactor for their cleavage. Recent data show that CD46 also plays a role in mediating acquired immune responses, and in triggering autophagy. In addition to these physiologic functions, a significant number of pathogens, including select adenoviruses, measles virus, human herpes virus 6 (HHV-6, Streptococci, and Neisseria, use CD46 as a cell attachment receptor. We have determined the crystal structure of the extracellular region of CD46 in complex with the human adenovirus type 11 fiber knob. Extracellular CD46 comprises four short consensus repeats (SCR1-SCR4 that form an elongated structure resembling a hockey stick, with a long shaft and a short blade. Domains SCR1, SCR2 and SCR3 are arranged in a nearly linear fashion. Unexpectedly, however, the structure reveals a profound bend between domains SCR3 and SCR4, which has implications for the interactions with ligands as well as the orientation of the protein at the cell surface. This bend can be attributed to an insertion of five hydrophobic residues in a SCR3 surface loop. Residues in this loop have been implicated in interactions with complement, indicating that the bend participates in binding to C3b and C4b. The structure provides an accurate framework for mapping all known ligand binding sites onto the surface of CD46, thereby advancing an understanding of how CD46 acts as a receptor for pathogens and physiologic ligands of the immune system.

  4. Structure of the extracellular portion of CD46 provides insights into its interactions with complement proteins and pathogens.

    Directory of Open Access Journals (Sweden)

    B David Persson

    Full Text Available The human membrane cofactor protein (MCP, CD46 is a central component of the innate immune system. CD46 protects autologous cells from complement attack by binding to complement proteins C3b and C4b and serving as a cofactor for their cleavage. Recent data show that CD46 also plays a role in mediating acquired immune responses, and in triggering autophagy. In addition to these physiologic functions, a significant number of pathogens, including select adenoviruses, measles virus, human herpes virus 6 (HHV-6, Streptococci, and Neisseria, use CD46 as a cell attachment receptor. We have determined the crystal structure of the extracellular region of CD46 in complex with the human adenovirus type 11 fiber knob. Extracellular CD46 comprises four short consensus repeats (SCR1-SCR4 that form an elongated structure resembling a hockey stick, with a long shaft and a short blade. Domains SCR1, SCR2 and SCR3 are arranged in a nearly linear fashion. Unexpectedly, however, the structure reveals a profound bend between domains SCR3 and SCR4, which has implications for the interactions with ligands as well as the orientation of the protein at the cell surface. This bend can be attributed to an insertion of five hydrophobic residues in a SCR3 surface loop. Residues in this loop have been implicated in interactions with complement, indicating that the bend participates in binding to C3b and C4b. The structure provides an accurate framework for mapping all known ligand binding sites onto the surface of CD46, thereby advancing an understanding of how CD46 acts as a receptor for pathogens and physiologic ligands of the immune system.

  5. Genome Sequencing of the Perciform Fish Larimichthys crocea Provides Insights into Molecular and Genetic Mechanisms of Stress Adaptation

    Science.gov (United States)

    Shi, Qiong; Zhu, Lv-Yun; Li, Ting; Ding, Yang; Nie, Li; Li, Qiuhua; Dong, Wei-ren; Jiang, Liang; Sun, Bing; Zhang, XinHui; Li, Mingyu; Zhang, Hai-Qi; Xie, ShangBo; Zhu, YaBing; Jiang, XuanTing; Wang, Xianhui; Mu, Pengfei; Chen, Wei; Yue, Zhen; Wang, Zhuo; Wang, Jun; Shao, Jian-Zhong; Chen, Xinhua

    2015-01-01

    The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea. PMID:25835551

  6. Germ warfare in a microbial mat community: CRISPRs provide insights into the co-evolution of host and viral genomes.

    Directory of Open Access Journals (Sweden)

    John F Heidelberg

    Full Text Available CRISPR arrays and associated cas genes are widespread in bacteria and archaea and confer acquired resistance to viruses. To examine viral immunity in the context of naturally evolving microbial populations we analyzed genomic data from two thermophilic Synechococcus isolates (Syn OS-A and Syn OS-B' as well as a prokaryotic metagenome and viral metagenome derived from microbial mats in hotsprings at Yellowstone National Park. Two distinct CRISPR types, distinguished by the repeat sequence, are found in both the Syn OS-A and Syn OS-B' genomes. The genome of Syn OS-A contains a third CRISPR type with a distinct repeat sequence, which is not found in Syn OS-B', but appears to be shared with other microorganisms that inhabit the mat. The CRISPR repeats identified in the microbial metagenome are highly conserved, while the spacer sequences (hereafter referred to as "viritopes" to emphasize their critical role in viral immunity were mostly unique and had no high identity matches when searched against GenBank. Searching the viritopes against the viral metagenome, however, yielded several matches with high similarity some of which were within a gene identified as a likely viral lysozyme/lysin protein. Analysis of viral metagenome sequences corresponding to this lysozyme/lysin protein revealed several mutations all of which translate into silent or conservative mutations which are unlikely to affect protein function, but may help the virus evade the host CRISPR resistance mechanism. These results demonstrate the varied challenges presented by a natural virus population, and support the notion that the CRISPR/viritope system must be able to adapt quickly to provide host immunity. The ability of metagenomics to track population-level variation in viritope sequences allows for a culture-independent method for evaluating the fast co-evolution of host and viral genomes and its consequence on the structuring of complex microbial communities.

  7. Live imaging provides new insights on dynamic F-actin filopodia and differential endocytosis during myoblast fusion in Drosophila.

    Directory of Open Access Journals (Sweden)

    Shruti Haralalka

    Full Text Available The process of myogenesis includes the recognition, adhesion, and fusion of committed myoblasts into multinucleate syncytia. In the larval body wall muscles of Drosophila, this elaborate process is initiated by Founder Cells and Fusion-Competent Myoblasts (FCMs, and cell adhesion molecules Kin-of-IrreC (Kirre and Sticks-and-stones (Sns on their respective surfaces. The FCMs appear to provide the driving force for fusion, via the assembly of protrusions associated with branched F-actin and the WASp, SCAR and Arp2/3 pathways. In the present study, we utilize the dorsal pharyngeal musculature that forms in the Drosophila embryo as a model to explore myoblast fusion and visualize the fusion process in live embryos. These muscles rely on the same cell types and genes as the body wall muscles, but are amenable to live imaging since they do not undergo extensive morphogenetic movement during formation. Time-lapse imaging with F-actin and membrane markers revealed dynamic FCM-associated actin-enriched protrusions that rapidly extend and retract into the myotube from different sites within the actin focus. Ultrastructural analysis of this actin-enriched area showed that they have two morphologically distinct structures: wider invasions and/or narrow filopodia that contain long linear filaments. Consistent with this, formin Diaphanous (Dia and branched actin nucleator, Arp3, are found decorating the filopodia or enriched at the actin focus, respectively, indicating that linear actin is present along with branched actin at sites of fusion in the FCM. Gain-of-function Dia and loss-of-function Arp3 both lead to fusion defects, a decrease of F-actin foci and prominent filopodia from the FCMs. We also observed differential endocytosis of cell surface components at sites of fusion, with actin reorganizing factors, WASp and SCAR, and Kirre remaining on the myotube surface and Sns preferentially taken up with other membrane proteins into early endosomes and

  8. Closed-flow column experiments—Insights into solute transport provided by a damped oscillating breakthrough behavior

    Science.gov (United States)

    Ritschel, Thomas; Totsche, Kai Uwe

    2016-03-01

    Transport studies that employ column experiments in closed-flow mode complement classical approaches by providing new characteristic features observed in the solute breakthrough and equilibrium between liquid and solid phase. Specific to the closed-flow mode is the recirculation of the effluent to the inflow via a mixing vessel. Depending on the ratio of volumes of mixing vessel and water-filled pore space, a damped oscillating solute concentration emerges in the effluent and mixing vessel. The oscillation characteristics, e.g., frequency, amplitude, and damping, allow for the investigation of solute transport in a similar fashion as known for classical open-flow column experiments. However, the closed loop conserves substances released during transport within the system. In this way, solute and porous medium can equilibrate with respect to physicochemical conditions. With this paper, the features emerging in the breakthrough curves of saturated column experiments run in closed-flow mode and methods of evaluation are illustrated under experimental boundary conditions forcing the appearance of oscillations. We demonstrate that the effective pore water volume and the pumping rate can be determined from a conservative tracer breakthrough curve uniquely. In this way, external preconditioning of the material, e.g., drying, can be avoided. A reactive breakthrough experiment revealed a significant increase in the pore water pH value as a consequence of the closed loop. These results highlight the specific impact of the closed mass balance. Furthermore, the basis for the modeling of closed-flow experiments is given by the derivation of constitutive equations and numerical implementation, validated with the presented experiments.

  9. Quantitative proteomics and bioinformatic analysis provide new insight into the dynamic response of porcine intestine to Salmonella Typhimurium.

    Directory of Open Access Journals (Sweden)

    Melania eCollado-Romero

    2015-09-01

    been established for the first time in pigs. Taken together, our results provide a better understanding of the porcine response to Salmonella infection and the molecular mechanisms underlying Salmonella-host interactions.

  10. De novo Transcriptome Assembly of Phomopsis liquidambari Provides Insights into Genes Associated with Different Lifestyles in Rice (Oryza sativa L.)

