Sample records for early genetic events

  1. Genetic parameters of eventing horse competition in France

    PubMed Central

    Ricard, Anne; Chanu, Isabelle

    2001-01-01

    Genetic parameters of eventing horse competitions were estimated. About 13 000 horses, 30 000 annual results during 17 years and 110 000 starts in eventing competitions during 8 years were recorded. The measures of performance were logarithmic transformations of annual earnings, annual earnings per start, and annual earnings per place, and underlying variables responsible for ranks in each competition. Heritabilities were low (0.11/0.17 for annual results, 0.07 for ranks). Genetic correlations between criteria were high (greater than 0.90) except between ranks and earnings per place (0.58) or per start (0.67). Genetic correlations between ages (from 5 to 10 years old) were also high (more than 0.85) and allow selection on early performances. The genetic correlation between the results in different levels of competition (high/international and low/amateur) was near 1. Genetic correlations of eventing with other disciplines, which included partial aptitude needed for eventing, were very low for steeplechase races (0.18) and moderate with sport: jumping (0.45), dressage (0.58). The results suggest that selection on jumping performance will lead to some positive correlated response for eventing performance, but much more response could be obtained if a specific breeding objective and selection criteria were developed for eventing. PMID:11333833

  2. Genetic and environmental correlations between subjective wellbeing and experience of life events in adolescence.

    PubMed

    Wootton, Robyn E; Davis, Oliver S P; Mottershaw, Abigail L; Wang, R Adele H; Haworth, Claire M A

    2017-09-01

    Some life events appear heritable due to the genetic influence on related behaviours. Shared genetic influence between negative behaviours and negative life events has previously been established. This study investigated whether subjective wellbeing and positive life events were genetically associated. Participants in the Twins Early Development Study (aged 16.32 ± .68 years) completed subjective wellbeing and life events assessments via two separate studies (overlapping N for wellbeing and life events measures ranged from 3527 to 9350). We conducted bivariate twin models between both positive and negative life events with subjective wellbeing and related positive psychological traits including subjective happiness, life satisfaction, optimism, hopefulness and gratitude measured at 16 years. Results suggested that the heritability of life events can partially be explained by shared genetic influences with the wellbeing indicators. Wellbeing traits were positively genetically correlated with positive life events and negatively correlated with negative life events (except curiosity where there was no correlation). Those positive traits that drive behaviour (grit and ambition) showed the highest genetic correlation with life events, whereas the reflective trait gratitude was less correlated. This suggests that gene-environment correlations might explain the observed genetic association between life events and wellbeing. Inheriting propensity for positive traits might cause you to seek environments that lead to positive life events and avoid environments which make negative life events more likely.

  3. Genetic and life-history consequences of extreme climate events

    PubMed Central

    Mangel, Marc; Jesensek, Dusan; Garza, John Carlos; Crivelli, Alain J.

    2017-01-01

    Climate change is predicted to increase the frequency and intensity of extreme climate events. Tests on empirical data of theory-based predictions on the consequences of extreme climate events are thus necessary to understand the adaptive potential of species and the overarching risks associated with all aspects of climate change. We tested predictions on the genetic and life-history consequences of extreme climate events in two populations of marble trout Salmo marmoratus that have experienced severe demographic bottlenecks due to flash floods. We combined long-term field and genotyping data with pedigree reconstruction in a theory-based framework. Our results show that after flash floods, reproduction occurred at a younger age in one population. In both populations, we found the highest reproductive variance in the first cohort born after the floods due to a combination of fewer parents and higher early survival of offspring. A small number of parents allowed for demographic recovery after the floods, but the genetic bottleneck further reduced genetic diversity in both populations. Our results also elucidate some of the mechanisms responsible for a greater prevalence of faster life histories after the extreme event. PMID:28148745

  4. Genetic and life-history consequences of extreme climate events.

    PubMed

    Vincenzi, Simone; Mangel, Marc; Jesensek, Dusan; Garza, John Carlos; Crivelli, Alain J

    2017-02-08

    Climate change is predicted to increase the frequency and intensity of extreme climate events. Tests on empirical data of theory-based predictions on the consequences of extreme climate events are thus necessary to understand the adaptive potential of species and the overarching risks associated with all aspects of climate change. We tested predictions on the genetic and life-history consequences of extreme climate events in two populations of marble trout Salmo marmoratus that have experienced severe demographic bottlenecks due to flash floods. We combined long-term field and genotyping data with pedigree reconstruction in a theory-based framework. Our results show that after flash floods, reproduction occurred at a younger age in one population. In both populations, we found the highest reproductive variance in the first cohort born after the floods due to a combination of fewer parents and higher early survival of offspring. A small number of parents allowed for demographic recovery after the floods, but the genetic bottleneck further reduced genetic diversity in both populations. Our results also elucidate some of the mechanisms responsible for a greater prevalence of faster life histories after the extreme event. © 2017 The Author(s).

  5. Loss of heterozygosity at D8S262: an early genetic event of hepatocarcinogenesis.

    PubMed

    Zhu, Qiao; Gong, Li; Liu, Xiaoyan; Wang, Jun; Ren, Pin; Zhang, Wendong; Yao, Li; Han, Xiujuan; Zhu, Shaojun; Lan, Miao; Li, Yanhong; Zhang, Wei

    2015-06-16

    Hepatocellular carcinoma (HCC) is a multi-factor, multi-step, multi-gene and complicated process resulting from the accumulation of sequential genetic and epigenetic alterations. An important change among them is from precancerous lesions to HCC. However, only few studies have been reported about the sequential genetic changes during hepatocarcinogenesis. We observed firstly molecular karyotypes of 10 matched HCC using Affymetrix single-nucleotide polymorphism (SNP) 6.0 arrays, and found chromosomal fragments with high incidence (more than 70%) of loss of heterozygosity (LOH). Then, we selected 28 microsatellite markers at some gene spanning these chromosomal fragments, and examined the frequency of LOH of 128 matched HCC and 43 matched precancerous lesions-dysplastic nodules (DN) by a PCR-based analysis. Finally, we investigated the expression of proteins encoded by these genes in HCC, DN and the surrounding hepatic tissues. The result of Affymetrix SNP6.0 arrays demonstrated that more than 70% (7/10) cases had chromosomal fragment deletion on 4q13.3-35.1, 8p23.2-21.2, 16q11.2-24.3, and 17p13.3-12. Among 28 microsatellite markers selected, LOH frequencies at D8S262 for DN and HCC were found to be the highest, 51.2% and 72.7%, respectively. Immunohistochemically, the positive rate of its adjacent gene CSMD1 in HCC, DN, and the surrounding hepatic tissues were 27.3% (35/128), 75% (33/44), and 82% (105/128), respectively. LOH at D8S262 may be associated with an early genetic event of hepatocarcinogenesis, and a predictor for the monitor and prevention of HCC. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1557074981159099 .

  6. Early traumatic events in psychopaths.

    PubMed

    Borja, Karina; Ostrosky, Feggy

    2013-07-01

    The relationship between diverse early traumatic events and psychopathy was studied in 194 male inmates. Criminal history transcripts were revised, and clinical interviews were conducted to determine the level of psychopathy using the Psychopathy Checklist-Revised (PCL-R) Form, and the Early Trauma Inventory was applied to assess the incidence of abuse before 18 years of age. Psychopathic inmates presented a higher victimization level and were more exposed to certain types of intended abuse than sociopathic inmates, while the sum of events and emotional abuse were associated with the PCL-R score. Our studies support the influence of early adverse events in the development of psychopathic offenders. © 2013 American Academy of Forensic Sciences.

  7. Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage

    PubMed Central

    Hervella, Montserrat; Rotea, Mihai; Izagirre, Neskuts; Constantinescu, Mihai; Alonso, Santos; Ioana, Mihai; Lazăr, Cătălin; Ridiche, Florin; Soficaru, Andrei Dorian; Netea, Mihai G.; de-la-Rua, Concepcion

    2015-01-01

    The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Cârcea, Gura Baciului and Negrileşti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations. PMID:26053041

  8. Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage.

    PubMed

    Hervella, Montserrat; Rotea, Mihai; Izagirre, Neskuts; Constantinescu, Mihai; Alonso, Santos; Ioana, Mihai; Lazăr, Cătălin; Ridiche, Florin; Soficaru, Andrei Dorian; Netea, Mihai G; de-la-Rua, Concepcion

    2015-01-01

    The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Cârcea, Gura Baciului and Negrileşti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations.

  9. Life events and personality in late adolescence: genetic and environmental relations.

    PubMed

    Billig, J P; Hershberger, S L; Iacono, W G; McGue, M

    1996-11-01

    The relationship between life events and personality was investigated in the Minnesota Twin/Family Study, using 216 monozygotic and 114 dizygotic 17-year-old male twin pairs. Participants completed a life events interview designed for adolescents and the Multidimensional Personality Questionnaire. Life events were categorized into three types: life events to which all members of a family would be subject and those affecting an individual, which can be broadly construed as either nonindependent or independent. Univariate genetic model fitting indicated the presence of significant genetic effects (h2 = 49%) for nonindependent nonfamily life events but not for the other two types of life events. Bivariate genetic model fitting further confirmed that the significant phenotypic correlation between nonindependent life events and personality is in part genetically mediated. Specifically, the findings suggest that genetically influenced individual differences in constraint play a substantial role in life events whose occurrence is not independent of the individual's behavior.

  10. Nutritional and Genetic Determinants of Early Puberty

    DTIC Science & Technology

    2007-06-01

    AD_________________ Award Number: W81XWH-04-1-0575 TITLE: Nutritional and Genetic Determinants...CONTRACT NUMBER Nutritional and Genetic Determinants of Early Puberty 5b. GRANT NUMBER W81XWH-04-1-0575 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...later in life. Nutritional factors during childhood and puberty, and inherited genetic factors are suspected to interact in modulating these early

  11. Genetics and Early Detection in Idiopathic Pulmonary Fibrosis

    PubMed Central

    Putman, Rachel K.; Rosas, Ivan O.

    2014-01-01

    Genetic studies hold promise in helping to identify patients with early idiopathic pulmonary fibrosis (IPF). Recent studies using chest computed tomograms (CTs) in smokers and in the general population have demonstrated that imaging abnormalities suggestive of an early stage of pulmonary fibrosis are not uncommon and are associated with respiratory symptoms, physical examination abnormalities, and physiologic decrements expected, but less severe than those noted in patients with IPF. Similarly, recent genetic studies have demonstrated strong and replicable associations between a common promoter polymorphism in the mucin 5B gene (MUC5B) and both IPF and the presence of abnormal imaging findings in the general population. Despite these findings, it is important to note that the definition of early-stage IPF remains unclear, limited data exist to definitively connect abnormal imaging findings to IPF, and genetic studies assessing early-stage pulmonary fibrosis remain in their infancy. In this perspective we provide updated information on interstitial lung abnormalities and their connection to IPF. We summarize information on the genetics of pulmonary fibrosis by focusing on the recent genetic findings of MUC5B. Finally, we discuss the implications of these findings and suggest a roadmap for the use of genetics in the detection of early IPF. PMID:24547893

  12. Genetic consequences of sequential founder events by an island-colonizing bird.

    PubMed

    Clegg, Sonya M; Degnan, Sandie M; Kikkawa, Jiro; Moritz, Craig; Estoup, Arnaud; Owens, Ian P F

    2002-06-11

    The importance of founder events in promoting evolutionary changes on islands has been a subject of long-running controversy. Resolution of this debate has been hindered by a lack of empirical evidence from naturally founded island populations. Here we undertake a genetic analysis of a series of historically documented, natural colonization events by the silvereye species-complex (Zosterops lateralis), a group used to illustrate the process of island colonization in the original founder effect model. Our results indicate that single founder events do not affect levels of heterozygosity or allelic diversity, nor do they result in immediate genetic differentiation between populations. Instead, four to five successive founder events are required before indices of diversity and divergence approach that seen in evolutionarily old forms. A Bayesian analysis based on computer simulation allows inferences to be made on the number of effective founders and indicates that founder effects are weak because island populations are established from relatively large flocks. Indeed, statistical support for a founder event model was not significantly higher than for a gradual-drift model for all recently colonized islands. Taken together, these results suggest that single colonization events in this species complex are rarely accompanied by severe founder effects, and multiple founder events and/or long-term genetic drift have been of greater consequence for neutral genetic diversity.

  13. Multi-model data fusion to improve an early warning system for hypo-/hyperglycemic events.

    PubMed

    Botwey, Ransford Henry; Daskalaki, Elena; Diem, Peter; Mougiakakou, Stavroula G

    2014-01-01

    Correct predictions of future blood glucose levels in individuals with Type 1 Diabetes (T1D) can be used to provide early warning of upcoming hypo-/hyperglycemic events and thus to improve the patient's safety. To increase prediction accuracy and efficiency, various approaches have been proposed which combine multiple predictors to produce superior results compared to single predictors. Three methods for model fusion are presented and comparatively assessed. Data from 23 T1D subjects under sensor-augmented pump (SAP) therapy were used in two adaptive data-driven models (an autoregressive model with output correction - cARX, and a recurrent neural network - RNN). Data fusion techniques based on i) Dempster-Shafer Evidential Theory (DST), ii) Genetic Algorithms (GA), and iii) Genetic Programming (GP) were used to merge the complimentary performances of the prediction models. The fused output is used in a warning algorithm to issue alarms of upcoming hypo-/hyperglycemic events. The fusion schemes showed improved performance with lower root mean square errors, lower time lags, and higher correlation. In the warning algorithm, median daily false alarms (DFA) of 0.25%, and 100% correct alarms (CA) were obtained for both event types. The detection times (DT) before occurrence of events were 13.0 and 12.1 min respectively for hypo-/hyperglycemic events. Compared to the cARX and RNN models, and a linear fusion of the two, the proposed fusion schemes represents a significant improvement.

  14. Genetic and Environmental Influences on Negative Life Events from Late Childhood to Adolescence

    ERIC Educational Resources Information Center

    Johnson, Daniel P.; Rhee, Soo Hyun; Whisman, Mark A.; Corley, Robin P.; Hewitt, John K.

    2013-01-01

    This multiwave longitudinal study tested two quantitative genetic developmental models to examine genetic and environmental influences on exposure to negative dependent and independent life events. Participants (N = 457 twin pairs) completed measures of life events annually from ages 9 to 16. The same genetic factors influenced exposure to…

  15. TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.

    PubMed

    Wang, Na; Liu, Tiantian; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Höög, Anders; Larsson, Catharina; Xu, Dawei

    2014-10-01

    The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how early these mutations occur in thyroid tumorigenesis. The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit. The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival. TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. © 2014 American Cancer Society.

  16. Genetic and Environmental Influences on Early Literacy

    ERIC Educational Resources Information Center

    Byrne, Brian; Olson, Richard K.; Samuelsson, Stefan; Wadsworth, Sally; Corley, Robin; DeFries, John C.; Willcutt, Erik

    2006-01-01

    Prereading and early reading skills of preschool twin children in Australia, Scandinavia and the United States were explored in a genetically sensitive design (max. N=627 preschool pairs and 422 kindergarten pairs). Analyses indicated a strong genetic influence on preschool phonological awareness, rapid naming and verbal memory. Print awareness,…

  17. A New Observation Technique Applied to Early/Fast VLF Scattering Events

    NASA Astrophysics Data System (ADS)

    Kotovsky, D. A.; Moore, R. C.

    2012-12-01

    Early/fast very low frequency (VLF, 3-30 kHz) events are understood to result from ionospheric conductivity changes associated with lightning. Early/fast amplitude and phase perturbations have been observed coincidentally with various optical observations of transient luminous events (TLEs), including elves, sprites, and sprite halos, each of which can have temporal characteristics consistent with those of early/fast VLF events. It is yet unresolved, however, whether a specific type of TLE is directly related to the ionospheric conductivity changes responsible for the typical early/fast event. In this paper, we present spread spectrum VLF scattering observations of early/fast events. The spread spectrum analysis technique determines the amplitude and phase of a subionospherically propagating VLF signal as a function of time during the early/fast event and as a function of frequency across the 200 Hz bandwidth of the VLF transmission. VLF scattering observations, each identified with causative lightning logged by the National Lightning Detection Network (NLDN), are compared with the predictions of the Long-Wave Propagation Capability (LWPC) code, a three-dimensional earth-ionosphere waveguide propagation and scattering model. Theoretical predictions for VLF scattering from ionization changes associated with elves are compared with those associated with sprite halos, and each are compared with experimental observations. Results indicate that the observed frequency dependence of VLF scattering during early/fast events results from the combination of scattering source properties and Earth-ionosphere waveguide propagation effects. Observations are more consistent with the modeled amplitude perturbations associated with sprite halos than those with elves.

  18. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics

    PubMed Central

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-01-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae–Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. PMID:27604225

  19. Calculating expected DNA remnants from ancient founding events in human population genetics

    PubMed Central

    Stacey, Andrew; Sheffield, Nathan C; Crandall, Keith A

    2008-01-01

    Background Recent advancements in sequencing and computational technologies have led to rapid generation and analysis of high quality genetic data. Such genetic data have achieved wide acceptance in studies of historic human population origins and admixture. However, in studies relating to small, recent admixture events, genetic factors such as historic population sizes, genetic drift, and mutation can have pronounced effects on data reliability and utility. To address these issues we conducted genetic simulations targeting influential genetic parameters in admixed populations. Results We performed a series of simulations, adjusting variable values to assess the affect of these genetic parameters on current human population studies and what these studies infer about past population structure. Final mean allele frequencies varied from 0.0005 to over 0.50, depending on the parameters. Conclusion The results of the simulations illustrate that, while genetic data may be sensitive and powerful in large genetic studies, caution must be used when applying genetic information to small, recent admixture events. For some parameter sets, genetic data will not be adequate to detect historic admixture. In such cases, studies should consider anthropologic, archeological, and linguistic data where possible. PMID:18928554

  20. Operational early warning platform for extreme meteorological events

    NASA Astrophysics Data System (ADS)

    Mühr, Bernhard; Kunz, Michael

    2015-04-01

    Operational early warning platform for extreme meteorological events Most natural disasters are related to extreme weather events (e.g. typhoons); weather conditions, however, are also highly relevant for humanitarian and disaster relief operations during and after other natural disaster like earthquakes. The internet service "Wettergefahren-Frühwarnung" (WF) provides various information on extreme weather events, especially when these events are associated with a high potential for large damage. The main focus of the platform is on Central Europe, but major events are also monitored worldwide on a daily routine. WF provides high-resolution forecast maps for many weather parameters which allow detailed and reliable predictions about weather conditions during the next days in the affected areas. The WF service became operational in February 2004 and is part of the Center for Disaster Management and Risk Reduction Technology (CEDIM) since 2007. At the end of 2011, CEDIM embarked a new type of interdisciplinary disaster research termed as forensic disaster analysis (FDA) in near real time. In case of an imminent extreme weather event WF plays an important role in CEDIM's FDA group. It provides early and precise information which are always available and updated several times during a day and gives advice and assists with articles and reports on extreme events.

  1. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

    PubMed

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-11-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Early Warning and Early Action during the 2015-16 El Nino Event

    NASA Astrophysics Data System (ADS)

    Robertson, A. W.; Goddard, L. M.

    2016-12-01

    Strong El Niño events have a marked impact on regional climate worldwide through their influence on large-scale atmospheric circulation. As a result, seasonal climate forecasts show greater skill during El Niño events, which provide communities, governments and humanitarian agencies greater ability to plan and prepare. The scientific community has advanced considerably in the quality and content of information provided about El Niño and its impacts. As a result, society has become better aware of and engaged with this information. This talk will present some details on how we navigate the fine line between expectations and probabilistic forecasts, and how this information was used during the 2015-16 El Niño event. Examples are drawn from the health sector and food security community. Specific attention will be given to the importance of problem-focus and data availability in the appropriate tailoring of climate information for Early Warning/Early Action.

  3. Genetic and Non-Genetic Factors Affecting the Quality of Anticoagulation Control and Vascular Events in Atrial Fibrillation.

    PubMed

    Park, Yun Kyung; Lee, Mi Ji; Kim, Jae Ha; Lee, Jin Soo; Park, Rae Woong; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Kim, June Soo; Lee, Soo-Youn; Bang, Oh Young

    2017-06-01

    Warfarin has a narrow therapeutic window. We hypothesized that genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1) would show stronger associations than modifiable factors with the quality of anticoagulation control and risks for thromboembolism and hemorrhage. In this retrospective cohort analysis, clinical and genetic data were collected from 380 patients with atrial fibrillation (AF) who were followed for an average observation period of 4 years. We evaluated the factors associated with time in therapeutic range (TTR, international normalized ratio [INR]: 2-3) and vascular events (either thromboembolic or hemorrhagic), including both genetic (CYP2C9 and VKORC1 genotype) and modifiable factors (anticoagulation service and warfarin dose assessment interval). The genotypic frequency of CYP2C9*3 (rs1057910) was 9.5% and that of VKORC1 1173C>T (rs9934438) was 16.3%. TTR showed dependence on VKORC1 polymorphism: TTR was higher in carriers of the VKORC1 1173C>T than of the VKORC1 TT genotype (61.7 ± 16.0% versus 56.7 ± 17.4%, P = .031). Multivariate testing showed that the VKORC1 genotype and anticoagulation service were independently related to labile INRs (TTR <65%). Vascular events were observed in 66 patients (18.4%) during the study period. A Cox proportional hazard model showed that the use of anticoagulation service and patients' characteristics, such as AF-thromboembolic risk (CHA 2 DS 2 -VASc score: Congestive heart failure, Hypertension, Age 75 years or older, Diabetes mellitus, previous Stroke or transient ischemic attack, Vascular disease, Age 65 to 74 years, female) and consequence (neurologic disability), but not genetic factors, were independently associated with vascular events. Both genetic factor (VKORC1 genotype) and clinical efforts (anticoagulation service) influenced the quality of anticoagulation control. However, clinical events were more strongly associated with patient characteristics and clinical

  4. Evidence for a genetic etiology of early-onset delinquency.

    PubMed

    Taylor, J; Iacono, W G; McGue, M

    2000-11-01

    Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

  5. Genetic and Environmental Influences on the Growth of Early Reading Skills

    ERIC Educational Resources Information Center

    Petrill, Stephen A.; Hart, Sara A.; Harlaar, Nicole; Logan, Jessica; Justice, Laura M.; Schatschneider, Christopher; Thompson, Lee; DeThorne, Laura S.; Deater-Deckard, Kirby; Cutting, Laurie

    2010-01-01

    Background: Studies have suggested genetic and environmental influences on overall level of early reading whereas the larger reading literature has shown environmental influences on the rate of growth of early reading skills. This study is the first to examine the genetic and environmental influences on both initial level of performance and rate…

  6. Genetic Risk, Coronary Heart Disease Events, and the Clinical Benefit of Statin Therapy

    PubMed Central

    Smith, JG; Chasman, DI; Caulfield, M; Devlin, JJ; Nordio, F; Hyde, C; Cannon, CP; Sacks, F; Poulter, N; Sever, P; Ridker, PM; Braunwald, E; Melander, O

    2015-01-01

    Background Genetic variants have been associated with the risk of coronary heart disease (CHD). We tested whether a composite of these variants could identify the risk of both incident as well as recurrent CHD events and distinguish individuals who derived greater clinical benefit from statin therapy. Methods A community-based cohort and four randomized controlled trials of both primary (JUPITER and ASCOT) and secondary (CARE and PROVE IT-TIMI 22) prevention with statin therapy totaling 48,421 individuals and 3,477 events were included in these analyses. We examined the association of a genetic risk score based on 27 genetic variants with incident or recurrent CHD, adjusting for established clinical predictors. We then investigated the relative and absolute risk reductions in CHD events with statin therapy stratified by genetic risk. Data from studies were combined using meta-analysis. Findings When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient of risk for incident or recurrent CHD was demonstrated with the multivariable-adjusted HRs (95% CI) for CHD for the intermediate and high genetic risk categories vs. low genetic risk category being 1.32 (1.20-1.46, P<0.0001) and 1.71 (1.54-1.91, P<0.0001), respectively. In terms of the benefit of statin therapy in the four randomized trials, there was a significant gradient of increasing relative risk reduction across the low, intermediate, and high genetic risk categories (13%, 29%, and 48%, P=0.0277). Similarly, greater absolute risk reductions were seen in those individuals in higher genetic risk categories (P=0.0101), resulting in an approximate three-fold gradient in the number needed to treat (NNT) in the primary prevention trials. Specifically, in the primary prevention trials, the NNT to prevent one MACE over 10 years for the low, intermediate, and high GRS individuals was 66, 42, and 25 in JUPITER and 57, 47, and 20

  7. Demographic Events and Evolutionary Forces Shaping European Genetic Diversity

    PubMed Central

    Veeramah, Krishna R.; Novembre, John

    2014-01-01

    Europeans have been the focus of some of the largest studies of genetic diversity in any species to date. Recent genome-wide data have reinforced the hypothesis that present-day European genetic diversity is strongly correlated with geography. The remaining challenge now is to understand more precisely how patterns of diversity in Europe reflect ancient demographic events such as postglacial expansions or the spread of farming. It is likely that recent advances in paleogenetics will give us some of these answers. There has also been progress in identifying specific segments of European genomes that reflect adaptations to selective pressures from the physical environment, disease, and dietary shifts. A growing understanding of how modern European genetic diversity has been shaped by demographic and evolutionary forces is not only of basic historical and anthropological interest but also aids genetic studies of disease. PMID:25059709

  8. Social anxiety and negative early life events in university students.

    PubMed

    Binelli, Cynthia; Ortiz, Ana; Muñiz, Armando; Gelabert, Estel; Ferraz, Liliana; S Filho, Alaor; Crippa, José Alexandre S; Nardi, Antonio E; Subirà, Susana; Martín-Santos, Rocío

    2012-06-01

    There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.

  9. The Relationship Between Early Life Events, Parental Attachment, and Psychopathic Tendencies in Adolescent Detainees.

    PubMed

    Christian, Erica J; Meltzer, Christine L; Thede, Linda L; Kosson, David S

    2017-04-01

    Despite increasing interest in understanding psychopathic traits in youth, the role of early environmental factors in the development of psychopathic traits is not well understood. No prior studies have directly examined the relationship between early life events and psychopathic traits. We examined links between life events in the first 4 years of life and indices of the core affective and interpersonal components of psychopathy. Additionally, we examined relationships between early life events, psychopathic traits, and attachment to parents among 206 adjudicated adolescents. Results indicated that the total number of early life events was positively correlated with indices of the affective component of psychopathy. Moreover, psychopathic traits moderated the relationship between the number of early life events and later reports of attachment to parents. Findings suggest that early environmental factors could have important implications for the development of psychopathic traits and may impact attachment to parents for youth with psychopathic traits.

  10. The impact of recent events on human genetic diversity

    PubMed Central

    Jobling, Mark A.

    2012-01-01

    The historical record tells us stories of migrations, population expansions and colonization events in the last few thousand years, but what was their demographic impact? Genetics can throw light on this issue, and has mostly done so through the maternally inherited mitochondrial DNA (mtDNA) and the male-specific Y chromosome. However, there are a number of problems, including marker ascertainment bias, possible influences of natural selection, and the obscuring layers of the palimpsest of historical and prehistorical events. Y-chromosomal lineages are particularly affected by genetic drift, which can be accentuated by recent social selection. A diversity of approaches to expansions in Europe is yielding insights into the histories of Phoenicians, Roma, Anglo-Saxons and Vikings, and new methods for producing and analysing genome-wide data hold much promise. The field would benefit from more consensus on appropriate methods, and better communication between geneticists and experts in other disciplines, such as history, archaeology and linguistics. PMID:22312046

  11. Early events in speciation: polymorphism for hybrid male sterility in Drosophila.

    PubMed

    Reed, Laura K; Markow, Therese A

    2004-06-15

    Capturing the process of speciation early enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an early stage.

  12. Method for early detection of cooling-loss events

    DOEpatents

    Bermudez, Sergio A.; Hamann, Hendrik; Marianno, Fernando J.

    2015-06-30

    A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

  13. Method for early detection of cooling-loss events

    DOEpatents

    Bermudez, Sergio A.; Hamann, Hendrik F.; Marianno, Fernando J.

    2015-12-22

    A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

  14. Early events in speciation: Polymorphism for hybrid male sterility in Drosophila

    PubMed Central

    Reed, Laura K.; Markow, Therese A.

    2004-01-01

    Capturing the process of speciation early enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an early stage. PMID:15184657

  15. Dermatoglyphics: a genetic marker of early childhood caries.

    PubMed

    Anitha, C; Konde, Sapna; Raj, N Sunil; Kumar, N C; Peethamber, Preetha

    2014-01-01

    It is an accepted fact that genetics plays an important role in determination of palmar dermatoglyphic patterns. Since caries is a multifactorial disease with the influence of genetic pattern, this study was undertaken to explore the possibility of dermatoglyphics as a noninvasive and early predictor of dental caries in children, so as to initiate preventive oral health measures at an early age. The study group comprised of 200 children aged between 4 and 5 years. The dmfs score was evaluated. The experimental group (Group 1), comprised of 100 children with early childhood caries (ECC) with dmfs >5. The control group (Group 2) comprised of 100 children with dmfs score of 0. An increased frequency of ulnar loops in caries-free children and whorls in children with ECC was observed. Low mean atd angle and low mean. Total ridge count was observed in the ECC group. There is definite variation in dermatoglyphics between the ECC and caries-free group, indicating that dermatoglyphic patterns can be used as a predictive tool for children with ECC.

  16. Genetic vulnerability interacts with parenting and early care education to predict increasing externalizing behavior.

    PubMed

    Lipscomb, Shannon T; Laurent, Heidemarie; Neiderhiser, Jenae M; Shaw, Daniel S; Natsuaki, Misaki N; Reiss, David; Leve, Leslie D

    2014-01-01

    The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home factors (center-based Early Care and Education; ECE). Overreactive parenting predicted more child externalizing behaviors. Attending center-based ECE was associated with increasing externalizing behaviors only for children with genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of overreactive parenting on externalizing behavior than other children.

  17. EpiGeNet: A Graph Database of Interdependencies Between Genetic and Epigenetic Events in Colorectal Cancer.

    PubMed

    Balaur, Irina; Saqi, Mansoor; Barat, Ana; Lysenko, Artem; Mazein, Alexander; Rawlings, Christopher J; Ruskin, Heather J; Auffray, Charles

    2017-10-01

    The development of colorectal cancer (CRC)-the third most common cancer type-has been associated with deregulations of cellular mechanisms stimulated by both genetic and epigenetic events. StatEpigen is a manually curated and annotated database, containing information on interdependencies between genetic and epigenetic signals, and specialized currently for CRC research. Although StatEpigen provides a well-developed graphical user interface for information retrieval, advanced queries involving associations between multiple concepts can benefit from more detailed graph representation of the integrated data. This can be achieved by using a graph database (NoSQL) approach. Data were extracted from StatEpigen and imported to our newly developed EpiGeNet, a graph database for storage and querying of conditional relationships between molecular (genetic and epigenetic) events observed at different stages of colorectal oncogenesis. We illustrate the enhanced capability of EpiGeNet for exploration of different queries related to colorectal tumor progression; specifically, we demonstrate the query process for (i) stage-specific molecular events, (ii) most frequently observed genetic and epigenetic interdependencies in colon adenoma, and (iii) paths connecting key genes reported in CRC and associated events. The EpiGeNet framework offers improved capability for management and visualization of data on molecular events specific to CRC initiation and progression.

  18. Geologic events coupled with Pleistocene climatic oscillations drove genetic variation of Omei treefrog (Rhacophorus omeimontis) in southern China.

    PubMed

    Li, Jun; Zhao, Mian; Wei, Shichao; Luo, Zhenhua; Wu, Hua

    2015-12-21

    Pleistocene climatic oscillations and historical geological events may both influence current patterns of genetic variation, and the species in southern China that faced unique climatic and topographical events have complex evolutionary histories. However, the relative contributions of climatic oscillations and geographical events to the genetic variation of these species remain undetermined. To investigate patterns of genetic variation and to test the hypotheses about the factors that shaped the distribution of this genetic variation in species of southern China, mitochondrial genes (cytochrome b and NADH dehydrogenase subunit 2) and nine microsatellite loci of the Omei tree frog (Rhacophorus omeimontis) were amplified in this study. The genetic diversity in the populations of R. omeimontis was high. The phylogenetic trees reconstructed from the mitochondrial DNA (mtDNA) haplotypes and the Bayesian genetic clustering analysis based on microsatellite data both revealed that all populations were divided into three lineages (SC, HG and YN). The two most recent splitting events among the lineages coincided with recent geological events (including the intense uplift of the Qinghai-Tibet Plateau, QTP and the subsequent movements of the Yun-Gui Plateau, YGP) and the Pleistocene glaciations. Significant expansion signals were not detected in mismatch analyses or neutrality tests. And the effective population size of each lineage was stable during the Pleistocene. Based on the results of this study, complex geological events (the recent dramatic uplift of the QTP and the subsequent movements of the YGP) and the Pleistocene glaciations were apparent drivers of the rapid divergence of the R. omeimontis lineages. Each diverged lineages survived in situ with limited gene exchanges, and the stable demographics of lineages indicate that the Pleistocene climatic oscillations were inconsequential for this species. The analysis of genetic variation in populations of R. omeimontis

  19. Genetic vulnerability interacts with parenting and early care education to predict increasing externalizing behavior

    PubMed Central

    Lipscomb, Shannon T.; Laurent, Heidemarie; Neiderhiser, Jenae M.; Shaw, Daniel S.; Natsuaki, Misaki N.; Reiss, David; Leve, Leslie D.

    2014-01-01

    The current study examined interactions among genetic influences and children’s early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home factors (center-based Early Care and Education; ECE). Overreactive parenting predicted more child externalizing behaviors. Attending center-based ECE was associated with increasing externalizing behaviors only for children with genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of overreactive parenting on externalizing behavior than other children. PMID:25067867

  20. Discrete mixture modeling to address genetic heterogeneity in time-to-event regression

    PubMed Central

    Eng, Kevin H.; Hanlon, Bret M.

    2014-01-01

    Motivation: Time-to-event regression models are a critical tool for associating survival time outcomes with molecular data. Despite mounting evidence that genetic subgroups of the same clinical disease exist, little attention has been given to exploring how this heterogeneity affects time-to-event model building and how to accommodate it. Methods able to diagnose and model heterogeneity should be valuable additions to the biomarker discovery toolset. Results: We propose a mixture of survival functions that classifies subjects with similar relationships to a time-to-event response. This model incorporates multivariate regression and model selection and can be fit with an expectation maximization algorithm, we call Cox-assisted clustering. We illustrate a likely manifestation of genetic heterogeneity and demonstrate how it may affect survival models with little warning. An application to gene expression in ovarian cancer DNA repair pathways illustrates how the model may be used to learn new genetic subsets for risk stratification. We explore the implications of this model for censored observations and the effect on genomic predictors and diagnostic analysis. Availability and implementation: R implementation of CAC using standard packages is available at https://gist.github.com/programeng/8620b85146b14b6edf8f Data used in the analysis are publicly available. Contact: kevin.eng@roswellpark.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24532723

  1. Evaluation of genetic variability among "Early Mature" Juglans regia using microsatellite markers and morphological traits.