    Science.gov (United States)

    Zhou, Jun; Li, Xin; Chen, Yan; Dai, Chuan-Chao

    2017-01-01

    The mechanisms that trigger the switch from endophytic fungi to saprophytic fungi are largely unexplored. Broad host range Phomopsis liquidambari is established in endophytic and saprophytic systems with rice (Oryza sativa L.). Endophytic P. liquidambari promotes rice growth, increasing rice yield and improving the efficiency of nitrogen fertilizer. This species's saprophytic counterpart can decompose rice litterfall, promoting litter organic matter cycling and the release of nutrients and improving the soil microbial environment. Fluorescence microscopy, confocal laser scanning microscopy and quantitative PCR investigated the colonization dynamics and biomass of P. liquidambari in rice in vivo. P. liquidambari formed infection structures similar to phytopathogens with infected vascular tissues that systematically spread to acrial parts. However, different from pathogenic infection, P. liquidambari colonization exhibits space restriction and quantity restriction. Direct comparison of a fungal transcriptome under three different habitats provided a better understanding of lifestyle conversion during plant-fungi interactions. The isolated total RNA of Ck (pure culture), EP (endophytic culture) and FP (saprophytic culture) was subjected to Illumina transcriptome sequencing. To the best of our knowledge, this study is the first to investigate Phomopsis sp. using RNA-seq technology to obtain whole transcriptome information. A total of 27,401,258 raw reads were generated and 22,700 unigenes were annotated. Functional annotation indicated that carbohydrate metabolism and biosynthesis of secondary metabolites played important roles. There were 2522 differentially expressed genes (DEGs) between the saprophytic and endophytic lifestyles. Quantitative PCR analysis validated the DEGs of RNA-seq. Analysis of DEGs between saprophytic and endophytic lifestyles revealed that most genes from amino acids metabolism, carbohydrate metabolism, fatty acid biosynthesis, secondary

  11. Vertical microbial community variability of carbonate-based cones may provide insight into ancient conical stromatolite formation

    Science.gov (United States)

    Bradley, James; Daille, Leslie; Trivedi, Christopher; Bojanowski, Caitlin; Nunn, Heather; Stamps, Blake; Johnson, Hope; Stevenson, Bradley; Berelson, Will; Corsetti, Frank; Spear, John

    2016-04-01

    Stromatolite morphogenesis is poorly understood, and the process by which microbial mats become mineralized is a primary question in microbialite formation. Ancient conical stromatolites are primarily carbonate-based whereas the few modern analogues in hot springs are either non-mineralized or mineralized by silica. A team from the 2015 International GeoBiology Course investigated carbonate-rich microbial cones from near Little Hot Creek (LHC), Long Valley Caldera, California, to investigate how conical stromatolites might form in a hot spring carbonate system. The cones rise up from a layered microbial mat on the east side of a 45° C pool with very low flow that is super-saturated with respect to CaCO3. Cone structures are 8-30 mm in height, are rigid and do not deform when removed from the pool. Morphological characterization through environmental scanning electronic microscopy revealed that the cone structure is maintained by a matrix of intertwining microbial filaments around carbonate grains. This matrix gives rise to cone-filaments that are arranged vertically or horizontally, and provides further stability to the cone. Preliminary 16S rRNA gene analysis indicated variability of community composition between different vertical levels of the cone. The cone tip had comparatively greater abundance of filamentous cyanobacteria including Leptolingbya, Phormidium and Isosphaera and fewer heterotrophs (e.g. Chloroflexi) compared to the cone bottom. This supports the hypothesis that cone formation may depend on the differential abundance of the microbial community and their potential functional roles. Metagenomic analyses of the cones revealed potential genes related to chemotaxis and motility. Specifically, a genomic bin identified as a member of the genus Isosphaera contained an hmp chemotaxis operon implicated in gliding motility in the cyanobacterium Nostoc punctiforme. Isosphaera is a Planctomycete shown to have phototactic capabilities, and may play a role in

  12. Interpersonal communication and contraception: Insights and evidences from Bangladesh demographic and health survey, 2011.

    Science.gov (United States)

    Raut, Manoj Kumar

    2015-01-01

    This paper examines the role of exposure to mass media and interpersonal communication in predicting the current use of contraception in Bangladesh. Bivariate and multivariate analyses were carried out using the Bangladesh Demographic and Health Survey (BDHS), 2011 data to explore the association between communication and the current use of contraception. After adjusting the related socioeconomic and demographic factors, the mass media did not seem to have any role in predicting contraceptive use behavior while the findings revealed that interpersonal communication [prevalence ratio (PR): 1.0984, 95% confidence interval (CI) 1.0801-1.1170] is a strong positive predictor of the current contraceptive use. It is a well-known fact that mass media performs only the knowledge function while interpersonal communication performs an additional function of persuasion. This analysis corroborates the statement that the role of interpersonal communication is quite important in predicting contraceptive use.

  13. Cultural differences in survey responding: Issues and insights in the study of response biases.

    Science.gov (United States)

    Kemmelmeier, Markus

    2016-12-01

    This paper introduces the special section "Cultural differences in questionnaire responding" and discusses central topics in the research on response biases in cross-cultural survey research. Based on current conceptions of acquiescent, extreme, and socially desirable responding, the author considers current data on the correlated nature of response biases and the conditions under which different response styles they emerge. Based on evidence relating different response styles to the cultural dimension of individualism-collectivism, the paper explores how research presented as part of this special section might help resolves some tensions in this literature. The paper concludes by arguing that response styles should not be treated merely as measurement error, but as cultural behaviors in themselves.

  14. Targeting adults who provide alcohol to underage youth: results from a national survey of local law enforcement agencies.

    Science.gov (United States)

    Jones-Webb, Rhonda; Toomey, Traci L; Lenk, Kathleen M; Nelson, Toben F; Erickson, Darin J

    2015-06-01

    We investigated what local enforcement agencies are doing to target adults who provide alcohol to underage youth; what types of enforcement activities are being conducted to target adult providers; and factors that encourage enforcement activities that target adult providers. We surveyed 1,056 local law enforcement agencies in the US and measured whether or not the agency conducted enforcement activities that target adults who provide alcohol to underage youth. We also measured whether certain agency and jurisdiction characteristics were associated with enforcement activities that target adults who provide alcohol to underage youth. Less than half (42%) of local enforcement agencies conducted enforcement efforts targeting adults who provide alcohol to underage youth. Agencies that conducted the enforcement activities targeting adult providers were significantly more likely to have a full time officer specific to alcohol enforcement, a division specific to alcohol enforcement, a social host law, and to perceive underage drinking was very common. Results suggest that targeting social providers (i.e., adults over 21 years of age) will require greater law enforcement resources, implementation of underage drinking laws (e.g., social host policies), and changing perceptions among law enforcement regarding underage drinking. Future studies are needed to identify the most effective enforcement efforts and to examine how enforcement efforts are prospectively linked to alcohol consumption.

  15. Pediatric asthma control in Asia: phase 2 of the Asthma Insights and Reality in Asia-Pacific (AIRIAP 2) survey.

    Science.gov (United States)

    Wong, G W K; Kwon, N; Hong, J G; Hsu, J-Y; Gunasekera, K D

    2013-04-01

    We conducted Phase 2 of the Asthma Insights and Reality in the Asia-Pacific (AIRIAP 2) survey in 2006 to determine the level of asthma control in this region and the validity of the Asthma Control Test (ACT) and childhood ACT (C-ACT) in relation to asthma control. Pediatric participants (0 to Asia. The survey consisted of the AIRIAP 2 questionnaire (asthma symptoms, use of urgent healthcare services and anti-asthma medication) and the ACT or C-ACT (English or Chinese translations only), both administered in the participant's preferred language. A symptom control index based on the Global Initiative for Asthma criteria (except lung function) was used to classify asthma control status. Most participants had inadequately controlled asthma ('uncontrolled' = 53.4%, 528/988; 'partly controlled' = 44.0%, 435/988). Only 2.5% (25/988) had 'controlled' asthma. Demand for urgent healthcare services (51.7%, 511/988) and use of short-acting beta-agonists (55.2%, 545/988) was high. The optimal ACT and C-ACT cutoff score for detecting uncontrolled asthma (compared with controlled or partly controlled asthma) was determined to be ≤19 (receiver operating characteristic analysis) with good agreement between the ACT and C-ACT and the symptom control index. Findings from this survey show that asthma control is suboptimal in many children in the Asia-Pacific region. Practical tools, such as the ACT or C-ACT, may help clinicians assess asthma control and facilitate adjustment of asthma medication. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  16. Cultural adaptation of a survey to assess medical providers' knowledge of and attitudes towards HIV/AIDS in Albania.

    Directory of Open Access Journals (Sweden)

    Shane D Morrison

    Full Text Available Though the HIV/AIDS epidemic in Southeastern Europe is one of low reported prevalence, numerous studies have described the pervasiveness of medical providers' lack of knowledge of HIV/AIDS in the Balkans. This study sought to culturally adapt an instrument to assess medical providers' knowledge of and attitudes towards HIV/AIDS in Albania. Cultural adaptation was completed through development of a survey from previously validated instruments, translation of the survey into Albanian, blinded back translation, expert committee review of the draft instrument, focus group pre-testing with community- and University Hospital Center of Tirana-based physicians and nurses, and test-retest reliability testing. Blinded back translation of the instrument supported the initial translation with slight changes to the idiomatic and conceptual equivalences. Focus group pre-testing generally supported the instrument, yet some experiential and idiomatic changes were implemented. Based on unweighted kappa and/or prevalence adjusted bias adjusted kappa (PABAK, 20 of the 43 questions were deemed statistically significant at kappa and/or PABAK ≥0.5, while 12 others did not cross zero on the 95% confidence interval for kappa, indicating their probable significance. Subsequently, an instrument to assess medical providers' knowledge of and attitudes toward HIV/AIDS for an Albanian population was developed which can be expanded within Albania and potentially to other countries within the Balkans, which have an Albanian-speaking population.

  17. Assessment of the structural validity of the domestic violence healthcare providers' survey questionnaire using a Nigerian sample.

    Science.gov (United States)

    John, Ime Akpan; Lawoko, Stephen

    2010-06-01

    There has been increased advocacy to involve healthcare providers in the prevention of intimate partner violence (IPV) through screening for it in healthcare. Yet, only one in ten providers screen for IPV, suggesting barriers. Understanding the readiness of healthcare providers to screen for IPV is therefore paramount. The Domestic Violence Healthcare Provider Survey Scales (DVHPSS) is a previously validated, comprehensive scale to study readiness of healthcare providers to screen for IPV. However, an understanding of its usefulness in the Sub-Saharan African context remains elusive. The current study undertook to examine the structural validity of the DVHPSS in Nigeria. Exploratory factor analysis and Cronbach's Alpha were run to reveal the factorial structure and reliability of the instrument/subscales respectively. Established thresholds were used to determine significant factor loadings and alphas coefficient. A six factor model emerged, with 2 factors similar to the original scale, another two differing slightly and a further two factors resulting from a splitting up of the original combination of victim/provider safety to having distinct victim and provider safety subscales. With slight modifications, the DVHPSS can be use to study IPV screening among Nigerian healthcare professionals. Introducing screening protocols could promote better understanding of crucial questions that were lost in the analysis. ‎

  18. Patient-provider discussions about lung cancer screening pre- and post-guidelines: Health Information National Trends Survey (HINTS).