    PubMed

    Ebrahimi, Aziz; Zarei, Abdolkarim; Zamani Fardadonbeh, Mojtaba; Lawson, Shaneka

    2017-01-01

    Limiting the juvenile phase and reducing tree size are the two main challenges for breeders to improve most fruit crops. Early maturation and dwarf cultivars have been reported for many fruit species. "Early mature" and low vigor walnut genotypes were found among seedlings of Persian walnut. Nine microsatellite markers were used to evaluate genetic diversity among "Early Mature" Persian walnut accessions and provide a comparison with "normal growth" accessions. Six maturation related characteristics were also measured in "Early Mature" samples. Phenotypic traits and diversity indices showed relatively high levels of genetic diversity in "Early Mature" seedlings and indicated high differentiation between individuals. Seedling height, the most diverse phenotypic trait, has an important role in the clustering of "Early Mature" accessions. The "Early Mature" type had higher number of alleles, number of effective allele, and Shannon index compared to the "Normal Growth" group. The two types of studied walnuts had different alleles, with more than half of produced alleles specific to a specific group. "Early Mature" and "Normal Growth" walnuts had 27 and 17 private alleles, respectively. Grouping with different methods separated "Early Mature" and "Normal Growth" samples entirely. The presence of moderate to high genetic diversity in "Early Mature" walnuts and high genetic differentiation with "Normal Growth" walnuts, indicated that "Early Mature" walnuts were more diverse and distinct from "Normal Growth" samples. Moreover, our results showed SSR markers were useful for differentiating between "Early Mature" and "Normal Growth" walnuts. A number of identified loci have potential in breeding programs for identification of "Early Mature" walnuts at the germination phase.

  2. Event-based cluster synchronization of coupled genetic regulatory networks

    NASA Astrophysics Data System (ADS)

    Yue, Dandan; Guan, Zhi-Hong; Li, Tao; Liao, Rui-Quan; Liu, Feng; Lai, Qiang

    2017-09-01

    In this paper, the cluster synchronization of coupled genetic regulatory networks with a directed topology is studied by using the event-based strategy and pinning control. An event-triggered condition with a threshold consisting of the neighbors' discrete states at their own event time instants and a state-independent exponential decay function is proposed. The intra-cluster states information and extra-cluster states information are involved in the threshold in different ways. By using the Lyapunov function approach and the theories of matrices and inequalities, we establish the cluster synchronization criterion. It is shown that both the avoidance of continuous transmission of information and the exclusion of the Zeno behavior are ensured under the presented triggering condition. Explicit conditions on the parameters in the threshold are obtained for synchronization. The stability criterion of a single GRN is also given under the reduced triggering condition. Numerical examples are provided to validate the theoretical results.

  3. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

    PubMed

    Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

    2004-09-30

    There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

  4. Quo Vadis, Medical Genetics?

    NASA Astrophysics Data System (ADS)

    Czeizel, Andrew E.

    The beginning of human genetics and its medical part: medical genetics was promising in the early decades of this century. Many genetic diseases and defects with Mendelian origin were identified and it helped families with significant genetic burden to limit their child number. Unfortunately this good start was shadowed by two tragic events. On the one hand, in the 1930s and early 1940s the German fascism brought about the dominance of an unscientific eugenics to mask vile political crimes. People with genetic diseases-defects were forced to sterilisation and several of them were killed. On the other hand, in the 1950s lysenkoism inhibitied the evolution of genetics in the Soviet Union and their satelite countries. Lysenko's doctrine declared genetics as a product of imperialism and a guilty science, therefore leading geneticists were ousted form their posts and some of them were executed or put in prison. Past decades genetics has resulted fantastic new results and achieved a leading position within the natural sciences. To my mind, however, the expected wider use of new eugenics indicates a new tragedy and this Cassandra's prediction is the topic of this presentation.

  5. Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins

    PubMed Central

    Silberg, Judy L.; Gillespie, Nathan; Moore, Ashlee A.; Eaves, Lindon J.; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

    2015-01-01

    Objective Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. Method We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Results Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. Conclusions There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children. PMID:25728588

  6. Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins.

    PubMed

    Silberg, Judy L; Gillespie, Nathan; Moore, Ashlee A; Eaves, Lindon J; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

    2015-04-01

    Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.

  7. Genetic Determinism of Primary Early-Onset Osteoarthritis.

    PubMed

    Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence.

    PubMed

    Humphreys, Kathryn L; Watts, Emily L; Dennis, Emily L; King, Lucy S; Thompson, Paul M; Gotlib, Ian H

    2018-05-21

    Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

  9. Unraveling Genetic and Environmental Components of Early Literacy: A Twin Study

    ERIC Educational Resources Information Center

    Bus, A. G.; Out, D.

    2009-01-01

    Even though the acquisition of early literacy skills obviously depends on stimuli and incentives in children's environment we may expect that genes define the constraints for acquiring some or all early literacy skills. Therefore behavior genetic analyses were carried out on twin data including 27 identical and 39 same sex dizygotic twins, 4 years…

  10. Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients.

    PubMed

    Lew, Daniel; Yoon, Soon Man; Yan, Xiaofei; Robbins, Lori; Haritunians, Talin; Liu, Zhenqiu; Li, Dalin; McGovern, Dermot Pb

    2017-10-28

    To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations. This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure. Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients (21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the anti-TNF agent. In total: n = 66 (5%) infusion reactions; n = 49 (4%) allergic/serum sickness reactions; n = 19 (1.5%) lupus-like reactions, n = 52 (4%) rash, n = 18 (1.4%) infections. In Crohn's disease, IgA ASCA ( P = 0.04) and IgG-ASCA ( P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions ( P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT (Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. Our study shows 1 in 5 IBD patients experience an adverse

  11. Tracking a genetic signal of extinction-recolonization events in a neotropical tree species: Vouacapoua americana Aublet in French Guiana.

    PubMed

    Dutech, Cyril; Maggia, Laurent; Tardy, Christophe; Joly, Hélène I; Jarne, Philippe

    2003-12-01

    Drier periods from the late Pleistocene and early Holocene have been hypothesized to have caused the disappearance of various rainforest species over large geographical areas in South America and restricted the extant populations to mesic sites. Subsequent improvement in climatic conditions has been associated with recolonization. Changes in population size associated with these extinction-recolonization events should have affected genetic diversity within species. However, these historical hypotheses and their genetic consequences have rarely been tested in South America. Here, we examine the diversity of the chloroplast and nuclear genomes in a Neotropical rainforest tree species, Vouacapoua americana (Leguminosae, Caesalpinioideae) in French Guiana. The chloroplast diversity was analyzed using a polymerase chain reaction-restriction fragment length polymorphism method (six pairs of primers) in 29 populations distributed over most of French Guiana, and a subset of 17 populations was also analyzed at nine polymorphic microsatellite loci. To determine whether this species has experienced extinction-recolonization, we sampled populations in areas supposedly not or only slightly affected by climatic changes, where the populations would not have experienced frequent extinction, and in areas that appear to have been recently recolonized. In the putatively recolonized areas, we found patches of several thousands of hectares homogeneous for chloroplast variation that can be interpreted as the effect of recolonization processes from several geographical origins. In addition, we observed that, for both chloroplast and nuclear genomes, the populations in newly recolonized areas exhibited a significantly smaller allelic richness than others. Controlling for geographic distance, we also detected a significant correlation between chloroplast and nuclear population differentiation. This result indicates a cytonuclear disequilibrium that can be interpreted as a historical signal

  12. Impacts of early viability selection on management of inbreeding and genetic diversity in conservation.

    PubMed

    Grueber, Catherine E; Hogg, Carolyn J; Ivy, Jamie A; Belov, Katherine

    2015-04-01

    Maintaining genetic diversity is a crucial goal of intensive management of threatened species, particularly for those populations that act as sources for translocation or re-introduction programmes. Most captive genetic management is based on pedigrees and a neutral theory of inheritance, an assumption that may be violated by selective forces operating in captivity. Here, we explore the conservation consequences of early viability selection: differential offspring survival that occurs prior to management or research observations, such as embryo deaths in utero. If early viability selection produces genotypic deviations from Mendelian predictions, it may undermine management strategies intended to minimize inbreeding and maintain genetic diversity. We use empirical examples to demonstrate that straightforward approaches, such as comparing litter sizes of inbred vs. noninbred breeding pairs, can be used to test whether early viability selection likely impacts estimates of inbreeding depression. We also show that comparing multilocus genotype data to pedigree predictions can reveal whether early viability selection drives systematic biases in genetic diversity, patterns that would not be detected using pedigree-based statistics alone. More sophisticated analysis combining genomewide molecular data with pedigree information will enable conservation scientists to test whether early viability selection drives deviations from neutrality across wide stretches of the genome, revealing whether this form of selection biases the pedigree-based statistics and inference upon which intensive management is based. © 2015 John Wiley & Sons Ltd.

  13. Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

    PubMed

    Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

    2014-10-13

    Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

  14. Dispersal, mating events and fine-scale genetic structure in the lesser flat-headed bats.

    PubMed

    Hua, Panyu; Zhang, Libiao; Guo, Tingting; Flanders, Jon; Zhang, Shuyi

    2013-01-01

    Population genetic structure has important consequences in evolutionary processes and conservation genetics in animals. Fine-scale population genetic structure depends on the pattern of landscape, the permanent movement of individuals, and the dispersal of their genes during temporary mating events. The lesser flat-headed bat (Tylonycteris pachypus) is a nonmigratory Asian bat species that roosts in small groups within the internodes of bamboo stems and the habitats are fragmented. Our previous parentage analyses revealed considerable extra-group mating in this species. To assess the spatial limits and sex-biased nature of gene flow in the same population, we used 20 microsatellite loci and mtDNA sequencing of the ND2 gene to quantify genetic structure among 54 groups of adult flat-headed bats, at nine localities in South China. AMOVA and F(ST) estimates revealed significant genetic differentiation among localities. Alternatively, the pairwise F(ST) values among roosting groups appeared to be related to the incidence of associated extra-group breeding, suggesting the impact of mating events on fine-scale genetic structure. Global spatial autocorrelation analyses showed positive genetic correlation for up to 3 km, indicating the role of fragmented habitat and the specialized social organization as a barrier in the movement of individuals among bamboo forests. The male-biased dispersal pattern resulted in weaker spatial genetic structure between localities among males than among females, and fine-scale analyses supported that relatedness levels within internodes were higher among females than among males. Finally, only females were more related to their same sex roost mates than to individuals from neighbouring roosts, suggestive of natal philopatry in females.

  15. The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

    PubMed

    Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

    2016-04-05

    Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. Copyright © 2016 Cadena et al.

  16. Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer.

    PubMed

    Sugishita, Mihoko; Imai, Tsuneo; Kikumori, Toyone; Mitsuma, Ayako; Shimokata, Tomoya; Shibata, Takashi; Morita, Sachi; Inada-Inoue, Megumi; Sawaki, Masataka; Hasegawa, Yoshinori; Ando, Yuichi

    2016-03-01

    Genetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear. This study retrospectively explored pharmacogenetic associations of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 2B7 (UGT2B7, rs7668258), glutathione-S-transferase pi 1 (GSTP1, rs1695), and microcephalin 1 (MCPH1, rs2916733) genes with chemotherapy-related adverse events in 102 Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer. The allele frequencies for all of the SNPs were in concordance with the Hap-Map data of Japanese individuals. Among the 24 patients who had FN at least once during all courses of chemotherapy, 23 had the A/A genotype, and 1 had the A/G genotype of the GSTP1 polymorphism (rs1695, P = 0.001); 23 of the 70 patients with the A/A genotype had FN, as compared with only 1 of the 32 patients with the A/G and G/G genotypes. The genotype distributions of the UGT2B7 and MCPH1 polymorphisms did not differ between the patients who had FN or grade 3/4 neutropenia and those who did not. Among Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer, those with the A/A genotype of the GSTP1 polymorphism (rs1695) were more likely to have FN.

  17. Chemical event chain model of coupled genetic oscillators.

    PubMed

    Jörg, David J; Morelli, Luis G; Jülicher, Frank

    2018-03-01

    We introduce a stochastic model of coupled genetic oscillators in which chains of chemical events involved in gene regulation and expression are represented as sequences of Poisson processes. We characterize steady states by their frequency, their quality factor, and their synchrony by the oscillator cross correlation. The steady state is determined by coupling and exhibits stochastic transitions between different modes. The interplay of stochasticity and nonlinearity leads to isolated regions in parameter space in which the coupled system works best as a biological pacemaker. Key features of the stochastic oscillations can be captured by an effective model for phase oscillators that are coupled by signals with distributed delays.

  18. Chemical event chain model of coupled genetic oscillators

    NASA Astrophysics Data System (ADS)

    Jörg, David J.; Morelli, Luis G.; Jülicher, Frank

    2018-03-01

    We introduce a stochastic model of coupled genetic oscillators in which chains of chemical events involved in gene regulation and expression are represented as sequences of Poisson processes. We characterize steady states by their frequency, their quality factor, and their synchrony by the oscillator cross correlation. The steady state is determined by coupling and exhibits stochastic transitions between different modes. The interplay of stochasticity and nonlinearity leads to isolated regions in parameter space in which the coupled system works best as a biological pacemaker. Key features of the stochastic oscillations can be captured by an effective model for phase oscillators that are coupled by signals with distributed delays.

  19. Plants with stacked genetically modified events: to assess or not to assess?

    PubMed

    Kok, Esther J; Pedersen, Jan; Onori, Roberta; Sowa, Slawomir; Schauzu, Marianna; De Schrijver, Adinda; Teeri, Teemu H

    2014-02-01

    The principles for the safety assessment of genetically modified (GM) organisms (GMOs) are harmonised worldwide to a large extent. There are, however, still differences between the European GMO regulations and the GMO regulations as they have been formulated in other parts of the world. One of these differences relates to the so-called 'stacked GM events', that is, GMOs, plants so far, where new traits are combined by conventional crossing of different GM plants. This paper advocates rethinking the current food/feed safety assessment of stacked GM events in Europe based on an analysis of different aspects that currently form the rationale for the safety assessment of stacked GM events. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Microdissecting the Genetic Events in Nephrogenic Rests and Wilms’ Tumor Development

    PubMed Central

    Charles, Adrian K.; Brown, Keith W.; Berry, P. Jeremy

    1998-01-01

    Nephrogenic rests are precursor lesions associated with about 40% of Wilms’ tumors. This study identifies genetic steps occurring in the development of Wilms’ tumor. Thirty-four Wilms’ tumors with nephrogenic rests and/or areas of anaplasia were microdissected from paraffin sections to determine whether and at what stage loss of heterozygosity (LOH) occurred, using polymerase chain reaction-based polymorphic markers at 11p13, 11p15, and 16q. LOH at these loci have been identified in Wilms’ tumors and are associated with identified or putative tumor suppressor genes. Three cystic nephromas/cystic partially differentiated nephroblastomas were also examined. LOH was detected in six cases at 11p13 and in six cases at 11p15, and two of these cases had LOH at both loci. All intralobar rests showing LOH also showed LOH in the tumor. A case with a small perilobar rest showed LOH of 11p13 only in the tumor. Five cases showing LOH at 16q were identified (this was identified only in the tumor, and not in the associated rest), and three of these had recurrence of the tumor. Two cases had a WT1 mutation (one germline and the other somatic), as well as LOH in both the intralobar rest and the tumor. A cystic partially differentiated nephroblastoma showed loss at 11p13 and 11p15, as well as at 16q. This study suggests that LOH at 11p13 and 11p15 and WT1 mutations are early events but that LOH at 16q occurs late in the pathogenesis of Wilms’ tumor. Intralobar and perilobar nephrogenic rests are known to have different biological behaviors, and this study suggests that they are genetically different. A multistep model of Wilms’ tumor pathogenesis is supported by these findings. PMID:9736048

  1. Combining epidemiological and genetic networks signifies the importance of early treatment in HIV-1 transmission.

    PubMed

    Zarrabi, Narges; Prosperi, Mattia; Belleman, Robert G; Colafigli, Manuela; De Luca, Andrea; Sloot, Peter M A

    2012-01-01

    Inferring disease transmission networks is important in epidemiology in order to understand and prevent the spread of infectious diseases. Reconstruction of the infection transmission networks requires insight into viral genome data as well as social interactions. For the HIV-1 epidemic, current research either uses genetic information of patients' virus to infer the past infection events or uses statistics of sexual interactions to model the network structure of viral spreading. Methods for a reliable reconstruction of HIV-1 transmission dynamics, taking into account both molecular and societal data are still lacking. The aim of this study is to combine information from both genetic and epidemiological scales to characterize and analyse a transmission network of the HIV-1 epidemic in central Italy.We introduce a novel filter-reduction method to build a network of HIV infected patients based on their social and treatment information. The network is then combined with a genetic network, to infer a hypothetical infection transmission network. We apply this method to a cohort study of HIV-1 infected patients in central Italy and find that patients who are highly connected in the network have longer untreated infection periods. We also find that the network structures for homosexual males and heterosexual populations are heterogeneous, consisting of a majority of 'peripheral nodes' that have only a few sexual interactions and a minority of 'hub nodes' that have many sexual interactions. Inferring HIV-1 transmission networks using this novel combined approach reveals remarkable correlations between high out-degree individuals and longer untreated infection periods. These findings signify the importance of early treatment and support the potential benefit of wide population screening, management of early diagnoses and anticipated antiretroviral treatment to prevent viral transmission and spread. The approach presented here for reconstructing HIV-1 transmission networks

  2. Early onset of disc degeneration in SM/J mice is associated with changes in ion transport systems and fibrotic events.

    PubMed

    Zhang, Ying; Xiong, Chi; Kudelko, Mateusz; Li, Yan; Wang, Cheng; Wong, Yuk Lun; Tam, Vivian; Rai, Muhammad Farooq; Cheverud, James; Lawson, Heather A; Sandell, Linda; Chan, Wilson C W; Cheah, Kathryn S E; Sham, Pak C; Chan, Danny

    2018-04-09

    Intervertebral disc degeneration (IDD) causes back pain and sciatica, affecting quality of life and resulting in high economic/social burden. The etiology of IDD is not well understood. Along with aging and environmental factors, genetic factors also influence the onset, progression and severity of IDD. Genetic studies of risk factors for IDD using human cohorts are limited by small sample size and low statistical power. Animal models amenable to genetic and functional studies of IDD provide desirable alternatives. Despite differences in size and cellular content as compared to human intervertebral discs (IVDs), the mouse is a powerful model for genetics and assessment of cellular changes relevant to human biology. Here, we provide evidence for early onset disc degeneration in SM/J relative to LG/J mice with poor and good tissue healing capacity respectively. In the first few months of life, LG/J mice maintain a relatively constant pool of notochordal-like cells in the nucleus pulposus (NP) of the IVD. In contrast, chondrogenic events are observed in SM/J mice beginning as early as one-week-old, with progressive fibrotic changes. Further, the extracellular matrix changes in the NP are consistent with IVD degeneration. Leveraging on the genomic data of two parental and two recombinant inbred lines, we assessed the genetic contribution to the NP changes and identified processes linked to the regulation of ion transport systems. Significantly, "transport" system is also in the top three gene ontology (GO) terms from a comparative proteomic analysis of the mouse NP. These findings support the potential of the SM/J, LG/J and their recombinant inbred lines for future genetic and biological analysis in mice and validation of candidate genes and biological relevance in human cohort studies. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008784. Copyright © 2017. Published by

  3. Early genetic evaluation of open-pollinated Douglas-fir families

    Treesearch

    Kurt H. Riitters; David A. Perry

    1987-01-01

    In a test of early genetic evaluation of the growth potential of 14 families of open-pollinated Douglas-fir (Pseudotsuga menziesii) [Mirb.] Franco), measures of growth and phenology of seedligns grown in a coldframe were correlated with height of saplings in evaluation plantations at 9, 12, and 15 years. fifteen-year height was most strongly...

  4. Callous-unemotional behaviors in early childhood: Genetic and environmental contributions to stability and change.

    PubMed

    Flom, Megan; Saudino, Kimberly J

    2017-10-01

    Callous-unemotional (CU) behaviors demonstrate meaningful individual differences in early childhood, even in nonclinical samples with low mean levels of CU, but the factors underlying this variation have not been examined. This study investigated genetic and environmental contributions to individual differences and to sources of continuity and change in CU in toddler twins (145 monozygotic, 169 dizygotic) assessed at ages 2 and 3 years. CU, as assessed by the Child Behavior Checklist 1.5-5 (Achenbach & Rescorla, 2000), was moderately stable across age (r = .45, p < .0001). Longitudinal biometric analyses revealed genetic and nonshared environmental influences on CU at both ages, with no significant contribution from shared environmental factors. Stability from age 2 to 3 was due to genetic factors, whereas change was due to both genetic and nonshared environmental influences. This genetic and nonshared environmental change was substantial, suggesting malleability of CU in early childhood. Over 50% of the genetic influences and 100% of the nonshared environmental influences on CU at age 3 were independent of those that operated at age 2. Implications of novel sources of variance across age are discussed.

  5. Heritable influences on behavioural problems from early childhood to mid-adolescence: evidence for genetic stability and innovation.

    PubMed

    Lewis, G J; Plomin, R

    2015-07-01

    Although behavioural problems (e.g., anxiety, conduct, hyperactivity, peer problems) are known to be heritable both in early childhood and in adolescence, limited work has examined prediction across these ages, and none using a genetically informative sample. We examined, first, whether parental ratings of behavioural problems (indexed by the Strengths and Difficulties questionnaire) at ages 4, 7, 9, 12, and 16 years were stable across these ages. Second, we examined the extent to which stability reflected genetic or environmental effects through multivariate quantitative genetic analysis on data from a large (n > 3000) population (UK) sample of monozygotic and dizygotic twins. Behavioural problems in early childhood (age 4 years) showed significant associations with the corresponding behavioural problem at all subsequent ages. Moreover, stable genetic influences were observed across ages, indicating that biological bases underlying behavioural problems in adolescence are underpinned by genetic influences expressed as early as age 4 years. However, genetic and environmental innovations were also observed at each age. These observations indicate that genetic factors are important for understanding stable individual differences in behavioural problems across childhood and adolescence, although novel genetic influences also facilitate change in such behaviours.

  6. Early/fast VLF events produced by the quiescent heating of the lower ionosphere by thunderstorms

    NASA Astrophysics Data System (ADS)

    Kabirzadeh, R.; Marshall, R. A.; Inan, U. S.

    2017-06-01

    Large and easily distinguishable perturbations of the VLF transmitter signals due to interactions with thundercloud-driven ionospheric modifications have been observed and studied for about three decades. These events are called "early/fast VLF" or "early VLF" events due to their immediate detection (˜20 ms) after the causative lightning flash on the ground and the fast rise time of the perturbed signal. Despite many years of study, the physical mechanisms responsible for these perturbations are still under investigation. Modifications of the sustained heating level of the ionosphere due to a lightning flash has been previously proposed as the causative mechanism of early/fast VLF events. The perturbations predicted by this mechanism, however, have been much smaller than experimental observations of 0.2-1 dB or higher. In this study, by using an improved 3-D thundercloud electrostatic upward coupling model which uses a realistic geomagnetic field, we find that the sustained heating model can predict perturbations that are consistent with reported experimental observations. Modifications in the quiescent heating of the lower ionosphere by thundercloud fields by individual lightning flashes may thus account for some observations of early/fast VLF events.

  7. The genetic-environmental etiology of cognitive school readiness and later academic achievement in early childhood.

    PubMed

    Lemelin, Jean-Pascal; Boivin, Michel; Forget-Dubois, Nadine; Dionne, Ginette; Séguin, Jean R; Brendgen, Mara; Vitaro, Frank; Tremblay, Richard E; Pérusse, Daniel

    2007-01-01

    Using a genetic design of 840 60-month-old twins, this study investigated the genetic and environmental contributions to (a) individual differences in four components of cognitive school readiness, (b) the general ability underlying these four components, and (c) the predictive association between school readiness and school achievement. Results revealed that the contribution of the shared environment for cognitive school readiness was substantial. Genetic effects were more important for the core abilities underlying school readiness than for each specific skill, although shared environment remained the largest factor overall. Genetic, shared, and nonshared environmental factors all accounted for the predictive association between school readiness and early school achievement. These results contribute to a better understanding of the early determinants of school readiness.

  8. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

    PubMed

    Mega, J L; Stitziel, N O; Smith, J G; Chasman, D I; Caulfield, M; Devlin, J J; Nordio, F; Hyde, C; Cannon, C P; Sacks, F; Poulter, N; Sever, P; Ridker, P M; Braunwald, E; Melander, O; Kathiresan, S; Sabatine, M S

    2015-06-06

    Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease

  9. Longitudinal stability of cognitive ability from infancy to early childhood: genetic and environmental etiologies.

    PubMed

    LaBuda, M C; DeFries, J C; Plomin, R; Fulker, D W

    1986-10-01

    A path model of genetic and shared family environmental transmission was fitted to general cognitive ability data from 1-, 2-, 3-, and 4-year-old adopted and nonadopted children and their parents in order to assess the etiology of longitudinal stability from infancy to early childhood. Stability across years is moderate and is due mainly to influences not predicted by parental IQ. Results of the present study, in conjunction with those of previous twin studies, suggest substantial genetic stability from infancy and early childhood to adulthood.

  10. Can mutation-mediated effects occurring early in development cause long-term seizure susceptibility in genetic generalized epilepsies?

    PubMed

    Reid, Christopher Alan; Rollo, Ben; Petrou, Steven; Berkovic, Samuel F

    2018-05-01

    Epilepsy has a strong genetic component, with an ever-increasing number of disease-causing genes being discovered. Most epilepsy-causing mutations are germ line and thus present from conception. These mutations are therefore well positioned to have a deleterious impact during early development. Here we review studies that investigate the role of genetic lesions within the early developmental window, specifically focusing on genetic generalized epilepsy (GGE). Literature on the potential pathogenic role of sub-mesoscopic structural changes in GGE is also reviewed. Evidence from rodent models of genetic epilepsy support the idea that functional and structural changes can occur in early development, leading to altered seizure susceptibility into adulthood. Both animal and human studies suggest that sub-mesoscopic structural changes occur in GGE. The existence of sub-mesoscopic structural changes prior to seizure onset may act as biomarkers of excitability in genetic epilepsies. We also propose that presymptomatic treatment may be essential for limiting the long-term consequences of disease-causing mutations in genetic epilepsies. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

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

    PubMed Central

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

    2017-01-01

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

  12. Persistence of carbon release events through the peak of early Eocene global warmth

    NASA Astrophysics Data System (ADS)

    Kirtland Turner, Sandra; Sexton, Philip F.; Charles, Christopher D.; Norris, Richard D.

    2014-10-01

    The Early Eocene Climatic Optimum (53-50 million years ago) was preceded by approximately six million years of progressive global warming. This warming was punctuated by a series of rapid hyperthermal warming events triggered by the release of greenhouse gases. Over these six million years, the carbon isotope record suggests that the events became more frequent but smaller in magnitude. This pattern has been suggested to reflect a thermodynamic threshold for carbon release that was more easily crossed as global temperature rose, combined with a decrease in the size of carbon reservoirs during extremely warm conditions. Here we present a continuous, 4.25-million-year-long record of the stable isotope composition of carbonate sediments from the equatorial Atlantic, spanning the peak of early Eocene global warmth. A composite of this and pre-existing records shows that the carbon isotope excursions that identify the hyperthermals exhibit continuity in magnitude and frequency throughout the approximately 10-million-year period covering the onset, peak and termination of the Early Eocene Climate Optimum. We suggest that the carbon cycle processes behind these events, excluding the largest event, the Palaeocene-Eocene Thermal Maximum (about 56 million years ago), were not exceptional. Instead, we argue that the hyperthermals may reflect orbital forcing of the carbon cycle analogous to the mechanisms proposed to operate in the cooler Oligocene and Miocene.

  13. Stressful life events and depressive problems in early adolescent boys and girls: the influence of parental depression, temperament and family environment.

    PubMed

    Bouma, Esther M C; Ormel, Johan; Verhulst, Frank C; Oldehinkel, Albertine J

    2008-01-01

    Stressful life events increase the probability of depressive problems in early adolescence. Several genetic and environmental risk factors may change individual sensitivity to the depressogenic effect of these events. We examined modification by parental depression and gender, and mediation of the former by temperament and family environment. Data were collected as part of a longitudinal cohort study of (pre)adolescents (n = 2127). During the first assessment wave at approximately age 11, we assessed parental depression, family functioning, perceived parenting behaviours, and temperamental frustration and fearfulness. At the second wave, about two and a half years later, stressful life events between the first and second assessment were assessed. Depressive problems were measured at both waves. Adolescents with parents who had a (lifetime) depressive episode were more sensitive to the depressogenic effect of stressful events than adolescents without depressed parents. Furthermore, girls are more sensitive to these effects than boys. The modifying effect of parental depression was not mediated by temperament, family functioning and perceived parenting. Life events were assessed without consideration of contextual information. Depressive problems were measured by questionnaires that did not directly represent DSM-IV criteria. The measure of parental depression was unspecific regarding severity and timing of depressive episodes. The results suggest that gender and parental depression are associated with increased sensitivity to depression after experiencing stressful life events during adolescence.

  14. Ophthalmic Vascular Events after Primary Unilateral Intra-arterial Chemotherapy for Retinoblastoma in Early and Recent Eras.

    PubMed

    Dalvin, Lauren A; Ancona-Lezama, David; Lucio-Alvarez, J Antonio; Masoomian, Babak; Jabbour, Pascal; Shields, Carol L

    2018-06-16

    To assess risk factors for ophthalmic vascular events after intra-arterial chemotherapy (IAC) for retinoblastoma. Retrospective cohort study. Patients who received unilateral IAC as primary treatment for retinoblastoma from January 1, 2009, to November 30, 2017, at a single center. Records were reviewed for patient demographics, tumor features, IAC parameters, and treatment-related vascular events in the early IAC era (2009-2011) compared with the recent era (2012-2017) using the t test and Fisher exact test. Change in event rates over time was assessed using Poisson regression analysis, with Spearman's rho used to test correlation. Rate of IAC-induced ophthalmic vascular events. There were 243 chemotherapy infusions in 76 eyes of 76 patients, divided into early (22 eyes, 57 infusions) and recent (54 eyes, 186 infusions) eras. Intra-arterial chemotherapy consisted of melphalan (243 infusions), topotecan (124 infusions), and carboplatin (9 infusions). A comparison (early vs. recent era) revealed fewer mean number of infusions (2.6 vs. 3.4, P = 0.02) with similar mean patient age and presenting tumor features. Event rates decreased over time (P < 0.01), with fewer ophthalmic vascular events (early era vs. recent era) in the recent era (59% vs. 9% per eye, 23% vs. 3% per infusion, P < 0.01), including peripheral retinal nonperfusion (5% vs. 2% per eye, P = 0.50), vitreous hemorrhage (9% vs. 2%, P = 0.20), subretinal hemorrhage (0% vs. 2%, P = 0.99), branch retinal vein occlusion (5% vs. 0%, P = 0.29), choroidal ischemia (14% vs. 4%, P = 0.14), and ophthalmic artery spasm/occlusion (27% vs. 0%, P < 0.01). Events did not correlate to patient age (P = 0.75), tumor diameter (P = 0.32), tumor thickness (P = 0.59), or cumulative dosage of melphalan (P = 0.13) or topotecan (P = 0.59). There were no IAC-induced vascular events in 72 infusions of 21 consecutively treated eyes in 2016 to 2017. Ophthalmic vascular events after IAC have decreased from the early era

  15. A review on neuroimaging studies of genetic and environmental influences on early brain development.

    PubMed

    Gao, Wei; Grewen, Karen; Knickmeyer, Rebecca C; Qiu, Anqi; Salzwedel, Andrew; Lin, Weili; Gilmore, John H

    2018-04-16

    The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Genetic and environmental factors affecting early rooting of six Populus genomic groups: implications for tree improvement

    Treesearch

    Ronald S., Jr. Zalesny

    2006-01-01

    Genetic and environmental factors affect the early rooting of Populus planted as unrooted hardwood cuttings. Populus genotypes of six genomic groups were tested in numerous studies for the quantitative genetics of rooting, along with effects of preplanting treatments and soil temperature. Genetics data (e.g. heritabilities,...

  17. Genetic and linguistic coevolution in Northern Island Melanesia.

    PubMed

    Hunley, Keith; Dunn, Michael; Lindström, Eva; Reesink, Ger; Terrill, Angela; Healy, Meghan E; Koki, George; Friedlaender, Françoise R; Friedlaender, Jonathan S

    2008-10-01

    Recent studies have detailed a remarkable degree of genetic and linguistic diversity in Northern Island Melanesia. Here we utilize that diversity to examine two models of genetic and linguistic coevolution. The first model predicts that genetic and linguistic correspondences formed following population splits and isolation at the time of early range expansions into the region. The second is analogous to the genetic model of isolation by distance, and it predicts that genetic and linguistic correspondences formed through continuing genetic and linguistic exchange between neighboring populations. We tested the predictions of the two models by comparing observed and simulated patterns of genetic variation, genetic and linguistic trees, and matrices of genetic, linguistic, and geographic distances. The data consist of 751 autosomal microsatellites and 108 structural linguistic features collected from 33 Northern Island Melanesian populations. The results of the tests indicate that linguistic and genetic exchange have erased any evidence of a splitting and isolation process that might have occurred early in the settlement history of the region. The correlation patterns are also inconsistent with the predictions of the isolation by distance coevolutionary process in the larger Northern Island Melanesian region, but there is strong evidence for the process in the rugged interior of the largest island in the region (New Britain). There we found some of the strongest recorded correlations between genetic, linguistic, and geographic distances. We also found that, throughout the region, linguistic features have generally been less likely to diffuse across population boundaries than genes. The results from our study, based on exceptionally fine-grained data, show that local genetic and linguistic exchange are likely to obscure evidence of the early history of a region, and that language barriers do not particularly hinder genetic exchange. In contrast, global patterns may

  18. Genetic and Linguistic Coevolution in Northern Island Melanesia

    PubMed Central

    Hunley, Keith; Dunn, Michael; Lindström, Eva; Reesink, Ger; Terrill, Angela; Healy, Meghan E.; Koki, George; Friedlaender, Françoise R.; Friedlaender, Jonathan S.

    2008-01-01

    Recent studies have detailed a remarkable degree of genetic and linguistic diversity in Northern Island Melanesia. Here we utilize that diversity to examine two models of genetic and linguistic coevolution. The first model predicts that genetic and linguistic correspondences formed following population splits and isolation at the time of early range expansions into the region. The second is analogous to the genetic model of isolation by distance, and it predicts that genetic and linguistic correspondences formed through continuing genetic and linguistic exchange between neighboring populations. We tested the predictions of the two models by comparing observed and simulated patterns of genetic variation, genetic and linguistic trees, and matrices of genetic, linguistic, and geographic distances. The data consist of 751 autosomal microsatellites and 108 structural linguistic features collected from 33 Northern Island Melanesian populations. The results of the tests indicate that linguistic and genetic exchange have erased any evidence of a splitting and isolation process that might have occurred early in the settlement history of the region. The correlation patterns are also inconsistent with the predictions of the isolation by distance coevolutionary process in the larger Northern Island Melanesian region, but there is strong evidence for the process in the rugged interior of the largest island in the region (New Britain). There we found some of the strongest recorded correlations between genetic, linguistic, and geographic distances. We also found that, throughout the region, linguistic features have generally been less likely to diffuse across population boundaries than genes. The results from our study, based on exceptionally fine-grained data, show that local genetic and linguistic exchange are likely to obscure evidence of the early history of a region, and that language barriers do not particularly hinder genetic exchange. In contrast, global patterns may

  19. Molecular-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation event in the VHL gene.

    PubMed

    Glushkova, Maria; Dimova, Petia; Yordanova, Iglika; Todorov, Tihomir; Tourtourikov, Ivan; Mitev, Vanyo; Todorova, Albena

    2018-02-01

    Von Hippel-Lindau syndrome is an autosomal-dominant disease characterized by the formation of various tumours and cysts in many different parts of the body. Von Hippel-Lindau syndrome is caused by VHL gene mutations leading to production of impaired tumor suppressor Von Hippel-Lindau syndrome protein or its complete absence. To study five patients with clinically suspected Von Hippel-Lindau syndrome, who were referred for molecular genetic testing. Sanger sequencing of the coding regions of the VHL gene. Five clinically relevant germline mutations were detected. One of the pathogenic variants has not been previously reported. This novel mutation is a complex mutation event combining a duplication and an indel, rearranging exon 3 of the VHL gene - c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4). Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, early genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.

  20. Embryological Development: Evolutionary History, Genetic Bias, and Cellular Environment Control the Flow of Developmental Events. Part I.

    ERIC Educational Resources Information Center

    Caplan, Arnold I.

    1981-01-01

    Describes development of the limb and various interactions necessary for the expression of its unique form and phenotypes to uncover the hierarchical controlling steps in the development process for the potential of avoiding abnormal events and manipulating what might be detrimental genetic events into a normal sequence. (Author/SK)

  1. Does Religious Involvement Protect against Early Drinking? A Behavior Genetic Approach

    ERIC Educational Resources Information Center

    Harden, K. Paige

    2010-01-01

    Background: Adolescent involvement in religious organizations has been hypothesized to protect against early age at first drink. However, the correlation between adolescent religiosity and later age at first drink may be confounded by environmental or genetic differences between families. This study tests whether, after controlling for shared…

  2. Molecular genetics of early-onset Alzheimer's disease revisited.

    PubMed

    Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

    2016-06-01

    As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Impact Constraints on Major Events in Early Mars History

    NASA Technical Reports Server (NTRS)

    Frey, H. V.

    2004-01-01

    MOLA data have revealed a large population of "Quasi-Circular Depressions" (QCDs) with little or no visible expression in image data. These likely buried impact basins have important implications for the age of the lowland crust, how that compares with original highland crust, and when and how the crustal dichotomy may have formed. The buried lowlands are of Early Noachian age, likely slightly younger than the buried highlands but older than the exposed (visible) highland surface. A depopulation of large visible basins at diameters 800 to 1300 km suggests some global scale event early in martian history, maybe related to the formation of the lowlands and/or the development of Tharsis. A suggested early disappearance of the global magnetic field can be placed within a temporal sequence of formation of the very largest impact basins. The global field appears to have disappeared at about the time the lowlands formed. It seems likely the topographic crustal dichotomy was produced very early in martian history by processes which operated very quickly. Thus there appears to have been a northern lowland throughout nearly all of martian history, predating the last of the really large impacts (Hellas, Argyre and Isidis) and their likely very significant environmental consequences.

  4. Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

    PubMed Central

    Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

    2011-01-01

    Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

  5. Event-specific qualitative and quantitative detection of five genetically modified rice events using a single standard reference molecule.

    PubMed

    Kim, Jae-Hwan; Park, Saet-Byul; Roh, Hyo-Jeong; Shin, Min-Ki; Moon, Gui-Im; Hong, Jin-Hwan; Kim, Hae-Yeong

    2017-07-01

    One novel standard reference plasmid, namely pUC-RICE5, was constructed as a positive control and calibrator for event-specific qualitative and quantitative detection of genetically modified (GM) rice (Bt63, Kemingdao1, Kefeng6, Kefeng8, and LLRice62). pUC-RICE5 contained fragments of a rice-specific endogenous reference gene (sucrose phosphate synthase) as well as the five GM rice events. An existing qualitative PCR assay approach was modified using pUC-RICE5 to create a quantitative method with limits of detection correlating to approximately 1-10 copies of rice haploid genomes. In this quantitative PCR assay, the square regression coefficients ranged from 0.993 to 1.000. The standard deviation and relative standard deviation values for repeatability ranged from 0.02 to 0.22 and 0.10% to 0.67%, respectively. The Ministry of Food and Drug Safety (Korea) validated the method and the results suggest it could be used routinely to identify five GM rice events. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Research Issues in Genetic Testing of Adolescents for Obesity

    PubMed Central

    Segal, Mary E.; Sankar, Pamela; Reed, Danielle R.

    2006-01-01

    Obesity is often established in adolescence, and advances are being made in identifying its genetic underpinnings. We examine issues related to the eventual likelihood of genetic tests for obesity targeted to adolescents: family involvement; comprehension of the test’s meaning; how knowledge of genetic status may affect psychological adaptation; minors’ ability to control events; parental/child autonomy; ability to make informed medical decisions; self-esteem; unclear distinctions between early/late onset for this condition; and social stigmatization. The public health arena will be important in educating families about possible future genetic tests for obesity. PMID:15478685

  7. Dose and Effect Thresholds for Early Key Events in a Mode of PPARa-Mediated Action

    EPA Science Inventory

    ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. T...

  8. Genetic and environmental influences on non-specific neck pain in early adolescence: A classical twin study

    PubMed Central

    Ståhl, Minna K; El-Metwally, Ashraf A; Mikkelsson, Marja K; Salminen, Jouko J; Pulkkinen, Lea R; Rose, Richard J; Kaprio, Jaakko A

    2012-01-01

    Background Prevalence of neck pain has increased among adolescents. The origins of adult chronic neck pain may lie in late childhood, but for early prevention, more information is needed about its aetiology. We investigated the relative roles of genetic and environmental factors in early adolescent neck pain with a classic twin study. Methods Frequency of neck pain was assessed with a validated pain questionnaire in a population-based sample of nearly 1800 pairs of 11–12-year-old Finnish twins. Twin pair similarity for neck pain was quantified by polychoric correlations, and variance components were estimated with biometric structural equation modelling. Results Prevalence of neck pain reported at least once monthly was 38% and at least once weekly 16%, with no significant differences between gender or zygosity. A greater polychoric correlation in liability to neck pain was found in monozygotic (0.67) than for dizygotic pairs (0.38), suggesting strong genetic influences. Model-fitting indicated that 68% (95% CI 62 to 74) of the variation in liability to neck pain could be attributed to genetic effects, with the remainder attributed to unshared environmental effects. No evidence for sex-specific genetic effects or for sex differences in the magnitude of genetic effects was found. Conclusions Genetic and unique environmental factors seem to play the most important roles in liability to neck pain in early adolescence. Future research should be directed to identifying pathways for genetic influences on neck pain and in exploring effectiveness of interventions that target already identified environmental risk factors. PMID:23139100

  9. Genetic Vulnerability Interacts with Parenting and Early Care and Education to Predict Increasing Externalizing Behavior

    ERIC Educational Resources Information Center

    Lipscomb, Shannon T.; Laurent, Heidemarie; Neiderhiser, Jenae M.; Shaw, Daniel S.; Natsuaki, Misaki N.; Reiss, David; Leve, Leslie D.

    2014-01-01

    The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental…

  10. Early events in Agrobacterium-mediated genetic transformation of citrus explants.

    PubMed

    Peña, Leandro; Pérez, Rosa M; Cervera, Magdalena; Juárez, José A; Navarro, Luis

    2004-07-01

    Genetic transformation of plants relies on two independent but concurrent processes: integration of foreign DNA into plant cells and regeneration of whole plants from these transformed cells. Cell competence for regeneration and for transformation does not always fall into the same cell type/developmental stage, and this is one of the main causes of the so-called recalcitrance for transformation of certain plant species. In this study, a detailed examination of the first steps of morphogenesis from citrus explants after co-cultivation with Agrobacterium tumefaciens was performed, and an investigation into which cells and tissues are competent for regeneration and transformation was carried out. Moreover, the role of phytohormones in the co-cultivation medium as possible enhancers of gene transfer was also studied. A highly responsive citrus genotype and well-established culture conditions were used to perform a histological analysis of morphogenesis and cell competence for transformation after co-cultivation of citrus epicotyl segments with A. tumefaciens. In addition, the role of phytohormones as transformation enhancers was investigated by flow cytometry. It is demonstrated that cells competent for transformation are located in the newly formed callus growing from the cambial ring. Conditions conducive to further development of this callus, such as treatment of explants in a medium rich in auxins, resulted in a more pronounced formation of cambial callus and a slower shoot regeneration process, both in Agrobacterium-inoculated and non-inoculated explants. Furthermore, co- cultivation in a medium rich in auxins caused a significant increase in the rate of actively dividing cells in S-phase, the stage in which cells are more prone to integrate foreign DNA. Use of proper co-cultivation medium and conditions led to a higher number of stably transformed cells and to an increase in the final number of regenerated transgenic plants.

  11. Genetic Stratigraphy of Key Demographic Events in Arabia

    PubMed Central

    Fernandes, Verónica; Triska, Petr; Pereira, Joana B.; Alshamali, Farida; Rito, Teresa; Machado, Alison; Fajkošová, Zuzana; Cavadas, Bruno; Černý, Viktor; Soares, Pedro

    2015-01-01

    At the crossroads between Africa and Eurasia, Arabia is necessarily a melting pot, its peoples enriched by successive gene flow over the generations. Estimating the timing and impact of these multiple migrations are important steps in reconstructing the key demographic events in the human history. However, current methods based on genome-wide information identify admixture events inefficiently, tending to estimate only the more recent ages, as here in the case of admixture events across the Red Sea (∼8–37 generations for African input into Arabia, and 30–90 generations for “back-to-Africa” migrations). An mtDNA-based founder analysis, corroborated by detailed analysis of the whole-mtDNA genome, affords an alternative means by which to identify, date and quantify multiple migration events at greater time depths, across the full range of modern human history, albeit for the maternal line of descent only. In Arabia, this approach enables us to infer several major pulses of dispersal between the Near East and Arabia, most likely via the Gulf corridor. Although some relict lineages survive in Arabia from the time of the out-of-Africa dispersal, 60 ka, the major episodes in the peopling of the Peninsula took place from north to south in the Late Glacial and, to a lesser extent, the immediate post-glacial/Neolithic. Exchanges across the Red Sea were mainly due to the Arab slave trade and maritime dominance (from ∼2.5 ka to very recent times), but had already begun by the early Holocene, fuelled by the establishment of maritime networks since ∼8 ka. The main “back-to-Africa” migrations, again undetected by genome-wide dating analyses, occurred in the Late Glacial period for introductions into eastern Africa, whilst the Neolithic was more significant for migrations towards North Africa. PMID:25738654

  12. Genetic stratigraphy of key demographic events in Arabia.

    PubMed

    Fernandes, Verónica; Triska, Petr; Pereira, Joana B; Alshamali, Farida; Rito, Teresa; Machado, Alison; Fajkošová, Zuzana; Cavadas, Bruno; Černý, Viktor; Soares, Pedro; Richards, Martin B; Pereira, Luísa

    2015-01-01

    At the crossroads between Africa and Eurasia, Arabia is necessarily a melting pot, its peoples enriched by successive gene flow over the generations. Estimating the timing and impact of these multiple migrations are important steps in reconstructing the key demographic events in the human history. However, current methods based on genome-wide information identify admixture events inefficiently, tending to estimate only the more recent ages, as here in the case of admixture events across the Red Sea (~8-37 generations for African input into Arabia, and 30-90 generations for "back-to-Africa" migrations). An mtDNA-based founder analysis, corroborated by detailed analysis of the whole-mtDNA genome, affords an alternative means by which to identify, date and quantify multiple migration events at greater time depths, across the full range of modern human history, albeit for the maternal line of descent only. In Arabia, this approach enables us to infer several major pulses of dispersal between the Near East and Arabia, most likely via the Gulf corridor. Although some relict lineages survive in Arabia from the time of the out-of-Africa dispersal, 60 ka, the major episodes in the peopling of the Peninsula took place from north to south in the Late Glacial and, to a lesser extent, the immediate post-glacial/Neolithic. Exchanges across the Red Sea were mainly due to the Arab slave trade and maritime dominance (from ~2.5 ka to very recent times), but had already begun by the early Holocene, fuelled by the establishment of maritime networks since ~8 ka. The main "back-to-Africa" migrations, again undetected by genome-wide dating analyses, occurred in the Late Glacial period for introductions into eastern Africa, whilst the Neolithic was more significant for migrations towards North Africa.

  13. Genetic and environmental influences on affiliation with deviant peers during adolescence and early adulthood.

    PubMed

    Tarantino, Nicholas; Tully, Erin C; Garcia, Sarah E; South, Susan; Iacono, William G; McGue, Matt

    2014-03-01

    Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youths exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence has suggested that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at 3 discrete ages: 15, 18, and 21 years of age. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping, whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  14. Genetic and Environmental Influences on Affiliation with Deviant Peers during Adolescence and Early Adulthood

    PubMed Central

    Tarantino, Nicholas; Tully, Erin C.; Garcia, Sarah E.; South, Susan; Iacono, William G.; McGue, Matt

    2014-01-01

    Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youth exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence suggests that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at three discrete ages-15-, 18-, and 21-years-old. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PMID:24015689

  15. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    PubMed Central

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

  16. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    PubMed

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

  17. Genetic homogeneity across Bantu-speaking groups from Mozambique and Angola challenges early split scenarios between East and West Bantu populations.

    PubMed

    Alves, Isabel; Coelho, Margarida; Gignoux, Christopher; Damasceno, Albertino; Prista, Antonio; Rocha, Jorge

    2011-02-01

    The large scale spread of Bantu-speaking populations remains one of the most debated questions in African population history. In this work we studied the genetic structure of 19 Bantu-speaking groups from Mozambique and Angola using a multilocus approach based on 14 newly developed compound haplotype systems (UEPSTRs), each consisting of a rapidly evolving short tandem repeat (STR) closely linked to a unique event polymorphism (UEP). We compared the ability of UEPs, STRs and UEPSTRs to document genetic variation at the intercontinental level and among the African Bantu populations, and found that UEPSTR systems clearly provided more resolution than UEPs or STRs alone. The observed patterns of genetic variation revealed high levels of genetic homogeneity between major populations from Angola and Mozambique, with two main outliers: the Kuvale from Angola and the Chopi from Mozambique. Within Mozambique, two Kaskazi-speaking populations from the far north (Yao and Mwani) and two Nyasa-speaking groups from the Zambezi River basin (Nyungwe and Sena) could be differentiated from the remaining groups, but no further population structure was observed across the country. The close genetic relationship between most sampled Bantu populations is consistent with high degrees of interaction between peoples living in savanna areas located to the south of the rainforest. Our results highlight the role of gene flow during the Bantu expansions and show that the genetic evidence accumulated so far is becoming increasingly difficult to reconcile with widely accepted models postulating an early split between eastern and western Bantu populations.

  18. Longitudinal Genetic Analysis of Early Reading: The Western Reserve Reading Project

    ERIC Educational Resources Information Center

    Petrill, Stephen A.; Deater-Deckard, Kirby; Thompson, Lee Anne; Schatschneider, Chris; DeThorne, Laura S.; Vandenbergh, David J.

    2007-01-01

    We examined the genetic and environmental contribution to the stability and instability of reading outcomes in early elementary school using a sample of 283 twin pairs drawn from the Western Reserve Reading Project. Twins were assessed across two measurement occasions. In Wave 1, children were either in kindergarten or first grade. Wave 2…

  19. Hospitalization for early bonding of the genetic mother after a surrogate pregnancy: report of two cases.

    PubMed

    Sharan, H; Yahav, J; Peleg, D; Ben-Rafael, Z; Merlob, P

    2001-12-01

    In surrogate pregnancies the genetic parents have little opportunity for early bonding to their infant, either prenatally (in utero) or in the immediate postnatal period. The purpose of this article is to describe a new method for encouraging early parent-infant bonding after surrogate pregnancy by hospitalizing the genetic mother in the maternity ward immediately after the delivery. Two genetic mothers were hospitalized in the maternity ward (rooming-in system) at the Rabin Medical Center in Israel immediately after delivery of their infants by surrogate arrangement. The first birth was a singleton pregnancy with vaginal delivery and the second, a twin pregnancy with delivery by cesarean section. The genetic parents were counseled by a social worker from the adoption agency, starting 3 months before the estimated date of delivery. The parents were referred to the hospital social worker before the delivery. To assess attachment, we observed the parents' behavior toward their children during two daily 15-minute periods of free, unstructured interaction. The parents showed good primary caregiving functions and established affective verbal and physical contact with the infants. They began to recognize the infants' needs and temperament, and exhibited an aura of self-confidence during their interactions. All expressed satisfaction with the method at discharge and reported on reduction of their fears about returning home with the infants. We believe that early hospitalization of the genetic mother in a surrogate delivery may be desirable to establish good and safe early mother-infant bonding, and that it should be considered for adoption as regular hospital policy. Further randomized studies with larger samples over the long term are warranted.

  20. Neighborhood Disadvantage, Stressful Life Events, and Adjustment among Mexican American Early Adolescents

    ERIC Educational Resources Information Center

    Roosa, Mark W.; Burrell, Ginger L.; Nair, Rajni L.; Coxe, Stefany; Tein, Jenn-Yun; Knight, George P.

    2010-01-01

    This study examined a stress process model in which stressful life events and association with delinquent peers mediated the relationship of neighborhood disadvantage to Mexican American early adolescents' mental health. The authors also proposed that child gender, child generation, and neighborhood informal social control would moderate the…

  1. Early Life Conditions, Adverse Life Events, and Chewing Ability at Middle and Later Adulthood

    PubMed Central

    Watt, Richard G.; Tsakos, Georgios

    2014-01-01

    Objectives. We sought to determine the extent to which early life conditions and adverse life events impact chewing ability in middle and later adulthood. Methods. Secondary analyses were conducted based on data from waves 2 and 3 of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in the years 2006 to 2009 and encompassing information on current chewing ability and the life history of persons aged 50 years or older from 13 European countries. Logistic regression models were estimated with sequential inclusion of explanatory variables representing living conditions in childhood and adverse life events. Results. After controlling for current determinants of chewing ability at age 50 years or older, certain childhood and later life course socioeconomic, behavioral, and cognitive factors became evident as correlates of chewing ability at age 50 years or older. Specifically, childhood financial hardship was identified as an early life predictor of chewing ability at age 50 years or older (odds ratio = 1.58; 95% confidence interval = 1.22, 2.06). Conclusions. Findings suggest a potential enduring impact of early life conditions and adverse life events on oral health in middle and later adulthood and are relevant for public health decision-makers who design strategies for optimal oral health. PMID:24625140

  2. Sensitivity to cocaine in adult mice is due to interplay between genetic makeup, early environment and later experience.

    PubMed

    Di Segni, Matteo; Andolina, Diego; Coassin, Alessandra; Accoto, Alessandra; Luchetti, Alessandra; Pascucci, Tiziana; Luzi, Carla; Lizzi, Anna Rita; D'Amato, Francesca R; Ventura, Rossella

    2017-10-01

    Although early aversive postnatal events are known to increase the risk to develop psychiatric disorders later in life, rarely they determine alone the nature and outcome of the psychopathology, indicating that interaction with genetic factors is crucial for expression of psychopathologies in adulthood. Moreover, it has been suggested that early life experiences could have negative consequences or confer adaptive value in different individuals. Here we suggest that resilience or vulnerability to adult cocaine sensitivity depends on a "triple interaction" between genetic makeup x early environment x later experience. We have recently showed that Repeated Cross Fostering (RCF; RCF pups were fostered by four adoptive mothers from postnatal day 1 to postnatal day 4. Pups were left with the last adoptive mother until weaning) experienced by pups affected the response to a negative experience in adulthood in opposite direction in two genotypes leading DBA2/J, but not C57BL/6J mice, toward an "anhedonia-like" phenotype. Here we investigate whether exposure to a rewarding stimulus, instead of a negative one, in adulthood induces an opposite behavioral outcome. To test this hypothesis, we investigated the long-lasting effects of RCF on cocaine sensitivity in C57 and DBA female mice by evaluating conditioned place preference induced by different cocaine doses and catecholamine prefrontal-accumbal response to cocaine using a "dual probe" in vivo microdialysis procedure. Moreover, cocaine-induced c-Fos activity was assessed in different brain regions involved in processing of rewarding stimuli. Finally, cocaine-induced spine changes were evaluated in the prefrontal-accumbal system. RCF experience strongly affected the behavioral, neurochemical and morphological responses to cocaine in adulthood in opposite direction in the two genotypes increasing and reducing, respectively, the sensitivity to cocaine in C57 and DBA mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood.

    PubMed

    Kendler, Kenneth S; Schmitt, Eric; Aggen, Steven H; Prescott, Carol A

    2008-06-01

    While both environmental and genetic factors are important in the etiology of psychoactive substance use (PSU), we know little of how these influences differ through development. To clarify the changing role of genes and environment in PSU from early adolescence through middle adulthood. Retrospective assessment by life history calendar, with univariate and bivariate structural modeling. General community. A total of 1796 members of male-male pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Levels of use of alcohol, caffeine, cannabis, and nicotine recorded for every year of the respondent's life. For nicotine, alcohol, and cannabis, familial environmental factors were critical in influencing use in early adolescence and gradually declined in importance through young adulthood. Genetic factors, by contrast, had little or no influence on PSU in early adolescence and gradually increased in their effect with increasing age. The sources of individual differences in caffeine use changed much more modestly over time. Substantial correlations were seen among levels of cannabis, nicotine, and alcohol use and specifically between caffeine and nicotine. In adolescence, those correlations were strongly influenced by shared effects from the familial environment. However, as individuals aged, more and more of the correlation in PSU resulted from genetic factors that influenced use of both substances. These results support an etiologic model for individual differences in PSU in which initiation and early patterns of use are strongly influenced by social and familial environmental factors while later levels of use are strongly influenced by genetic factors. The substantial correlations seen in levels of PSU across substances are largely the result of social environmental factors in adolescence, with genetic factors becoming progressively more important through early and middle adulthood.

  4. Genetic and Environmental Influences on Alcohol, Caffeine, Cannabis, and Nicotine Use From Early Adolescence to Middle Adulthood

    PubMed Central

    Kendler, Kenneth S.; Schmitt, Eric; Aggen, Steven H.; Prescott, Carol A.

    2009-01-01

    Context While both environmental and genetic factors are important in the etiology of psychoactive substance use (PSU), we know little of how these influences differ through development. Objective To clarify the changing role of genes and environment in PSU from early adolescence through middle adulthood. Design Retrospective assessment by life history calendar, with univariate and bivariate structural modeling. Setting General community. Participants A total of 1796 members of male-male pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measures Levels of use of alcohol, caffeine, cannabis, and nicotine recorded for every year of the respondent's life. Results For nicotine, alcohol, and cannabis, familial environmental factors were critical in influencing use in early adolescence and gradually declined in importance through young adulthood. Genetic factors, by contrast, had little or no influence on PSU in early adolescence and gradually increased in their effect with increasing age. The sources of individual differences in caffeine use changed much more modestly over time. Substantial correlations were seen among levels of cannabis, nicotine, and alcohol use and specifically between caffeine and nicotine. In adolescence, those correlations were strongly influenced by shared effects from the familial environment. However, as individuals aged, more and more of the correlation in PSU resulted from genetic factors that influenced use of both substances. Conclusions These results support an etiologic model for individual differences in PSU in which initiation and early patterns of use are strongly influenced by social and familial environmental factors while later levels of use are strongly influenced by genetic factors. The substantial correlations seen in levels of PSU across substances are largely the result of social environmental factors in adolescence, with genetic factors becoming progressively more important

  5. Environmental change during the Late Berriasian - Early Valanginian: a prelude to the late Early Valanginian carbon-isotope event?

    NASA Astrophysics Data System (ADS)

    Morales, Chloé; Schnyder, Johann; Spangenberg, Jorge; Adatte, Thierry; Westermann, Stephane; Föllmi, Karl

    2010-05-01

    The Valanginian period is well known for a positive excursion in marine and terrestrial δ13C records, which has been interpreted as the consequence of a major perturbation in the global carbon cycle (Lini et al., 1992; Erba et al., 2004). In contrast to the positive δ13C excursions of the Early Aptian and latest Cenomanian, marine organic-rich sediments have only been recognized from a few localities (van de Schootbrugge et al., 2003; Reboulet et al., 2003; Gröcke et al., 2005; Westermann et al., in press). The δ13C excursion began in the late Early Valanginian (campylotoxus ammonite zone) and gradually ended during the Late Valanginian. It is associated with a phase of widespread carbonate-platform drowning on the shelf (Föllmi et al., 1994) and a decline in calcareous nannofossils in the pelagic realm (Erba et al., 2004). As a triggering mechanism, numerous authors invoke the formation of the Parañà-Etendeka flood basalt. The correlation of this episode with the Valanginian δ13C event depends, however, on the absolute ages attributed to the Valanginian stage. The recent geological timescale by Ogg et al. (2008) shows that the major eruptional phase occurred during the Late Valanginian. This may imply that the late Early Valanginian δ13C event resulted from a combination of different factors. Important paleoenvironmental change occurred already in the latest Berriasian and earliest Valanginian, prior to the positive δ13C excursion. An increase in nutrient input near the onset of the δ13C excursion (campylotoxus ammonite zone), which may be considered as a trigger of the carbon cycle perturbation, has been identified in different studies, (Hennig, 2003; Duchamp-Alphonse et al., 2007; Bornemann & Mutterlose, 2008). Heterozoan faunal associations became dominant since the Early Valanginian on the northern Tethyan Helvetic platform and may indicate the beginning of sea-water eutrophication (Föllmi et al., 2007). Clay assemblages in the Tethys and Western

  6. Single-Event Transgene Product Levels Predict Levels in Genetically Modified Breeding Stacks.

    PubMed

    Gampala, Satyalinga Srinivas; Fast, Brandon J; Richey, Kimberly A; Gao, Zhifang; Hill, Ryan; Wulfkuhle, Bryant; Shan, Guomin; Bradfisch, Greg A; Herman, Rod A

    2017-09-13

    The concentration of transgene products (proteins and double-stranded RNA) in genetically modified (GM) crop tissues is measured to support food, feed, and environmental risk assessments. Measurement of transgene product concentrations in breeding stacks of previously assessed and approved GM events is required by many regulatory authorities to evaluate unexpected transgene interactions that might affect expression. Research was conducted to determine how well concentrations of transgene products in single GM events predict levels in breeding stacks composed of these events. The concentrations of transgene products were compared between GM maize, soybean, and cotton breeding stacks (MON-87427 × MON-89034 × DAS-Ø15Ø7-1 × MON-87411 × DAS-59122-7 × DAS-40278-9 corn, DAS-81419-2 × DAS-44406-6 soybean, and DAS-21023-5 × DAS-24236-5 × SYN-IR102-7 × MON-88913-8 × DAS-81910-7 cotton) and their component single events (MON-87427, MON-89034, DAS-Ø15Ø7-1, MON-87411, DAS-59122-7, and DAS-40278-9 corn, DAS-81419-2, and DAS-44406-6 soybean, and DAS-21023-5, DAS-24236-5, SYN-IR102-7, MON-88913-8, and DAS-81910-7 cotton). Comparisons were made within a crop and transgene product across plant tissue types and were also made across transgene products in each breeding stack for grain/seed. Scatter plots were generated comparing expression in the stacks to their component events, and the percent of variability accounted for by the line of identity (y = x) was calculated (coefficient of identity, I 2 ). Results support transgene concentrations in single events predicting similar concentrations in breeding stacks containing the single events. Therefore, food, feed, and environmental risk assessments based on concentrations of transgene products in single GM events are generally applicable to breeding stacks composed of these events.

  7. Genetic Causes of Recurrent Pregnancy Loss.

    PubMed

    Page, Jessica M; Silver, Robert M

    2016-09-01

    Pregnancy loss is one of the most common obstetric complications, affecting over 30% of conceptions. A considerable proportion of losses are due to genetic abnormalities. Indeed, over 50% of early pregnancy losses have been associated with chromosomal abnormalities. Most are due to de novo nondisjunctional events but balanced parental translocations are responsible for a small but important percentage of genetic abnormalities in couples with recurrent pregnancy loss. In the past, assessment of genetic abnormalities was limited to karyotype performed on placental or fetal tissue. However, advances in molecular genetic technology now provide rich genetic information about additional genetic causes of and risk factors for pregnancy loss. In addition, the use of preimplantation genetic testing in couples undergoing in vitro fertilization has the potential to decrease the risk of pregnancy loss from genetic abnormalities. To date, efficacy is uncertain but considerable potential remains. This chapter will review what is known about genetic causes of recurrent pregnancy loss with a focus on novel causes and potential treatments. Remaining knowledge gaps will be highlighted.

  8. The onset of childhood amnesia in childhood: A prospective investigation of the course and determinants of forgetting of early-life events

    PubMed Central

    Bauer, Patricia J.; Larkina, Marina

    2013-01-01

    The present research was an examination of the onset of childhood amnesia and how it relates to maternal narrative style, an important determinant of autobiographical memory development. Children and their mothers discussed unique events when the children were 3 years of age. Different subgroups of children were tested for recall of the events at ages 5, 6, 7, 8, and 9 years. At the later session, they were interviewed by an experimenter about the events discussed 2 to 6 years previously with their mothers (early-life events). Children ages 5, 6, and 7 remembered 60% or more of the early-life events. In contrast, children ages 8 and 9 years remembered fewer than 40% of the early-life events. Overall maternal narrative style predicted children's contributions to mother-child conversations at age 3 years; it did not have cross-lagged relations to memory for early-life events at ages 5 to 9 years. Maternal deflections of the conversational turn to the child predicted the amount of information children later reported about the early-life events. The findings have implications for our understanding of the onset of childhood amnesia and the achievement of an adult-like distribution of memories in the school years. They highlight the importance of forgetting processes in explanations of the amnesia. PMID:24236647

  9. [Environmental and genetic variables related with alterations in language acquisition in early childhood].

    PubMed

    Moriano-Gutierrez, A; Colomer-Revuelta, J; Sanjuan, J; Carot-Sierra, J M

    2017-01-01

    A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment.

  10. Development and Evaluation of Event-Specific Quantitative PCR Method for Genetically Modified Soybean MON87701.

    PubMed

    Tsukahara, Keita; Takabatake, Reona; Masubuchi, Tomoko; Futo, Satoshi; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Nishimaki-Mogami, Tomoko; Kurashima, Takeyo; Mano, Junichi; Kitta, Kazumi

    2016-01-01

    A real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) soybean event, MON87701. First, a standard plasmid for MON87701 quantification was constructed. The conversion factor (C f ) required to calculate the amount of genetically modified organism (GMO) was experimentally determined for a real-time PCR instrument. The determined C f for the real-time PCR instrument was 1.24. For the evaluation of the developed method, a blind test was carried out in an inter-laboratory trial. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDr), respectively. The determined biases and the RSDr values were less than 30 and 13%, respectively, at all evaluated concentrations. The limit of quantitation of the method was 0.5%, and the developed method would thus be applicable for practical analyses for the detection and quantification of MON87701.

  11. Fractional dynamics of globally slow transcription and its impact on deterministic genetic oscillation.

    PubMed

    Wei, Kun; Gao, Shilong; Zhong, Suchuan; Ma, Hong

    2012-01-01

    In dynamical systems theory, a system which can be described by differential equations is called a continuous dynamical system. In studies on genetic oscillation, most deterministic models at early stage are usually built on ordinary differential equations (ODE). Therefore, gene transcription which is a vital part in genetic oscillation is presupposed to be a continuous dynamical system by default. However, recent studies argued that discontinuous transcription might be more common than continuous transcription. In this paper, by appending the inserted silent interval lying between two neighboring transcriptional events to the end of the preceding event, we established that the running time for an intact transcriptional event increases and gene transcription thus shows slow dynamics. By globally replacing the original time increment for each state increment by a larger one, we introduced fractional differential equations (FDE) to describe such globally slow transcription. The impact of fractionization on genetic oscillation was then studied in two early stage models--the Goodwin oscillator and the Rössler oscillator. By constructing a "dual memory" oscillator--the fractional delay Goodwin oscillator, we suggested that four general requirements for generating genetic oscillation should be revised to be negative feedback, sufficient nonlinearity, sufficient memory and proper balancing of timescale. The numerical study of the fractional Rössler oscillator implied that the globally slow transcription tends to lower the chance of a coupled or more complex nonlinear genetic oscillatory system behaving chaotically.

  12. Genetic Risk Score Analysis in Early-Onset Bipolar Disorder

    PubMed Central

    Croarkin, Paul E.; Luby, Joan L.; Cercy, Kelly; Geske, Jennifer R.; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T.; Wagner, Karen Dineen; Walkup, John T.; Nassan, Malik M.; Cuellar-Barboza, Alfredo B.; Casuto, Leah; McElroy, Susan L.; Jensen, Peter S.; Frye, Mark A.; Biernacka, Joanna M.

    2018-01-01

    Objective In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder. Method Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003–2008. Mayo Clinic Bipolar Biobank samples were collected from 2009–2013. Genotyping and analyses for the present study took place from 2013–2014. The diagnosis of bipolar disorder was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with bipolar disorder, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly “odz, odd Oz/ten-m homolog 4 {Drosophila}, ODZ4”]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n=69), adult patients with bipolar disorder (n=732) including a subset with early-onset illness [n=192]), and healthy controls (n=776). GRS analyses were performed comparing early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. Results GRS analysis revealed associations of the risk score with early-onset bipolar disorder (P=.01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset bipolar disorder with a CACNA1C haplotype (global test, P=.01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset bipolar disorder (P=.017), which did not remain significant after correction for multiple comparisons. Conclusion These preliminary analyses suggest that previously identified bipolar disorder risk loci

  13. Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

    PubMed

    Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

    In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD.

  14. How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2006

    2006-01-01

    Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…

  15. A Further Extension of the Tahiti-Darwin SOI, Early ENSO Events and Darwin Pressure.

    NASA Astrophysics Data System (ADS)

    Allan, Robert J.; Nicholls, Neville; Jones, Phil D.; Butterworth, Ian J.

    1991-07-01

    An extension of the Tahiti minus Darwin Southern Oscillation Index (SOI) from 1882 back to 1876 is reported following the recovery of early Darwin mean sea-level pressure data spanning the period 1865-81. As a result, we are able to compare, for the first time, the major 1877-78 and 1982-83 ENSO events on the basis of this commonly used index. Early Darwin and Jakarta data are also examined in terms of a measure of the Australian response to documented El Niño and/or ENSO events in 1866, 1868, 1871, 1873, 1874 and 1875.The SOI during the 1877-78 ENSO event has a similar temporal response to that in 1982-83, but the index is slightly weaker than in the recent event. Examination of documentary evidence confirms the severity of the drought conditions that affected the Australian continent during the 1877-78 ENSO, and shows that this response is in line with the wider Indo-Pacific impacts reported in the literature. Earlier El Niño phases in 1868 and 1873 are not resolved distinctly in either the Darwin or Jakarta pressure data. This appears to illustrate that El Niño event histories do not always indicate wider ENSO influences in the Indo-Pacific basin, particularly during weak to moderate phases.

  16. Early event related fields during visually evoked pain anticipation.

    PubMed

    Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

    2016-03-01

    Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. A Genetically Informed Cross-lagged Analysis of Autistic-Like Traits and Affective Problems in Early Childhood

    PubMed Central

    Micalizzi, Lauren; Ronald, Angelica; Saudino, Kimberly J.

    2015-01-01

    A genetically informed cross-lagged model was applied to twin data to explore etiological links between autistic-like traits and affective problems in early childhood. The sample comprised 310 same-sex twin pairs (143 monozygotic and 167 dizygotic; 53% male). Autistic-like traits and affective problems were assessed at ages 2 and 3 using parent ratings. Both constructs were related within and across age (r = .30−.53) and showed moderate stability (r = .45−.54). Autistic-like traits and affective problems showed genetic and environmental influences at both ages. Whereas at age 2, the covariance between autistic-like traits and affective problems was entirely due to environmental influences (shared and nonshared), at age 3, genetic factors also contributed to the covariance between constructs. The stability paths, but not the cross-lagged paths, were significant, indicating that there is stability in both autistic-like traits and affective problems but they do not mutually influence each other across age. Stability effects were due to genetic, shared, and nonshared environmental influences. Substantial novel genetic and nonshared environmental influences emerge at age 3 and suggest change in the etiology of these constructs over time. During early childhood, autistic-like traits tend to occur alongside affective problems and partly overlapping genetic and environmental influences explain this association. PMID:26456961

  18. Atmospheric pCO2 reconstructed across five early Eocene global warming events

    NASA Astrophysics Data System (ADS)

    Cui, Ying; Schubert, Brian A.