    Science.gov (United States)

    Carter-Harris, Lisa; Tan, Andy S L; Salloum, Ramzi G; Young-Wolff, Kelly C

    2016-11-01

    In 2013, the USPSTF issued a Grade B recommendation that long-term current and former smokers receive lung cancer screening. Shared decision-making is important for individuals considering screening, and patient-provider discussions an essential component of the process. We examined prevalence and predictors of lung cancer screening discussions pre- and post-USPSTF guidelines. Data were obtained from two cycles of the Health Information National Trends Survey (2012; 2014). The analyzed sample comprised screening-eligible current and former smokers with no personal history of lung cancer (n=746 in 2012; n=795 in 2014). Descriptive and multiple logistic regression analyses were conducted; patient-reported discussion about lung cancer screening with provider was the outcome of interest. Contrary to expectations, patient-provider discussions about lung cancer screening were more prevalent pre-guideline, but overall patient-provider discussions were low in both years (17% in 2012; 10% in 2014). Current smokers were more likely to have had a discussion than former smokers. Significant predictors of patient-provider discussions included family history of cancer and having healthcare coverage. The prevalence of patient-provider discussions about lung cancer screening is suboptimal. There is a critical need for patient and provider education about shared decision-making and its importance in cancer screening decisions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Insights on the stellar mass-metallicity relation from the CALIFA survey

    CERN Document Server

    Delgado, R M González; García-Benito, R; Pérez, E; de Amorim, A L; Cortijo-Ferrero, C; Lacerda, E A D; Fernández, R López; Sánchez, S F; Asari, N Vale; Alves, J; Bland-Hawthorn, J; Galbany, L; Gallazzi, A; Husemann, B; Bekeraite, S; Jungwiert, B; López-Sánchez, A R; de Lorenzo-Cáceres, A; Marino, R A; Mast, D; Mollá, M; del Olmo, A; Sánchez-Blázquez, P; van de Ven, G; Vílchez, J M; Walcher, C J; Wisotzki, L; Ziegler, B

    2014-01-01

    We use spatially and temporally resolved maps of stellar population properties of 300 galaxies from the CALIFA integral field survey to investigate how the stellar metallicity (Z*) relates to the total stellar mass (M*) and the local mass surface density ($\\mu$*) in both spheroidal and disk dominated galaxies. The galaxies are shown to follow a clear stellar mass-metallicity relation (MZR) over the whole 10$^9$ to 10$^{12}$ M$_{\\odot}$ range. This relation is steeper than the one derived from nebular abundances, which is similar to the flatter stellar MZR derived when we consider only young stars. We also find a strong relation between the local values of $\\mu$* and Z* (the $\\mu$ZR), betraying the influence of local factors in determining Z*. This shows that both local ($\\mu$*-driven) and global (M*-driven) processes are important in determining the metallicity in galaxies. We find that the overall balance between local and global effects varies with the location within a galaxy. In disks, $\\mu$* regulates Z*...

  20. New insights from high resolution bathymetric surveys in the Panarea volcanic complex (Aeolian Islands, Italy)

    Science.gov (United States)

    Anzidei, M.; Esposito, A.

    2003-04-01

    During November 2002 the portion of the Panarea volcanic complex (Aeolian Islands, Italy), which includes the islets of Dattilo, Panarelli, Lisca Bianca, Bottaro and Lisca Nera, experienced an intense submarine gaseous exhalation that produced a spectacular submarine fumarolic field. The submarine volcanic activity of the Aeolian area was already known during historical times by Tito Livio, Strabone and Plinio (SGA, 1996), that reported exhalation episodes and submarine eruptions. During the last decade geological, structural, geochemical and volcanological studies performed on the Panarea volcanic complex, evidenced a positive gravimetric anomaly, tectonic discontinuities and several centres of geothermal fluid emission (Barberi et al., 1974; Lanzafame and Rossi, 1984; Bellia et al., 1986; Gabianelli et al., 1990; Italiano and Nuccio, 1991; Calanchi et al., 1995,1999). With the aim to estimate the crustal deformation of the submarine area of the archipelago, connected with the exhalation activity, we produced a detailed Marine Digital Terrain Model (MDTM) of the seafloor by means of a high resolution bathymetric survey. We used the multi beam technique coupled with GPS positioning in RTK mode. We obtained a MDTM with an average pixel of 0.5 m. Our MDTM allowed to estimate the location, deep, shape and size of the exhalation centres and seafloor morphological-structural features, opening new questions for the evaluation of the volcanic hazard of Panarea area which date is still debated.

  1. The Gaia-ESO Survey: Insights on the inner-disc evolution from open clusters

    CERN Document Server

    Magrini, L; Donati, P; Bragaglia, A; Adibekyan, V; Romano, D; Smiljanic, R; Blanco-Cuaresma, S; Tautvaisiene, G; Friel, E; Overbeek, J; Jacobson, H; Cantat-Gaudin, T; Vallenari, A; Sordo, R; Pancino, E; Geisler, D; Roman, I San; Villanova, S; Casey, A; Hourihane, A; Worley, C C; Francois, P; Gilmore, G; Bensby, T; Flaccomio, E; Korn, A J; Recio-Blanco, A; Carraro, G; Costado, M T; Franciosini, E; Heiter, U; Jofree, P; Lardo, C; de Laverny, P; Monaco, L; Morbidelli, L; Sacco, G; Sousa, S G; Zaggia, S

    2015-01-01

    Context. The inner disc, linking the thin disc with the bulge, has been somehow neglected in the past because of intrinsic difficulties in its study, due, e.g., to crowding and high extinction. Open clusters located in the inner disc are among the best tracers of its chemistry at different ages and distances. Aims. We analyse the chemical patterns of four open clusters located within 7 kpc of the Galactic Centre and of field stars to infer the properties of the inner disc with the Gaia-ESO survey idr2/3 data release. Methods. We derive the parameters of the newly observed cluster, Berkeley 81, finding an age of about 1 Gyr and a Galactocentric distance of 5.4 kpc. We construct the chemical patterns of clusters and we compare them with those of field stars in the Solar neighbourhood and in the inner-disc samples. Results. Comparing the three populations we observe that inner-disc clusters and field stars are both, on average, enhanced in [O/Fe], [Mg/Fe] and [Si/Fe]. Using the idr2/3 results of M67, we estimate...

  2. Achieving Better Integration in Trauma Care Delivery in India: Insights from a Patient Survey

    DEFF Research Database (Denmark)

    Prætorius, Thim; Chaudhuri, Atanu; Venkataramanaiah, S

    2018-01-01

    impact on patient health. But, there is limited understanding about how coordination takes place across and within the different health care service providers and how this influence hospital transfer time and length of stay. This article addresses this gap in literature by studying trauma care delivery...

  3. Large-scale malaria survey in Cambodia: Novel insights on species distribution and risk factors

    Directory of Open Access Journals (Sweden)

    Doung Socheat

    2007-03-01

    Full Text Available Abstract Background In Cambodia, estimates of the malaria burden rely on a public health information system that does not record cases occurring among remote populations, neither malaria cases treated in the private sector nor asymptomatic carriers. A global estimate of the current malaria situation and associated risk factors is, therefore, still lacking. Methods A large cross-sectional survey was carried out in three areas of multidrug resistant malaria in Cambodia, enrolling 11,652 individuals. Fever and splenomegaly were recorded. Malaria prevalence, parasite densities and spatial distribution of infection were determined to identify parasitological profiles and the associated risk factors useful for improving malaria control programmes in the country. Results Malaria prevalence was 3.0%, 7.0% and 12.3% in Sampovloun, Koh Kong and Preah Vihear areas. Prevalences and Plasmodium species were heterogeneously distributed, with higher Plasmodium vivax rates in areas of low transmission. Malaria-attributable fevers accounted only for 10–33% of malaria cases, and 23–33% of parasite carriers were febrile. Multivariate multilevel regression analysis identified adults and males, mostly involved in forest activities, as high risk groups in Sampovloun, with additional risks for children in forest-fringe villages in the other areas along with an increased risk with distance from health facilities. Conclusion These observations point to a more complex malaria situation than suspected from official reports. A large asymptomatic reservoir was observed. The rates of P. vivax infections were higher than recorded in several areas. In remote areas, malaria prevalence was high. This indicates that additional health facilities should be implemented in areas at higher risk, such as remote rural and forested parts of the country, which are not adequately served by health services. Precise malaria risk mapping all over the country is needed to assess the

  4. INSIGHTS ON THE STELLAR MASS-METALLICITY RELATION FROM THE CALIFA SURVEY

    Energy Technology Data Exchange (ETDEWEB)

    González Delgado, R. M.; García-Benito, R.; Pérez, E.; Cortijo-Ferrero, C.; López Fernández, R.; Sánchez, S. F. [Instituto de Astrofísica de Andalucía (CSIC), Glorieta de la Astronomía s/n, E-18008 Granada (Spain); Cid Fernandes, R.; De Amorim, A. L.; Lacerda, E. A. D.; Vale Asari, N. [Departamento de Física, Universidade Federal de Santa Catarina, P.O. Box 476, 88040-900 Florianópolis, SC (Brazil); Alves, J. [University of Vienna, Türkenschanzstrasse 17, A-1180 Vienna (Austria); Bland-Hawthorn, J. [Sydney Institute for Astronomy, The University of Sydney, NSW 2006 (Australia); Galbany, L. [Millennium Institute of Astrophysics and Departamento de Astronomía, Universidad de Chile, Casilla 36-D, Santiago (Chile); Gallazzi, A. [INAF—Osservatorio Astrofisico di Arcetri, Largo Enrico Fermi 5, I-50125 Firenze (Italy); Husemann, B. [European Southern Observatory, Karl-Schwarzschild-Strasse 2, D-85748 Garching b. München (Germany); Bekeraite, S. [Leibniz-Institut für Astrophysik Potsdam, An der Sternwarte 16, D-14482 Potsdam (Germany); Jungwiert, B. [Astronomical Institute of the Academy of Sciences of the Czech Republic, v.v.i., Bocni II 1401, 14131 Prague (Czech Republic); López-Sánchez, A. R. [Australian Astronomical Observatory, P.O. Box 915, North Ryde, NSW 1670 (Australia); De Lorenzo-Cáceres, A. [School of Physics and Astronomy, University of St. Andrews, North Haugh, St. Andrews, KY16 9SS (United Kingdom); Marino, R. A. [CEI Campus Moncloa, UCM-UPM, Departamento de Astrofísica y CC. de la Atmósfera, Facultad de CC. Físicas, Universidad Complutense de Madrid, Avda. Complutense s/n, E-28040 Madrid (Spain); Collaboration: CALIFA collaboration920; and others

    2014-08-10

    We use spatially and temporally resolved maps of stellar population properties of 300 galaxies from the CALIFA integral field survey to investigate how the stellar metallicity (Z {sub *}) relates to the total stellar mass (M {sub *}) and the local mass surface density (μ{sub *}) in both spheroidal- and disk-dominated galaxies. The galaxies are shown to follow a clear stellar mass-metallicity relation (MZR) over the whole 10{sup 9}-10{sup 12} M {sub ☉} range. This relation is steeper than the one derived from nebular abundances, which is similar to the flatter stellar MZR derived when we consider only young stars. We also find a strong relation between the local values of μ{sub *} and Z {sub *} (the μZR), betraying the influence of local factors in determining Z {sub *}. This shows that both local (μ{sub *}-driven) and global (M {sub *}-driven) processes are important in determining metallicity in galaxies. We find that the overall balance between local and global effects varies with the location within a galaxy. In disks, μ{sub *} regulates Z {sub *}, producing a strong μZR whose amplitude is modulated by M {sub *}. In spheroids it is M {sub *} that dominates the physics of star formation and chemical enrichment, with μ{sub *} playing a minor, secondary role. These findings agree with our previous analysis of the star formation histories of CALIFA galaxies, which showed that mean stellar ages are mainly governed by surface density in galaxy disks and by total mass in spheroids.