    2017-11-01

    Multiple short-lived global warming events, known as hyperthermals, occurred during the early Eocene (56-52 Ma). Five of these events - the Paleocene-Eocene Thermal Maximum (PETM or ETM1), H1 (or ETM2), H2, I1, and I2 - are marked by a carbon isotope excursion (CIE) within both marine and terrestrial sediments. The magnitude of CIE, which is a function of the amount and isotopic composition of carbon added to the ocean-atmosphere system, varies significantly between marine versus terrestrial substrates. Here we use the increase in carbon isotope fractionation by C3 land plants in response to increased pCO2 to reconcile this difference and reconstruct a range of background pCO2 and peak pCO2 for each CIE, provided two potential carbon sources: methane hydrate destabilization and permafrost-thawing/organic matter oxidation. Although the uncertainty on each pCO2 estimate using this approach is low (e.g., median uncertainty = + 23% / - 18%), this work highlights the potential for significant systematic bias in the pCO2 estimate resulting from sampling resolution, substrate type, diagenesis, and environmental change. Careful consideration of each of these factors is required especially when applying this approach to a single marine-terrestrial CIE pair. Given these limitations, we provide an upper estimate for background early Eocene pCO2 of 463 +248/-131 ppmv (methane hydrate scenario) to 806 +127/-104 ppmv (permafrost-thawing/organic matter oxidation scenario). These results, which represent the first pCO2 proxy estimates directly tied to the Eocene hyperthermals, demonstrate that early Eocene warmth was supported by background pCO2 less than ∼3.5× preindustrial levels and that pCO2 > 1000 ppmv may have occurred only briefly, during hyperthermal events.

  19. Dose and Effect Thresholds for Early Key Events in a Mode of ...

    EPA Pesticide Factsheets

    ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor-alpha (PPARα). Male B6C3F1 mice were exposed for 7 days to di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), and n-butyl benzyl phthalate (BBP), which vary in PPARα activity and liver tumorigenicity. Each phthalate increased expression of select PPARα target genes at 7 days, while only DEHP significantly increased liver cell proliferation labeling index (LI). Transcriptional benchmark dose (BMDT) estimates for dose-related genomic markers stratified phthalates according to hypothetical tumorigenic potencies, unlike BMDs for non-genomic endpoints (liver weights or proliferation). The 7-day BMDT values for Acot1 as a surrogate measure for PPARα activation were 29, 370, and 676 mg/kg-d for DEHP, DNOP, and BBP, respectively, distinguishing DEHP (liver tumor BMD of 35 mg/kg-d) from non-tumorigenic DNOP and BBP. Effect thresholds were generated using linear regression of DEHP effects at 7 days and 2-year tumor incidence values to anchor early response molec

  20. Ancient gene flow from early modern humans into Eastern Neanderthals.

    PubMed

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-02-25

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.

  1. Oxygen and Early Animal Evolution

    NASA Astrophysics Data System (ADS)

    Xiao, S.

    2012-12-01

    It is often hypothesized that the rise of animals was triggered by an increase in O2 levels in the atmosphere and oceans. However, this hypothesis is remarkably difficult to test, because the timing of animal divergences is poorly resolved, the physiology of early animals is often unknown, estimates of past pO2 levels come with large error bars, and causal relationships between oxygenation and animal evolution are difficult to establish. Nonetheless, existing phylogenetic, paleontological, and geochemical data indicate that the evolution of macroscopic animals and motile macrometazoans with energetically expensive lifestyles may be temporally coupled with ocean oxygenation events in the Ediacaran Period. Thus, it is plausible that ocean oxygenation may have been a limiting factor in the early evolution of macroscopic, complex, and metabolically aggressive animals (particularly bilaterian animals). However, ocean oxygenation and animal evolution were likely engaged in two-way interactions: Ediacaran oxygenation may have initially lifted a physiological barrier for the evolution of animal size, motility, and active lifestyles, but subsequent animal diversification in the Paleozoic may have also changed oceanic redox structures. Viewed in a broader context, the early evolutionary history of animals was contingent upon a series of events, including genetic preparation (developmental genetics), environmental facilitation (oceanic oxygenation), and ecological escalation (Cambrian explosion), but the rise of animals to ecological importance also had important geobiological impacts on oceanic redox structures, sedimentary fabrics, and global geochemical cycles.

  2. Constraints on early events in Martian history as derived from the cratering record

    NASA Technical Reports Server (NTRS)

    Barlow, Nadine G.

    1990-01-01

    Constrains on early events in Martian history are derived using the planet's cratering record. Variations in the shapes of the crater size-frequency distribution curves are interpreted as indicative of the size-frequency distribution of the production populations, thus providing information about the age of the unit relative to the end of the heavy bombardment period. Results from the analysis of craters superposed on heavily cratered units across the Martian surface provide constraints on the hemispheric dichotomy and the early erosional conditions on Mars.

  3. Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

    PubMed

    Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

    2008-12-01

    This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

  4. The early Toarcian anoxic event: what the beginning and the end of the story are?

    NASA Astrophysics Data System (ADS)

    Mattioli, Emanuela; Plancq, Julien; Raucsik, Béla

    2010-05-01

    The early Toarcian anoxic event: what the beginning and the end of the story are? E. Mattioli (1), J. Plancq (1), and B. Rauksik (2) (1) UMR 5125 PEPS, CNRS, France; Université Lyon 1, Campus de la DOUA, Bâtiment Géode, 69622 Villeurbanne Cedex, France (emanuela.mattioli@univ-lyon1.fr) (2) Department of Earth and Environmental Sciences, University of Pannonia, Veszprém, Hungary The early Toarcian anoxic event (T-OAE) and the associated biotic crisis have received much attention in the last decade. However, the events forewarning the crisis as well as its aftermath are still poorly known. The T-OAE coincides with a prominent carbon isotope negative excursion (T-CIE) that is preceded by an excursion of similar intensity at the Pliensbachian-Toarcian boundary (Hesselbo et al., 2007). The onset of T-CIE occurred some 700 kyr later than the end of the Boundary-CIE (Suan et al., 2008a). This succession of events demonstrates that the T-OAE was a complex suite of environmental perturbations. In this work, we focused on calcareous nannofossil assemblages occurring in the Peniche section (Portugal) during the Boundary-CIE with the aim to understand if calcifying plankton reacted in a similar/different way to the two CIEs. Also, two sections and one borehole located along a W-E transect, along the NW-Tethyan shelf (in the Yorkshire coast, in the E Paris Basin, and in Mecsek Basin, respectively), were investigated to assess which way calcareous nannoplankton recovered after the crisis, and if the recovery was a synchronous event. The production by nannoplankton collapsed during the T-CIE, as demonstrated by the lowest absolute abundance of nannofossils measured in Peniche and other studied sites (Mattioli et al., 2008). Besides this nannofossil abundance decrease, also the size of the incertae sedis Schizosphaerella test was drastically reduced (Suan et al., 2008b). If a similar size decrease is also recorded during the Boundary-CIE, calcareous nannofossil abundances are

  5. Implicit Association to Infant Faces: How Genetics, Early Care Experiences, and Cultural Factors Influence Caregiving Propensities

    PubMed Central

    Senese, Vincenzo Paolo; Shinohara, Kazuyuki; Esposito, Gianluca; Doi, Hirokazu; Venuti, Paola; Bornstein, Marc H.

    2018-01-01

    Genetics, early experience, and culture shape caregiving, but it is still not clear how genetics, early experiences, and cultural factors might interact to influence specific caregiving propensities, such as adult responsiveness to infant cues. To address this gap, 80 Italian adults (50% M; 18-25 years) were (1) genotyped for two oxytocin receptor gene polymorphisms (rs53576 and rs2254298) and the serotonin transporter gene polymorphism (5-HTTLPR), which are implicated in parenting behaviour, (2) completed the Adult Parental Acceptance/Rejection Questionnaire to evaluate their recollections of parental behaviours toward them in childhood, and (3) were administered a Single Category Implicit Association Test to evaluate their implicit responses to faces of Italian infants, Japanese infants, and Italian adults. Analysis of implicit associations revealed that Italian infant faces were evaluated as most positive; participants in the rs53576 GG group had the most positive implicit associations to Italian infant faces; the serotonin polymorphism moderated the effect of early care experiences on adults’ implicit association to both Italian infant and adult female faces. Finally, 5-HTTLPR S carriers showed less positive implicit responses to Japanese infant faces. We conclude that adult in-group preference extends to in-group infant faces and that implicit responses to social cues are influenced by interactions of genetics, early care experiences, and cultural factors. These findings have implications for understanding processes that regulate adult caregiving. PMID:27650102

  6. Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

    PubMed

    Hartz, Sarah M; Short, Susan E; Saccone, Nancy L; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Gubjartsson, Daniel; Hansel, Nadia N; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo-Pekka; Michel, Martha; Rawal, Rajesh; Rosenberger, Albert; Scheet, Paul; Shaffer, John R; Teumer, Alexander; Thompson, John R; Vink, Jacqueline M; Vogelzangs, Nicole; Wenzlaff, Angela S; Wheeler, William; Xiao, Xiangjun; Yang, Bao-Zhu; Aggen, Steven H; Balmforth, Anthony J; Baumeister, Sebastian E; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W; Boyd, Heather A; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu-Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M; Hayward, Caroline; Heikkilä, Kauko; Hewitt, John K; Hottenga, Jouke Jan; Jensen, Majken K; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J; Konte, Bettina; Korhonen, Tellervo; Landi, Maria-Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M; Mathias, Rasika A; McNeil, Daniel W; Medland, Sarah E; Montgomery, Grant W; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J; Francks, Clyde; Gejman, Pablo V; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S; Lehtimäki, Terho; Levinson, Douglas F; Marazita, Mary L; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D; Murray, Jeffrey C; Nöthen, Markus M; Penninx, Brenda W; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J; Sanders, Alan R; Schwartz, Ann G; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H-Erich; Amos, Christopher I; Breslau, Naomi; Cannon, Dale S; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G; Stevens, Victoria L; Stitzel, Jerry A; Weiss, Robert B; Kraft, Peter; Bierut, Laura J

    2012-08-01

    Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

  7. How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

    ERIC Educational Resources Information Center

    Fox, Sharon E.; Levitt, Pat; Nelson, Charles A., III.

    2010-01-01

    Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this study a conceptual framework is provided for considering how the structure of early experience gets "under the skin." The study begins with a description of the genetic framework that lays the foundation for brain…

  8. Response to Early Literacy Instruction in the United States, Australia, and Scandinavia: A Behavioral-Genetic Analysis

    ERIC Educational Resources Information Center

    Samuelsson, Stefan; Byrne, Brian; Olson, Richard K.; Hulslander, Jacqueline; Wadsworth, Sally; Corley, Robin; Willcutt, Erik G.; DeFries, John C.

    2008-01-01

    Genetic and environmental influences on early reading and spelling at the end of kindergarten and Grade 1 were compared across three twin samples tested in the United States, Australia, and Scandinavia. Proportions of variance due to genetic influences on kindergarten reading were estimated at 0.84 in Australia, 0.68 in the U.S., and 0.33 in…

  9. Early events governing memory CD8+ T-cell differentiation.

    PubMed

    Obar, Joshua J; Lefrançois, Leo

    2010-08-01

    Understanding the regulation of the CD8(+) T-cell response and how protective memory cells are generated has been intensely studied. It is now appreciated that a naive CD8(+) T cell requires at least three signals to mount an effective immune response: (i) TCR triggering, (ii) co-stimulation and (iii) inflammatory cytokines. Only recently have we begun to understand the molecular integration of those signals and how early events regulate the fate decisions of the responding CD8(+) T cells. This review will discuss the recent findings about both the extracellular and intracellular factors that regulate the destiny of responding CD8(+) T cells.

  10. Development and validation of an event-specific quantitative PCR method for genetically modified maize MIR162.

    PubMed

    Takabatake, Reona; Masubuchi, Tomoko; Futo, Satoshi; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Kitta, Kazumi

    2014-01-01

    A novel real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) maize event, MIR162. We first prepared a standard plasmid for MIR162 quantification. The conversion factor (Cf) required to calculate the genetically modified organism (GMO) amount was empirically determined for two real-time PCR instruments, the Applied Biosystems 7900HT (ABI7900) and the Applied Biosystems 7500 (ABI7500) for which the determined Cf values were 0.697 and 0.635, respectively. To validate the developed method, a blind test was carried out in an interlaboratory study. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDr). The determined biases were less than 25% and the RSDr values were less than 20% at all evaluated concentrations. These results suggested that the limit of quantitation of the method was 0.5%, and that the developed method would thus be suitable for practical analyses for the detection and quantification of MIR162.

  11. One Novel Multiple-Target Plasmid Reference Molecule Targeting Eight Genetically Modified Canola Events for Genetically Modified Canola Detection.

    PubMed

    Li, Zhuqing; Li, Xiang; Wang, Canhua; Song, Guiwen; Pi, Liqun; Zheng, Lan; Zhang, Dabing; Yang, Litao

    2017-09-27

    Multiple-target plasmid DNA reference materials have been generated and utilized as good substitutes of matrix-based reference materials in the analysis of genetically modified organisms (GMOs). Herein, we report the construction of one multiple-target plasmid reference molecule, pCAN, which harbors eight GM canola event-specific sequences (RF1, RF2, MS1, MS8, Topas 19/2, Oxy235, RT73, and T45) and a partial sequence of the canola endogenous reference gene PEP. The applicability of this plasmid reference material in qualitative and quantitative PCR assays of the eight GM canola events was evaluated, including the analysis of specificity, limit of detection (LOD), limit of quantification (LOQ), and performance of pCAN in the analysis of various canola samples, etc. The LODs are 15 copies for RF2, MS1, and RT73 assays using pCAN as the calibrator and 10 genome copies for the other events. The LOQ in each event-specific real-time PCR assay is 20 copies. In quantitative real-time PCR analysis, the PCR efficiencies of all event-specific and PEP assays are between 91% and 97%, and the squared regression coefficients (R 2 ) are all higher than 0.99. The quantification bias values varied from 0.47% to 20.68% with relative standard deviation (RSD) from 1.06% to 24.61% in the quantification of simulated samples. Furthermore, 10 practical canola samples sampled from imported shipments in the port of Shanghai, China, were analyzed employing pCAN as the calibrator, and the results were comparable with those assays using commercial certified materials as the calibrator. Concluding from these results, we believe that this newly developed pCAN plasmid is one good candidate for being a plasmid DNA reference material in the detection and quantification of the eight GM canola events in routine analysis.

  12. [Influence of early childhood stress exposure and traumatic life events on pain perception].

    PubMed

    Tesarz, J; Gerhardt, A; Eich, W

    2018-06-05

    Adult pain perception is influenced substantially by interactions between mind, body, and social environment during early life. Early stress exposure and traumatic life events induce powerful psychophysical stress reactions that exert multiple neurofunctional processes. This has significant implications for pain perception and pain processing. As part of this review, the complex relationships between traumatic stress experiences and associated psychobiological mechanisms of chronic pain will be discussed. Based on selected studies, psychophysiological findings are presented and possible underlying mechanisms are discussed. The article concludes with a discussion of potential implications for treatment.

  13. Genetic variants and early cigarette smoking and nicotine dependence phenotypes in adolescents.

    PubMed

    O'Loughlin, Jennifer; Sylvestre, Marie-Pierre; Labbe, Aurélie; Low, Nancy C; Roy-Gagnon, Marie-Hélène; Dugas, Erika N; Karp, Igor; Engert, James C

    2014-01-01

    While the heritability of cigarette smoking and nicotine dependence (ND) is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs) that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes. In a prospective study of 1294 adolescents aged 12-13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7-8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs) in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator). The pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a p-value <0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and self-medication phenotypes were both 0.076. Because the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3). Dopaminergic pathways may be salient during early smoking and the development of ND.

  14. Early changes in physical tree characteristics during an oak decline event in the Ozark highlands

    Treesearch

    Martin A. Spetich

    2006-01-01

    An oak decline event is severely affecting up to 120 000 ha in the Ozark National Forest of Arkansas. Results of early changes in physical tree characteristics during that event are presented. In the fall and winter of 1999 and 2000, we established research plots on a site that would become a center of severe oak decline. In August 2000, standing trees > 14 cm in...

  15. Marine ecosystem resilience during extreme deoxygenation: the Early Jurassic oceanic anoxic event.

    PubMed

    Caswell, Bryony A; Frid, Christopher L J

    2017-01-01

    Global warming during the Early Jurassic, and associated widespread ocean deoxygenation, was comparable in scale with the changes projected for the next century. This study quantifies the impact of severe global environmental change on the biological traits of marine communities that define the ecological roles and functions they deliver. We document centennial-millennial variability in the biological trait composition of Early Jurassic (Toarcian) seafloor communities and examine how this changed during the event using biological traits analysis. Environmental changes preceding the global oceanic anoxic event (OAE) produced an ecological shift leading to stressed benthic palaeocommunities with reduced resilience to the subsequent OAE. Changes in traits and ecological succession coincided with major environmental changes; and were of similar nature and magnitude to those in severely deoxygenated benthic communities today despite the very different timescales. Changes in community composition were linked to local redox conditions whereas changes in populations of opportunists were driven by primary productivity. Throughout most of the OAE substitutions by tolerant taxa conserved the trait composition and hence functioning, but periods of severe deoxygenation caused benthic defaunation that would have resulted in functional collapse. Following the OAE recovery was slow probably because the global nature of the event restricted opportunities for recruitment from outside the basin. Our findings suggest that future systems undergoing deoxygenation may initially show functional resilience, but severe global deoxygenation will impact traits and ecosystem functioning and, by limiting the species pool, will slow recovery rates.

  16. Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study

    PubMed Central

    Alemany, Silvia; Rijsdijk, Frühling V.; Haworth, Claire Margaret Alison; Fañanás, Lourdes; Plomin, Robert

    2013-01-01

    Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added asa covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors. PMID:23627958

  17. Early events in copper-ion catalyzed oxidation of α-synuclein.

    PubMed

    Tiwari, Manish K; Leinisch, Fabian; Sahin, Cagla; Møller, Ian Max; Otzen, Daniel E; Davies, Michael J; Bjerrum, Morten J

    2018-04-22

    Previous studies on metal-ion catalyzed oxidation of α-synuclein oxidation have mostly used conditions that result in extensive modification precluding an understanding of the early events in this process. In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu 2+ /H 2 O 2 /protein and Cu 2+ /H 2 O 2 /ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu 2+ /H 2 O 2 /protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15 min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including inter- and intra-molecular dityrosine cross-links and protein oligomers, as determined by SDS-PAGE and Western blot analysis. Limited histidine (His) modification was observed. The rapid formation of dityrosine cross-links was confirmed by fluorescence and mass-spectrometry. These data indicate that Met and Tyr oxidation are early events in Cu 2+ /H 2 O 2 -mediated damage, with carbonyl formation being a minor process. With the Cu 2+ /H 2 O 2 /ascorbate system, rapid protein carbonyl formation was detected with the first 5 min, but after this time point, little additional carbonyl formation was detected. With this system, lower levels of Met and Tyr oxidation were detected (2 Met and 1 Tyr modified with a Cu 2+ /H 2 O 2 /ascorbate/protein ratio of 2.3:7.8:7.8:1), but greater His oxidation. Only low levels of intra- dityrosine cross-links and no inter- dityrosine oligomers were detected under these conditions, suggesting that ascorbate limits Cu 2+ /H 2 O 2 -induced α-synuclein modification. Copyright © 2018. Published by Elsevier Inc.

  18. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

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

    Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo

    Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes inmore » the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.« less

  19. Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment.

    PubMed

    Yang, Xian-Ming; Lou, Heng; Sun, Jing-Tao; Zhu, Yi-Ming; Xue, Xiao-Feng; Hong, Xiao-Yue

    2015-07-03

    Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range.

  20. Detection of rain events in radiological early warning networks with spectro-dosimetric systems

    NASA Astrophysics Data System (ADS)

    Dąbrowski, R.; Dombrowski, H.; Kessler, P.; Röttger, A.; Neumaier, S.

    2017-10-01

    Short-term pronounced increases of the ambient dose equivalent rate, due to rainfall are a well-known phenomenon. Increases in the same order of magnitude or even below may also be caused by a nuclear or radiological event, i.e. by artificial radiation. Hence, it is important to be able to identify natural rain events in dosimetric early warning networks and to distinguish them from radiological events. Novel spectrometric systems based on scintillators may be used to differentiate between the two scenarios, because the measured gamma spectra provide significant nuclide-specific information. This paper describes three simple, automatic methods to check whether an dot H*(10) increase is caused by a rain event or by artificial radiation. These methods were applied to measurements of three spectrometric systems based on CeBr3, LaBr3 and SrI2 scintillation crystals, investigated and tested for their practicability at a free-field reference site of PTB.

  1. Aligning policy to promote cascade genetic screening for prevention and early diagnosis of heritable diseases.

    PubMed

    George, Rani; Kovak, Karen; Cox, Summer L

    2015-06-01

    Cascade genetic screening is a methodology for identifying and testing close blood relatives of individuals at increased risk for heritable conditions and follows a sequential process, minimizing testing costs and the number of family members who need to be tested. It offers considerable potential for cost savings and increased awareness of heritable conditions within families. CDC-classified Tier 1 genomic applications for hereditary breast and ovarian cancer syndrome (HBOC), Lynch Syndrome (LS), and familial hypercholesterolemia (FH) are recommended for clinical use and support the use of cascade genetic screening. Most individuals are unaware of their increased risk for heritable conditions such as HBOC, LS, and FH. Consistent implementation of cascade genetic screening could significantly increase awareness and prevention of heritable conditions. Limitations to effective implementation of cascade genetic screening include: insufficient genetic risk assessment and knowledge by a majority of healthcare providers without genetics credentials; a shortage of genetic specialists, especially in rural areas; a low rate of reimbursement for comprehensive genetic counseling services; and an individual focus on prevention by clinical guidelines and insurance coverage. The family-centric approach of cascade genetic screening improves prevention and early diagnosis of heritable diseases on a population health level. Cascade genetic screening could be better supported and augmented through changes in health policy.

  2. The maternal genetic make-up of the Iberian Peninsula between the Neolithic and the Early Bronze Age.

    PubMed

    Szécsényi-Nagy, Anna; Roth, Christina; Brandt, Guido; Rihuete-Herrada, Cristina; Tejedor-Rodríguez, Cristina; Held, Petra; García-Martínez-de-Lagrán, Íñigo; Arcusa Magallón, Héctor; Zesch, Stephanie; Knipper, Corina; Bánffy, Eszter; Friederich, Susanne; Meller, Harald; Bueno Ramírez, Primitiva; Barroso Bermejo, Rosa; de Balbín Behrmann, Rodrigo; Herrero-Corral, Ana M; Flores Fernández, Raúl; Alonso Fernández, Carmen; Jiménez Echevarria, Javier; Rindlisbacher, Laura; Oliart, Camila; Fregeiro, María-Inés; Soriano, Ignacio; Vicente, Oriol; Micó, Rafael; Lull, Vicente; Soler Díaz, Jorge; López Padilla, Juan Antonio; Roca de Togores Muñoz, Consuelo; Hernández Pérez, Mauro S; Jover Maestre, Francisco Javier; Lomba Maurandi, Joaquín; Avilés Fernández, Azucena; Lillios, Katina T; Silva, Ana Maria; Magalhães Ramalho, Miguel; Oosterbeek, Luiz Miguel; Cunha, Claudia; Waterman, Anna J; Roig Buxó, Jordi; Martínez, Andrés; Ponce Martínez, Juana; Hunt Ortiz, Mark; Mejías-García, Juan Carlos; Pecero Espín, Juan Carlos; Cruz-Auñón Briones, Rosario; Tomé, Tiago; Carmona Ballestero, Eduardo; Cardoso, João Luís; Araújo, Ana Cristina; Liesau von Lettow-Vorbeck, Corina; Blasco Bosqued, Concepción; Ríos Mendoza, Patricia; Pujante, Ana; Royo-Guillén, José I; Esquembre Beviá, Marco Aurelio; Dos Santos Goncalves, Victor Manuel; Parreira, Rui; Morán Hernández, Elena; Méndez Izquierdo, Elena; Vega Y Miguel, Jorge; Menduiña García, Roberto; Martínez Calvo, Victoria; López Jiménez, Oscar; Krause, Johannes; Pichler, Sandra L; Garrido-Pena, Rafael; Kunst, Michael; Risch, Roberto; Rojo-Guerra, Manuel A; Haak, Wolfgang; Alt, Kurt W

    2017-11-15

    Agriculture first reached the Iberian Peninsula around 5700 BCE. However, little is known about the genetic structure and changes of prehistoric populations in different geographic areas of Iberia. In our study, we focus on the maternal genetic makeup of the Neolithic (~ 5500-3000 BCE), Chalcolithic (~ 3000-2200 BCE) and Early Bronze Age (~ 2200-1500 BCE). We report ancient mitochondrial DNA results of 213 individuals (151 HVS-I sequences) from the northeast, central, southeast and southwest regions and thus on the largest archaeogenetic dataset from the Peninsula to date. Similar to other parts of Europe, we observe a discontinuity between hunter-gatherers and the first farmers of the Neolithic. During the subsequent periods, we detect regional continuity of Early Neolithic lineages across Iberia, however the genetic contribution of hunter-gatherers is generally higher than in other parts of Europe and varies regionally. In contrast to ancient DNA findings from Central Europe, we do not observe a major turnover in the mtDNA record of the Iberian Late Chalcolithic and Early Bronze Age, suggesting that the population history of the Iberian Peninsula is distinct in character.

  3. Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?

    PubMed

    Scott, Ian C; Rijsdijk, Frühling; Walker, Jemma; Quist, Jelmar; Spain, Sarah L; Tan, Rachael; Steer, Sophia; Okada, Yukinori; Raychaudhuri, Soumya; Cope, Andrew P; Lewis, Cathryn M

    2015-07-01

    Genetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA. We evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants - 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions - for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models. HLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP - rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) - associated with HAQ scores over 6-24 months. HLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.

  4. Early animal evolution: emerging views from comparative biology and geology

    NASA Technical Reports Server (NTRS)

    Knoll, A. H.; Carroll, S. B.

    1999-01-01

    The Cambrian appearance of fossils representing diverse phyla has long inspired hypotheses about possible genetic or environmental catalysts of early animal evolution. Only recently, however, have data begun to emerge that can resolve the sequence of genetic and morphological innovations, environmental events, and ecological interactions that collectively shaped Cambrian evolution. Assembly of the modern genetic tool kit for development and the initial divergence of major animal clades occurred during the Proterozoic Eon. Crown group morphologies diversified in the Cambrian through changes in the genetic regulatory networks that organize animal ontogeny. Cambrian radiation may have been triggered by environmental perturbation near the Proterozoic-Cambrian boundary and subsequently amplified by ecological interactions within reorganized ecosystems.

  5. [60 years of medical genetics in Israel].

    PubMed

    Shalev, Stavit A; Borochowitz, Zvi U; Zlotogora, Joel

    2010-02-01

    The principle deeds of genetics in Israel consist of a wide array of disciplines including agriculture, nutrients, biotechnology, pharmacology and pharmacogenetics, pertaining to criminal as well as medical aspects. In the scope of this state of the art historical review, the authors emphasize the medical issues. The initial stimulus for genetic studies and medical awareness among the various ethnic populations in Israel was the immigration, in the early 1950s, of over a million Jewish immigrants from more than 100 countries from all continents. It was soon recognized that frequencies of genetic diseases differed markedly among the various communities, serving as a trigger for studying and managing these populations. In this state of the art historical review, particular emphasize was given to the historical events concerning genetics in the land of Israel, as well as in the state of Israel. Highlights of genetic diversity of the various ethnic and sub-populations are added, along with the advances and major achievements of the human genetics discipline in the state of Israel.

  6. The Genetic and Environmental Etiologies of Individual Differences in Early Reading Growth in Australia, the United States, and Scandinavia

    PubMed Central

    Christopher, Micaela E.; Hulslander, Jacqueline; Byrne, Brian; Samuelsson, Stefan; Keenan, Janice M.; Pennington, Bruce; DeFries, John C.; Wadsworth, Sally J.; Willcutt, Erik; Olson, Richard K.

    2013-01-01

    This first cross-country twin study of individual differences in reading growth from post-kindergarten to post-2nd grade analyzed data from 487 twin pairs from the United States, 267 pairs from Australia, and 280 pairs from Scandinavia. Data from two reading measures were fit to biometric latent growth models. Individual differences for the reading measures at post-kindergarten in the U.S. and Australia were due primarily to genetic influences, and to both genetic and shared environmental influences in Scandinavia. In contrast, individual differences in growth generally had large genetic influences in all countries. These results suggest that genetic influences are largely responsible for individual differences in early reading development. In addition, the timing of the start of formal literacy instruction may affect the etiology of individual differences in early reading development, but have only limited influence on the etiology of individual differences in growth. PMID:23665180

  7. Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment

    PubMed Central

    Yang, Xian-Ming; Lou, Heng; Sun, Jing-Tao; Zhu, Yi-Ming; Xue, Xiao-Feng; Hong, Xiao-Yue

    2015-01-01

    Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range. PMID:26138760

  8. Modeling the Etiology of Individual Differences in Early Reading Development: Evidence for Strong Genetic Influences

    PubMed Central

    Christopher, Micaela E.; Hulslander, Jacqueline; Byrne, Brian; Samuelsson, Stefan; Keenan, Janice M.; Pennington, Bruce; DeFries, John C.; Wadsworth, Sally J.; Willcutt, Erik; Olson, Richard K.

    2012-01-01

    We explored the etiology of individual differences in reading development from post-kindergarten to post-4th grade by analyzing data from 487 twin pairs tested in Colorado. Data from three reading measures and one spelling measure were fit to biometric latent growth curve models, allowing us to extend previous behavioral genetic studies of the etiology of early reading development at specific time points. We found primarily genetic influences on individual differences at post-1st grade for all measures. Genetic influences on variance in growth rates were also found, with evidence of small, nonsignificant, shared environmental influences for two measures. We discuss our results, including their implications for educational policy. PMID:24489459

  9. The underlying process of early ecological and genetic differentiation in a facultative mutualistic Sinorhizobium meliloti population.

    PubMed

    Toro, Nicolás; Villadas, Pablo J; Molina-Sánchez, María Dolores; Navarro-Gómez, Pilar; Vinardell, José M; Cuesta-Berrio, Lidia; Rodríguez-Carvajal, Miguel A

    2017-04-06

    The question of how genotypic and ecological units arise and spread in natural microbial populations remains controversial in the field of evolutionary biology. Here, we investigated the early stages of ecological and genetic differentiation in a highly clonal sympatric Sinorhizobium meliloti population. Whole-genome sequencing revealed that a large DNA region of the symbiotic plasmid pSymB was replaced in some isolates with a similar synteny block carrying densely clustered SNPs and displaying gene acquisition and loss. Two different versions of this genomic island of differentiation (GID) generated by multiple genetic exchanges over time appear to have arisen recently, through recombination in a particular clade within this population. In addition, these isolates display resistance to phages from the same geographic region, probably due to the modification of surface components by the acquired genes. Our results suggest that an underlying process of early ecological and genetic differentiation in S. meliloti is primarily triggered by acquisition of genes that confer resistance to soil phages within particular large genomic DNA regions prone to recombination.

  10. A new PCR-CGE (size and color) method for simultaneous detection of genetically modified maize events.

    PubMed

    Nadal, Anna; Coll, Anna; La Paz, Jose-Luis; Esteve, Teresa; Pla, Maria

    2006-10-01

    We present a novel multiplex PCR assay for simultaneous detection of multiple transgenic events in maize. Initially, five PCR primers pairs specific to events Bt11, GA21, MON810, and NK603, and Zea mays L. (alcohol dehydrogenase) were included. The event specificity was based on amplification of transgene/plant genome flanking regions, i.e., the same targets as for validated real-time PCR assays. These short and similarly sized amplicons were selected to achieve high and similar amplification efficiency for all targets; however, its unambiguous identification was a technical challenge. We achieved a clear distinction by a novel CGE approach that combined the identification by size and color (CGE-SC). In one single step, all five targets were amplified and specifically labeled with three different fluorescent dyes. The assay was specific and displayed an LOD of 0.1% of each genetically modified organism (GMO). Therefore, it was adequate to fulfill legal thresholds established, e.g., in the European Union. Our CGE-SC based strategy in combination with an adequate labeling design has the potential to simultaneously detect higher numbers of targets. As an example, we present the detection of up to eight targets in a single run. Multiplex PCR-CGE-SC only requires a conventional sequencer device and enables automation and high throughput. In addition, it proved to be transferable to a different laboratory. The number of authorized GMO events is rapidly growing; and the acreage of genetically modified (GM) varieties cultivated and commercialized worldwide is rapidly increasing. In this context, our multiplex PCR-CGE-SC can be suitable for screening GM contents in food.

  11. Reconstructing demographic events from population genetic data: the introduction of bumblebees to New Zealand.

    PubMed

    Lye, G C; Lepais, O; Goulson, D

    2011-07-01

    Four British bumblebee species (Bombus terrestris, Bombus hortorum, Bombus ruderatus and Bombus subterraneus) became established in New Zealand following their introduction at the turn of the last century. Of these, two remain common in the United Kingdom (B. terrestris and B. hortorum), whilst two (B. ruderatus and B. subterraneus) have undergone marked declines, the latter being declared extinct in 2000. The presence of these bumblebees in New Zealand provides an unique system in which four related species have been isolated from their source population for over 100 years, providing a rare opportunity to examine the impacts of an initial bottleneck and introduction to a novel environment on their population genetics. We used microsatellite markers to compare modern populations of B. terrestris, B. hortorum and B. ruderatus in the United Kingdom and New Zealand and to compare museum specimens of British B. subterraneus with the current New Zealand population. We used approximate Bayesian computation to estimate demographic parameters of the introduction history, notably to estimate the number of founders involved in the initial introduction. Species-specific patterns derived from genetic analysis were consistent with the predictions based on the presumed history of these populations; demographic events have left a marked genetic signature on all four species. Approximate Bayesian analyses suggest that the New Zealand population of B. subterraneus may have been founded by as few as two individuals, giving rise to low genetic diversity and marked genetic divergence from the (now extinct) UK population. © 2011 Blackwell Publishing Ltd.

  12. Occurrence of early adverse events after vaccination against influenza at a Brazilian reference center.

    PubMed

    Lopes, Marta Heloísa; Mascheretti, Melissa; Franco, Marilia Miranda; Vasconcelos, Ricardo; Gutierrez, Eliana Battaggia

    2008-02-01

    Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.

  13. Not Just the 8.2 event: Dynamic Early Holocene Climate in Arctic Canada

    NASA Astrophysics Data System (ADS)

    Axford, Y.; Briner, J. P.; Miller, G. H.; Francis, D. R.

    2006-12-01

    Temperature reconstructions from a lake in the eastern Canadian Arctic indicate that peak warmth in the early Holocene was interrupted by two abrupt, short-lived temperature reversals at ~9.l and ~8.5 ka. Summer temperatures at Lake CF8, Baffin Island (~500 km west of Greenland) are inferred from subfossil midge (Chironomidae) assemblages. Our results indicate that the site, like others on Baffin Island, experienced exceptionally warm summers (almost 5°C warmer than present) through much of the early Holocene, presumably in response to enhanced summer insolation. After 1000 years of very warm, stable climate, warmth was interrupted by two discrete cold reversals at ~9.1 and ~8.5 ka, during which multiple cold-stenothermous midge taxa appeared in the lake and summer temperatures dropped more than 3°C. These two clearly-defined reversals, well beyond the range of background variability, were of similar amplitude and duration, and were separated by several centuries of near-peak warmth. The only Holocene events of comparable amplitude at this site are the rapid onset of Holocene warmth, and the more gradual Neoglacial cooling after 8 ka. Abrupt cooling events over the Baffin region are consistent with model simulations of the impacts of freshwater outbursts into the Labrador Sea, such as the Lake Agassiz outburst flood that occurred ~8.4 ka. That there are two discrete events recorded at this site indicates that the "8.2 event" was not uniquely significant in this region; rather, the period between approximately ~9.2 and 8 ka was characterized by repeated climate fluctuations forced by multiple outburst floods or other mechanisms. Thus global correlations among paleoclimate records need not assume that climate perturbations during this time period necessarily correlate with the draining of Lake Agassiz or the 8.2 ka cooling in central Greenland.

  14. The role of parent, teacher, and peer events in maintaining depressive symptoms during early adolescence.

    PubMed

    Herres, Joanna; Kobak, Roger

    2015-02-01

    Negative interpersonal events have been consistently identified as both antecedents and sequalae of adolescent depressive symptoms. However, little is known about the relative contributions of specific domains of interpersonal events (parents, peers or teachers) to the maintenance of depressive symptoms during early adolescence or whether a lack of positive interpersonal interactions plays a direct role in maintaining depressive symptoms. Further, few studies have examined whether positive interpersonal events moderate associations between negative events and adolescents' depressive symptoms. This study combined stress generation and exposure models to evaluate the contribution of daily events to the maintenance of depressive symptoms in a sample of 132 adolescents (53 % female) followed from ages 13 to 15. Daily phone diaries collected at age 14 assessed adolescents' negative and positive interactions with parents, teachers, and peers in a sample of adolescents from economically disadvantaged families. Negative peer events uniquely accounted for the maintenance of depressive symptoms over the 2 years period. Results did not differ by gender; however, positive parent events buffered the effects of negative parent events for females but not for males. Findings highlight the significance of peer relationships during a period of vulnerability for depressive symptoms.

  15. Genetics of human hydrocephalus

    PubMed Central

    Williams, Michael A.; Rigamonti, Daniele

    2006-01-01

    Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human

  16. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions.

    PubMed

    Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

    2017-09-01

    Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. New Early Jurassic Tetrapod Assemblages Constrain Triassic-Jurassic Tetrapod Extinction Event

    NASA Astrophysics Data System (ADS)

    Olsen, P. E.; Shubin, N. H.; Anders, M. H.

    1987-08-01

    The discovery of the first definitively correlated earliest Jurassic (200 million years before present) tetrapod assemblage (Fundy basin, Newark Supergroup, Nova Scotia) allows reevaluation of the duration of the Triassic-Jurassic tetrapod extinction event. Present are tritheledont and mammal-like reptiles, prosauropod, theropod, and ornithischian dinosaurs, protosuchian and sphenosuchian crocodylomorphs, sphenodontids, and hybodont, semionotid, and palaeonisciform fishes. All of the families are known from Late Triassic and Jurassic strata from elsewhere; however, pollen and spore, radiometric, and geochemical correlation indicate an early Hettangian age for these assemblages. Because all ``typical Triassic'' forms are absent from these assemblages, most Triassic-Jurassic tetrapod extinctions occurred before this time and without the introduction of new families. As was previously suggested by studies of marine invertebrates, this pattern is consistent with a global extinction event at the Triassic-Jurassic boundary. The Manicouagan impact structure of Quebec provides dates broadly compatible with the Triassic-Jurassic boundary and, following the impact theory of mass extinctions, may be implicated in the cause.

  18. Obesity-programmed mice are rescued by early genetic intervention

    PubMed Central

    Bumaschny, Viviana F.; Yamashita, Miho; Casas-Cordero, Rodrigo; Otero-Corchón, Verónica; de Souza, Flávio S.J.; Rubinstein, Marcelo; Low, Malcolm J.

    2012-01-01

    Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity. PMID:23093774

  19. Difficult temperament and negative parenting in early childhood: a genetically informed cross-lagged analysis.

    PubMed

    Micalizzi, Lauren; Wang, Manjie; Saudino, Kimberly J

    2017-03-01

    A genetically informed longitudinal cross-lagged model was applied to twin data to explore etiological links between difficult temperament and negative parenting in early childhood. The sample comprised 313 monozygotic (MZ) and dizygotic (DZ) twin pairs. Difficult temperament and negative parenting were assessed at ages 2 and 3 using parent ratings. Both constructs were interrelated within and across age (rs .34-.47) and showed substantial stability (rs .65-.68). Difficult temperament and negative parenting were influenced by genetic and environmental factors at ages 2 and 3. The genetic and nonshared environmental correlations (rs .21-.76) at both ages suggest overlap at the level of etiology between the phenotypes. Significant bidirectional associations between difficult temperament and negative parenting were found. The cross-lagged association from difficult temperament at age 2 to negative parenting at age 3 and from negative parenting at age 2 and difficult temperament at age 3 were due to genetic, shared environmental, and nonshared environmental factors. Substantial novel genetic and nonshared environmental influences emerged at age 3 and suggest change in the etiology of these constructs over time. © 2015 John Wiley & Sons Ltd.

  20. Difficult temperament and negative parenting in early childhood: a genetically informed cross-lagged analysis

    PubMed Central

    Micalizzi, Lauren; Wang, Manjie; Saudino, Kimberly J.

    2015-01-01

    A genetically informed longitudinal cross-lagged model was applied to twin data to explore etiological links between difficult temperament and negative parenting in early childhood. The sample comprised 313 monozygotic (MZ) and dizygotic (DZ) twin pairs. Difficult temperament and negative parenting were assessed at ages 2 and 3 using parent ratings. Both constructs were interrelated within and across age (rs .34–.47) and showed substantial stability (rs .65–.68). Difficult temperament and negative parenting were influenced by genetic and environmental factors at ages 2 and 3. The genetic and nonshared environmental correlations (rs .21–.76) at both ages suggest overlap at the level of etiology between the phenotypes. Significant bidirectional associations between difficult temperament and negative parenting were found. The cross-lagged association from difficult temperament at age 2 to negative parenting at age 3 and from negative parenting at age 2 and difficult temperament at age 3 were due to genetic, shared environmental, and nonshared environmental factors. Substantial novel genetic and nonshared environmental influences emerged at age 3 and suggest change in the etiology of these constructs over time. PMID:26490166

  1. Early onset prostate cancer has a significant genetic component.

    PubMed

    Lange, Ethan M; Salinas, Claudia A; Zuhlke, Kimberly A; Ray, Anna M; Wang, Yunfei; Lu, Yurong; Ho, Lindsey A; Luo, Jingchun; Cooney, Kathleen A

    2012-02-01

    Prostate cancer (PCa) affects more than 190,000 men each year with ∼10% of men diagnosed at ≤55 years, that is, early onset (EO) PCa. Based on historical findings for other cancers, EO PCa likely reflects a stronger underlying genetic etiology. We evaluated the association between EO PCa and previously identified single nucleotide polymorphisms (SNPs) in 754 Caucasian cases from the Michigan Prostate Cancer Genetics Project (mean 49.8 years at diagnosis), 2,713 Caucasian controls from Illumina's iControlDB database and 1,163 PCa cases diagnosed at >55 years from the Cancer Genetic Markers of Susceptibility Study (CGEMS). Significant associations existed for 13 of 14 SNPs (rs9364554 on 6q25, rs10486567 on 7p15, rs6465657 on 7q21, rs6983267 on 8q24, rs1447295 on 8q24, rs1571801 on 9q33, rs10993994 on 10q11, rs4962416 on 10q26, rs7931342 on 11q13, rs4430796 on 17q12, rs1859962 on 17q24.3, rs2735839 on 19q13, and rs5945619 on Xp11.22, but not rs2660753 on 3p12). EO PCa cases had a significantly greater cumulative number of risk alleles (mean 12.4) than iControlDB controls (mean 11.2; P = 2.1 × 10(-33)) or CGEMS cases (mean 11.9; P = 1.7 × 10(-5)). Notably, EO PCa cases had a higher frequency of the risk allele than CGEMS cases at 11 of 13 associated SNPs, with significant differences for five SNPs. EO PCa cases diagnosed at <50 (mean 12.8) also had significantly more risk alleles than those diagnosed at 50-55 years (mean 12.1; P = 0.0003). These results demonstrate the potential for identifying PCa-associated genetic variants by focusing on the subgroup of men diagnosed with EO disease. Copyright © 2011 Wiley Periodicals, Inc.

  2. Early Onset Prostate Cancer Has A Significant Genetic Component

    PubMed Central

    Lange, Ethan M.; Salinas, Claudia A.; Zuhlke, Kimberly A.; Ray, Anna M.; Wang, Yunfei; Lu, Yurong; Ho, Lindsey A.; Luo, Jingchun; Cooney, Kathleen A.

    2011-01-01

    BACKGROUND Prostate cancer (PCa) affects more than 190,000 men each year with ~10% of men diagnosed at ≤ 55 years, i.e., early onset (EO) PCa. Based on historical findings for other cancers, EO PCa likely reflects a stronger underlying genetic etiology. METHODS We evaluated the association between EO PCa and previously identified single nucleotide polymorphisms (SNPs) in 754 Caucasian cases from the Michigan Prostate Cancer Genetics Project (mean 49.8 years at diagnosis), 2,713 Caucasian controls from Illumina’s iControlDB database and 1,163 PCa cases diagnosed at >55 years from the Cancer Genetic Markers of Susceptibility Study (CGEMS). RESULTS Significant associations existed for 13 of 14 SNPs (rs9364554 on 6q25, rs10486567 on 7p15, rs6465657 on 7q21, rs6983267 on 8q24, rs1447295 on 8q24, rs1571801 on 9q33, rs10993994 on 10q11, rs4962416 on 10q26, rs7931342 on 11q13, rs4430796 on 17q12, rs1859962 on 17q24.3, rs2735839 on 19q13, and rs5945619 on Xp11.22, but not rs2660753 on 3p12). EO PCa cases had a significantly greater cumulative number of risk alleles (mean 12.4) than iControlDB controls (mean 11.2; p=2.1×10−33) or CGEMS cases (mean 11.9; p=1.7 × 10−5). Notably, EO PCa cases had a higher frequency of the risk allele than CGEMS cases at 11 of13 associated SNPs, with significant differences for five SNPs. EO PCa cases diagnosed at <50 (mean 12.8) also had significantly more risk alleles than those diagnosed at 50–55 years (mean 12.1; p = 0.0003). CONCLUSIONS These results demonstrate the potential for identifying PCa-associated genetic variants by focusing on the subgroup of men diagnosed with EO disease. PMID:21538423

  3. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

    PubMed

    Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

    2009-09-01

    Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

  4. Genetic moderation of multiple pathways linking early cumulative socioeconomic adversity and young adults' cardiometabolic disease risk.

    PubMed

    Wickrama, Kandauda A S; Lee, Tae Kyoung; O'Neal, Catherine Walker

    2018-02-01

    Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined. Second, moderation of these pathways by the serotonin transporter linked polymorphic region gene (5-HTTLPR) was examined. There was evidence for the association between early socioeconomic adversity and young adults' cardiometabolic disease risk directly and indirectly through educational attainment and accelerated transitions. These direct and mediating pathways were amplified by the 5-HTTLPR polymorphism. These findings elucidate how early adversity can have an enduring influence on young adults' cardiometabolic disease risk directly and indirectly through psychosocial resources and life stressors and their genetic moderation. This information suggests that effective intervention and prevention programs should focus on early adversity, youth educational attainment, and their transition to young adulthood.

  5. Early Intravascular Events are Associated with Development of ARDS.

    PubMed

    Abdulnour, Raja-Elie E; Gunderson, Tina; Barkas, Ioanna; Timmons, Jack Y; Barnig, Cindy; Gong, Michelle; Kor, Daryl J; Gajic, Ognjen; Talmor, Daniel; Carter, Rickey E; Levy, Bruce D

    2018-05-21

    The acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. To determine select peripheral blood lipid mediator and leukocyte responses in patients at-risk for ARDS. Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (LIPS-A; NCT01504867). Plasma thromboxane B2 (TxB2), 15-epi-LXA4 (aspirin-triggered lipoxin A4, ATL), and peripheral blood leukocyte number and activation were determined upon enrollment and after treatment with either aspirin or placebo. Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte (IntMo) counts, and Mo-PA were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased over time. Of note, 9 subjects developed ARDS after randomization yet prior to study drug initiation, including 7 subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TxB2 and increased the ATL/TxB2 ratio. Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS, and represent potential vascular biomarkers of ARDS risk.

  6. Quantitative genetics of plumage color: lifetime effects of early nest environment on a colorful sexual signal

    PubMed Central

    Hubbard, Joanna K; Jenkins, Brittany R; Safran, Rebecca J

    2015-01-01

    Phenotypic differences among individuals are often linked to differential survival and mating success. Quantifying the relative influence of genetic and environmental variation on phenotype allows evolutionary biologists to make predictions about the potential for a given trait to respond to selection and various aspects of environmental variation. In particular, the environment individuals experience during early development can have lasting effects on phenotype later in life. Here, we used a natural full-sib/half-sib design as well as within-individual longitudinal analyses to examine genetic and various environmental influences on plumage color. We find that variation in melanin-based plumage color – a trait known to influence mating success in adult North American barn swallows (Hirundo rustica erythrogaster) – is influenced by both genetics and aspects of the developmental environment, including variation due to the maternal phenotype and the nest environment. Within individuals, nestling color is predictive of adult color. Accordingly, these early environmental influences are relevant to the sexually selected plumage color variation in adults. Early environmental conditions appear to have important lifelong implications for individual reproductive performance through sexual signal development in barn swallows. Our results indicate that feather color variation conveys information about developmental conditions and maternal care alleles to potential mates in North American barn swallows. Melanin-based colors are used for sexual signaling in many organisms, and our study suggests that these signals may be more sensitive to environmental variation than previously thought. PMID:26380676

  7. Early events of citrus greening (Huanglongbing) disease development at the ultrastructural level.

    PubMed

    Folimonova, Svetlana Y; Achor, Diann S

    2010-09-01

    Citrus greening (Huanglongbing [HLB]) is one of the most destructive diseases of citrus worldwide. The causal agent of HLB in Florida is thought to be 'Candidatus Liberibacter asiaticus'. Understanding of the early events in HLB infection is critical for the development of effective measures to control the disease. In this work, we conducted cytopathological studies by following the development of the disease in citrus trees graft inoculated with 'Ca. L. asiaticus'-containing material under greenhouse conditions to examine the correlation between ultrastructural changes and symptom production, with the main objective of characterizing the early events of infection. Based on our observations, one of the first degenerative changes induced upon invasion of the pathogen appears to be swelling of middle lamella between cell walls surrounding sieve elements. This anatomical aberration was often observed in samples from newly growing flushes in inoculated sweet orange and grapefruit trees at the early "presymptomatic" stage of HLB infection. Development of symptoms and their progression correlated with an increasing degree of microscopic aberrations. Remarkably, the ability to observe the bacterium in the infected tissue also correlated with the degree of the disease progression. Large numbers of bacterial cells were found in phloem sieve tubes in tissue samples from presymptomatic young flushes. In contrast, we did not observe the bacteria in highly symptomatic leaf samples, suggesting a possibility that, at more advanced stages of the disease, a major proportion of 'Ca. L. asiaticus' is present in a nonviable state. We trust that observations reported here advance our understanding of how 'Ca. L. asiaticus' causes disease. Furthermore, they may be an important aid in answering a question: when and where within an infected tree the tissue serves as a better inoculum source for acquisition and transmission of the bacterium by its psyllid vector.

  8. Early maritime economy and El Nino events at Quebrada Tacahuay, Peru

    USGS Publications Warehouse

    Keefer, D.K.; DeFrance, Susan D.; Moseley, M.E.; Richardson, J. B.; Satterlee, D.R.; Day-Lewis, A.

    1998-01-01

    The archaeological site of Quebrada Tacahuay, Peru, dates to 12,700 to 12,500 calibrated years before the present (10,770 to 10,530 carbon-14 years before the present). It contains some of the oldest evidence of maritime- based economic activity in the New World. Recovered materials include a hearth, lithic cutting tools and flakes, and abundant processed marine fauna, primarily seabirds and fish. Sediments below and above the occupation layer were probably generated by El Nino events, indicating that El Nino was active during the Pleistocene as well as during the early and middle Holocene.

  9. Ancient DNA reveals genetic connections between early Di-Qiang and Han Chinese.

    PubMed

    Li, Jiawei; Zeng, Wen; Zhang, Ye; Ko, Albert Min-Shan; Li, Chunxiang; Zhu, Hong; Fu, Qiaomei; Zhou, Hui

    2017-12-04

    Ancient Di-Qiang people once resided in the Ganqing region of China, adjacent to the Central Plain area from where Han Chinese originated. While gene flow between the Di-Qiang and Han Chinese has been proposed, there is no evidence to support this view. Here we analyzed the human remains from an early Di-Qiang site (Mogou site dated ~4000 years old) and compared them to other ancient DNA across China, including an early Han-related site (Hengbei site dated ~3000 years old) to establish the underlying genetic relationship between the Di-Qiang and ancestors of Han Chinese. We found Mogou mtDNA haplogroups were highly diverse, comprising 14 haplogroups: A, B, C, D (D*, D4, D5), F, G, M7, M8, M10, M13, M25, N*, N9a, and Z. In contrast, Mogou males were all Y-DNA haplogroup O3a2/P201; specifically one male was further assigned to O3a2c1a/M117 using targeted unique regions on the non-recombining region of the Y-chromosome. We compared Mogou to 7 other ancient and 38 modern Chinese groups, in a total of 1793 individuals, and found that Mogou shared close genetic distances with Taojiazhai (a more recent Di-Qiang population), Hengbei, and Northern Han. We modeled their interactions using Approximate Bayesian Computation, and support was given to a potential admixture of ~13-18% between the Mogou and Northern Han around 3300-3800 years ago. Mogou harbors the earliest genetically identifiable Di-Qiang, ancestral to the Taojiazhai, and up to ~33% paternal and ~70% of its maternal haplogroups could be found in present-day Northern Han Chinese.

  10. Effect of endogenous reference genes on digital PCR assessment of genetically engineered canola events.

    PubMed

    Demeke, Tigst; Eng, Monika

    2018-05-01

    Droplet digital PCR (ddPCR) has been used for absolute quantification of genetically engineered (GE) events. Absolute quantification of GE events by duplex ddPCR requires the use of appropriate primers and probes for target and reference gene sequences in order to accurately determine the amount of GE materials. Single copy reference genes are generally preferred for absolute quantification of GE events by ddPCR. Study has not been conducted on a comparison of reference genes for absolute quantification of GE canola events by ddPCR. The suitability of four endogenous reference sequences ( HMG-I/Y , FatA(A), CruA and Ccf) for absolute quantification of GE canola events by ddPCR was investigated. The effect of DNA extraction methods and DNA quality on the assessment of reference gene copy numbers was also investigated. ddPCR results were affected by the use of single vs. two copy reference genes. The single copy, FatA(A), reference gene was found to be stable and suitable for absolute quantification of GE canola events by ddPCR. For the copy numbers measured, the HMG-I/Y reference gene was less consistent than FatA(A) reference gene. The expected ddPCR values were underestimated when CruA and Ccf (two copy endogenous Cruciferin sequences) were used because of high number of copies. It is important to make an adjustment if two copy reference genes are used for ddPCR in order to obtain accurate results. On the other hand, real-time quantitative PCR results were not affected by the use of single vs. two copy reference genes.

  11. Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts.

    PubMed

    Jelenkovic, Aline; Sund, Reijo; Hur, Yoon-Mi; Yokoyama, Yoshie; Hjelmborg, Jacob V B; Möller, Sören; Honda, Chika; Magnusson, Patrik K E; Pedersen, Nancy L; Ooki, Syuichi; Aaltonen, Sari; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Freitas, Duarte L; Maia, José Antonio; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Busjahn, Andreas; Kandler, Christian; Saudino, Kimberly J; Jang, Kerry L; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Gao, Wenjing; Yu, Canqing; Li, Liming; Corley, Robin P; Huibregtse, Brooke M; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Heikkilä, Kauko; Wardle, Jane; Llewellyn, Clare H; Fisher, Abigail; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; He, Mingguang; Ding, Xiaohu; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D; Tarnoki, David L; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Burt, S Alexandra; Klump, Kelly L; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Gatz, Margaret; Butler, David A; Bartels, Meike; van Beijsterveldt, Toos C E M; Craig, Jeffrey M; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Swan, Gary E; Krasnow, Ruth; Tynelius, Per; Lichtenstein, Paul; Haworth, Claire M A; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Harden, K Paige; Tucker-Drob, Elliot M; Spector, Timothy; Mangino, Massimo; Lachance, Genevieve; Baker, Laura A; Tuvblad, Catherine; Duncan, Glen E; Buchwald, Dedra; Willemsen, Gonneke; Skytthe, Axel; Kyvik, Kirsten O; Christensen, Kaare; Öncel, Sevgi Y; Aliev, Fazil; Rasmussen, Finn; Goldberg, Jack H; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko; Silventoinen, Karri

    2016-06-23

    Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.

  12. Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts

    PubMed Central

    Jelenkovic, Aline; Sund, Reijo; Hur, Yoon-Mi; Yokoyama, Yoshie; Hjelmborg, Jacob v. B.; Möller, Sören; Honda, Chika; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Ooki, Syuichi; Aaltonen, Sari; Stazi, Maria A.; Fagnani, Corrado; D’Ippolito, Cristina; Freitas, Duarte L.; Maia, José Antonio; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Busjahn, Andreas; Kandler, Christian; Saudino, Kimberly J.; Jang, Kerry L.; Cozen, Wendy; Hwang, Amie E.; Mack, Thomas M.; Gao, Wenjing; Yu, Canqing; Li, Liming; Corley, Robin P.; Huibregtse, Brooke M.; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Heikkilä, Kauko; Wardle, Jane; Llewellyn, Clare H.; Fisher, Abigail; McAdams, Tom A.; Eley, Thalia C.; Gregory, Alice M.; He, Mingguang; Ding, Xiaohu; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D.; Tarnoki, David L.; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Burt, S. Alexandra; Klump, Kelly L.; Silberg, Judy L.; Eaves, Lindon J.; Maes, Hermine H.; Krueger, Robert F.; McGue, Matt; Pahlen, Shandell; Gatz, Margaret; Butler, David A.; Bartels, Meike; van Beijsterveldt, Toos C. E. M.; Craig, Jeffrey M.; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Swan, Gary E.; Krasnow, Ruth; Tynelius, Per; Lichtenstein, Paul; Haworth, Claire M. A.; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Harden, K. Paige; Tucker-Drob, Elliot M.; Spector, Timothy; Mangino, Massimo; Lachance, Genevieve; Baker, Laura A.; Tuvblad, Catherine; Duncan, Glen E.; Buchwald, Dedra; Willemsen, Gonneke; Skytthe, Axel; Kyvik, Kirsten O.; Christensen, Kaare; Öncel, Sevgi Y.; Aliev, Fazil; Rasmussen, Finn; Goldberg, Jack H.; Sørensen, Thorkild I. A.; Boomsma, Dorret I.; Kaprio, Jaakko; Silventoinen, Karri

    2016-01-01

    Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1–19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments. PMID:27333805

  13. The Genetic and Environmental Origins of Learning Abilities and Disabilities in the Early School Years

    ERIC Educational Resources Information Center

    Kovas, Yulia; Haworth, Claire M. A.; Dale, Philip S.; Plomin, Robert

    2007-01-01

    Despite the importance of learning abilities and disabilities in education and child development, little is known about their genetic and environmental origins in the early school years. We report results for English (which includes reading, writing, and speaking), mathematics, and science as well as general cognitive ability in a large and…

  14. Which early life events or current environmental and lifestyle factors influence lung function in adolescents? - results from the GINIplus & LISAplus studies.

    PubMed

    Luzak, Agnes; Fuertes, Elaine; Flexeder, Claudia; Standl, Marie; von Berg, Andrea; Berdel, Dietrich; Koletzko, Sibylle; Heinrich, Joachim; Nowak, Dennis; Schulz, Holger

    2017-07-12

    Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. Best subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF 25-75 )) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. A higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF 25-75 . Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (≤23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were consistently negatively associated with airway function. Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents.

  15. Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.

    PubMed

    Di Iorio, Christina R; Carey, Caitlin E; Michalski, Lindsay J; Corral-Frias, Nadia S; Conley, Emily Drabant; Hariri, Ahmad R; Bogdan, Ryan

    2017-06-01

    Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Genetic Structure in the Seabuckthorn Carpenter Moth (Holcocerus hippophaecolus) in China: The Role of Outbreak Events, Geographical and Host Factors

    PubMed Central

    Tao, Jing; Chen, Min; Zong, Shi-Xiang; Luo, You-Qing

    2012-01-01

    Understanding factors responsible for structuring genetic diversity is of fundamental importance in evolutionary biology. The seabuckthorn carpenter moth (Holcocerus hippophaecolus Hua) is a native species throughout the north of China and is considered the main threat to seabuckthorn, Hippophae rhamnoides L. We assessed the influence of outbreaks, environmental factors and host species in shaping the genetic variation and structure of H. hippophaecolus by using Amplified Fragment Length Polymorphism (AFLP) markers. We rejected the hypothesis that outbreak-associated genetic divergence exist, as evidenced by genetic clusters containing a combination of populations from historical outbreak areas, as well as non-outbreak areas. Although a small number of markers (4 of 933 loci) were identified as candidates under selection in response to population densities. H. hippophaecolus also did not follow an isolation-by-distance pattern. We rejected the hypothesis that outbreak and drought events were driving the genetic structure of H. hippophaecolus. Rather, the genetic structure appears to be influenced by various confounding bio-geographical factors. There were detectable genetic differences between H. hippophaecolus occupying different host trees from within the same geographic location. Host-associated genetic divergence should be confirmed by further investigation. PMID:22291983

  17. Early events in speciation: Cryptic species of Drosophila aldrichi.

    PubMed

    Castro Vargas, Cynthia; Richmond, Maxi Polihronakis; Ramirez Loustalot Laclette, Mariana; Markow, Therese Ann

    2017-06-01

    Understanding the earliest events in speciation remains a major challenge in evolutionary biology. Thus identifying species whose populations are beginning to diverge can provide useful systems to study the process of speciation. Drosophila aldrichi , a cactophilic fruit fly species with a broad distribution in North America, has long been assumed to be a single species owing to its morphological uniformity. While previous reports either of genetic divergence or reproductive isolation among different D. aldrichi strains have hinted at the existence of cryptic species, the evolutionary relationships of this species across its range have not been thoroughly investigated. Here we show that D. aldrichi actually is paraphyletic with respect to its closest relative, Drosophila wheeleri , and that divergent D. aldrichi lineages show complete hybrid male sterility when crossed. Our data support the interpretation that there are at least two species of D. aldrichi, making these flies particularly attractive for studies of speciation in an ecological and geographical context.

  18. Genetic signals of past demographic changes and the history of oak populations in California

    NASA Astrophysics Data System (ADS)

    Dodd, R. S.

    2009-04-01

    A retrospective view of species' demographic changes can inform on population stability through times of climatic change and the origins and spatial structure of genetic diversity in contemporary populations. The former provides the means to predict responses to future climatic change, while the latter allows us to infer the ability of populations to buffer the effects of reductions in population size and fragmentation. The approximately 1.8 my of the Pleistocene is believed to have had a significant impact on diversity through high rates of extinction during early glacial cycles and population expansions and contractions during the later cycles. In the Mediterranean basin, early emphasis on taxa with wide latitudinal ranges led to models of refugial sites and subsequent recolonization routes that could explain geographic patterns in genetic diversity, with a trend towards reduced genetic diversity in the north. More recently, the study of strictly Mediterranean taxa has revealed relictual sites that have persisted over very long periods of time, commonly relatively poor in diversity, but populations well differentiated from one site to another. In California, relatively little is known of the population dynamics of plant taxa during the Pleistocene glacial cycles, or to what extent differentiation today is a result of pre-Pleistocene events. For several animal taxa, differentiation between Coastal and Sierran taxa are believed to date to the Pliocene. Major demographic changes resulting in population isolation, bottlenecks, founder events and population expansions leave a genetic signal that can be detected through appropriate genetic markers and analyses. Such signals help to infer whether past climate fluctuations have had important effects on population demographics. Here, I will focus on key oak species of the California mediterranean climate zone. I will explore the likely effects of the last glacial maximum on oak populations using palaeoclimate and niche

  19. A Behavior-Genetic Study of the Legacy of Early Caregiving Experiences: Academic Skills, Social Competence, and Externalizing Behavior in Kindergarten

    ERIC Educational Resources Information Center

    Roisman, Glenn I.; Fraley, R. Chris

    2012-01-01

    A critique of research examining whether early experiences with primary caregivers are reflected in adaptation is that relevant longitudinal studies have generally not employed genetically informed research designs capable of unconfounding shared genes and environments. Using the twin subsample (N = 485 pairs) of the Early Childhood Longitudinal…

  20. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    PubMed Central

    Grégoire, Laurent; Caparos, Serge; Leblanc, Carole-Anne; Brisson, Benoit; Blanchette, Isabelle

    2018-01-01

    This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology. PMID:29379428

  1. Divergent response of the neritic carbonate factory to environmental changes during the Early Bajocian Event

    NASA Astrophysics Data System (ADS)

    Bodin, Stephane; Hönig, Martin; Krencker, Francois-Nicolas; Danisch, Jan; Kabiri, Lahcen

    2017-04-01

    The Early Bajocian witnessed a global environmental perturbation, characterized by faunal and floral turnovers and a positive carbon isotope excursion. In Italy, this environmental perturbation coincided with an eutrophication event and a carbonate crisis, but this has so far not been adequately reported from other settings, leaving doubt about the extent and nature of these phenomena. Here, we are reporting on an extensive neritic carbonate factory demise that occurs in the upper Lower Bajocian of the Central High Atlas of Morocco, more precisely in the upper Propinquans - lower Humphriesianum Zones. This demise coincided with the acme of the global carbon isotope perturbation, recorded by a 3‰ positive carbon isotope excursion in the bulk organic matter of Morocco. Recovery of the neritic carbonate system occurs during the Early to Late Bajocian transition. The duration of the neritic carbonate factory demise was therefore in the order of 1 Myr. Furthermore, we observe that the Lower Bajocian of Morocco is relatively enriched in arenitic siliciclastic deposits, suggesting increased weathering and nutrient levels along the northwestern margin of Africa during the Early Bajocian. However, comparison with neighboring European basins highlights the non-uniqueness and different timing of the response of shallow-water carbonates to the Early Bajocian environmental perturbations, as some regions present no sign of carbonate factory crisis. Hence, we postulate that local factors were important in mediating the response of neritic carbonate factories to this global environmental perturbation. We notably highlight the role of large Early Bajocian sea-level fluctuation as a trigger for carbonate factory change and demise in Morocco. Indeed, in the Central High Atlas Basin, transgressive intervals are seeing the development of a mud-dominated carbonate factory whereas regressive intervals are associated with grain-dominated carbonate factory. We speculate that the

  2. Mutation scanning in a single and a stacked genetically modified (GM) event by real-time PCR and high resolution melting (HRM) analysis.

    PubMed

    Ben Ali, Sina-Elisabeth; Madi, Zita Erika; Hochegger, Rupert; Quist, David; Prewein, Bernhard; Haslberger, Alexander G; Brandes, Christian

    2014-10-31

    Genetic mutations must be avoided during the production and use of seeds. In the European Union (EU), Directive 2001/18/EC requires any DNA construct introduced via transformation to be stable. Establishing genetic stability is critical for the approval of genetically modified organisms (GMOs). In this study, genetic stability of two GMOs was examined using high resolution melting (HRM) analysis and real-time polymerase chain reaction (PCR) employing Scorpion primers for amplification. The genetic variability of the transgenic insert and that of the flanking regions in a single oilseed rape variety (GT73) and a stacked maize (MON88017×MON810) was studied. The GT73 and the 5' region of MON810 showed no instabilities in the examined regions. However; two out of 100 analyzed samples carried a heterozygous point mutation in the 3' region of MON810 in the stacked variety. These results were verified by direct sequencing of the amplified PCR products as well as by sequencing of cloned PCR fragments. The occurrence of the mutation suggests that the 5' region is more suitable than the 3' region for the quantification of MON810. The identification of the single nucleotide polymorphism (SNP) in a stacked event is in contrast to the results of earlier studies of the same MON810 region in a single event where no DNA polymorphism was found.

  3. Mutation Scanning in a Single and a Stacked Genetically Modified (GM) Event by Real-Time PCR and High Resolution Melting (HRM) Analysis

    PubMed Central

    Ben Ali, Sina-Elisabeth; Madi, Zita Erika; Hochegger, Rupert; Quist, David; Prewein, Bernhard; Haslberger, Alexander G.; Brandes, Christian

    2014-01-01

    Genetic mutations must be avoided during the production and use of seeds. In the European Union (EU), Directive 2001/18/EC requires any DNA construct introduced via transformation to be stable. Establishing genetic stability is critical for the approval of genetically modified organisms (GMOs). In this study, genetic stability of two GMOs was examined using high resolution melting (HRM) analysis and real-time polymerase chain reaction (PCR) employing Scorpion primers for amplification. The genetic variability of the transgenic insert and that of the flanking regions in a single oilseed rape variety (GT73) and a stacked maize (MON88017 × MON810) was studied. The GT73 and the 5' region of MON810 showed no instabilities in the examined regions. However; two out of 100 analyzed samples carried a heterozygous point mutation in the 3' region of MON810 in the stacked variety. These results were verified by direct sequencing of the amplified PCR products as well as by sequencing of cloned PCR fragments. The occurrence of the mutation suggests that the 5' region is more suitable than the 3' region for the quantification of MON810. The identification of the single nucleotide polymorphism (SNP) in a stacked event is in contrast to the results of earlier studies of the same MON810 region in a single event where no DNA polymorphism was found. PMID:25365178

  4. Modeling Tool for Decision Support during Early Days of an Anthrax Event.

    PubMed

    Rainisch, Gabriel; Meltzer, Martin I; Shadomy, Sean; Bower, William A; Hupert, Nathaniel

    2017-01-01

    Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat.

  5. Adenomas - Genetic factors in colorectal cancer prevention.

    PubMed

    Witold, Kycler; Anna, Kubiak; Maciej, Trojanowski; Jakub, Janowski

    2018-01-01

    Colorectal cancer is the second most common type of cancer both in Europe and Poland. During the last 30 years more than a 3-fold increase has been observed in Poland due to environmental and genetic factors. Almost all colorectal malignancies are related to the formation and malignant transformation of colorectal dysplasia and adenoma. Efforts aiming to decrease the number of colorectal cancer deaths are focused on the disease early detection. Genetic diagnosis for hereditary syndromes predisposing to colorectal cancer has been developed and is a part of the routine treatment. Most cancers are sporadic. They often develop from polyps in the colon. In addition to the genetic events described in the 1990s, showing the adenoma transformation into carcinoma that has been a prime example of malignant transformation for a long time, there are also other possibilities of neoplastic transformation. The recognition of colorectal cancer risk factors make sense as their nature is lifestyle- and diet-related. In this review paper those risk factors are presented and the prevention of colorectal cancer is discussed taking into account genetic factors.

  6. Genetic recombination events between sympatric Clade A and Clade C lice in Africa.

    PubMed

    Veracx, Aurélie; Boutellis, Amina; Raoult, Didier

    2013-09-01

    Human head and body lice have been classified into three phylogenetic clades (Clades A, B, and C) based on mitochondrial DNA. Based on nuclear markers (the 18S rRNA gene and the PM2 spacer), two genotypes of Clade A head and body lice, including one that is specifically African (Clade A2), have been described. In this study, we sequenced the PM2 spacer of Clade C head lice from Ethiopia and compared these sequences with sequences from previous works. Trees were drawn, and an analysis of genetic diversity based on the cytochrome b gene and the PM2 spacer was performed for African and non-African lice. In the tree drawn based on the PM2 spacer, the African and non-African lice formed separate clusters. However, Clade C lice from Ethiopia were placed within the African Clade A subcluster (Clade A2). This result suggests that recombination events have occurred between Clade A2 lice and Clade C lice, reflecting the sympatric nature of African lice. Finally, the PM2 spacer and cytochrome b gene sequences of human lice revealed a higher level of genetic diversity in Africa than in other regions.