  5. Results from an online survey investigating ED patients' insights and treatment expectations.

    Science.gov (United States)

    Burri, A; Porst, H

    2015-01-01

    Data suggest that the currently available therapies for erectile dysfunction (ED) do not meet all the patients' and their partners' expectations. The aim was to assess ED patients' treatment expectations for a variety of sex- and drug-related aspects such as importance of spontaneity, partner satisfaction, ideal onset of action and ideal duration of action. A total of n=1124 men with ED and n=410 healthy men, aged 30-75, participated in this online survey. The ED sample was further divided into patients currently undergoing treatment (CTG), patients who had been undergoing treatment in the past (PTG) and naïve patients (NG). The International Index of Erectile Function as well as a mix of study-specific questions was used. All groups considered 'maintaining an erection until the partner reaches orgasm' the most important aspect regarding erectile function. 'Being able to please the partner' was considered as the most important aspect for a fulfilled sex life. The majority of men (38.1%) further considered an onset of action of about 15 min to be desirable. In all, 95.9% further considered a duration of action up to 4 h to be desirable whereas approximately 71% of men considered a duration of more than 12 h to be too long. It seems that once the basic functional aspects related to erectile function have been covered, additional benefits such as 'spontaneity' and 'pleasing the partner' become important and may be critical for choosing the optimum individual treatment, to improve the sexual satisfaction and the adherence to the treatment.

  6. Large-scale malaria survey in Cambodia: novel insights on species distribution and risk factors.

    Science.gov (United States)

    Incardona, Sandra; Vong, Sirenda; Chiv, Lim; Lim, Pharath; Nhem, Sina; Sem, Rithy; Khim, Nimol; Doung, Socheat; Mercereau-Puijalon, Odile; Fandeur, Thierry

    2007-03-27

    In Cambodia, estimates of the malaria burden rely on a public health information system that does not record cases occurring among remote populations, neither malaria cases treated in the private sector nor asymptomatic carriers. A global estimate of the current malaria situation and associated risk factors is, therefore, still lacking. A large cross-sectional survey was carried out in three areas of multidrug resistant malaria in Cambodia, enrolling 11,652 individuals. Fever and splenomegaly were recorded. Malaria prevalence, parasite densities and spatial distribution of infection were determined to identify parasitological profiles and the associated risk factors useful for improving malaria control programmes in the country. Malaria prevalence was 3.0%, 7.0% and 12.3% in Sampovloun, Koh Kong and Preah Vihear areas. Prevalences and Plasmodium species were heterogeneously distributed, with higher Plasmodium vivax rates in areas of low transmission. Malaria-attributable fevers accounted only for 10-33% of malaria cases, and 23-33% of parasite carriers were febrile. Multivariate multilevel regression analysis identified adults and males, mostly involved in forest activities, as high risk groups in Sampovloun, with additional risks for children in forest-fringe villages in the other areas along with an increased risk with distance from health facilities. These observations point to a more complex malaria situation than suspected from official reports. A large asymptomatic reservoir was observed. The rates of P. vivax infections were higher than recorded in several areas. In remote areas, malaria prevalence was high. This indicates that additional health facilities should be implemented in areas at higher risk, such as remote rural and forested parts of the country, which are not adequately served by health services. Precise malaria risk mapping all over the country is needed to assess the extensive geographical heterogeneity of malaria endemicity and risk

  7. Deglycosylating enzymes acting on N-glycans in fungi: Insights from a genome survey.

    Science.gov (United States)

    Tzelepis, Georgios; Karlsson, Magnus; Suzuki, Tadashi

    2017-11-01

    N-Glycosylation, one of the most prominent post-translational modifications of proteins, is found in all domains of life, i.e. eukaryotes, bacteria and archaea, and has been shown to play a crucial role in modulating the physicochemical/physiological properties of carrier proteins. Deglycosylating enzymes that act on N-glycans are widely used in analyzing the structures/functions of N-glycans. Fungi are known to produce various deglycosylating enzymes, some of which are fungi-specific. While such enzymes likely are biologically relevant in fungal biology, their properties as well as their functions have not been explored in detail. In this review, we summarize the current knowledge of fungal deglycosylating enzymes and discuss their biological significance. As of this writing, five types of deglycosylating enzymes that act on N-glycans are known to occur in fungi; (1) the cytosolic peptide: N-glycanase (PNGase), (2) the acidic PNGase, (3) the glycoside hydrolase family (GH) 85 endo-β-N-acetylglucosaminidase (ENGase), (4) the GH18 cytosolic ENGase, and (5) the GH18 secreted ENGase. Interestingly, genome surveys indicate that the loss of cytosolic PNGase activity in certain fungi coincide with the occurrence of GH18 cytosolic ENGase, implying that the GH18 ENGase serves to replace the deglycosylation function of the cytosolic PNGase in those filamentous ascomycete fungi. Our review concludes that fungi promise to be valuable organisms for developing an understanding of the biological functions of PNGases/ENGases. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Assessing the ability of sequence-based methods to provide functional insight within membrane integral proteins: a case study analyzing the neurotransmitter/Na+ symporter family

    Directory of Open Access Journals (Sweden)

    Eskandari Sepehr

    2007-10-01

    Full Text Available Abstract Background Efforts to predict functional sites from globular proteins is increasingly common; however, the most successful of these methods generally require structural insight. Unfortunately, despite several recent technological advances, structural coverage of membrane integral proteins continues to be sparse. ConSequently, sequence-based methods represent an important alternative to illuminate functional roles. In this report, we critically examine the ability of several computational methods to provide functional insight within two specific areas. First, can phylogenomic methods accurately describe the functional diversity across a membrane integral protein family? And second, can sequence-based strategies accurately predict key functional sites? Due to the presence of a recently solved structure and a vast amount of experimental mutagenesis data, the neurotransmitter/Na+ symporter (NSS family is an ideal model system to assess the quality of our predictions. Results The raw NSS sequence dataset contains 181 sequences, which have been aligned by various methods. The resultant phylogenetic trees always contain six major subfamilies are consistent with the functional diversity across the family. Moreover, in well-represented subfamilies, phylogenetic clustering recapitulates several nuanced functional distinctions. Functional sites are predicted using six different methods (phylogenetic motifs, two methods that identify subfamily-specific positions, and three different conservation scores. A canonical set of 34 functional sites identified by Yamashita et al. within the recently solved LeuTAa structure is used to assess the quality of the predictions, most of which are predicted by the bioinformatic methods. Remarkably, the importance of these sites is largely confirmed by experimental mutagenesis. Furthermore, the collective set of functional site predictions qualitatively clusters along the proposed transport pathway, further

  9. National indicators of health literacy: ability to understand health information and to engage actively with healthcare providers - a population-based survey among Danish adults.

    Science.gov (United States)

    Bo, Anne; Friis, Karina; Osborne, Richard H; Maindal, Helle Terkildsen

    2014-10-22

    Health literacy is a multidimensional concept covering a range of cognitive and social skills necessary for participation in health care. Knowledge of health literacy levels in general populations and how health literacy levels impacts on social health inequity is lacking. The primary aim of this study was to perform a population-based assessment of dimensions of health literacy related to understanding health information and to engaging with healthcare providers. Secondly, the aim was to examine associations between socio-economic characteristics with these dimensions of health literacy. A population-based survey was conducted between January and April 2013 in the Central Denmark Region. Postal invitations were sent to a random sample of 46,354 individuals >25 years of age. Two health literacy dimensions were selected from the Health Literacy Questionnaire (HLQ™): i) Understanding health information well enough to know what to do (5 items), and ii) Ability to actively engage with health care providers (5 items). Response options ranged from 1 (very difficult) to 4 (very easy). We investigated the level of perceived difficulty of each task, and the associations between the two dimensions and socio-economic characteristics. A total of 29,473 (63.6%) responded to the survey. Between 8.8%, 95% CI: 8.4-9.2 and 20.2%, 95% CI: 19.6-20.8 of the general population perceived the health literacy tasks as difficult or very difficult at the individual item level. On the scale level, the mean rating for i) understanding health information was 3.10, 95% CI: 3.09-3.10, and 3.07, 95% CI: 3.07-3.08 for ii) engagement with health care providers. Low levels of the two dimensions were associated with low income, low education level, living alone, and to non-Danish ethnicity. Associations with sex and age differed by the specific health literacy dimension. Estimates on two key dimensions of health literacy in a general population are now available. A substantial proportion of the

  10. Barriers to rural induced abortion services in Canada: findings of the British Columbia Abortion Providers Survey (BCAPS.

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    Wendy V Norman

    Full Text Available BACKGROUND: Rural induced abortion service has declined in Canada. Factors influencing abortion provision by rural physicians are unknown. This study assessed distribution, practice, and experiences among rural compared to urban abortion providers in the Canadian province of British Columbia (BC. METHODS: We used mixed methods to assess physicians on the BC registry of abortion providers. In 2011 we distributed a previously-published questionnaire and conducted semi-structured interviews. RESULTS: Surveys were returned by 39/46 (85% of BC abortion providers. Half were family physicians, within both rural and urban cohorts. One-quarter (17/67 of rural hospitals offer abortion service. Medical abortions comprised 14.7% of total reported abortions. The three largest urban areas reported 90% of all abortions, although only 57% of reproductive age women reside in the associated health authority regions. Each rural physician provided on average 76 (SD 52 abortions annually, including 35 (SD 30 medical abortions. Rural physicians provided surgical abortions in operating rooms, often using general anaesthesia, while urban physicians provided the same services primarily in ambulatory settings using local anaesthesia. Rural providers reported health system barriers, particularly relating to operating room logistics. Urban providers reported occasional anonymous harassment and violence. CONCLUSIONS: Medical abortions represented 15% of all BC abortions, a larger proportion than previously reported (under 4% for Canada. Rural physicians describe addressable barriers to service provision that may explain the declining accessibility of rural abortion services. Moving rural surgical abortions out of operating rooms and into local ambulatory care settings has the potential to improve care and costs, while reducing logistical challenges facing rural physicians.

  11. Barriers to rural induced abortion services in Canada: findings of the British Columbia Abortion Providers Survey (BCAPS).

    Science.gov (United States)

    Norman, Wendy V; Soon, Judith A; Maughn, Nanamma; Dressler, Jennifer

    2013-01-01

    Rural induced abortion service has declined in Canada. Factors influencing abortion provision by rural physicians are unknown. This study assessed distribution, practice, and experiences among rural compared to urban abortion providers in the Canadian province of British Columbia (BC). We used mixed methods to assess physicians on the BC registry of abortion providers. In 2011 we distributed a previously-published questionnaire and conducted semi-structured interviews. Surveys were returned by 39/46 (85%) of BC abortion providers. Half were family physicians, within both rural and urban cohorts. One-quarter (17/67) of rural hospitals offer abortion service. Medical abortions comprised 14.7% of total reported abortions. The three largest urban areas reported 90% of all abortions, although only 57% of reproductive age women reside in the associated health authority regions. Each rural physician provided on average 76 (SD 52) abortions annually, including 35 (SD 30) medical abortions. Rural physicians provided surgical abortions in operating rooms, often using general anaesthesia, while urban physicians provided the same services primarily in ambulatory settings using local anaesthesia. Rural providers reported health system barriers, particularly relating to operating room logistics. Urban providers reported occasional anonymous harassment and violence. Medical abortions represented 15% of all BC abortions, a larger proportion than previously reported (under 4%) for Canada. Rural physicians describe addressable barriers to service provision that may explain the declining accessibility of rural abortion services. Moving rural surgical abortions out of operating rooms and into local ambulatory care settings has the potential to improve care and costs, while reducing logistical challenges facing rural physicians.