  7. Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

    PubMed

    Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H

    2002-10-15

    Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

  8. Resampling to Address the Winner's Curse in Genetic Association Analysis of Time to Event

    PubMed Central

    Poirier, Julia G.; Faye, Laura L.; Dimitromanolakis, Apostolos; Paterson, Andrew D.; Sun, Lei

    2015-01-01

    ABSTRACT The “winner's curse” is a subtle and difficult problem in interpretation of genetic association, in which association estimates from large‐scale gene detection studies are larger in magnitude than those from subsequent replication studies. This is practically important because use of a biased estimate from the original study will yield an underestimate of sample size requirements for replication, leaving the investigators with an underpowered study. Motivated by investigation of the genetics of type 1 diabetes complications in a longitudinal cohort of participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Genetics Study, we apply a bootstrap resampling method in analysis of time to nephropathy under a Cox proportional hazards model, examining 1,213 single‐nucleotide polymorphisms (SNPs) in 201 candidate genes custom genotyped in 1,361 white probands. Among 15 top‐ranked SNPs, bias reduction in log hazard ratio estimates ranges from 43.1% to 80.5%. In simulation studies based on the observed DCCT/EDIC genotype data, genome‐wide bootstrap estimates for false‐positive SNPs and for true‐positive SNPs with low‐to‐moderate power are closer to the true values than uncorrected naïve estimates, but tend to overcorrect SNPs with high power. This bias‐reduction technique is generally applicable for complex trait studies including quantitative, binary, and time‐to‐event traits. PMID:26411674

  9. The role of impact events play in redistributing and sequestering water on Early Mars

    NASA Astrophysics Data System (ADS)

    Osinski, G.; Tornabene, L. L.

    2017-12-01

    Impact cratering is one of the most fundamental geological process in the Solar System. Several workers have considered the effect that impact events may have had on the climate of Early Mars. The proposed effects range from impact-induced precipitation to the production of runaway stable climates to the impact delivery of climatically active gases. The role of impact events in forming hydrated minerals has been touched upon but remains debated. In this contribution, we focus on the role that impact events may have played in redistributing and sequestering water on Early Mars; a record that may still be preserved in the Noachian crust. It has been previously proposed that the sequestration of significant quantities of water may have occurred within various hydrated minerals, in particular clays, in the martian crust. There is undoubtedly no single origin for clay-bearing rocks on Mars and the purpose of this contribution is not to review all the possible formation mechanisms. What we do propose, however, is that it is theoretically possible for impact events to create all known occurrences of clays on Mars. We show that clays can form within and around impact craters in two main ways: through the solid-state devitrification of hydrous impact melts and/or impact-generated hydrothermal alteration. Neither of these mechanisms requires a warmer or wetter climate scenario on Early Mars. Notwithstanding the original origin of clays, any clays may be widely redistributed over the Martian surface in the ejecta deposits of large impact craters. However, ejecta deposits are much more complex than commonly thought, with evidence in many instances for two different types of ejecta deposits around martian craters. The first is a ballistic ejecta layer that is low-shock, melt-poor and low-temperature; it will likely not induce the formation of new clays through the mechanisms described above, but could redistribute pre-impact clays over 100's and 1000's of km over the martian

  10. Integrating Genetic, Neuropsychological and Neuroimaging Data to Model Early-Onset Obsessive Compulsive Disorder Severity

    PubMed Central

    Mas, Sergi; Gassó, Patricia; Morer, Astrid; Calvo, Anna; Bargalló, Nuria; Lafuente, Amalia; Lázaro, Luisa

    2016-01-01

    We propose an integrative approach that combines structural magnetic resonance imaging data (MRI), diffusion tensor imaging data (DTI), neuropsychological data, and genetic data to predict early-onset obsessive compulsive disorder (OCD) severity. From a cohort of 87 patients, 56 with complete information were used in the present analysis. First, we performed a multivariate genetic association analysis of OCD severity with 266 genetic polymorphisms. This association analysis was used to select and prioritize the SNPs that would be included in the model. Second, we split the sample into a training set (N = 38) and a validation set (N = 18). Third, entropy-based measures of information gain were used for feature selection with the training subset. Fourth, the selected features were fed into two supervised methods of class prediction based on machine learning, using the leave-one-out procedure with the training set. Finally, the resulting model was validated with the validation set. Nine variables were used for the creation of the OCD severity predictor, including six genetic polymorphisms and three variables from the neuropsychological data. The developed model classified child and adolescent patients with OCD by disease severity with an accuracy of 0.90 in the testing set and 0.70 in the validation sample. Above its clinical applicability, the combination of particular neuropsychological, neuroimaging, and genetic characteristics could enhance our understanding of the neurobiological basis of the disorder. PMID:27093171

  11. Genetic structure and early effects of inbreeding in fragmented temperate forests of a self-incompatible tree, Embothrium coccineum.

    PubMed

    Mathiasen, Paula; Rovere, Adriana E; Premoli, Andrea C

    2007-02-01

    Deforestation of temperate forests has created landscapes of forest remnants in matrices of intense human use. We studied the genetic effects of fragmentation in southern Chile on Embothrium coccineum J.R. et G. Forster, an early colonizing, bird-pollinated tree. We tested the hypothesis that, because of its self-incompatibility and life-history strategy, E. coccineum is less strongly affected by fragmentation. We studied the effects of reduced population size and increased isolation on population genetic structure and early performance of progeny. Samples were collected from spatially isolated trees and six fragments of differing sizes (small, 1 ha; medium, 20 ha; large, >150 ha). Based on isozyme polymorphisms we estimated parameters of genetic diversity, divergence, and inbreeding for adults and greenhouse-grown progeny. We also measured germination, seedling growth, and outcrossing rates on progeny arrays. Genetic variation of adults did not correlate significantly with population size, as expected, given that fragmentation occurred relatively recently. Weak effects of fragmentation were measured on progeny. Only adults yielded significant inbreeding. Similar total genetic diversity was found in adults and progeny. Low but significant genetic differentiation existed among adult and progeny populations. Seedling growth correlated positively with the effective number of alleles, showing deleterious effects of inbreeding on progeny. Seeds from small fragments had the highest outcrossing rates and germination success, indicating that higher pollinator activity in such fragments reduced selfing, thereby buffering genetic erosion and maintaining adaptive variation. The effects of forest fragmentation were detectable in E. coccineum, but these effects will probably not be detrimental to the viability of remnant populations because small, fragmented populations demonstrated higher levels of gene flow and lower inbreeding than larger stands. Pioneer species that are

  12. Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.

    PubMed

    Markkula, Andrea; Simonsson, Maria; Rosendahl, Ann H; Gaber, Alexander; Ingvar, Christian; Rose, Carsten; Jernström, Helena

    2014-10-15

    The COX2 rs5277 (306G>C) polymorphism has been associated with inflammation-associated cancers. In breast cancer, tumor COX-2 expression has been associated with increased estrogen levels in estrogen receptor (ER)-positive and activated Akt-pathway in ER-negative tumors. Our study investigated the impact of COX2 genotypes on early breast cancer events and treatment response in relation to tumor ER status and body constitution. In Sweden, between 2002 and 2008, 634 primary breast cancer patients, aged 25-99 years, were included. Disease-free survival was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained preoperatively. Clinical data, patient- and tumor-characteristics were obtained from questionnaires, patients' charts, population registries and pathology reports. Minor allele(C) frequency was 16.1%. Genotype was not linked to COX-2 tumor expression. Median follow-up was 5.1 years. G/G genotype was not associated with early events in patients with ER-positive tumors, adjusted HR 0.77 (0.46-1.29), but conferred an over 4-fold increased risk in patients with ER-negative tumors, adjusted HR 4.41 (1.21-16.02)(p(interaction) = 0.015). Chemotherapy-treated G/G-carriers with a breast volume ≥ 850 ml had an increased risk of early events irrespective of ER status, adjusted HR 8.99 (1.14-70.89). Endocrine-treated C-allele carriers with ER-positive tumors and a breast volume ≥ 850 ml had increased risk of early events, adjusted HR 2.30 (1.12-4.75). COX2 genotype, body constitution and ER status had a combined effect on the risk of early events and treatment response. The high risk for early events in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may identify patients in need of more personalized treatment. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  13. Persistent Genetic and Family-Wide Environmental Contributions to Early Number Knowledge and Later Achievement in Mathematics.

    PubMed

    Garon-Carrier, Gabrielle; Boivin, Michel; Kovas, Yulia; Feng, Bei; Brendgen, Mara; Vitaro, Frank; Séguin, Jean R; Tremblay, Richard E; Dionne, Ginette

    2017-12-01

    This study investigated the stable and transient genetic and environmental contributions to individual differences in number knowledge in the transition from preschool (age 5) to Grade 1 (age 7) and to the predictive association between early number knowledge and later math achievement (age 10-12). We conducted genetic simplex modeling across these three time points. Genetic variance was transmitted from preschool number knowledge to late-elementary math achievement; in addition, significant genetic innovation (i.e., new influence) occurred at ages 10 through 12 years. The shared and nonshared environmental contributions decreased during the transition from preschool to school entry, but shared and nonshared environment contributed to the continuity across time from preschool number knowledge to subsequent number knowledge and math achievement. There was no new environmental contribution at time points subsequent to preschool. Results are discussed in light of their practical implications for children who have difficulties with mathematics, as well as for preventive intervention.

  14. The Effects of Age at Drinking Onset and Stressful Life Events on Alcohol Use in Adulthood: A Replication and Extension Using a Population-Based Twin Sample

    PubMed Central

    Lee, Lewina O.; Young Wolff, Kelly C.; Kendler, Kenneth S.; Prescott, Carol A.

    2012-01-01

    Background A study by Dawson and colleagues (Alcohol Clin Exp Res 2007; 31:69) using data from National Epidemiologic Survey on Alcohol and Related Condition found earlier drinking onset age, and higher levels of past-year stressful life events (SLE) were associated with higher past-year alcohol consumption. The aims of our study were as follows: (i) to attempt to replicate this interaction; (ii) to extend it by examining sex and event dependence as potential moderators of the effect; and (iii) to estimate the roles of genetic and environmental factors in mediating the overlap of early drinking onset and SLE in their relations with alcohol consumption. Methods Data were from 1,382 female and 2,218 male drinkers interviewed as part of the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Regression models were used to evaluate the main and interactive effects of early drinking onset and moderate or severe past-year SLE on past-year drinking density (PYDD), a weighted quantity-frequency measure of alcohol consumption. Analyses adjusted for demographic covariates and were stratified by sex and whether SLE were independent or dependent on the person’s actions, as rated by interviewers. Structural twin models were used to estimate the degree to which early drinking onset, SLE, and their interaction accounted for additive genetic, common environmental and individual-specific variance in PYDD. Results We replicated the prior finding of a main effect of higher alcohol consumption among individuals reporting earlier drinking onset. Age at drinking onset accounted for about 5% of the variation in PYDD, and this association was mostly attributable to overlapping genetic influences. Evidence for an interaction between onset age and SLE was generally weak, possibly because of lower power and other methodological differences from Dawson and colleagues’ study. However, there was some evidence consistent with an interaction of higher PYDD among early

  15. Is early-onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

    PubMed

    Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N

    2008-02-15

    Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.

  16. Is an Early Age at Illness Onset in Schizophrenia Associated With Increased Genetic Susceptibility? Analysis of Data From the Nationwide Danish Twin Register.

    PubMed

    Hilker, Rikke; Helenius, Dorte; Fagerlund, Birgitte; Skytthe, Axel; Christensen, Kaare; Werge, Thomas M; Nordentoft, Merete; Glenthøj, Birte

    2017-04-01

    Early age at illness onset has been viewed as an important liability marker for schizophrenia, which may be associated with an increased genetic vulnerability. A twin approach can be valuable, because it allows for the investigation of specific illness markers in individuals with a shared genetic background. We linked nationwide registers to identify a cohort of twin pairs born in Denmark from 1951 to 2000 (N=31,524 pairs), where one or both twins had a diagnosis in the schizophrenia spectrum. We defined two groups consisting of; N=788 twin pairs (affected with schizophrenia spectrum) and a subsample of N=448 (affected with schizophrenia). Survival analysis was applied to investigate the effect of age at illness onset. We found that early age at illness onset compared to later onset in the first diagnosed twin can be considered a major risk factor for developing schizophrenia in the second twin. Additionally, we found that the stronger genetic component in MZ twins compared to DZ twins is manifested in the proximity of assigned diagnosis within pairs. Early onset schizophrenia could be linked to a more severe genetic predisposition, indicating that age might be perceived as a clinical marker for genetic vulnerability for the illness. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Role of overlapping genetic and environmental factors in the relationship between early adolescent conduct problems and substance use in young adulthood

    PubMed Central

    Verweij, Karin J.H.; Creemers, H.E.; Korhonen, T.; Latvala, A.; Dick, D.M.; Rose, R. J.; Huizink, A.C.; Kaprio, J.

    2016-01-01

    Aims To determine 1) the prospective associations of conduct problems during early adolescence with tobacco, alcohol and cannabis use in young adulthood and 2) to what extent these associations are due to overlapping genetic versus environmental influences. Design A prospective twin study using biometric twin modelling. Setting Finland. Participants 1847 Finnish twins (943 males and 904 females) were interviewed in early adolescence, of which 73% (N=1353, 640 males and 713 females) were retained in young adulthood. Measurements Symptom counts of conduct disorder (CD) criteria were obtained from a semi-structured clinical interview in early adolescence (age 14–15 years, M=14.2, SD=0.15). Frequency of alcohol, tobacco, and cannabis use was obtained from a semi-structured clinical interview in young adulthood (age 19.9–26.6 years, M=22.4, SD=0.7). Findings We found modest to moderate phenotypic correlations (r=0.16 to 0.35) between early adolescent CD symptoms and substance use in young adulthood. In males, the phenotypic correlations of CD symptoms with all three substance use variables are largely explained by overlapping genetic influences. In females, overlapping shared environmental influences predominantly explain the phenotypic correlation between CD symptoms and tobacco and cannabis use. Conclusions Conduct disorder symptoms in early adolescence appear to moderately predict substance use in early adulthood. In males, genetic influences seem to be most important in explaining the relationship between conduct disorder symptoms and substance use whereas in females, shared environmental influences seem to be most important. PMID:26748618

  18. Early Onset Diabetes - Genetic And Hormonal Analysis In Pakistani Population.

    PubMed

    Wahid, Maryam; Kamran, Mohammad

    2016-01-01

    Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population.

  19. Development of an event-specific hydrolysis probe quantitative real-time polymerase chain reaction assay for Embrapa 5.1 genetically modified common bean (Phaseolus vulgaris).

    PubMed

    Treml, Diana; Venturelli, Gustavo L; Brod, Fábio C A; Faria, Josias C; Arisi, Ana C M

    2014-12-10

    A genetically modified (GM) common bean event, namely Embrapa 5.1, resistant to the bean golden mosaic virus (BGMV), was approved for commercialization in Brazil. Brazilian regulation for genetically modified organism (GMO) labeling requires that any food containing more than 1% GMO be labeled. The event-specific polymerase chain reaction (PCR) method has been the primary trend for GMO identification and quantitation because of its high specificity based on the flanking sequence. This work reports the development of an event-specific assay, named FGM, for Embrapa 5.1 detection and quantitation by use of SYBR Green or hydrolysis probe. The FGM assay specificity was tested for Embrapa 2.3 event (a noncommercial GM common bean also resistant to BGMV), 46 non-GM common bean varieties, and other crop species including maize, GM maize, soybean, and GM soybean. The FGM assay showed high specificity to detect the Embrapa 5.1 event. Standard curves for the FGM assay presented a mean efficiency of 95% and a limit of detection (LOD) of 100 genome copies in the presence of background DNA. The primers and probe developed are suitable for the detection and quantitation of Embrapa 5.1.

  20. The Genetic Ancestry of African Americans, Latinos, and European Americans across the United States

    PubMed Central

    Bryc, Katarzyna; Durand, Eric Y.; Macpherson, J. Michael; Reich, David; Mountain, Joanna L.

    2015-01-01

    Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical events, such as early Spanish colonization, waves of immigration from many regions of Europe, and forced relocation of Native Americans within the US. This study sheds light on the fine-scale differences in ancestry within and across the United States and informs our understanding of the relationship between racial and ethnic identities and genetic ancestry. PMID:25529636

  1. Evolution of a genetic polymorphism with climate change in a Mediterranean landscape

    PubMed Central

    Thompson, John; Charpentier, Anne; Bouguet, Guillaume; Charmasson, Faustine; Roset, Stephanie; Buatois, Bruno; Vernet, Philippe; Gouyon, Pierre-Henri

    2013-01-01

    Many species show changes in distribution and phenotypic trait variation in response to climatic warming. Evidence of genetically based trait responses to climate change is, however, less common. Here, we detected evolutionary variation in the landscape-scale distribution of a genetically based chemical polymorphism in Mediterranean wild thyme (Thymus vulgaris) in association with modified extreme winter freezing events. By comparing current data on morph distribution with that observed in the early 1970s, we detected a significant increase in the proportion of morphs that are sensitive to winter freezing. This increase in frequency was observed in 17 of the 24 populations in which, since the 1970s, annual extreme winter freezing temperatures have risen above the thresholds that cause mortality of freezing-sensitive morphs. Our results provide an original example of rapid ongoing evolutionary change associated with relaxed selection (less extreme freezing events) on a local landscape scale. In species whose distribution and genetic variability are shaped by strong selection gradients, there may be little time lag associated with their ecological and evolutionary response to long-term environmental change. PMID:23382198

  2. Irregularities in Early Seismic Rupture Propagation for Large Events in a Crustal Earthquake Model

    NASA Astrophysics Data System (ADS)

    Lapusta, N.; Rice, J. R.; Rice, J. R.

    2001-12-01

    We study early seismic propagation of model earthquakes in a 2-D model of a vertical strike-slip fault with depth-variable rate and state friction properties. Our model earthquakes are obtained in fully dynamic simulations of sequences of instabilities on a fault subjected to realistically slow tectonic loading (Lapusta et al., JGR, 2000). This work is motivated by results of Ellsworth and Beroza (Science, 1995), who observe that for many earthquakes, far-field velocity seismograms during initial stages of dynamic rupture propagation have irregular fluctuations which constitute a "seismic nucleation phase". In our simulations, we find that such irregularities in velocity seismograms can be caused by two factors: (1) rupture propagation over regions of stress concentrations and (2) partial arrest of rupture in neighboring creeping regions. As rupture approaches a region of stress concentration, it sees increasing background stress and its moment acceleration (to which velocity seismographs in the far field are proportional) increases. After the peak in stress concentration, the rupture sees decreasing background stress and moment acceleration decreases. Hence a fluctuation in moment acceleration is created. If rupture starts sufficiently far from a creeping region, then partial arrest of rupture in the creeping region causes a decrease in moment acceleration. As the other parts of rupture continue to develop, moment acceleration then starts to grow again, and a fluctuation again results. Other factors may cause the irregularities in moment acceleration, e.g., phenomena such as branching and/or intermittent rupture propagation (Poliakov et al., submitted to JGR, 2001) which we have not studied here. Regions of stress concentration are created in our model by arrest of previous smaller events as well as by interactions with creeping regions. One such region is deep in the fault zone, and is caused by the temperature-induced transition from seismogenic to creeping

  3. Childhood adverse life events and parental psychopathology as risk factors for bipolar disorder.

    PubMed

    Bergink, V; Larsen, J T; Hillegers, M H J; Dahl, S K; Stevens, H; Mortensen, P B; Petersen, L; Munk-Olsen, T

    2016-10-25

    Childhood adverse events are risk factors for later bipolar disorder. We quantified the risks for a later diagnosis of bipolar disorder after exposure to adverse life events in children with and without parental psychopathology. This register-based population cohort study included all persons born in Denmark from 1980 to 1998 (980 554 persons). Adversities before age 15 years were: familial disruption; parental somatic illness; any parental psychopathology; parental labour market exclusion; parental imprisonment; placement in out-of-home care; and parental natural and unnatural death. We calculated risk estimates of each of these eight life events as single exposure and risk estimates for exposure to multiple life events. Main outcome variable was a diagnosis of bipolar disorder after the age of 15 years, analysed with Cox proportional hazard regression. Single exposure to most of the investigated adversities were associated with increased risk for bipolar disorder, exceptions were parental somatic illness and parental natural death. By far the strongest risk factor for bipolar disorder in our study was any mental disorder in the parent (hazard ratio 3.53; 95% confidence interval 2.73-4.53) and the additional effects of life events on bipolar risk were limited. An effect of early adverse life events on bipolar risk later in life was mainly observed in children without parental psychopathology. Our findings do not exclude early-life events as possible risk factors, but challenge the concept of adversities as important independent determinants of bipolar disorder in genetically vulnerable individuals.

  4. Genetics Home Reference: Blau syndrome

    MedlinePlus

    ... inherited version of the disorder called early-onset sarcoidosis. Related Information What does it mean if a ... Genetic Testing Registry: Blau syndrome Genetic Testing Registry: Sarcoidosis, early-onset Other Diagnosis and Management Resources (2 ...

  5. Locally adapted fish populations maintain small-scale genetic differentiation despite perturbation by a catastrophic flood event

    PubMed Central

    2010-01-01

    Background Local adaptation to divergent environmental conditions can promote population genetic differentiation even in the absence of geographic barriers and hence, lead to speciation. Perturbations by catastrophic events, however, can distort such parapatric ecological speciation processes. Here, we asked whether an exceptionally strong flood led to homogenization of gene pools among locally adapted populations of the Atlantic molly (Poecilia mexicana, Poeciliidae) in the Cueva del Azufre system in southern Mexico, where two strong environmental selection factors (darkness within caves and/or presence of toxic H2S in sulfidic springs) drive the diversification of P. mexicana. Nine nuclear microsatellites as well as heritable female life history traits (both as a proxy for quantitative genetics and for trait divergence) were used as markers to compare genetic differentiation, genetic diversity, and especially population mixing (immigration and emigration) before and after the flood. Results Habitat type (i.e., non-sulfidic surface, sulfidic surface, or sulfidic cave), but not geographic distance was the major predictor of genetic differentiation. Before and after the flood, each habitat type harbored a genetically distinct population. Only a weak signal of individual dislocation among ecologically divergent habitat types was uncovered (with the exception of slightly increased dislocation from the Cueva del Azufre into the sulfidic creek, El Azufre). By contrast, several lines of evidence are indicative of increased flood-induced dislocation within the same habitat type, e.g., between different cave chambers of the Cueva del Azufre. Conclusions The virtual absence of individual dislocation among ecologically different habitat types indicates strong natural selection against migrants. Thus, our current study exemplifies that ecological speciation in this and other systems, in which extreme environmental factors drive speciation, may be little affected by temporary

  6. Locally adapted fish populations maintain small-scale genetic differentiation despite perturbation by a catastrophic flood event.

    PubMed

    Plath, Martin; Hermann, Bernd; Schröder, Christiane; Riesch, Rüdiger; Tobler, Michael; García de León, Francisco J; Schlupp, Ingo; Tiedemann, Ralph

    2010-08-23

    Local adaptation to divergent environmental conditions can promote population genetic differentiation even in the absence of geographic barriers and hence, lead to speciation. Perturbations by catastrophic events, however, can distort such parapatric ecological speciation processes. Here, we asked whether an exceptionally strong flood led to homogenization of gene pools among locally adapted populations of the Atlantic molly (Poecilia mexicana, Poeciliidae) in the Cueva del Azufre system in southern Mexico, where two strong environmental selection factors (darkness within caves and/or presence of toxic H2S in sulfidic springs) drive the diversification of P. mexicana. Nine nuclear microsatellites as well as heritable female life history traits (both as a proxy for quantitative genetics and for trait divergence) were used as markers to compare genetic differentiation, genetic diversity, and especially population mixing (immigration and emigration) before and after the flood. Habitat type (i.e., non-sulfidic surface, sulfidic surface, or sulfidic cave), but not geographic distance was the major predictor of genetic differentiation. Before and after the flood, each habitat type harbored a genetically distinct population. Only a weak signal of individual dislocation among ecologically divergent habitat types was uncovered (with the exception of slightly increased dislocation from the Cueva del Azufre into the sulfidic creek, El Azufre). By contrast, several lines of evidence are indicative of increased flood-induced dislocation within the same habitat type, e.g., between different cave chambers of the Cueva del Azufre. The virtual absence of individual dislocation among ecologically different habitat types indicates strong natural selection against migrants. Thus, our current study exemplifies that ecological speciation in this and other systems, in which extreme environmental factors drive speciation, may be little affected by temporary perturbations, as adaptations

  7. Affiliation buffers stress: cumulative genetic risk in oxytocin-vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children.

    PubMed

    Feldman, R; Vengrober, A; Ebstein, R P

    2014-03-11

    Research indicates that risk for post-traumatic stress disorder (PTSD) is shaped by the interaction between genetic vulnerability and early caregiving experiences; yet, caregiving has typically been assessed by adult retrospective accounts. Here, we employed a prospective longitudinal design with real-time observations of early caregiving combined with assessment of genetic liability along the axis of vasopressin-oxytocin (OT) gene pathways to test G × E contributions to PTSD. Participants were 232 young Israeli children (1.5-5 years) and their parents, including 148 living in zones of continuous war and 84 controls. A cumulative genetic risk factor was computed for each family member by summing five risk alleles across three genes (OXTR, CD38 and AVPR1a) previously associated with psychopathology, sociality and caregiving. Child PTSD was diagnosed and mother-child interactions were observed in multiple contexts. In middle childhood (7-8 years), child psychopathology was re-evaluated. War exposure increased propensity to develop Axis-I disorder by threefold: 60% of exposed children displayed a psychiatric disorder by middle childhood and 62% of those showed several comorbid disorders. On the other hand, maternal sensitive support reduced risk for psychopathology. G × E effect was found for child genetic risk: in the context of war exposure, greater genetic risk on the vasopressin-OT pathway increased propensity for psychopathology. Among exposed children, chronicity of PTSD from early to middle childhood was related to higher child, maternal and paternal genetic risk, low maternal support and greater initial avoidance symptoms. Child avoidance was predicted by low maternal support and reduced mother-child reciprocity. These findings underscore the saliency of both genetic and behavioral facets of the human affiliation system in shaping vulnerability to PTSD as well as providing an underlying mechanism of post-traumatic resilience.

  8. Affiliation buffers stress: cumulative genetic risk in oxytocin–vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children

    PubMed Central

    Feldman, R; Vengrober, A; Ebstein, R P

    2014-01-01

    Research indicates that risk for post-traumatic stress disorder (PTSD) is shaped by the interaction between genetic vulnerability and early caregiving experiences; yet, caregiving has typically been assessed by adult retrospective accounts. Here, we employed a prospective longitudinal design with real-time observations of early caregiving combined with assessment of genetic liability along the axis of vasopressin–oxytocin (OT) gene pathways to test G × E contributions to PTSD. Participants were 232 young Israeli children (1.5–5 years) and their parents, including 148 living in zones of continuous war and 84 controls. A cumulative genetic risk factor was computed for each family member by summing five risk alleles across three genes (OXTR, CD38 and AVPR1a) previously associated with psychopathology, sociality and caregiving. Child PTSD was diagnosed and mother–child interactions were observed in multiple contexts. In middle childhood (7–8 years), child psychopathology was re-evaluated. War exposure increased propensity to develop Axis-I disorder by threefold: 60% of exposed children displayed a psychiatric disorder by middle childhood and 62% of those showed several comorbid disorders. On the other hand, maternal sensitive support reduced risk for psychopathology. G × E effect was found for child genetic risk: in the context of war exposure, greater genetic risk on the vasopressin–OT pathway increased propensity for psychopathology. Among exposed children, chronicity of PTSD from early to middle childhood was related to higher child, maternal and paternal genetic risk, low maternal support and greater initial avoidance symptoms. Child avoidance was predicted by low maternal support and reduced mother–child reciprocity. These findings underscore the saliency of both genetic and behavioral facets of the human affiliation system in shaping vulnerability to PTSD as well as providing an underlying mechanism of post-traumatic resilience. PMID:24618689

  9. Reasoning over genetic variance information in cause-and-effect models of neurodegenerative diseases

    PubMed Central

    Naz, Mufassra; Kodamullil, Alpha Tom

    2016-01-01

    The work we present here is based on the recent extension of the syntax of the Biological Expression Language (BEL), which now allows for the representation of genetic variation information in cause-and-effect models. In our article, we describe, how genetic variation information can be used to identify candidate disease mechanisms in diseases with complex aetiology such as Alzheimer’s disease and Parkinson’s disease. In those diseases, we have to assume that many genetic variants contribute moderately to the overall dysregulation that in the case of neurodegenerative diseases has such a long incubation time until the first clinical symptoms are detectable. Owing to the multilevel nature of dysregulation events, systems biomedicine modelling approaches need to combine mechanistic information from various levels, including gene expression, microRNA (miRNA) expression, protein–protein interaction, genetic variation and pathway. OpenBEL, the open source version of BEL, has recently been extended to match this requirement, and we demonstrate in our article, how candidate mechanisms for early dysregulation events in Alzheimer’s disease can be identified based on an integrative mining approach that identifies ‘chains of causation’ that include single nucleotide polymorphism information in BEL models. PMID:26249223

  10. On-site detection of stacked genetically modified soybean based on event-specific TM-LAMP and a DNAzyme-lateral flow biosensor.

    PubMed

    Cheng, Nan; Shang, Ying; Xu, Yuancong; Zhang, Li; Luo, Yunbo; Huang, Kunlun; Xu, Wentao

    2017-05-15

    Stacked genetically modified organisms (GMO) are becoming popular for their enhanced production efficiency and improved functional properties, and on-site detection of stacked GMO is an urgent challenge to be solved. In this study, we developed a cascade system combining event-specific tag-labeled multiplex LAMP with a DNAzyme-lateral flow biosensor for reliable detection of stacked events (DP305423× GTS 40-3-2). Three primer sets, both event-specific and soybean species-specific, were newly designed for the tag-labeled multiplex LAMP system. A trident-like lateral flow biosensor displayed amplified products simultaneously without cross contamination, and DNAzyme enhancement improved the sensitivity effectively. After optimization, the limit of detection was approximately 0.1% (w/w) for stacked GM soybean, which is sensitive enough to detect genetically modified content up to a threshold value established by several countries for regulatory compliance. The entire detection process could be shortened to 120min without any large-scale instrumentation. This method may be useful for the in-field detection of DP305423× GTS 40-3-2 soybean on a single kernel basis and on-site screening tests of stacked GM soybean lines and individual parent GM soybean lines in highly processed foods. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Role of overlapping genetic and environmental factors in the relationship between early adolescent conduct problems and substance use in young adulthood.

    PubMed

    Verweij, Karin J H; Creemers, Hanneke E; Korhonen, Tellervo; Latvala, Antti; Dick, Danielle M; Rose, Richard J; Huizink, Anja C; Kaprio, Jaakko

    2016-06-01

    To determine (1) the prospective associations of conduct problems during early adolescence with tobacco, alcohol and cannabis use in young adulthood and (2) to what extent these associations are due to overlapping genetic versus environmental influences. A prospective twin study using biometric twin modelling. Finland. A total of 1847 Finnish twins (943 males and 904 females) were interviewed in early adolescence, 73% of whom (n = 1353, 640 males and 713 females) were retained in young adulthood. Symptom counts of conduct disorder (CD) criteria were obtained from a semi-structured clinical interview in early adolescence [age 14-15 years, mean = 14.2, standard deviation (SD) = 0.15]. Frequency of alcohol, tobacco and cannabis use was obtained from a semi-structured clinical interview in young adulthood (age 19.9-26.6 years, mean = 22.4, SD = 0.7). We found modest to moderate phenotypical correlations (r = 0.16-0.35) between early adolescent CD symptoms and substance use in young adulthood. In males, the phenotypical correlations of CD symptoms with all three substance use variables are explained largely by overlapping genetic influences. In females, overlapping shared environmental influences predominantly explain the phenotypical correlation between CD symptoms and tobacco and cannabis use. Conduct disorder symptoms in early adolescence appear to moderately predict substance use in early adulthood. In males, genetic influences seem to be most important in explaining the relationship between conduct disorder symptoms and substance use whereas in females, shared environmental influences seem to be most important. © 2016 Society for the Study of Addiction.

  12. Quantifying the extent to which index event biases influence large genetic association studies.

    PubMed

    Yaghootkar, Hanieh; Bancks, Michael P; Jones, Sam E; McDaid, Aaron; Beaumont, Robin; Donnelly, Louise; Wood, Andrew R; Campbell, Archie; Tyrrell, Jessica; Hocking, Lynne J; Tuke, Marcus A; Ruth, Katherine S; Pearson, Ewan R; Murray, Anna; Freathy, Rachel M; Munroe, Patricia B; Hayward, Caroline; Palmer, Colin; Weedon, Michael N; Pankow, James S; Frayling, Timothy M; Kutalik, Zoltán

    2017-03-01

    As genetic association studies increase in size to 100 000s of individuals, subtle biases may influence conclusions. One possible bias is 'index event bias' (IEB) that appears due to the stratification by, or enrichment for, disease status when testing associations between genetic variants and a disease-associated trait. We aimed to test the extent to which IEB influences some known trait associations in a range of study designs and provide a statistical framework for assessing future associations. Analyzing data from 113 203 non-diabetic UK Biobank participants, we observed three (near TCF7L2, CDKN2AB and CDKAL1) overestimated (body mass index (BMI) decreasing) and one (near MTNR1B) underestimated (BMI increasing) associations among 11 type 2 diabetes risk alleles (at P  <  0.05). IEB became even stronger when we tested a type 2 diabetes genetic risk score composed of these 11 variants (-0.010 standard deviations BMI per allele, P  =  5 × 10- 4), which was confirmed in four additional independent studies. Similar results emerged when examining the effect of blood pressure increasing alleles on BMI in normotensive UK Biobank samples. Furthermore, we demonstrated that, under realistic scenarios, common disease alleles would become associated at P <  5 × 10- 8 with disease-related traits through IEB alone, if disease prevalence in the sample differs appreciably from the background population prevalence. For example, some hypertension and type 2 diabetes alleles will be associated with BMI in sample sizes of  >500 000 if the prevalence of those diseases differs by >10% from the background population. In conclusion, IEB may result in false positive or negative genetic associations in very large studies stratified or strongly enriched for/against disease cases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Maternal genetic effects on adaptive divergence between anadromous and resident brook charr during early life history.

    PubMed

    Perry, G M L; Audet, C; Bernatchez, L

    2005-09-01

    The importance of directional selection relative to neutral evolution may be determined by comparing quantitative genetic variation in phenotype (Q(ST)) to variation at neutral molecular markers (F(ST)). Quantitative divergence between salmonid life history types is often considerable, but ontogenetic changes in the significance of major sources of genetic variance during post-hatch development suggest that selective differentiation varies by developmental stage. In this study, we tested the hypothesis that maternal genetic differentiation between anadromous and resident brook charr (Salvelinus fontinalis Mitchill) populations for early quantitative traits (embryonic size/growth, survival, egg number and developmental time) would be greater than neutral genetic differentiation, but that the maternal genetic basis for differentiation would be higher for pre-resorption traits than post-resorption traits. Quantitative genetic divergence between anadromous (seawater migratory) and resident Laval River (Québec) brook charr based on maternal genetic variance was high (Q(ST) > 0.4) for embryonic length, yolk sac volume, embryonic growth rate and time to first response to feeding relative to neutral genetic differentiation [F(ST) = 0.153 (0.071-0.214)], with anadromous females having positive genetic coefficients for all of the above characters. However, Q(ST) was essentially zero for all traits post-resorption of the yolk sac. Our results indicate that the observed divergence between resident and anadromous brook charr has been driven by directional selection, and may therefore be adaptive. Moreover, they provide among the first evidence that the relative importance of selective differentiation may be highly context-specific, and varies by genetic contributions to phenotype by parental sex at specific points in offspring ontogeny. This in turn suggests that interpretations of Q(ST)-F(ST) comparisons may be improved by considering the structure of quantitative genetic

  14. Preserving the Past: An Early Interview Improves Delayed Event Memory in Children With Intellectual Disabilities

    PubMed Central

    Brown, Deirdre A; Lewis, Charlie N; Lamb, Michael E

    2015-01-01

    The influence of an early interview on children's (N = 194) later recall of an experienced event was examined in children with mild and moderate intellectual disabilities (CWID; 7–12 years) and typically developing (TD) children matched for chronological (7–12 years) or mental (4–9 years) age. Children previously interviewed were more informative, more accurate, and less suggestible. CWID (mild) recalled as much information as TD mental age matches, and were as accurate as TD chronological age matches. CWID (moderate) recalled less than TD mental age matches but were as accurate. Interviewers should elicit CWID's recall as early as possible and consider developmental level and severity of impairments when evaluating eyewitness testimony. PMID:25876042

  15. Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

    PubMed Central

    Tezcan, Gulcin; Tunca, Berrin; Ak, Secil; Cecener, Gulsah; Egeli, Unal

    2016-01-01

    Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach. PMID:26798439

  16. Tumor necrosis factor-α inhibitor treatment and the risk of incident cardiovascular events in patients with early rheumatoid arthritis: a nested case-control study.