  12. Barriers to Rural Induced Abortion Services in Canada: Findings of the British Columbia Abortion Providers Survey (BCAPS)

    Science.gov (United States)

    Norman, Wendy V.; Soon, Judith A.; Maughn, Nanamma; Dressler, Jennifer

    2013-01-01

    Background Rural induced abortion service has declined in Canada. Factors influencing abortion provision by rural physicians are unknown. This study assessed distribution, practice, and experiences among rural compared to urban abortion providers in the Canadian province of British Columbia (BC). Methods We used mixed methods to assess physicians on the BC registry of abortion providers. In 2011 we distributed a previously-published questionnaire and conducted semi-structured interviews. Results Surveys were returned by 39/46 (85%) of BC abortion providers. Half were family physicians, within both rural and urban cohorts. One-quarter (17/67) of rural hospitals offer abortion service. Medical abortions comprised 14.7% of total reported abortions. The three largest urban areas reported 90% of all abortions, although only 57% of reproductive age women reside in the associated health authority regions. Each rural physician provided on average 76 (SD 52) abortions annually, including 35 (SD 30) medical abortions. Rural physicians provided surgical abortions in operating rooms, often using general anaesthesia, while urban physicians provided the same services primarily in ambulatory settings using local anaesthesia. Rural providers reported health system barriers, particularly relating to operating room logistics. Urban providers reported occasional anonymous harassment and violence. Conclusions Medical abortions represented 15% of all BC abortions, a larger proportion than previously reported (under 4%) for Canada. Rural physicians describe addressable barriers to service provision that may explain the declining accessibility of rural abortion services. Moving rural surgical abortions out of operating rooms and into local ambulatory care settings has the potential to improve care and costs, while reducing logistical challenges facing rural physicians. PMID:23840578

  13. Integrative Tissue-Specific Functional Annotations in the Human Genome Provide Novel Insights on Many Complex Traits and Improve Signal Prioritization in Genome Wide Association Studies.

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    Qiongshi Lu

    2016-04-01

    Full Text Available Extensive efforts have been made to understand genomic function through both experimental and computational approaches, yet proper annotation still remains challenging, especially in non-coding regions. In this manuscript, we introduce GenoSkyline, an unsupervised learning framework to predict tissue-specific functional regions through integrating high-throughput epigenetic annotations. GenoSkyline successfully identified a variety of non-coding regulatory machinery including enhancers, regulatory miRNA, and hypomethylated transposable elements in extensive case studies. Integrative analysis of GenoSkyline annotations and results from genome-wide association studies (GWAS led to novel biological insights on the etiologies of a number of human complex traits. We also explored using tissue-specific functional annotations to prioritize GWAS signals and predict relevant tissue types for each risk locus. Brain and blood-specific annotations led to better prioritization performance for schizophrenia than standard GWAS p-values and non-tissue-specific annotations. As for coronary artery disease, heart-specific functional regions was highly enriched of GWAS signals, but previously identified risk loci were found to be most functional in other tissues, suggesting a substantial proportion of still undetected heart-related loci. In summary, GenoSkyline annotations can guide genetic studies at multiple resolutions and provide valuable insights in understanding complex diseases. GenoSkyline is available at http://genocanyon.med.yale.edu/GenoSkyline.

  14. Transcriptomes and expression profiling of deep-sea corals from the Red Sea provide insight into the biology of azooxanthellate corals

    KAUST Repository

    Yum, Lauren K.

    2017-07-19

    Despite the importance of deep-sea corals, our current understanding of their ecology and evolution is limited due to difficulties in sampling and studying deep-sea environments. Moreover, a recent re-evaluation of habitat limitations has been suggested after characterization of deep-sea corals in the Red Sea, where they live at temperatures of above 20 °C at low oxygen concentrations. To gain further insight into the biology of deep-sea corals, we produced reference transcriptomes and studied gene expression of three deep-sea coral species from the Red Sea, i.e. Dendrophyllia sp., Eguchipsammia fistula, and Rhizotrochus typus. Our analyses suggest that deep-sea coral employ mitochondrial hypometabolism and anaerobic glycolysis to manage low oxygen conditions present in the Red Sea. Notably, we found expression of genes related to surface cilia motion that presumably enhance small particle transport rates in the oligotrophic deep-sea environment. This is the first study to characterize transcriptomes and in situ gene expression for deep-sea corals. Our work offers several mechanisms by which deep-sea corals might cope with the distinct environmental conditions present in the Red Sea As such, our data provide direction for future research and further insight to organismal response of deep-sea coral to environmental change and ocean warming.

  15. DNA from bird-dispersed seed and wind-disseminated pollen provides insights into postglacial colonization and population genetic structure of whitebark pine (Pinus albicaulis).

    Science.gov (United States)

    Richardson, B A; Brunsfeld, S J; Klopfenstein, N B

    2002-02-01

    Uniparentally inherited mitochondrial (mt)DNA and chloroplast (cp)DNA microsatellites (cpSSRs) were used to examine population genetic structure and biogeographic patterns of bird-dispersed seed and wind-disseminated pollen of whitebark pine (Pinus albicaulis Engelm.). Sampling was conducted from 41 populations throughout the range of the species. Analyses provide evidence for an ancestral haplotype and two derived mtDNA haplotypes with distinct regional distributions. An abrupt contact zone between mtDNA haplotypes in the Cascade Range suggests postglacial biogeographic movements. Among three cpSSR loci, 42 haplotypes were detected within 28 cpSSR sample populations that were aggregated into six regions. Analysis of molecular variance (amova) was used to determine the hierarchical genetic structure of cpSSRs. amova and population pairwise comparisons (FST ) of cpSSR, and geographical distribution of mtDNA haplotypes provide insights into historical changes in biogeography. The genetic data suggest that whitebark pine has been intimately tied to climatic change and associated glaciation, which has led to range movements facilitated by seed dispersal by Clark's nutcracker (Nucifraga columbiana Wilson). The two hypotheses proposed to explain the genetic structure are: (i) a northward expansion into Canada and the northern Cascades in the early Holocene; and (ii) historical gene flow between Idaho and the Oregon Cascades when more continuous habitat existed in Central Oregon during the late Pleistocene. Genetic structure and insights gained from historical seed movements provide a basis on which to develop recovery plans for a species that is at risk from multiple threats.

  16. Proteome of Plasmopara viticola-infected Vitis vinifera provides insights into grapevine Rpv1/Rpv3 pyramided resistance to downy mildew.

    Science.gov (United States)

    Nascimento-Gavioli, Maria Carolina Andrade; Agapito-Tenfen, Sarah Zanon; Nodari, Rubens Onofre; Welter, Leocir José; Sanchez Mora, Fernando David; Saifert, Luciano; da Silva, Aparecido Lima; Guerra, Miguel Pedro

    2017-01-16

    Grapevine is one of the major fruit crops worldwide and requires phytochemical use due to susceptibility to numerous pests, including downy mildew. The pyramiding of previous identified QTL resistance regions allows selection of genotypes with combined resistance loci in order to build up sustainable resistance. This study investigates resistance response of pyramided plants containing Rpv1 and Rpv3 loci to Plasmopara viticola infection process. Phenotypic characterization showed complete resistance and lack of necrotic hypersensitive response spots. Principal Component Analysis revealed infected 96hpi (hours post-inoculation) samples with the most distant proteomes of the entire dataset, followed by the proteome of infected 48hpi samples. Quantitative and qualitative protein differences observed using 2-DE gels coupled to nanoHPLC-ESI-MS/MS analysis showed a lack of transient breakdown in defense responses (biphasic modulation) accompanying the onset of disease. Forty-one proteins were identified, which were mainly included into functional categories of redox and energy metabolism. l-ascorbate degradation pathway was the major altered pathway and suggests up-regulation of anti-oxidant metabolism in response to apoplastic oxidative burst after infection. Overall, these data provide new insights into molecular basis of this incompatible interaction and suggests several targets that could potentially be exploited to develop new protection strategies against this pathogen. This study provide new insights into the molecular basis of incompatible interaction between Plasmopara viticola and pyramided Rpv1/Rpv3 grapevine and suggests several targets that could potentially be exploited to develop new protection strategies against this pathogen. This is the first proteomic characterization of resistant grapevine available in the literature and it presents contrasting proteomic profiles of that of susceptible plants. The resistance against downy mildew in grapevine has been

  17. A novel approach for multi-domain and multi-gene family identification provides insights into evolutionary dynamics of disease resistance genes in core eudicot plants.

    Science.gov (United States)

    Hofberger, Johannes A; Zhou, Beifei; Tang, Haibao; Jones, Jonathan D G; Schranz, M Eric

    2014-11-08

    Recent advances in DNA sequencing techniques resulted in more than forty sequenced plant genomes representing a diverse set of taxa of agricultural, energy, medicinal and ecological importance. However, gene family curation is often only inferred from DNA sequence homology and lacks insights into evolutionary processes contributing to gene family dynamics. In a comparative genomics framework, we integrated multiple lines of evidence provided by gene synteny, sequence homology and protein-based Hidden Markov Modelling to extract homologous super-clusters composed of multi-domain resistance (R)-proteins of the NB-LRR type (for NUCLEOTIDE BINDING/LEUCINE-RICH REPEATS), that are involved in plant innate immunity. To assess the diversity of R-proteins within and between species, we screened twelve eudicot plant genomes including six major crops and found a total of 2,363 NB-LRR genes. Our curated R-proteins set shows a 50% average for tandem duplicates and a 22% fraction of gene copies retained from ancient polyploidy events (ohnologs). We provide evidence for strong positive selection and show significant differences in molecular evolution rates (Ka/Ks-ratio) among tandem- (mean = 1.59), ohnolog (mean = 1.36) and singleton (mean = 1.22) R-gene duplicates. To foster the process of gene-edited plant breeding, we report species-specific presence/absence of all 140 NB-LRR genes present in the model plant Arabidopsis and describe four distinct clusters of NB-LRR "gatekeeper" loci sharing syntenic orthologs across all analyzed genomes. By curating a near-complete set of multi-domain R-protein clusters in an eudicot-wide scale, our analysis offers significant insight into evolutionary dynamics underlying diversification of the plant innate immune system. Furthermore, our methods provide a blueprint for future efforts to identify and more rapidly clone functional NB-LRR genes from any plant species.