    PubMed

    Desai, Rishi J; Rao, Jaya K; Hansen, Richard A; Fang, Gang; Maciejewski, Matthew; Farley, Joel

    2014-11-01

    To compare the risk of cardiovascular (CV) events between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA). A nested case-control study was conducted using data from Truven's MarketScan commercial and Medicare claims database for patients with early RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV event diagnosis for cases was defined as the event date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the event date. Conditional logistic regression models were used to derive incidence rate ratios (IRR). From the cohort of patients with early RA, 279 cases of incident CV events and 3348 matched controls were identified. The adjusted risk of CV events was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59-1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04-2.08). No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with early RA.

  17. Early Adverse Environments and Genetic Influences on Age at First Sex: Evidence for Gene × Environment Interaction

    ERIC Educational Resources Information Center

    Carlson, Marie D.; Mendle, Jane; Harden, K. Paige

    2014-01-01

    Youth who experience adverse environments in early life initiate sexual activity at a younger age, on average, than those from more advantaged circumstances. Evolutionary theorists have posited that ecological stress precipitates earlier reproductive and sexual onset, but it is unclear how stressful environments interact with genetic influences on…

  18. Potential of Breastmilk Analysis to Inform Early Events in Breast Carcinogenesis: Rationale and Considerations

    PubMed Central

    Murphy, Jeanne; Sherman, Mark E.; Browne, Eva P.; Caballero, Ana I.; Punska, Elizabeth C.; Pfeiffer, Ruth M.; Yang, Hannah P.; Lee, Maxwell; Yang, Howard; Gierach, Gretchen L.; Arcaro, Kathleen F.

    2016-01-01

    This review summarizes methods related to the study of human breastmilk in etiologic and biomarkers research. Despite the importance of reproductive factors in breast carcinogenesis, factors that act early in life are difficult to study because young women rarely require breast imaging or biopsy, and analysis of critical circulating factors (e.g. hormones) is often complicated by the requirement to accurately account for menstrual cycle date. Accordingly, novel approaches are needed to understand how events such as pregnancy, breastfeeding, weaning, and post-weaning breast remodeling influence breast cancer risk. Analysis of breastmilk offers opportunities to understand mechanisms related to carcinogenesis in the breast, and to identify risk markers that may inform efforts to identify high-risk women early in the carcinogenic process. In addition, analysis of breastmilk could have value in early detection or diagnosis of breast cancer. In this article we describe the potential for using breastmilk to characterize the microenvironment of the lactating breast with the goal of advancing research on risk assessment, prevention, and detection of breast cancer. PMID:27107568

  19. Bayesian regression model for recurrent event data with event-varying covariate effects and event effect.

    PubMed

    Lin, Li-An; Luo, Sheng; Davis, Barry R

    2018-01-01

    In the course of hypertension, cardiovascular disease events (e.g., stroke, heart failure) occur frequently and recurrently. The scientific interest in such study may lie in the estimation of treatment effect while accounting for the correlation among event times. The correlation among recurrent event times come from two sources: subject-specific heterogeneity (e.g., varied lifestyles, genetic variations, and other unmeasurable effects) and event dependence (i.e., event incidences may change the risk of future recurrent events). Moreover, event incidences may change the disease progression so that there may exist event-varying covariate effects (the covariate effects may change after each event) and event effect (the effect of prior events on the future events). In this article, we propose a Bayesian regression model that not only accommodates correlation among recurrent events from both sources, but also explicitly characterizes the event-varying covariate effects and event effect. This model is especially useful in quantifying how the incidences of events change the effects of covariates and risk of future events. We compare the proposed model with several commonly used recurrent event models and apply our model to the motivating lipid-lowering trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (ALLHAT-LLT).

  20. Bayesian regression model for recurrent event data with event-varying covariate effects and event effect

    PubMed Central

    Lin, Li-An; Luo, Sheng; Davis, Barry R.

    2017-01-01

    In the course of hypertension, cardiovascular disease events (e.g., stroke, heart failure) occur frequently and recurrently. The scientific interest in such study may lie in the estimation of treatment effect while accounting for the correlation among event times. The correlation among recurrent event times come from two sources: subject-specific heterogeneity (e.g., varied lifestyles, genetic variations, and other unmeasurable effects) and event dependence (i.e., event incidences may change the risk of future recurrent events). Moreover, event incidences may change the disease progression so that there may exist event-varying covariate effects (the covariate effects may change after each event) and event effect (the effect of prior events on the future events). In this article, we propose a Bayesian regression model that not only accommodates correlation among recurrent events from both sources, but also explicitly characterizes the event-varying covariate effects and event effect. This model is especially useful in quantifying how the incidences of events change the effects of covariates and risk of future events. We compare the proposed model with several commonly used recurrent event models and apply our model to the motivating lipid-lowering trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (ALLHAT-LLT). PMID:29755162

  1. Genetic Testing Confirmed the Early Diagnosis of X-Linked Hypophosphatemic Rickets in a 7-Month-Old Infant

    PubMed Central

    Poon, Kok Siong; Sng, Andrew Anjian; Ho, Cindy Weili; Koay, Evelyn Siew-Chuan

    2015-01-01

    Loss-of-function mutations in the phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) have been causally associated with X-linked hypophosphatemic rickets (XLHR). The early diagnosis of XLHR in infants is challenging when it is based solely on clinical features and biochemical findings. We report a 7-month-old boy with a family history of hypophosphatemic rickets., who demonstrated early clinical evidence of rickets, although serial biochemical findings could not definitively confirm rickets. A sequencing assay targeting the PHEX gene was first performed on the mother’s DNA to screen for mutations in the 5′UTR, 22 coding exons, and the exon-intron junctions. Targeted mutation analysis and mRNA studies were subsequently performed on the boys’ DNA to investigate the pathogenicity of the identified mutation. Genetic screening of the PHEX gene revealed a novel mutation, c.1080-2A>C, at the splice acceptor site in intron 9. The detection of an aberrant mRNA transcript with skipped (loss of) exon 10 establishes its pathogenicity and confirms the diagnosis of XLHR in this infant. Genetic testing of the PHEX gene resulted in early diagnosis of XLHR, thus enabling initiation of therapy and prevention of progressive rachitic changes in the infant. PMID:26904698

  2. Relation of Cardiac Complications in the Early Phase of Community-Acquired Pneumonia to Long-Term Mortality and Cardiovascular Events.

    PubMed

    Cangemi, Roberto; Calvieri, Camilla; Falcone, Marco; Bucci, Tommaso; Bertazzoni, Giuliano; Scarpellini, Maria G; Barillà, Francesco; Taliani, Gloria; Violi, Francesco

    2015-08-15

    Community-acquired pneumonia (CAP) is complicated by cardiac events in the early phase of the disease. Aim of this study was to assess if these intrahospital cardiac complications may account for overall mortality and cardiovascular events occurring during a long-term follow-up. Three hundred one consecutive patients admitted to the University-Hospital, Policlinico Umberto I, with community-acquired pneumonia were prospectively recruited and followed up for a median of 17.4 months. Primary end point was the occurrence of death for any cause, and secondary end point was the occurrence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction [MI], and stroke). During the intrahospital stay, 55 patients (18%) experienced a cardiac complication. Of these, 32 had an MI (29 non-ST-elevation MI and 3 ST-elevation MI) and 30 had a new episode of atrial fibrillation (7 nonmutually exclusive events). During the follow-up, 89 patients died (51% of patients with an intrahospital cardiac complication and 26% of patients without, p <0.001) and 73 experienced a cardiovascular event (47% of patients with and 19% of patients without an intrahospital cardiac complication, p <0.001). A Cox regression analysis showed that intrahospital cardiac complications, age, and Pneumonia Severity Index were significantly associated with overall mortality, whereas intrahospital cardiac complications, age, hypertension, and diabetes were significantly associated with cardiovascular events during the follow-up. In conclusion, this prospective study shows that intrahospital cardiac complications in the early phase of pneumonia are associated with an enhanced risk of death and cardiovascular events during long-term follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. The Modern Value of Early Writings in Medicine and Dentistry.

    PubMed

    Peck, Sheldon

    2016-01-01

    This article illustrates three examples supporting the modern value of early writings in dentistry and medicine. First, by studying cases described in works published long before the era of genetic science, we are able to develop new hypotheses about familial conditions and their genetic roots. Tooth transposition is presented as an example. Second, old writings may lead us to valuable historical insights and perspectives in medicine that can be revealed only in retrospective analysis. An example of this kind of historical analysis uncovers why dentistry became unnaturally separated from mainstream medicine in the 19th century. Third, early writings become keys to unlocking forgotten knowledge that enriches our understanding of historically significant people and events. The discovery of Norman Kingsley's long forgotten pyrographic paintings after Rembrandt portraits is used as an example. Libraries, the traditional custodians of these valued old texts, must continue to be supported, and not undermined by the paperless digital revolution. Copyright American Academy of the History of Dentistry.

  4. Association Between the Presence of Carotid Artery Plaque and Cardiovascular Events in Patients With Genetic Hypercholesterolemia.

    PubMed

    Bea, Ana M; Civeira, Fernando; Jarauta, Estíbaliz; Lamiquiz-Moneo, Itziar; Pérez-Calahorra, Sofía; Marco-Benedí, Victoria; Cenarro, Ana; Mateo-Gallego, Rocío

    2017-07-01

    The equations used in the general population to calculate cardiovascular risk are not useful in genetic hypercholesterolemia (GH). Carotid plaque detection has proved useful in cardiovascular prediction and risk reclassification but there have been no studies of its usefulness in GH. The aim of this study was to determine the association between the presence of carotid artery plaque and the occurrence of cardiovascular events in patients with GH. This study included 1778 persons with GH. The mean follow-up until the occurrence of cardiovascular events was 6.26 years. At presentation, the presence of carotid artery plaque was studied by high-resolution ultrasound. Carotid artery plaque was found in 661 (37.2%) patients: 31.9% with familial hypercholesterolemia, 39.8% with familial combined hyperlipidemia, 45.5% with dysbetalipoproteinemia, and 43.2% with polygenic hypercholesterolemia. During follow-up, 58 patients had a cardiovascular event. Event rates were 6354/100 000 (95%CI, 4432.4-8275.6) in the group with plaque and 1432/100 000 (95%CI, 730.6-2134.3) in the group without plaque, with significant differences between the 2 groups (P < .001). The relative risk of an event was 4.34 (95CI%, 2.44-7.71; P < .001) times higher in patients with plaque and was 2.40 (95%CI, 1.27-4.56; P = .007) times higher after adjustment for major risk factors. The number of carotid artery plaques was positively associated with the risk of cardiovascular events. Most cardiovascular events occur in a subgroup of patients who can be identified by carotid plaque detection. These results support the use of plaque screening in this population and should help in risk stratification and treatment in GH. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  5. Approximate entropy analysis of event-related potentials in patients with early vascular dementia.

    PubMed

    Xu, Jin; Sheng, Hengsong; Lou, Wutao; Zhao, Songzhen

    2012-06-01

    This study investigated differences in event-related potential (ERP) parameters among early vascular dementia (VD) patients, healthy elder controls (ECs), and young controls (YCs). A visual "oddball" color identification task was performed while individuals' electroencephalograms (EEGs) were recorded. Approximate entropy (ApEn), a nonlinear measure, along with P300 latencies and amplitudes were used to analyze ERP data and compare these three groups. The patients with VD showed more complex ERP waveforms and higher ApEn values than did ECs while performing the visual task. It was further found that patients with VD showed reduced P300 amplitudes and increased latencies. The results indicate that patients with VD have fewer attention resources to devote to processing stimuli, lower speed of stimulus classification, and lower synchrony in their cortical activity during the response period. We suggest that ApEn, as a measure of ERP complexity, is a promising marker for early diagnosis of VD.

  6. How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

    PubMed Central

    Fox, Sharon E.; Levitt, Pat; Nelson, Charles A.

    2009-01-01

    Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this paper a conceptual framework is provided for considering how the structure of early experience gets “under the skin.” The paper begins with a description of the genetic framework that lays the foundation for brain development, and then to the ways experience interacts with and modifies the structures and functions of the developing brain. Much of the attention is focused on early experience and sensitive periods, although it is made clear that later experience also plays an important role in maintaining and elaborating this early wiring diagram, which is critical to establishing a solid footing for development beyond the early years. PMID:20331653

  7. Performance of Earthquake Early Warning Systems during the Major Events of the 2016-2017 Central Italy Seismic Sequence.

    NASA Astrophysics Data System (ADS)

    Festa, G.; Picozzi, M.; Alessandro, C.; Colombelli, S.; Cattaneo, M.; Chiaraluce, L.; Elia, L.; Martino, C.; Marzorati, S.; Supino, M.; Zollo, A.

    2017-12-01

    Earthquake early warning systems (EEWS) are systems nowadays contributing to the seismic risk mitigation actions, both in terms of losses and societal resilience, by issuing an alert promptly after the earthquake origin and before the ground shaking impacts the targets to be protected. EEWS systems can be grouped in two main classes: network based and stand-alone systems. Network based EEWS make use of dense seismic networks surrounding the fault (e.g. Near Fault Observatory; NFO) generating the event. The rapid processing of the P-wave early portion allows for the location and magnitude estimation of the event then used to predict the shaking through ground motion prediction equations. Stand-alone systems instead analyze the early P-wave signal to predict the ground shaking carried by the late S or surface waves, through empirically calibrated scaling relationships, at the recording site itself. We compared the network-based (PRESTo, PRobabilistic and Evolutionary early warning SysTem, www.prestoews.org, Satriano et al., 2011) and the stand-alone (SAVE, on-Site-Alert-leVEl, Caruso et al., 2017) systems, by analyzing their performance during the 2016-2017 Central Italy sequence. We analyzed 9 earthquakes having magnitude 5.0 < M < 6.5 at about 200 stations located within 200 km from the epicentral area, including stations of The Altotiberina NFO (TABOO). Performances are evaluated in terms of rate of success of ground shaking intensity prediction and available lead-time, i.e. the time available for security actions. PRESTo also evaluated the accuracy of location and magnitude. Both systems well predict the ground shaking nearby the event source, with a success rate around 90% within the potential damage zone. The lead-time is significantly larger for the network based system, increasing to more than 10s at 40 km from the event epicentre. The stand-alone system better performs in the near-source region showing a positive albeit small lead-time (<3s). Far away from

  8. Early warm-rewarding parenting moderates the genetic contributions to callous-unemotional traits in childhood.

    PubMed

    Henry, Jeffrey; Dionne, Ginette; Viding, Essi; Vitaro, Frank; Brendgen, Mara; Tremblay, Richard E; Boivin, Michel

    2018-04-23

    Previous gene-environment interaction studies of CU traits have relied on the candidate gene approach, which does not account for the entire genetic load of complex phenotypes. Moreover, these studies have not examined the role of positive environmental factors such as warm/rewarding parenting. The aim of the present study was to determine whether early warm/rewarding parenting moderates the genetic contributions (i.e., heritability) to callous-unemotional (CU) traits at school age. Data were collected in a population sample of 662 twin pairs (Quebec Newborn Twin Study - QNTS). Mothers reported on their warm/rewarding parenting. Teachers assessed children's CU traits. These reports were subjected to twin modeling. Callous-unemotional traits were highly heritable, with the remaining variance accounted for by nonshared environmental factors. Warm/rewarding parenting significantly moderated the role of genes in CU traits; heritability was lower when children received high warm/rewarding parenting than when they were exposed to low warm/rewarding parenting. High warm/rewarding parenting may partly impede the genetic expression of CU traits. Developmental models of CU traits need to account for such gene-environment processes. © 2018 Association for Child and Adolescent Mental Health.

  9. African ancestry, early life exposures, and respiratory morbidity in early childhood.

    PubMed

    Kumar, R; Tsai, H-J; Hong, X; Gignoux, C; Pearson, C; Ortiz, K; Fu, M; Pongracic, J A; Burchard, E G; Bauchner, H; Wang, X

    2012-02-01

    Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05-1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and

  10. African ancestry, early life exposures, and respiratory morbidity in early childhood

    PubMed Central

    Kumar, R.; Tsai, H.-J.; Hong, X.; Gignoux, C.; Pearson, C.; Ortiz, K.; Fu, M.; Pongracic, J. A.; Burchard, E. G.; Bauchner, H.; Wang, X.

    2012-01-01

    Summary Background Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. Objective To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. Methods We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. Results Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02–1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19–1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14–1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05–1.34) and European ancestry (OR: 0.84, 95% CI: 0.74–0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (ORwhites: 0.31, 95% CI: 0.09–1.14; ORhispanic: 0.47, 95% CI: 0.20–1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. Conclusions and Clinical Relevance In contrast to self-identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to

  11. Lack of association between lipoprotein(a) genetic variants and subsequent cardiovascular events in Chinese Han patients with coronary artery disease after percutaneous coronary intervention.

    PubMed

    Li, Zhi-Gen; Li, Guang; Zhou, Ying-Ling; Chen, Zhu-Jun; Yang, Jun-Qing; Zhang, Ying; Sun, Shuo; Zhong, Shi-Long

    2013-08-27

    Elevated lipoprotein(a) [Lp(a)] levels predict cardiovascular events incidence in patients with coronary artery disease (CAD). Genetic variants in the rs3798220, rs10455872 and rs6415084 single-nucleotide polymorphisms (SNPs) in the Lp(a) gene (LPA) correlate with elevated Lp(a) levels, but whether these SNPs have prognostic value for CAD patients is unknown. The present study evaluated the association of LPA SNPs with incidence of subsequent cardiovascular events in CAD patients after percutaneous coronary intervention (PCI). TaqMan SNP genotyping assays were performed to detect the rs6415084, rs3798220 and rs10455872 genotypes in 517 Chinese Han patients with CAD after PCI. We later assessed whether there was an association of these SNPs with incidence of major adverse cardiovascular events (MACE: cardiac death, nonfatal myocardial infarction, ischemic stroke and coronary revascularization). Serum lipid profiles were also determined using biochemical methods. Only the rs6415084 variant allele was associated with higher Lp(a) levels [41.3 (20.8, 74.6) vs. 18.6 (10.3, 40.9) mg/dl, p < 0.001]. During a 2-year follow-up period, 102 patients suffered MACE, and Cox regression analysis demonstrated that elevated Lp(a) (≥30 mg/dl) levels correlated with increased MACE (adjusted HR, 1.69; 95% CI 1.13-2.53), but there was no association between LPA genetic variants (rs6415084 and rs3798220) and MACE incidence (p > 0.05). Our data did not support a relationship between genetic LPA variants (rs6415084 and rs3798220) and subsequent cardiovascular events after PCI in Chinese Han CAD patients.

  12. Predicting adverse obstetric outcome after early pregnancy events and complications: a review.

    PubMed

    van Oppenraaij, R H F; Jauniaux, E; Christiansen, O B; Horcajadas, J A; Farquharson, R G; Exalto, N

    2009-01-01

    BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited or small uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care.

  13. Complex Ancient Genetic Structure and Cultural Transitions in Southern African Populations.

    PubMed

    Montinaro, Francesco; Busby, George B J; Gonzalez-Santos, Miguel; Oosthuitzen, Ockie; Oosthuitzen, Erika; Anagnostou, Paolo; Destro-Bisol, Giovanni; Pascali, Vincenzo L; Capelli, Cristian

    2017-01-01

    The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries. Copyright © 2017 Montinaro et al.

  14. Ancient gene flow from early modern humans into Eastern Neanderthals

    PubMed Central

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J.; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A.; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M.; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-01-01

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here, we analyze the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and of modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously reported. PMID:26886800

  15. Distinct genetic evolution patterns of relapsing diffuse large B-cell lymphoma revealed by genome-wide copy number aberration and targeted sequencing analysis.

    PubMed

    Juskevicius, D; Lorber, T; Gsponer, J; Perrina, V; Ruiz, C; Stenner-Liewen, F; Dirnhofer, S; Tzankov, A

    2016-12-01

    Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore, lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses to track tumors' genetic evolution and to investigate the genetic background of DLBCL recurrence. Three clonally unrelated DLBCL relapses were identified (15%). Also, two distinct patterns of genetic evolution in clonally related relapses were detected as follows: (1) early-divergent/branching evolution from a common progenitor in 6 patients (30%), and (2) late-divergent/linear progression of relapses in 11 patients (65%). Analysis of recurrent genetic events identified potential early drivers of lymphomagenesis (KMT2D, MYD88, CD79B and PIM1). The most frequent relapse-specific events were additional mutations in KMT2D and alterations of MEF2B. SOCS1 mutations were exclusive to non-relapsing DLBCL, whereas primaries of relapsing DLBCL more commonly displayed gains of 10p15.3-p12.1 containing the potential oncogenes PRKCQ, GATA3, MLLT10 and ABI1. Altogether, our study expands the knowledge on clonal relationship, genetic evolution and mutational basis of DLBCL relapses.

  16. Infection of Brachypodium distachyon by Formae Speciales of Puccinia graminis: Early Infection Events and Host-Pathogen Incompatibility

    PubMed Central

    Figueroa, Melania; Alderman, Stephen; Garvin, David F.; Pfender, William F.

    2013-01-01

    Puccinia graminis causes stem rust, a serious disease of cereals and forage grasses. Important formae speciales of P. graminis and their typical hosts are P. graminis f. sp. tritici (Pg-tr) in wheat and barley, P. graminis f. sp. lolii (Pg-lo) in perennial ryegrass and tall fescue, and P. graminis f. sp. phlei-pratensis (Pg-pp) in timothy grass. Brachypodium distachyon is an emerging genetic model to study fungal disease resistance in cereals and temperate grasses. We characterized the P. graminis-Brachypodium pathosystem to evaluate its potential for investigating incompatibility and non-host resistance to P. graminis. Inoculation of eight Brachypodium inbred lines with Pg-tr, Pg-lo or Pg-pp resulted in sporulating lesions later accompanied by necrosis. Histological analysis of early infection events in one Brachypodium inbred line (Bd1-1) indicated that Pg-lo and Pg-pp were markedly more efficient than Pg-tr at establishing a biotrophic interaction. Formation of appressoria was completed (60–70% of germinated spores) by 12 h post-inoculation (hpi) under dark and wet conditions, and after 4 h of subsequent light exposure fungal penetration structures (penetration peg, substomatal vesicle and primary infection hyphae) had developed. Brachypodium Bd1-1 exhibited pre-haustorial resistance to Pg-tr, i.e. infection usually stopped at appressorial formation. By 68 hpi, only 0.3% and 0.7% of the Pg-tr urediniospores developed haustoria and colonies, respectively. In contrast, development of advanced infection structures by Pg-lo and Pg-pp was significantly more common; however, Brachypodium displayed post-haustorial resistance to these isolates. By 68 hpi the percentage of urediniospores that only develop a haustorium mother cell or haustorium in Pg-lo and Pg-pp reached 8% and 5%, respectively. The formation of colonies reached 14% and 13%, respectively. We conclude that Brachypodium is an apt grass model to study the molecular and genetic components of incompatiblity

  17. Characteristics of long recovery early VLF events observed by the North African AWESOME Network

    NASA Astrophysics Data System (ADS)

    Naitamor, S.; Cohen, M. B.; Cotts, B. R. T.; Ghalila, H.; Alabdoadaim, M. A.; Graf, K.

    2013-08-01

    Lightning strokes are capable of initiating disturbances in the lower ionosphere, whose recoveries persist for many minutes. These events are remotely sensed via monitoring subionospherically propagating very low frequency (VLF) transmitter signals, which are perturbed as they pass through the region above the lightning stroke. In this paper we describe the properties and characteristics of the early VLF signal perturbations, which exhibit long recovery times using subionospheric VLF transmitter data from three identical receivers located at Algiers (Algeria), Tunis (Tunisia), and Sebha (Libya). The results indicate that the observation of long recovery events depends strongly on the modal structure of the signal electromagnetic field and the distance from the disturbed region and the receiver or transmitter locations. Comparison of simultaneously collected data at the three sites indicates that the role of the causative lightning stroke properties (e.g., peak current and polarity), or that of transient luminous events may be much less important. The dominant parameter which determines the duration of the recovery time and amplitude appears to be the modal structure of the subionospheric VLF probe signal at the ionospheric disturbance, where scattering occurs, and the subsequent modal structure that propagates to the receiver location.

  18. EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.

    EPA Science Inventory

    Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.

    Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.

    Environmental exposure to arsenic is a m...

  19. Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.

    PubMed

    Holland, Michelle L; Lowe, Robert; Caton, Paul W; Gemma, Carolina; Carbajosa, Guillermo; Danson, Amy F; Carpenter, Asha A M; Loche, Elena; Ozanne, Susan E; Rakyan, Vardhman K

    2016-07-29

    A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults. Copyright © 2016, American Association for the Advancement of Science.

  20. High-density genetic linkage map construction by F2 populations and QTL analysis of early-maturity traits in upland cotton (Gossypium hirsutum L.).

    PubMed

    Li, Libei; Zhao, Shuqi; Su, Junji; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Gu, Lijiao; Zhang, Chi; Liu, Guoyuan; Yu, Dingwei; Liu, Qibao; Zhang, Xianlong; Yu, Shuxun

    2017-01-01

    Due to China's rapidly increasing population, the total arable land area has dramatically decreased; as a consequence, the competition for farming land allocated for grain and cotton production has become fierce. Therefore, to overcome the existing contradiction between cotton grain and fiber production and the limited farming land, development of early-maturing cultivars is necessary. In this research, a high-density linkage map of upland cotton was constructed using genotyping by sequencing (GBS) to discover single nucleotide polymorphism (SNP) markers associated with early maturity in 170 F2 individuals derived from a cross between LU28 and ZHONG213. The high-density genetic map, which was composed of 3978 SNP markers across the 26 cotton chromosomes, spanned 2480 cM with an average genetic distance of 0.62 cM. Collinearity analysis showed that the genetic map was of high quality and accurate and agreed well with the Gossypium hirsutum reference genome. Based on this high-density linkage map, QTL analysis was performed on cotton early-maturity traits, including FT, FBP, WGP, NFFB, HNFFB and PH. A total 47 QTLs for the six traits were detected; each of these QTLs explained between 2.61% and 32.57% of the observed phenotypic variation. A major region controlling early-maturity traits in Gossypium hirsutum was identified for FT, FBP, WGP, NFFB and HNFFB on chromosome D03. QTL analyses revealed that phenotypic variation explained (PVE) ranged from 10.42% to 32.57%. Two potential candidate genes, Gh_D03G0885 and Gh_D03G0922, were predicted in a stable QTL region and had higher expression levels in the early-maturity variety ZHONG213 than in the late-maturity variety LU28. However, further evidence is required for functional validation. This study could provide useful information for the dissection of early-maturity traits and guide valuable genetic loci for molecular-assisted selection (MAS) in cotton breeding.

  1. High-density genetic linkage map construction by F2 populations and QTL analysis of early-maturity traits in upland cotton (Gossypium hirsutum L.)

    PubMed Central

    Li, Libei; Zhao, Shuqi; Su, Junji; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Gu, Lijiao; Zhang, Chi; Liu, Guoyuan; Yu, Dingwei; Liu, Qibao; Zhang, Xianlong

    2017-01-01

    Due to China’s rapidly increasing population, the total arable land area has dramatically decreased; as a consequence, the competition for farming land allocated for grain and cotton production has become fierce. Therefore, to overcome the existing contradiction between cotton grain and fiber production and the limited farming land, development of early-maturing cultivars is necessary. In this research, a high-density linkage map of upland cotton was constructed using genotyping by sequencing (GBS) to discover single nucleotide polymorphism (SNP) markers associated with early maturity in 170 F2 individuals derived from a cross between LU28 and ZHONG213. The high-density genetic map, which was composed of 3978 SNP markers across the 26 cotton chromosomes, spanned 2480 cM with an average genetic distance of 0.62 cM. Collinearity analysis showed that the genetic map was of high quality and accurate and agreed well with the Gossypium hirsutum reference genome. Based on this high-density linkage map, QTL analysis was performed on cotton early-maturity traits, including FT, FBP, WGP, NFFB, HNFFB and PH. A total 47 QTLs for the six traits were detected; each of these QTLs explained between 2.61% and 32.57% of the observed phenotypic variation. A major region controlling early-maturity traits in Gossypium hirsutum was identified for FT, FBP, WGP, NFFB and HNFFB on chromosome D03. QTL analyses revealed that phenotypic variation explained (PVE) ranged from 10.42% to 32.57%. Two potential candidate genes, Gh_D03G0885 and Gh_D03G0922, were predicted in a stable QTL region and had higher expression levels in the early-maturity variety ZHONG213 than in the late-maturity variety LU28. However, further evidence is required for functional validation. This study could provide useful information for the dissection of early-maturity traits and guide valuable genetic loci for molecular-assisted selection (MAS) in cotton breeding. PMID:28809947

  2. Genetic, morphological, and acoustic evidence reveals lack of diversification in the colonization process in an island bird.

    PubMed

    Illera, Juan Carlos; Palmero, Ana M; Laiolo, Paola; Rodríguez, Felipe; Moreno, Ángel C; Navascués, Miguel

    2014-08-01

    Songbirds with recently (i.e., early Holocene) founded populations are suitable models for studying incipient differentiation in oceanic islands. On such systems each colonization event represents a different evolutionary episode that can be studied by addressing sets of diverging phenotypic and genetic traits. We investigate the process of early differentiation in the spectacled warbler (Sylvia conspicillata) in 14 populations separated by sea barriers from three Atlantic archipelagos and from continental regions spanning from tropical to temperate latitudes. Our approach involved the study of sexual acoustic signals, morphology, and genetic data. Mitochondrial DNA did not provide clear population structure. However, microsatellites analyses consistently identified two genetic groups, albeit without correspondence to subspecies classification and little correspondence to geography. Coalescent analyses showed significant evidence for gene flow between the two genetic groups. Discriminant analyses could not correctly assign morphological or acoustic traits to source populations. Therefore, although theory predicting that in isolated populations genetic, morphological, or acoustic traits can lead to radiation, we have strikingly failed to document differentiation on these attributes in a resident passerine throughout three oceanic archipelagos. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  3. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.

    PubMed

    Schwartz, G G; Olsson, A G; Ezekowitz, M D; Ganz, P; Oliver, M F; Waters, D; Zeiher, A; Chaitman, B R; Leslie, S; Stern, T

    2001-04-04

    Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12

  4. Middle Devonian to Early Carboniferous event stratigraphy of Devils Gate and Northern Antelope Range sections, Nevada, U.S.A

    USGS Publications Warehouse

    Sandberg, C.A.; Morrow, J.R.; Poole, F.G.; Ziegler, W.

    2003-01-01

    The classic type section of the Devils Gate Limestone at Devils Gate Pass is situated on the eastern slope of a proto-Antler forebulge that resulted from convergence of the west side of the North American continent with an ocean plate. The original Late Devonian forebulge, the site of which is now located between Devils Gate Pass and the Northern Antelope Range, separated the continental-rise to deep-slope Woodruff basin on the west from the backbulge Pilot basin on the east. Two connections between these basins are recorded by deeper water siltstone beds at Devils Gate; the older one is the lower tongue of the Woodruff Formation, which forms the basal unit of the upper member of the type Devils Gate, and the upper one is the overlying, thin lower member of the Pilot Shale. The forebulge and the backbulge Pilot basin originated during the middle Frasnian (early Late Devonian) Early hassi Zone, shortly following the Alamo Impact within the punctata Zone in southern Nevada. Evidence of this impact is recorded by coeval and reworked shocked quartz grains in the Northern Antelope Range and possibly by a unique bypass-channel or megatsunami-uprush sandy diamictite within carbonate-platform rocks of the lower member of the type Devils Gate Limestone. Besides the Alamo Impact and three regional events, two other important global events are recorded in the Devils Gate section. The semichatovae eustatic rise, the maximum Late Devonian flooding event, coincides with the sharp lithogenetic change at the discordant boundary above the lower member of the Devils Gate Limestone. Most significantly, the Devils Gate section contains the thickest and most complete rock record in North America across the late Frasnian linguiformis Zone mass extinction event. Excellent exposures include not only the extinction shale, but also a younger. Early triangularis Zone tsunamite breccia, produced by global collapse of carbonate platforms during a shallowing event that continued into the next

  5. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    DOE PAGES

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

    2017-03-22

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  6. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

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

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  7. The effect of early life stress on the cognitive phenotype of children with an extra X chromosome (47,XXY/47,XXX).

    PubMed

    van Rijn, Sophie; Barneveld, Petra; Descheemaeker, Mie-Jef; Giltay, Jacques; Swaab, Hanna

    2018-02-01

    Studies on gene-environment interactions suggest that some individuals may be more susceptible to life adversities than others due to their genetic profile. This study assesses whether or not children with an extra X chromosome are more vulnerable to the negative impact of early life stress on cognitive functioning than typically-developing children. A total of 50 children with an extra X chromosome and 103 non-clinical controls aged 9 to 18 years participated in the study. Cognitive functioning in domains of language, social cognition and executive functioning were assessed. Early life stress was measured with the Questionnaire of Life Events. High levels of early life stress were found to be associated with compromised executive functioning in the areas of mental flexibility and inhibitory control, irrespective of group membership. In contrast, the children with an extra X chromosome were found to be disproportionally vulnerable to deficits in social cognition on top of executive dysfunction, as compared to typically-developing children. Within the extra X group the number of negative life events is significantly correlated with more problems in inhibition, mental flexibility and social cognition. It is concluded that children with an extra X chromosome are vulnerable to adverse life events, with social cognition being particularly impacted in addition to the negative effects on executive functioning. The findings that developmental outcome is codependent on early environmental factors in genetically vulnerable children also underscores opportunities for training and support to positively influence the course of development.

  8. Age-related differences in event-related potentials for early visual processing of emotional faces.

    PubMed

    Hilimire, Matthew R; Mienaltowski, Andrew; Blanchard-Fields, Fredda; Corballis, Paul M

    2014-07-01

    With advancing age, processing resources are shifted away from negative emotional stimuli and toward positive ones. Here, we explored this 'positivity effect' using event-related potentials (ERPs). Participants identified the presence or absence of a visual probe that appeared over photographs of emotional faces. The ERPs elicited by the onsets of angry, sad, happy and neutral faces were recorded. We examined the frontocentral emotional positivity (FcEP), which is defined as a positive deflection in the waveforms elicited by emotional expressions relative to neutral faces early on in the time course of the ERP. The FcEP is thought to reflect enhanced early processing of emotional expressions. The results show that within the first 130 ms young adults show an FcEP to negative emotional expressions, whereas older adults show an FcEP to positive emotional expressions. These findings provide additional evidence that the age-related positivity effect in emotion processing can be traced to automatic processes that are evident very early in the processing of emotional facial expressions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Development and evaluation of event-specific quantitative PCR method for genetically modified soybean A2704-12.