  18. Is Sugar the new Tobacco? Insights from Laboratory Studies, Consumer Surveys and Public Health.

    Science.gov (United States)

    Le Bodo, Yann; Paquette, Marie-Claude; Vallières, Maggie; Alméras, Natalie

    2015-03-01

    In the Americas, mean energy intake from added sugar exceeds recent World Health Organization recommendations for free sugars in the diet. As a leading contributor to this excess, sugar-sweetened beverage (SSB) overconsumption represents a risk for the population's health. This article provides an overview of clinical and epidemiological evidence, marketing practices, corporate influence and prevention strategies related to added sugar and SSB. For each aspect of this multidimensional profile, we briefly compare SSB to the case of tobacco pointing to similarities but also major differences. Tobacco control has demonstrated the effectiveness of long term multifaceted prevention strategies in multiple settings supported by strong public policies which may be applied to the consumption of SSB. However, translating these policies to the specific case of SSB is urgently needed, to inform preventive actions, decide which intervention mix will be used, and evaluate the process and impact of the chosen strategy.

  19. Current Practices in Home Management of Nasogastric Tube Placement in Pediatric Patients: A Survey of Parents and Homecare Providers.

    Science.gov (United States)

    Northington, LaDonna; Lyman, Beth; Guenter, Peggi; Irving, Sharon Y; Duesing, Lori

    Enteral feeding tubes are used in pediatric patients to deliver nutrition, fluids or medications. The literature related to short-term feeding tube (nasogastric [NG], hereafter known as NGT, or orogastric [OGT],) use in pediatric homecare patients is sparse. This descriptive study sought to gather baseline information about these children and how their feeding tubes are managed at home. Specifically, we sought to better understand how the tubes are placed and the method(s) used for tube placement verification. Two surveys were distributed: one to parents and one to homecare providers who have direct patient contact. Responses were obtained from 144 parents and 66 homecare providers. Over half of the children were 12months of age or younger and had a 6 Fr feeding tube. Over 75% (108) had an NGT for 1year or less. Predominantly parents replaced the NGT but a few children self-inserted their tubes. Feeding tube placement was verified by auscultation (44%) or measurement of gastric pH (25%) in the parent's survey. Twenty-six percent of parents indicated they had misplaced an NGT at least once and 35 parents described symptoms of pulmonary misplacement. The homecare provider data indicated auscultation (39%) and pH measurement of gastric contents (28%) to verify NG tube placement location. Study results confirms a need for consistency of practice among health care professionals and in parent education for those children who require NGTs at home. It is troubling that auscultation is still widely used for NGT location confirmation despite practice alerts that warn against its use. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Attitudes, skill and use of evidence-based practice among US Western herbal medicine providers: a national survey.

    Science.gov (United States)

    Snow, James E; Leach, Matthew J; Clare, Bevin A

    2017-03-01

    Background Evidence-based practice (EBP) has been the focus of increasing attention in the teaching and delivery of both complementary and conventional healthcare. Western herbal medicine (WHM) is a system of complementary healthcare rooted in tradition. How WHM practitioners perceive, are prepared for, and use EBP, has to date been largely ignored. We therefore examined the use, opinion, skills, and training in EBP, and barriers and facilitators of EBP uptake, among herbal practitioners in the United States (US). Methods The study utilized a cross-sectional, descriptive survey design. A sample of US clinical herbalists was invited to complete a validated online questionnaire, the Evidence-Based practice Attitude and utilization SurvEy (EBASE). Results Seventy-four US herbal practitioners completed the survey (response rate=35 %). Participants demonstrated a generally positive attitude toward EBP (median attitude subscore 31 [possible range=8-40]), a moderate to high level of self-assessed skill in EBP (median skill subscore 46 [13-65]) and a moderate level of EBP uptake (median use subscore 12 [0-24]). Apart from a lack of clinical evidence in herbal medicine, there were few perceived barriers to EBP uptake among herbal practitioners. Access to the Internet, online databases and full-text journal articles were considered most useful in facilitating the uptake of EBP in WHM practice. Conclusions Respondents' attitudes, skill level, and uptake of EBP were generally consistent with other complementary and alternative medicine providers. Educational initiatives, including those focused on the appraisal and application of evidence, may help to optimize the use of EBP among WHM practitioners.

  1. Role of private sector in providing tuberculosis care: Evidence from a population-based survey in India

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    Indrajit Hazarika

    2011-01-01

    Full Text Available Background: In India, a large segment of the population seeks health care services from individual or institutional private health-care providers for health care. We analyzed a nationally representative data to identify the role of private providers in delivering health care for patients with tuberculosis. Materials and Methods: The primary data source for the present analysis was the 60 th round of the National Sample Survey. Distribution frequencies were used to analyze the distribution of key sociodemographic variables and multiple logistic regression was used to analyze the association between these variables and healthcare seeking behavior. Results: A sample of 2203 respondents who had received ambulatory care for tuberculosis, and 4568 respondents who had received inpatient treatment were analyzed. About half of the respondents had attended private facilities for TB care. Sociodemographic variables such as paediatric age group, females, higher level of education, and economic groups were associated with attendance at private sector. Dissatisfaction with services in government facilities was cited as the main reason for preferring private facilities. Conclusions: Private providers play an important role in providing health care services to a large proportion of patients with tuberculosis. There is a need for innovative measures to increase participation of the private sector in the national TB control program and to improve the quality of services in government facilities.

  2. Insights from a national survey into why substance abuse treatment units add prevention and outreach services

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    Lemak Christy

    2006-08-01

    Full Text Available Abstract Background Previous studies have found that even limited prevention-related interventions can affect health behaviors such as substance use and risky sex. Substance abuse treatment providers are ideal candidates to provide these services, but typically have little or no financial incentive to do so. The purpose of this study was therefore to explore why some substance abuse treatment units have added new prevention and outreach services. Based on an ecological framework of organizational strategy, three categories of predictors were tested: (1 environmental, (2 unit-level, and (3 unit leadership. Results A lagged cross-sectional logistic model of 450 outpatient substance abuse treatment units revealed that local per capita income, mental health center affiliation, and clinical supervisors' graduate degrees were positively associated with likelihood of adding prevention-related education and outreach services. Managed care contracts and methadone treatment were negatively associated with addition of these services. No hospital-affiliated agencies added prevention and outreach services during the study period. Conclusion Findings supported the study's ecological perspective on organizational strategy, with factors at environmental, unit, and unit leadership levels associated with additions of prevention and outreach services. Among the significant predictors, ties to managed care payers and unit leadership graduate education emerge as potential leverage points for public policy. In the current sample, units with managed care contracts were less likely to add prevention and outreach services. This is not surprising, given managed care's emphasis on cost control. However, the association with this payment source suggests that public managed care programs might affects prevention and outreach differently through revised incentives. Specifically, government payers could explicitly compensate substance abuse treatment units in managed care

  3. Insights from a national survey into why substance abuse treatment units add prevention and outreach services.

    Science.gov (United States)

    Wells, Rebecca; Lemak, Christy Harris; D'Aunno, Thomas A

    2006-08-03

    Previous studies have found that even limited prevention-related interventions can affect health behaviors such as substance use and risky sex. Substance abuse treatment providers are ideal candidates to provide these services, but typically have little or no financial incentive to do so. The purpose of this study was therefore to explore why some substance abuse treatment units have added new prevention and outreach services. Based on an ecological framework of organizational strategy, three categories of predictors were tested: (1) environmental, (2) unit-level, and (3) unit leadership. A lagged cross-sectional logistic model of 450 outpatient substance abuse treatment units revealed that local per capita income, mental health center affiliation, and clinical supervisors' graduate degrees were positively associated with likelihood of adding prevention-related education and outreach services. Managed care contracts and methadone treatment were negatively associated with addition of these services. No hospital-affiliated agencies added prevention and outreach services during the study period. Findings supported the study's ecological perspective on organizational strategy, with factors at environmental, unit, and unit leadership levels associated with additions of prevention and outreach services. Among the significant predictors, ties to managed care payers and unit leadership graduate education emerge as potential leverage points for public policy. In the current sample, units with managed care contracts were less likely to add prevention and outreach services. This is not surprising, given managed care's emphasis on cost control. However, the association with this payment source suggests that public managed care programs might affects prevention and outreach differently through revised incentives. Specifically, government payers could explicitly compensate substance abuse treatment units in managed care contracts for prevention and outreach. The effects of

  4. A survey of management of congenital nasolacrimal duct obstruction by pediatric primary health care providers in Spain.

    Science.gov (United States)

    Galindo-Ferreiro, Alicia; Palencia-Ercilla, Teresa; Ferreira, Livia Mendoza; Galvez-Ruiz, Alberto; Zornoff, Denise C M; Khandekar, Rajiv; Schellini, Silvana A

    2017-06-26

    To survey the management of congenital nasolacrimal duct obstruction (CNLDO) by pediatric primary health care providers in Spain. This was a descriptive study using a web-based questionnaire to evaluate the perceptions of the members of the Pediatric Primary Care Society in Castilla-León, Spain (APAPCYL), regarding management of CNLDO. The questionnaire contained 14 direct questions and was sent by e-mail to all the pediatricians. All the responses were analyzed by the frequency of occurrence and percentages. Ninety physicians responded to the questionnaire. Massage 2 or 3 times a day was the initial treatment advised by 60.47% of pediatricians. Nearly half of the pediatricians recommended continuing massage until symptoms resolved. Fewer than 50% of children required referral to an ophthalmologist. Reasons for an ophthalmic consult included persistence of symptoms among 87.21% of pediatricians and parental/guardian request among 10.5% of pediatricians. According to 45.6% of pediatricians, their knowledge about CNLDO is limited, and 92.2% would like to receive further training on CNLDO. Massage was the main initial treatment for managing CNLDO among pediatricians. The outcomes of this survey indicated that massage fails in fewer than 50% of patients and an ophthalmic referral is required for these cases.

  5. Mixed Methods Survey of Zoonotic Disease Awareness and Practice among Animal and Human Healthcare Providers in Moshi, Tanzania.

    Directory of Open Access Journals (Sweden)

    Helen L Zhang

    2016-03-01

    Full Text Available Zoonoses are common causes of human and livestock illness in Tanzania. Previous studies have shown that brucellosis, leptospirosis, and Q fever account for a large proportion of human febrile illness in northern Tanzania, yet they are infrequently diagnosed. We conducted this study to assess awareness and knowledge regarding selected zoonoses among healthcare providers in Moshi, Tanzania; to determine what diagnostic and treatment protocols are utilized; and obtain insights into contextual factors contributing to the apparent under-diagnosis of zoonoses.We conducted a questionnaire about zoonoses knowledge, case reporting, and testing with 52 human health practitioners and 10 livestock health providers. Immediately following questionnaire administration, we conducted semi-structured interviews with 60 of these respondents, using the findings of a previous fever etiology study to prompt conversation. Sixty respondents (97% had heard of brucellosis, 26 (42% leptospirosis, and 20 (32% Q fever. Animal sector respondents reported seeing cases of animal brucellosis (4, rabies (4, and anthrax (3 in the previous 12 months. Human sector respondents reported cases of human brucellosis (15, 29%, rabies (9, 18% and anthrax (6, 12%. None reported leptospirosis or Q fever cases. Nineteen respondents were aware of a local diagnostic test for human brucellosis. Reports of tests for human leptospirosis or Q fever, or for any of the study pathogens in animals, were rare. Many respondents expressed awareness of malaria over-diagnosis and zoonoses under-diagnosis, and many identified low knowledge and testing capacity as reasons for zoonoses under-diagnosis.This study revealed differences in knowledge of different zoonoses and low case report frequencies of brucellosis, leptospirosis, and Q fever. There was a lack of known diagnostic services for leptospirosis and Q fever. These findings emphasize a need for improved diagnostic capacity alongside healthcare

  6. A survey of Canadian mechanical pulp and paper mill effluents: insights concerning the potential to affect fish reproduction.

    Science.gov (United States)

    Kovacs, Tibor G; Martel, Pierre H; O'Connor, Brian I; Hewitt, L Mark; Parrott, Joanne L; McMaster, Mark E; MacLatchy, Deborah L; Van Der Kraak, Glen J; Van Den Heuvel, Michael R

    2013-01-01

    Building on breakthroughs recently made at kraft mills, a survey of mechanical pulp and paper mill effluents was undertaken to gain insights concerning potential effects on fish reproduction. Effluents from seven Canadian mills were characterized chemically for conventional parameters such as biochemical oxygen demand (BOD) and total suspended solids (TSS). Each sample was further subjected to solvent extraction followed by gas chromatographic separation for the determination of resin/fatty acids and for the estimation of a gas chromatography (GC) profile index. Each mill effluent was assessed for the potential to affect fish reproduction in the laboratory using a five day adult fathead minnow (Pimephales promelas) egg production bioassay with exposures to 100% effluent. The seven effluents were found to have substantial variation both in terms of chemical characterization and effects on fish reproduction. Temporal variations were also noted in effluent quality at mills sampled on different occasions. Similar to what has been observed for kraft mills, a general trend of greater reductions in egg production caused by effluents with greater BOD concentrations and GC profile indices was noted. Effluents with BOD > 25 mg/L and GC Profile indices >5.0 caused a complete cessation of egg production. At the same time, about half of the total effluents sampled had BOD reproductive effects caused by such effluents is presently unclear. The effluent quality parameters considered in this study may require further refinement to address their utility in predicting the adverse reproductive effects induced by effluents from mechanical pulp and paper mills.

  7. Oxygen and pulse oximetry in childhood pneumonia: a survey of healthcare providers in resource-limited settings.

    Science.gov (United States)

    Ginsburg, Amy Sarah; Van Cleve, William C; Thompson, Mary I W; English, Mike

    2012-10-01

    Globally, pneumonia is the leading cause of death in children provider perceptions and practices regarding their role in childhood pneumonia, we conducted a survey using a convenience sampling strategy targeting clinicians working in resource-limited countries. Most respondents were physicians from public district and provincial hospitals with access to oxygen and pulse oximetry; however, reported therapeutic use for childhood pneumonia was low. Common barriers included insufficient supply, competition for use, lack of policies, guidelines and training and perceived high cost. Despite the frequency of hypoxemia, the inaccuracy of clinical predictors, the poor outcome hypoxemia portends and the effectiveness of pulse oximetry and oxygen in childhood pneumonia, our data indicate that these tools may be underused in resource-limited settings.

  8. Soil Survey Geographic (SSURGO) Special Point Features for the State of Rhode Island: Bristol, Kent, Newport, Providence, and Washington Counties

    Data.gov (United States)

    University of Rhode Island Geospatial Extension Program — This data set is a digital soil survey and generally is the most detailed level of soil geographic data developed by the National Cooperative Soil Survey. The...

  9. Soil Survey Geographic (SSURGO) Special Line Features for the State of Rhode Island: Bristol, Kent, Newport, Providence, and Washington County

    Data.gov (United States)

    University of Rhode Island Geospatial Extension Program — This data set is a digital soil survey and generally is the most detailed level of soil geographic data developed by the National Cooperative Soil Survey. The...

  10. Barriers to Office-Based Mental Health Care and Interest in E-Communication With Providers: A Survey Study.

    Science.gov (United States)

    Rai, Minnie; Vigod, Simone N; Hensel, Jennifer M

    2016-08-01

    With rising availability and use of Internet and mobile technology in society, the demand and need for its integration into health care is growing. Despite great potential within mental health care and growing uptake, there is still little evidence to guide how these tools should be integrated into traditional care, and for whom. To examine factors that might inform how e-communication should be implemented in our local outpatient mental health program, including barriers to traditional office-based care, patient preferences, and patient concerns. We conducted a survey in the waiting room of our outpatient mental health program located in an urban, academic ambulatory hospital. The survey assessed (1) age, mobile phone ownership, and general e-communication usage, (2) barriers to attending office-based appointments, (3) preferences for, and interest in, e-communication for mental health care, and (4) concerns about e-communication use for mental health care. We analyzed the data descriptively and examined associations between the presence of barriers, identifying as a social media user, and interest level in e-communication. Respondents (N=68) were predominantly in the age range of 25-54 years. The rate of mobile phone ownership was 91% (62/68), and 59% (40/68) of respondents identified as social media users. There was very low existing use of e-communication between providers and patients, with high levels of interest endorsed by survey respondents. Respondents expressed an interest in using e-communication with their provider to share updates and get feedback, coordinate care, and get general information. In regression analysis, both a barrier to care and identifying as a social media user were significantly associated with e-communication interest (P=.03 and P=.003, respectively). E-communication interest was highest among people who both had a barrier to office-based care and were a social media user. Despite high interest, there were also many concerns

  11. Pain relief in labor: a survey of awareness, attitude, and practice of health care providers in Zaria, Nigeria

    Directory of Open Access Journals (Sweden)

    Ogboli-Nwasor E

    2011-08-01

    Full Text Available E Ogboli-Nwasor1, SE Adaji2, SB Bature2, OS Shittu21Department of Anesthesia, 2Department of Obstetrics and Gynecology, Ahmadu Bello University Teaching Hospital, Zaria, NigeriaBackground: The purpose of this study was to assess the attitudes of maternal health care providers to pain relief during labor in Zaria, Nigeria.Methods: This was a multicenter, collaborative, cross-sectional pilot study of provider perspectives concerning pain relief during labor. A structured, self-administered, questionnaire was completed by 95 consenting maternal health care providers at three high-volume facilities in Zaria, an ancient northern Nigerian city. Descriptive statistics was performed on the data.Results: Most respondents (94.8% agreed that pain relief is needed during labor. Only 2.1% of respondents were undecided about the provision of pain relief during labor and 3.2% were of the opinion that pain relief was not necessary during labor. Most respondents (93.7% had attended a woman in labor in the 4 weeks preceding the survey. Of these, 56.8% had counseled a parturient in labor. Most of the counseling (42.1% took place during labor. Less than half of the respondents (48.4% had administered pain relief in labor in the preceding 4 weeks and systemic opioids was the most commonly form of pain relief. Among the respondents who did not offer pain relief agents in labor, the majority (54.5% had no reason for not offering it. Unavailability of methods, inability to afford the cost of pain relief, lack of knowledge and skills, as well as lack of essential equipment to provide the procedure were also given by respondents as reasons for not offering pain relief.Conclusion: Even though maternal health care providers in this environment have a positive attitude to pain relief in labor, most women go through labor without the benefit of analgesia. There exists a gap between provider attitudes to pain relief in labor and practice of the same, with many providers

  12. Is there a demand for physical activity interventions provided by the health care sector? Findings from a population survey

    Directory of Open Access Journals (Sweden)

    Walter Lars

    2010-01-01

    Full Text Available Abstract Background Health care providers in many countries have delivered interventions to improve physical activity levels among their patients. Thus far, less is known about the population's interest to increase their physical activity levels and their opinion about the health care provider's role in physical activity promotion. The aims of this paper were to investigate the self-reported physical activity levels of the population and intention to increase physical activity levels, self-perceived need for support, and opinions about the responsibilities of both individuals and health care providers to promote physical activity. Methods A regional public health survey was mailed to 13 440 adults (aged 18-84 years living in Östergötland County (Sweden in 2006. The survey was part of the regular effort by the regional Health Authorities. Results About 25% of the population was categorised as physically active, 38% as moderately active, 27% as somewhat active, and 11% as low active. More than one-third (37% had no intentions to increase their physical activity levels, 36% had thought about change, while 27% were determined to change. Lower intention to change was mainly associated with increased age and lower education levels. 28% answered that physical activity was the most important health-related behaviour to change "right now" and 15% of those answered that they wanted or needed support to make this change. Of respondents who might be assumed to be in greatest need of increased activity (i.e. respondents reporting poor general health, BMI>30, and inactivity more than one-quarter wanted support to make improvements to their health. About half of the respondents who wanted support to increase their physical activity levels listed health care providers as a primary source for support. Conclusions These findings suggest that there is considerable need for physical activity interventions in this population. Adults feel great responsibility for

  13. Sociodemographic correlates of eye care provider visits in the 2006-2009 Behavioral Risk Factor Surveillance Survey.

    Science.gov (United States)

    Caban-Martinez, Alberto J; Davila, Evelyn P; Lam, Byron L; Arheart, Kristopher L; McCollister, Kathryn E; Fernandez, Cristina A; Ocasio, Manuel A; Lee, David J

    2012-05-23

    Research has suggested that adults 40 years old and over are not following eye care visit recommendations. In the United States, the proportion of older adults is expected to increase drastically in the coming years. This has important implications for population ocular disease burden, given the relationship between older age and the development of many ocular diseases and conditions. Understanding individual level determinants of vision health could support the development of tailored vision health campaigns and interventions among our growing older population. Thus, we assessed correlates of eye care visits among participants of the Behavior Risk Factor Surveillance System (BRFSS) survey. We pooled and analyzed 2006-2009 BRFSS data from 16 States (N = 118,075). We assessed for the proportion of survey respondents 40 years of age and older reporting having visited an eye care provider within the past two years, two or more years ago, or never by socio-demographic characteristics. Nearly 80% of respondents reported an eye care visit within the previous two years. Using the 'never visits' as the referent category, the groups with greater odds of having an ocular visit within the past two years included those: greater than 70 years of age (OR = 6.8 [95% confidence interval = 3.7-12.6]), with college degree (5.2[3.0-8.8]), reporting an eye disease, (4.74[1.1-21.2]), diagnosed with diabetes (3.5[1.7-7.5]), of female gender (2.9[2.1-3.9]), with general health insurance (2.7[1.8-3.9]), with eye provider insurance coverage (2.1[1.5-3.0]), with high blood pressure (1.5[1.1-2.2]), and with moderate to extreme near vision difficulties (1.42[1.11-2.08]). We found significant variation by socio-demographic characteristics and some variation in state-level estimates in this study. The present findings suggest that there remains compliance gaps of screening guidelines among select socio-demographic sub-groups, as well as provide evidence and support to the CDC

  14. Sociodemographic Correlates of Eye Care Provider Visits in the 2006–2009 Behavioral Risk Factor Surveillance Survey

    Directory of Open Access Journals (Sweden)

    Caban-Martinez Alberto J

    2012-05-01

    Full Text Available Abstract Background Research has suggested that adults 40 years old and over are not following eye care visit recommendations. In the United States, the proportion of older adults is expected to increase drastically in the coming years. This has important implications for population ocular disease burden, given the relationship between older age and the development of many ocular diseases and conditions. Understanding individual level determinants of vision health could support the development of tailored vision health campaigns and interventions among our growing older population. Thus, we assessed correlates of eye care visits among participants of the Behavior Risk Factor Surveillance System (BRFSS survey. We pooled and analyzed 2006–2009 BRFSS data from 16 States (N = 118,075. We assessed for the proportion of survey respondents 40 years of age and older reporting having visited an eye care provider within the past two years, two or more years ago, or never by socio-demographic characteristics. Results Nearly 80% of respondents reported an eye care visit within the previous two years. Using the ‘never visits’ as the referent category, the groups with greater odds of having an ocular visit within the past two years included those: greater than 70 years of age (OR = 6.8 [95% confidence interval = 3.7–12.6], with college degree (5.2[3.0–8.8], reporting an eye disease, (4.74[1.1–21.2], diagnosed with diabetes (3.5[1.7–7.5], of female gender (2.9[2.1–3.9], with general health insurance (2.7[1.8–3.9], with eye provider insurance coverage (2.1[1.5–3.0], with high blood pressure (1.5[1.1–2.2], and with moderate to extreme near vision difficulties (1.42[1.11–2.08]. Conclusion We found significant variation by socio-demographic characteristics and some variation in state-level estimates in this study. The present findings suggest that there remains compliance gaps of screening guidelines among select socio

  15. Logistic support provided to Australian disaster medical assistance teams: results of a national survey of team members

    Directory of Open Access Journals (Sweden)

    Peter Aitken

    2012-02-01

    Full Text Available It is likely that calls for disaster medical assistance teams (DMATs continue in response to international disasters. As part of a national survey, the present study was designed to evaluate the Australian DMAT experience and the need for logistic support.Data were collected via an anonymous mailed survey distributed via State and Territory representatives on the Australian Health Protection Committee, who identified team members associated with Australian DMAT deployments from the 2004 Asian Tsunami disaster.The response rate for this survey was 50% (59/118. Most of the personnel had deployed to the South East Asian Tsunami affected areas. The DMAT members had significant clinical and international experience. There was unanimous support for dedicated logistic support with 80% (47/59 strongly agreeing. Only one respondent (2% disagreed with teams being self sufficient for a minimum of 72 hours. Most felt that transport around the site was not a problem (59%; 35/59, however, 34% (20/59 felt that transport to the site itself was problematic. Only 37% (22/59 felt that pre-deployment information was accurate. Communication with local health providers and other agencies was felt to be adequate by 53% (31/59 and 47% (28/59 respectively, while only 28% (17/59 felt that documentation methods were easy to use and reliable. Less than half (47%; 28/59 felt that equipment could be moved easily between areas by team members and 37% (22/59 that packaging enabled materials to be found easily. The maximum safe container weight was felt to be between 20 and 40 kg by 58% (34/59.This study emphasises the importance of dedicated logistic support for DMAT and the need for teams to be self sufficient for a minimum period of 72 hours. There is a need for accurate pre deployment information to guide resource prioritisation with clearly labelled pre packaging to assist access on site. Container weights should be restricted to between 20 and 40 kg, which would assist

  16. Development of a scale for "difficulties felt by ICU nurses providing end-of-life care" (DFINE): a survey study.

    Science.gov (United States)

    Kinoshita, Satomi; Miyashita, Mitsunori

    2011-08-01

    To develop a scale for assessing "difficulties felt by intensive care unit (ICU) nurses providing end-of-life care" (DFINE). A questionnaire survey of nurses in ICUs at general hospitals in the Kanto region, Japan. The scale was evaluated by exploratory factor analysis, calculation of Cronbach's α and test-retest reliability. The Frommelt Attitudes Toward Care of the Dying Scale (FATCOD-B-J) and the Nursing Job Stressor Scale (NJSS) were used to investigate concurrent validity. Respondents were 224 ICU nurses (response rate, 78%) at 18 hospitals. Five factors comprising 28 items were identified, involving difficulties related to: "the purpose of the ICU is recovery and survival"; "nursing system and model nurse for end-of-life care"; "building confidence in end-of-life care"; "caring for patients and families at end-of-life"; and "converting from curative care to end-of-life care". Cronbach's α for each factor ranged from 0.61 to 0.8. In terms of test-retest reliability, intraclass correlations for each factor ranged from 0.62 to 0.72. "Building confidence in end-of-life care" in DFINE showed a negative correlation with "positive attitudes towards caring for dying patient" in the FATCOD-B-J (r=-0.4). "Nursing system and model nurse for end-of-life care" in DFINE showed a positive correlation with "conflict with other nursing staffs" (r=0.32) and "conflict with physicians/autonomy" (r=0.31) in the NJSS. DFINE demonstrated acceptable reliability and validity. However, additional surveys need to be conducted with a larger sample to further characterise the scale. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Survey of HIV care providers on management of HIV serodiscordant couples - assessment of attitudes, knowledge, and practices.

    Science.gov (United States)

    Scherer, Matthew L; Douglas, Nataki C; Churnet, Bethlehem H; Grossman, Lisa C; Kline, Melissa; Yin, Michael T; Sauer, Mark V; Olender, Susan A

    2014-01-01

    Human immunodeficiency virus (HIV) serodiscordant couples are at risk of sexual transmission of HIV between the infected and uninfected partner. We assessed New York area care providers for people living with HIV regarding attitudes, knowledge, and practice patterns toward fertility and conception in serodiscordant couples. Data were collected via a survey distributed in October 2013. Seventeen percent of respondents reported prescribing antiretroviral preexposure prophylaxis (PrEP) for a woman in a serodiscordant couple, and 38% percent of respondents reported having counseled serodiscordant couples on timed, unprotected intercourse without PrEP. Respondents who reported being "very" familiar with the data on HIV transmission in serodiscordant couples were more likely to report counseling their patients in timed, unprotected intercourse compared with those who reported less familiarity with the data (41% vs. 8%, p = 0.001). Although only 20% reported being "very" or "somewhat" familiar with the data on the safety of sperm washing with intrauterine insemination, those who did were more likely to have reported referring a patient for assisted reproductive technology (61% vs. 32%, p = 0.006). Effective patient counseling and referral for appropriate reproductive options were associated with knowledge of the literature pertaining to these options. This emphasizes the need for further provider education on reproductive options and appropriate counseling for serodiscordant couples.

  18. Sampling survey methodology issues of SBS- survey

    OpenAIRE

    Liljana Boci; Elona Berberi

    2015-01-01

    This paper aims at providing an insight on what is required to build an efficient and high quality business statistics from sample survey procedures, and on the effective and appropriate use of survey data in analysis. It aims at describing a general overview of what is required to have a good survey estimate. It shows in practice how to estimate characteristics of the population in SBS considering: weighting, non-response adjustments, post stratification, estimating a population totals, the ...

  19. Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates.

    Science.gov (United States)

    Liu, Hai-Jing; Tang, Zhen-Xin; Han, Xue-Min; Yang, Zhi-Ling; Zhang, Fu-Min; Yang, Hai-Ling; Liu, Yan-Jing; Zeng, Qing-Yin

    2015-11-01

    Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.

  20. Comparative Characterization of CTX-M-64 and CTX-M-14 Provides Insights into the Structure and Catalytic Activity of the CTX-M Class of Enzymes.

    Science.gov (United States)

    He, Dandan; Chiou, Jiachi; Zeng, Zhenling; Chan, Edward Wai-Chi; Liu, Jian-Hua; Chen, Sheng

    2016-10-01

    Clinical isolates producing hybrid CTX-M β-lactamases, presumably due to recombination between the blaCTX-M-15 and blaCTX-M-14 elements, have emerged in recent years. Among the hybrid enzymes, CTX-M-64 and CTX-M-14 display the most significant difference in catalytic activity. This study aims to investigate the mechanisms underlying such differential enzymatic activities in order to provide insight into the structure/function relationship of this class of enzymes. Sequence alignment analysis showed that the major differences between the amino acid composition of CTX-M-64 and CTX-M-14 lie at both the N and C termini of the enzymes. Single or multiple amino acid substitutions introduced into CTX-M-64 and CTX-M-14 were found to produce only minor effects on hydrolytic functions; such a finding is consistent with the notion that the discrepancy between the functional activities of the two enzymes is not the result of only a few amino acid changes but is attributable to interactions between a unique set of amino acid residues in each enzyme. This theory is supported by the results of the thermal stability assay, which confirmed that CTX-M-64 is significantly more stable than CTX-M-14. Our data confirmed that, in addition to the important residues located in the active site, residues distal to the active site also contribute to the catalytic activity of the enzyme through stabilizing its structural integrity.

  1. iTRAQ and RNA-Seq Analyses Provide New Insights into Regulation Mechanism of Symbiotic Germination of Dendrobium officinale Seeds (Orchidaceae).

    Science.gov (United States)

    Chen, Juan; Liu, Si Si; Kohler, Annegret; Yan, Bo; Luo, Hong Mei; Chen, Xiao Mei; Guo, Shun Xing

    2017-06-02

    Mycorrhizal fungi colonize orchid seeds and induce germination. This so-called symbiotic germination is a critical developmental process in the lifecycle of all orchid species. However, the molecular changes that occur during orchid seed symbiotic germination remain largely unknown. To better understand the molecular mechanism of orchid seed germination, we performed a comparative transcriptomic and proteomic analysis of the Chinese traditional medicinal orchid Dendrobium officinale to explore the change in protein expression at the different developmental stages during asymbiotic and symbiotic germination and identify the key proteins that regulate the symbiotic germination of orchid seeds. Among 2256 identified plant proteins, 308 were differentially expressed across three developmental stages during asymbiotic and symbiotic germination, and 229 were differentially expressed during symbiotic germination compared to asymbiotic development. Of these, 32 proteins were coup-regulated at both the proteomic and transcriptomic levels during symbiotic germination compared to asymbiotic germination. Our results suggest that symbiotic g