    PubMed

    Takabatake, Reona; Akiyama, Hiroshi; Sakata, Kozue; Onishi, Mari; Koiwa, Tomohiro; Futo, Satoshi; Minegishi, Yasutaka; Teshima, Reiko; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi

    2011-01-01

    A novel real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) soybean event; A2704-12. During the plant transformation, DNA fragments derived from pUC19 plasmid were integrated in A2704-12, and the region was found to be A2704-12 specific. The pUC19-derived DNA sequences were used as primers for the specific detection of A2704-12. We first tried to construct a standard plasmid for A2704-12 quantification using pUC19. However, non-specific signals appeared with both qualitative and quantitative PCR analyses using the specific primers with pUC19 as a template, and we then constructed a plasmid using pBR322. The conversion factor (C(f)), which is required to calculate the amount of the genetically modified organism (GMO), was experimentally determined with two real-time PCR instruments, the Applied Biosystems 7900HT and the Applied Biosystems 7500. The determined C(f) values were both 0.98. The quantitative method was evaluated by means of blind tests in multi-laboratory trials using the two real-time PCR instruments. The limit of quantitation for the method was estimated to be 0.1%. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSD(R)), and the determined bias and RSD(R) values for the method were each less than 20%. These results suggest that the developed method would be suitable for practical analyses for the detection and quantification of A2704-12.

  10. Early Events Leading to the Host Protective Th2 Immune Response to an Intestinal Nematode Parasite

    DTIC Science & Technology

    2005-01-01

    expansion, eosinophilia , and IL-4 production (51;52). Similar down regulations of Th2 associated cytokines were observed using monoclonal antibodies...1. Kightlinger,L.K., Seed,J.R., and Kightlinger,M.B., The epidemiology of Ascaris lumbricoides, Trichuris trichiura, and hookworm in children in...Copyright Statement The author hereby certifies that the use of any copyrighted material in the thesis manuscript entitled: “Early Events

  11. Contemporary paternal genetic landscape of Polish and German populations: from early medieval Slavic expansion to post-World War II resettlements.

    PubMed

    Rębała, Krzysztof; Martínez-Cruz, Begoña; Tönjes, Anke; Kovacs, Peter; Stumvoll, Michael; Lindner, Iris; Büttner, Andreas; Wichmann, H-Erich; Siváková, Daniela; Soták, Miroslav; Quintana-Murci, Lluís; Szczerkowska, Zofia; Comas, David

    2013-04-01

    Homogeneous Proto-Slavic genetic substrate and/or extensive mixing after World War II were suggested to explain homogeneity of contemporary Polish paternal lineages. Alternatively, Polish local populations might have displayed pre-war genetic heterogeneity owing to genetic drift and/or gene flow with neighbouring populations. Although sharp genetic discontinuity along the political border between Poland and Germany indisputably results from war-mediated resettlements and homogenisation, it remained unknown whether Y-chromosomal diversity in ethnically/linguistically defined populations was clinal or discontinuous before the war. In order to answer these questions and elucidate early Slavic migrations, 1156 individuals from several Slavic and German populations were analysed, including Polish pre-war regional populations and an autochthonous Slavic population from Germany. Y chromosomes were assigned to 39 haplogroups and genotyped for 19 STRs. Genetic distances revealed similar degree of differentiation of Slavic-speaking pre-war populations from German populations irrespective of duration and intensity of contacts with German speakers. Admixture estimates showed minor Slavic paternal ancestry (~20%) in modern eastern Germans and hardly detectable German paternal ancestry in Slavs neighbouring German populations for centuries. BATWING analysis of isolated Slavic populations revealed that their divergence was preceded by rapid demographic growth, undermining theory that Slavic expansion was primarily linguistic rather than population spread. Polish pre-war regional populations showed within-group heterogeneity and lower STR variation within R-M17 subclades compared with modern populations, which might have been homogenised by war resettlements. Our results suggest that genetic studies on early human history in the Vistula and Oder basins should rely on reconstructed pre-war rather than modern populations.

  12. Contemporary paternal genetic landscape of Polish and German populations: from early medieval Slavic expansion to post-World War II resettlements

    PubMed Central

    Rębała, Krzysztof; Martínez-Cruz, Begoña; Tönjes, Anke; Kovacs, Peter; Stumvoll, Michael; Lindner, Iris; Büttner, Andreas; Wichmann, H-Erich; Siváková, Daniela; Soták, Miroslav; Quintana-Murci, Lluís; Szczerkowska, Zofia; Comas, David

    2013-01-01

    Homogeneous Proto-Slavic genetic substrate and/or extensive mixing after World War II were suggested to explain homogeneity of contemporary Polish paternal lineages. Alternatively, Polish local populations might have displayed pre-war genetic heterogeneity owing to genetic drift and/or gene flow with neighbouring populations. Although sharp genetic discontinuity along the political border between Poland and Germany indisputably results from war-mediated resettlements and homogenisation, it remained unknown whether Y-chromosomal diversity in ethnically/linguistically defined populations was clinal or discontinuous before the war. In order to answer these questions and elucidate early Slavic migrations, 1156 individuals from several Slavic and German populations were analysed, including Polish pre-war regional populations and an autochthonous Slavic population from Germany. Y chromosomes were assigned to 39 haplogroups and genotyped for 19 STRs. Genetic distances revealed similar degree of differentiation of Slavic-speaking pre-war populations from German populations irrespective of duration and intensity of contacts with German speakers. Admixture estimates showed minor Slavic paternal ancestry (∼20%) in modern eastern Germans and hardly detectable German paternal ancestry in Slavs neighbouring German populations for centuries. BATWING analysis of isolated Slavic populations revealed that their divergence was preceded by rapid demographic growth, undermining theory that Slavic expansion was primarily linguistic rather than population spread. Polish pre-war regional populations showed within-group heterogeneity and lower STR variation within R-M17 subclades compared with modern populations, which might have been homogenised by war resettlements. Our results suggest that genetic studies on early human history in the Vistula and Oder basins should rely on reconstructed pre-war rather than modern populations. PMID:22968131

  13. Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

    PubMed Central

    Berghella, Libera; Ferraro, Elisabetta

    2012-01-01

    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

  14. Evidence of resilience to past climate change in Southwest Asia: Early farming communities and the 9.2 and 8.2 ka events

    NASA Astrophysics Data System (ADS)

    Flohr, Pascal; Fleitmann, Dominik; Matthews, Roger; Matthews, Wendy; Black, Stuart

    2016-03-01

    Climate change is often cited as a major factor in social change. The so-called 8.2 ka event was one of the most pronounced and abrupt Holocene cold and arid events. The 9.2 ka event was similar, albeit of a smaller magnitude. Both events affected the Northern Hemisphere climate and caused cooling and aridification in Southwest Asia. Yet, the impacts of the 8.2 and 9.2 ka events on early farming communities in this region are not well understood. Current hypotheses for an effect of the 8.2 ka event vary from large-scale site abandonment and migration (including the Neolithisation of Europe) to continuation of occupation and local adaptation, while impacts of the 9.2 ka have not previously been systematically studied. In this paper, we present a thorough assessment of available, quality-checked radiocarbon (14C) dates for sites from Southwest Asia covering the time interval between 9500 and 7500 cal BP, which we interpret in combination with archaeological evidence. In this way, the synchronicity between changes observed in the archaeological record and the rapid climate events is tested. It is shown that there is no evidence for a simultaneous and widespread collapse, large-scale site abandonment, or migration at the time of the events. However, there are indications for local adaptation. We conclude that early farming communities were resilient to the abrupt, severe climate changes at 9250 and 8200 cal BP.

  15. Endpoint visual detection of three genetically modified rice events by loop-mediated isothermal amplification.

    PubMed

    Chen, Xiaoyun; Wang, Xiaofu; Jin, Nuo; Zhou, Yu; Huang, Sainan; Miao, Qingmei; Zhu, Qing; Xu, Junfeng

    2012-11-07

    Genetically modified (GM) rice KMD1, TT51-1, and KF6 are three of the most well known transgenic Bt rice lines in China. A rapid and sensitive molecular assay for risk assessment of GM rice is needed. Polymerase chain reaction (PCR), currently the most common method for detecting genetically modified organisms, requires temperature cycling and relatively complex procedures. Here we developed a visual and rapid loop-mediated isothermal amplification (LAMP) method to amplify three GM rice event-specific junction sequences. Target DNA was amplified and visualized by two indicators (SYBR green or hydroxy naphthol blue [HNB]) within 60 min at an isothermal temperature of 63 °C. Different kinds of plants were selected to ensure the specificity of detection and the results of the non-target samples were negative, indicating that the primer sets for the three GM rice varieties had good levels of specificity. The sensitivity of LAMP, with detection limits at low concentration levels (0.01%−0.005% GM), was 10- to 100-fold greater than that of conventional PCR. Additionally, the LAMP assay coupled with an indicator (SYBR green or HNB) facilitated analysis. These findings revealed that the rapid detection method was suitable as a simple field-based test to determine the status of GM crops.

  16. A catastrophic event in Lake Geneva region during the Early Bronze Age?

    NASA Astrophysics Data System (ADS)

    Kremer, Katrina; Yrro, Blé; Marillier, François; Hilbe, Michael; Corboud, Pierre; Rachoud-Schneider, Anne-Marie; Girardclos, Stéphanie

    2013-04-01

    Similarly to steep oceanic continental margins, lake slopes can collapse, producing large sublacustrine landslides and tsunamis. Lake sediments are excellent natural archives of such mass movements and their study allows the reconstructions of these prehistoric events, such as the 563 AD large tsunami over Lake Geneva (Kremer et al, 2012). In Lake Geneva, more than 100 km of high-resolution seismic reflection profiles reveal the late Holocene sedimentation history. The seismic record shows a succession of five large lens-shaped seismic units (A to I), characterized by transparent/chaotic seismic facies with irregular lower boundaries, and interpreted as mass-movement deposits. These units are interbedded with parallel, continuous and strong amplitude reflections, interpreted as the 'background' lake sediments. The oldest dated mass movement (Unit D) covers a surface of 22 km2 in the deep basin, near the city of Lausanne. This deposit has an estimated minimum volume of 0.18 km3 and thus was very likely tsunamigenic (Kremer et al, 2012). A 12-m-long sediment core confirms the seismic interpretation of the mass movement unit and shows that the uppermost 3 m of Unit D are characterized by deformed hemipelagic sediments topped by a 5 cm thick turbidite. This deposit can be classified as a slump whose scar can be interpreted in the seismic data and visualized by multibeam bathymetry. This slump of Lausanne was likely triggered by an earthquake but a spontaneous slope collapse cannot be excluded (Girardclos et al, 2007). Radiocarbon dating of plant macro-remains reveals that the unit D happened during Early Bronze Age. Three other mass wasting deposits occurred during the same time period and may have been triggered during the same event, either by a single earthquake or by a tsunami generated by the slump of Lausanne. Although the exact trigger mechanism of the all these mass-wasting deposits remains unknown, a tsunami likely generated by this event may have affected the

  17. Membrane remodeling, an early event in benzo[alpha]pyrene-induced apoptosis

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

    Tekpli, Xavier; Rissel, Mary; Huc, Laurence

    2010-02-15

    Benzo[alpha]pyrene (B[alpha]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[alpha]P-induced apoptotic process. In this study, we report that B[alpha]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[alpha]P exposure. B[alpha]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[alpha]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[alpha]P-related H{submore » 2}O{sub 2} formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[alpha]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[alpha]P altered the composition of plasma membrane microstructures through AhR and H{sub 2}O{sub 2} dependent-regulation of lipid biosynthesis. In F258 cells, the B[alpha]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization.« less

  18. Adults' perceptions of genetic counseling and genetic testing.

    PubMed

    Houfek, Julia Fisco; Soltis-Vaughan, Brigette S; Atwood, Jan R; Reiser, Gwendolyn M; Schaefer, G Bradley

    2015-02-01

    This study described the perceptions of genetic counseling and testing of adults (N = 116) attending a genetic education program. Understanding perceptions of genetic counseling, including the importance of counseling topics, will contribute to patient-focused care as clinical genetic applications for common, complex disorders evolve. Participants completed a survey addressing: the importance of genetic counseling topics, benefits and negative effects of genetic testing, and sharing test results. Topics addressing practical information about genetic conditions were rated most important; topics involving conceptual genetic/genomic principles were rated least important. The most frequently identified benefit and negative effect of testing were prevention/early detection/treatment and psychological distress. Participants perceived that they were more likely to share test results with first-degree than other relatives. Findings suggest providing patients with practical information about genetic testing and genetic contributions to disease, while also determining whether their self-care abilities would be enhanced by teaching genetic/genomic principles. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Life Events, Genetic Susceptibility, and Smoking among Adolescents

    PubMed Central

    Pampel, Fred C.; Boardman, Jason D.; Daw, Jonathan; Stallings, Michael C.; Smolen, Andrew; Haberstick, Brett; Widaman, Keith F.; Neppl, Tricia K.; Conger, Rand D.

    2015-01-01

    Although stressful life events during adolescence are associated with the adoption of unhealthy behaviors such as smoking, both social circumstances and physical traits can moderate the relationship. This study builds on the stress paradigm and gene-environment approach to social behavior by examining how a polymorphism in the serotonin transporter gene 5-HTTLPR moderates the effect of life events on adolescent smoking. Tests of interaction hypotheses use data from the Family Transitions Project, a longitudinal study of 7th graders followed for 5 years. A sibling-pair design with separate models for the gender composition of pairs (brothers, sisters, or brother/sister) controls for unmeasured family background. The results show that negative life events are significantly and positively associated with smoking. Among brother pairs but not other pairs, the results provide evidence of gene-environment interaction by showing that life events more strongly influence smoking behavior for those with more copies of the 5-HTTLPR S allele. PMID:26463545

  20. Coping with a life event in bipolar disorder: ambulatory measurement, signalling and early treatment.

    PubMed

    Knapen, Stefan E; Riemersma-van der Lek, Rixt F; Haarman, Bartholomeus C M; Schoevers, Robert A

    2016-10-13

    Disruption of the biological rhythm in patients with bipolar disorder is a known risk factor for a switch in mood. This case study describes how modern techniques using ambulatory assessment of sleep parameters can help in signalling a mood switch and start early treatment. We studied a 40-year-old woman with bipolar disorder experiencing a life event while wearing an actigraph to measure sleep-wake parameters. The night after the life event the woman had sleep later and shorter sleep duration. Adequate response of both the woman and the treating psychiatrist resulted in two normal nights with the use of 1 mg lorazepam, possibly preventing further mood disturbances. Ambulatory assessment of the biological rhythm can function as an add-on to regular signalling plans for prevention of episodes in patients with bipolar disorder. More research should be conducted to validate clinical applicability, proper protocols and to understand underlying mechanisms. 2016 BMJ Publishing Group Ltd.

  1. Breast cancer and psychosocial factors: early stressful life events, social support, and well-being.

    PubMed

    Ginzburg, Karni; Wrensch, Margaret; Rice, Terri; Farren, Georgianna; Spiegel, David

    2008-01-01

    The allostasis theory postulates that stress causes the body to activate physiologic systems in order to maintain stability. The authors sought to examine the relationship between earlier stress and later development of breast cancer (BC). Authors correlated discrete and interactive relationships of stressful life events, social support, and well-being during childhood and adolescence with the occurrence of BC in adulthood among 300 women with primary BC and 305 matched control subjects. BC patients and control subjects reported similar childhood experiences. Yet, although childhood stressful life events were associated with reports of less family support and well being among the controls, those in the BC group who experienced high stress in early childhood actually expressed higher levels of family support and well-being than did those who had experienced lower levels of stress. These findings may reflect a tendency toward a repressive coping style among the BC group, which may be either a risk factor for the disease or a result of having it.

  2. Maintaining intestinal health: the genetics and immunology of very early onset inflammatory bowel disease.

    PubMed

    Kelsen, Judith R; Baldassano, Robert N; Artis, David; Sonnenberg, Gregory F

    2015-09-01

    Inflammatory bowel disease (IBD) is a multifactoral disease caused by dysregulated immune responses to commensal or pathogenic microbes in the intestine, resulting in chronic intestinal inflammation. An emerging population of patients with IBD occurring before the age of 5 represent a unique form of disease, termed Very Early Onset (VEO)-IBD, which is phenotypically- and genetically-distinct from older-onset IBD. VEO-IBD is associated with increased disease severity, aggressive progression and poor responsiveness to most conventional therapies. Further investigation into the causes and pathogenesis of VEO-IBD will help improve treatment strategies, and may lead to a better understanding of the mechanisms that are essential to maintain intestinal health or provoke the development of targeted therapeutic strategies to limit intestinal disease. Here we discuss the phenotypic nature of VEO-IBD, the recent identification of novel gene variants associated with disease, and functional immunologic studies interrogating the contribution of specific genetic variants to the development of chronic intestinal inflammation.

  3. A genetic atlas of human admixture history.

    PubMed

    Hellenthal, Garrett; Busby, George B J; Band, Gavin; Wilson, James F; Capelli, Cristian; Falush, Daniel; Myers, Simon

    2014-02-14

    Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed by using genetic data alone and encompassing over 100 events occurring over the past 4000 years. We identified events whose dates and participants suggest they describe genetic impacts of the Mongol empire, Arab slave trade, Bantu expansion, first millennium CE migrations in Eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations.

  4. Event specific qualitative and quantitative polymerase chain reaction detection of genetically modified MON863 maize based on the 5'-transgene integration sequence.

    PubMed

    Yang, Litao; Xu, Songci; Pan, Aihu; Yin, Changsong; Zhang, Kewei; Wang, Zhenying; Zhou, Zhigang; Zhang, Dabing

    2005-11-30

    Because of the genetically modified organisms (GMOs) labeling policies issued in many countries and areas, polymerase chain reaction (PCR) methods were developed for the execution of GMO labeling policies, such as screening, gene specific, construct specific, and event specific PCR detection methods, which have become a mainstay of GMOs detection. The event specific PCR detection method is the primary trend in GMOs detection because of its high specificity based on the flanking sequence of the exogenous integrant. This genetically modified maize, MON863, contains a Cry3Bb1 coding sequence that produces a protein with enhanced insecticidal activity against the coleopteran pest, corn rootworm. In this study, the 5'-integration junction sequence between the host plant DNA and the integrated gene construct of the genetically modified maize MON863 was revealed by means of thermal asymmetric interlaced-PCR, and the specific PCR primers and TaqMan probe were designed based upon the revealed 5'-integration junction sequence; the conventional qualitative PCR and quantitative TaqMan real-time PCR detection methods employing these primers and probes were successfully developed. In conventional qualitative PCR assay, the limit of detection (LOD) was 0.1% for MON863 in 100 ng of maize genomic DNA for one reaction. In the quantitative TaqMan real-time PCR assay, the LOD and the limit of quantification were eight and 80 haploid genome copies, respectively. In addition, three mixed maize samples with known MON863 contents were detected using the established real-time PCR systems, and the ideal results indicated that the established event specific real-time PCR detection systems were reliable, sensitive, and accurate.

  5. Establishment and application of event-specific polymerase chain reaction methods for two genetically modified soybean events, A2704-12 and A5547-127.

    PubMed

    Li, Xiang; Pan, Liangwen; Li, Junyi; Zhang, Qigang; Zhang, Shuya; Lv, Rong; Yang, Litao

    2011-12-28

    For implementation of the issued regulations and labeling policies for genetically modified organism (GMO) supervision, the polymerase chain reaction (PCR) method has been widely used due to its high specificity and sensitivity. In particular, use of the event-specific PCR method based on the flanking sequence of transgenes has become the primary trend. In this study, both qualitative and quantitative PCR methods were established on the basis of the 5' flanking sequence of transgenic soybean A2704-12 and the 3' flanking sequence of transgenic soybean A5547-127, respectively. In qualitative PCR assays, the limits of detection (LODs) were 10 copies of haploid soybean genomic DNA for both A2704-12 and A5547-127. In quantitative real-time PCR assays, the LODs were 5 copies of haploid soybean genomic DNA for both A2704-12 and A5547-127, and the limits of quantification (LOQs) were 10 copies for both. Low bias and acceptable SD and RSD values were also achieved in quantification of four blind samples using the developed real-time PCR assays. In addition, the developed PCR assays for the two transgenic soybean events were used for routine analysis of soybean samples imported to Shanghai in a 6 month period from October 2010 to March 2011. A total of 27 lots of soybean from the United States and Argentina were analyzed: 8 lots from the Unites States were found to have the GM soybean A2704-12 event, and the GM contents were <1.5% in all eight analyzed lots. On the contrary, no GM soybean A5547-127 content was found in any of the eight lots. These results demonstrated that the established event-specific qualitative and quantitative PCR methods could be used effectively in routine identification and quantification of GM soybeans A2704-12 and A5547-127 and their derived products.

  6. Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice

    PubMed Central

    Nemmar, Abderrahim; Hemeiri, Ahmed Al; Hammadi, Naser Al; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

    2015-01-01

    Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored “moasel” tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are

  7. Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice.

    PubMed

    Nemmar, Abderrahim; Al Hemeiri, Ahmed; Al Hammadi, Naser; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

    2015-03-01

    Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored "moasel" tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are early

  8. [Chromosome as a chronicler: Genetic dating, historical events, and DNA-genealogic temptation].

    PubMed

    Balanovsky, O P; Zaporozhchenko, V V

    2016-07-01

    history events leave distinct traces in the history of haplogroups only under certain demographic conditions. Direct identification of national history with the history of its occurring haplogroups is inappropriate and is avoided in population genetic studies, although because of its simplicity and attractiveness it is a constant temptation for researchers. An example of DNA genealogy, an amateur field that went beyond the borders of even citizen science and is consistently using the principle of equating haplogroup with lineage and population, which leads to absurd results (e.g., Eurasia as an origin of humankind), can serve as a warning against a simplified approach for interpretation of genetic dating results.

  9. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

    PubMed

    Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

    2012-04-15

    Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

  10. Early Holocene hydroclimate of Baffin Bay: Understanding the interplay between abrupt climate change events and ice sheet fluctuations

    NASA Astrophysics Data System (ADS)

    Corcoran, M. C.; Thomas, E. K.; Castañeda, I. S.; Briner, J. P.

    2017-12-01

    Understanding the causes of ice sheet fluctuations resulting in sea level rise is essential in today's warming climate. In high-latitude ice-sheet-proximal environments such as Baffin Bay, studying both the cause and the rate of ice sheet variability during past abrupt climate change events aids in predictions. Past climate reconstructions are used to understand ice sheet responses to changes in temperature and precipitation. The 9,300 and 8,200 yr BP events are examples of abrupt climate change events in the Baffin Bay region during which there were multiple re-advances of the Greenland and Laurentide ice sheets. High-resolution (decadal-scale) hydroclimate variability near the ice sheet margins during these abrupt climate change events is still unknown. We will generate a decadal-scale record of early Holocene temperature and precipitation using leaf wax hydrogen isotopes, δ2Hwax, from a lake sediment archive on Baffin Island, western Baffin Bay, to better understand abrupt climate change in this region. Shifts in temperature and moisture source result in changes in environmental water δ2H, which in turn is reflected in δ2Hwax, allowing for past hydroclimate to be determined from these compound-specific isotopes. The combination of terrestrial and aquatic δ2Hwax is used to determine soil evaporation and is ultimately used to reconstruct moisture variability. We will compare our results with a previous analysis of δ2Hwax and branched glycerol dialkyl glycerol tetraethers, a temperature and pH proxy, in lake sediment from western Greenland, eastern Baffin Bay, which indicates that cool and dry climate occurred in response to freshwater forcing events in the Labrador Sea. Reconstructing and comparing records on both the western and eastern sides of Baffin Bay during the early Holocene will allow for a spatial understanding of temperature and moisture balance changes during abrupt climate events, aiding in ice sheet modeling and predictions of future sea level

  11. Detecting event-related changes in organizational networks using optimized neural network models.

    PubMed

    Li, Ze; Sun, Duoyong; Zhu, Renqi; Lin, Zihan

    2017-01-01

    Organizational external behavior changes are caused by the internal structure and interactions. External behaviors are also known as the behavioral events of an organization. Detecting event-related changes in organizational networks could efficiently be used to monitor the dynamics of organizational behaviors. Although many different methods have been used to detect changes in organizational networks, these methods usually ignore the correlation between the internal structure and external events. Event-related change detection considers the correlation and could be used for event recognition based on social network modeling and supervised classification. Detecting event-related changes could be effectively useful in providing early warnings and faster responses to both positive and negative organizational activities. In this study, event-related change in an organizational network was defined, and artificial neural network models were used to quantitatively determine whether and when a change occurred. To achieve a higher accuracy, Back Propagation Neural Networks (BPNNs) were optimized using Genetic Algorithms (GAs) and Particle Swarm Optimization (PSO). We showed the feasibility of the proposed method by comparing its performance with that of other methods using two cases. The results suggested that the proposed method could identify organizational events based on a correlation between the organizational networks and events. The results also suggested that the proposed method not only has a higher precision but also has a better robustness than the previously used techniques.

  12. Detecting event-related changes in organizational networks using optimized neural network models

    PubMed Central

    Sun, Duoyong; Zhu, Renqi; Lin, Zihan

    2017-01-01

    Organizational external behavior changes are caused by the internal structure and interactions. External behaviors are also known as the behavioral events of an organization. Detecting event-related changes in organizational networks could efficiently be used to monitor the dynamics of organizational behaviors. Although many different methods have been used to detect changes in organizational networks, these methods usually ignore the correlation between the internal structure and external events. Event-related change detection considers the correlation and could be used for event recognition based on social network modeling and supervised classification. Detecting event-related changes could be effectively useful in providing early warnings and faster responses to both positive and negative organizational activities. In this study, event-related change in an organizational network was defined, and artificial neural network models were used to quantitatively determine whether and when a change occurred. To achieve a higher accuracy, Back Propagation Neural Networks (BPNNs) were optimized using Genetic Algorithms (GAs) and Particle Swarm Optimization (PSO). We showed the feasibility of the proposed method by comparing its performance with that of other methods using two cases. The results suggested that the proposed method could identify organizational events based on a correlation between the organizational networks and events. The results also suggested that the proposed method not only has a higher precision but also has a better robustness than the previously used techniques. PMID:29190799

  13. Ancient genomes link early farmers from Atapuerca in Spain to modern-day Basques.

    PubMed

    Günther, Torsten; Valdiosera, Cristina; Malmström, Helena; Ureña, Irene; Rodriguez-Varela, Ricardo; Sverrisdóttir, Óddny Osk; Daskalaki, Evangelia A; Skoglund, Pontus; Naidoo, Thijessen; Svensson, Emma M; Bermúdez de Castro, José María; Carbonell, Eudald; Dunn, Michael; Storå, Jan; Iriarte, Eneko; Arsuaga, Juan Luis; Carretero, José-Miguel; Götherström, Anders; Jakobsson, Mattias

    2015-09-22

    The consequences of the Neolithic transition in Europe--one of the most important cultural changes in human prehistory--is a subject of great interest. However, its effect on prehistoric and modern-day people in Iberia, the westernmost frontier of the European continent, remains unresolved. We present, to our knowledge, the first genome-wide sequence data from eight human remains, dated to between 5,500 and 3,500 years before present, excavated in the El Portalón cave at Sierra de Atapuerca, Spain. We show that these individuals emerged from the same ancestral gene pool as early farmers in other parts of Europe, suggesting that migration was the dominant mode of transferring farming practices throughout western Eurasia. In contrast to central and northern early European farmers, the Chalcolithic El Portalón individuals additionally mixed with local southwestern hunter-gatherers. The proportion of hunter-gatherer-related admixture into early farmers also increased over the course of two millennia. The Chalcolithic El Portalón individuals showed greatest genetic affinity to modern-day Basques, who have long been considered linguistic and genetic isolates linked to the Mesolithic whereas all other European early farmers show greater genetic similarity to modern-day Sardinians. These genetic links suggest that Basques and their language may be linked with the spread of agriculture during the Neolithic. Furthermore, all modern-day Iberian groups except the Basques display distinct admixture with Caucasus/Central Asian and North African groups, possibly related to historical migration events. The El Portalón genomes uncover important pieces of the demographic history of Iberia and Europe and reveal how prehistoric groups relate to modern-day people.

  14. Genetic moderation of stability in attachment security from early childhood to age 18 years: A replication study.

    PubMed

    Raby, K Lee; Roisman, Glenn I; Booth-LaForce, Cathryn

    2015-11-01

    A longstanding question for attachment theory and research is whether genetically based characteristics of the child influence the development of attachment security and its stability over time. This study attempted to replicate and extend recent findings indicating that the developmental stability of attachment security is moderated by oxytocin receptor (OXTR) genetic variants. Using longitudinal data from over 550 individuals, there was no evidence that OXTR rs53576 moderated the association between attachment security during early childhood and overall coherence of mind ("security") during the Adult Attachment Interview at age 18 years. Additional analyses involving a second commonly investigated OXTR variant (rs2254298) and indices of individuals' dismissing and preoccupied attachment states of mind also failed to provide robust evidence for oxytonergic moderation of the stability in attachment security across development. The discussion focuses on research strategies for investigating genetic contributions to attachment security across the life span. (c) 2015 APA, all rights reserved).

  15. A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

    PubMed

    Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

    2018-04-25

    Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

  16. Parental Substance Abuse As an Early Traumatic Event. Preliminary Findings on Neuropsychological and Personality Functioning in Young Drug Addicts Exposed to Drugs Early

    PubMed Central

    Parolin, Micol; Simonelli, Alessandra; Mapelli, Daniela; Sacco, Marianna; Cristofalo, Patrizia

    2016-01-01

    Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic events. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents' addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved three groups, each consisting of 15 young adults (aged 18–24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non-exposed youth with SUDs. Alternative multi-focused prevention and

  17. The genetic prehistory of the Baltic Sea region.

    PubMed

    Mittnik, Alissa; Wang, Chuan-Chao; Pfrengle, Saskia; Daubaras, Mantas; Zariņa, Gunita; Hallgren, Fredrik; Allmäe, Raili; Khartanovich, Valery; Moiseyev, Vyacheslav; Tõrv, Mari; Furtwängler, Anja; Andrades Valtueña, Aida; Feldman, Michal; Economou, Christos; Oinonen, Markku; Vasks, Andrejs; Balanovska, Elena; Reich, David; Jankauskas, Rimantas; Haak, Wolfgang; Schiffels, Stephan; Krause, Johannes

    2018-01-30

    While the series of events that shaped the transition between foraging societies and food producers are well described for Central and Southern Europe, genetic evidence from Northern Europe surrounding the Baltic Sea is still sparse. Here, we report genome-wide DNA data from 38 ancient North Europeans ranging from ~9500 to 2200 years before present. Our analysis provides genetic evidence that hunter-gatherers settled Scandinavia via two routes. We reveal that the first Scandinavian farmers derive their ancestry from Anatolia 1000 years earlier than previously demonstrated. The range of Mesolithic Western hunter-gatherers extended to the east of the Baltic Sea, where these populations persisted without gene-flow from Central European farmers during the Early and Middle Neolithic. The arrival of steppe pastoralists in the Late Neolithic introduced a major shift in economy and mediated the spread of a new ancestry associated with the Corded Ware Complex in Northern Europe.

  18. In search for genetic determinants of clinically meaningful differential cardiovascular event reduction by pravastatin in the PHArmacogenetic study of Statins in the Elderly at risk (PHASE)/PROSPER study.

    PubMed

    Postmus, Iris; Johnson, Paul C D; Trompet, Stella; de Craen, Anton J M; Slagboom, P Eline; Devlin, James J; Shiffman, Dov; Sacks, Frank M; Kearney, Patricia M; Stott, David J; Buckley, Brendan M; Sattar, Naveed; Ford, Ian; Westendorp, Rudi G J; Jukema, J Wouter

    2014-07-01

    Statin therapy is widely used in the prevention and treatment of cardiovascular events and is associated with significant risk reductions. However, there is considerable variation in response to statin therapy both in terms of LDL cholesterol reduction and clinical outcomes. It has been hypothesized that genetic variation contributes importantly to this individual drug response. We investigated the interaction between genetic variants and pravastatin or placebo therapy on the incidence of cardiovascular events by performing a genome-wide association study in the participants of the PROspective Study of Pravastatin in the Elderly at Risk for vascular disease--PHArmacogenetic study of Statins in the Elderly at risk (PROSPER/PHASE) study (n = 5244). We did not observe genome-wide significant associations with a clinically meaningful differential cardiovascular event reduction by pravastatin therapy. In addition, SNPs with p-values lower than 1 × 10(-4) were assessed for replication in a case-only analysis within two randomized placebo controlled pravastatin trials, CARE (n = 711) and WOSCOPS (n = 522). rs7102569, on chromosome 11 near the ODZ4 gene, was replicated in the CARE study (p = 0.008), however the direction of effect was opposite. This SNP was not associated in WOSCOPS. In addition, none of the SNPs replicated significantly after correcting for multiple testing. We could not identify genetic variation that was significantly associated at genome-wide level with a clinically meaningful differential event reduction by pravastatin treatment in a large prospective study. We therefore assume that in daily practice the use of genetic characteristics to personalize pravastatin treatment to improve prevention of cardiovascular disease will be limited. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. A genetic atlas of human admixture history

    PubMed Central

    Hellenthal, Garrett; Busby, George B.J.; Band, Gavin; Wilson, James F.; Capelli, Cristian

    2014-01-01

    Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed using genetic data alone and encompassing over 100 events occurring over the past 4,000 years. We identify events whose dates and participants suggest they describe genetic impacts of the Mongol Empire, Arab slave trade, Bantu expansion, first millennium CE migrations in eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations. PMID:24531965

  20. Clinical and genetic predictors of major cardiac events in patients with Anderson-Fabry Disease.

    PubMed

    Patel, Vimal; O'Mahony, Constantinos; Hughes, Derralynn; Rahman, Mohammad Shafiqur; Coats, Caroline; Murphy, Elaine; Lachmann, Robin; Mehta, Atul; Elliott, Perry M

    2015-06-01

    Anderson-Fabry Disease (AFD) is an X linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Some mutations are associated with prominent and, in many cases, exclusive cardiac involvement. The primary aims of this study were to determine the incidence of major cardiac events in AFD and to identify clinical and genetic predictors of adverse outcomes. We studied 207 patients with AFD (47% male, mean age 44 years, mean follow-up 7.1 years). Fifty-eight (28%) individuals carried mutations that have been previously associated with a cardiac predominant phenotype. Twenty-one (10%) developed severe heart failure (New York Heart Association functional class (NYHA) ≥3), 13 (6%) developed atrial fibrillation (AF), 13 (6%) received devices for the treatment of bradycardia; there were a total of 7 (3%) cardiac deaths. The incidence of the primary endpoint (a composite of new onset AF, NYHA ≥ 3 symptoms, device insertion for bradycardia and cardiac death) was 2.64 per 100 person-years (CI 1.78 to 3.77). Age (HR 1.04, CI 1.01 to 1.08, p=0.004), Mainz Severity Score Index score (HR 1.05, CI 1.01 to 1.09, p=0.012) and QRS duration (HR 1.03, CI 1.00 to 1.05, p=0.020) were significant independent predictors of the primary endpoint. The presence of a cardiac genetic variant did not predict the primary end point. AFD is associated with a high burden of cardiac morbidity and mortality. Adverse cardiac outcomes are associated with age, global disease severity and advanced cardiac disease but not the presence of cardiac genetic variants. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. An Alternative Explanation for "Step-Like" Early VLF Event

    NASA Astrophysics Data System (ADS)

    Moore, R. C.

    2016-12-01

    A newly-deployed array of VLF receivers along the East Coast of the United States is ideally suited for detecting VLF scattering from lightning-induced disturbances to the lower ionosphere. The array was deployed in May 2016, and one VLF receiver was deployed only 20 km from the NAA transmitter (24.0 kHz) in Cutler, Maine. The phase of the NAA signal at this closest site varies significantly with time, due simply to the impedance match of the transmitter varying with time. Additionally, both the amplitude and phase exhibit periods of rapid shifts that could possibly explain at least some "step-like" VLF scattering events. Here, we distinguish between "step-like" VLF scattering events and other events in that "step-like" events are typically not closely associated with a detected causative lightning flash and also tend to exhibit little or no recovery to ambient conditions after the event onset. We present an analysis of VLF observations from the East Coast array that demonstrates interesting examples of step-like VLF events far from the transmitter that are associated with step-like events very close to the transmitter. We conclude that step-like VLF events should be treated with caution, unless definitively associated with a causative lightning flash and/or detected using observations of multiple transmitter signals.

  2. Early 20th-century research at the interfaces of genetics, development, and evolution: reflections on progress and dead ends.

    PubMed

    Deichmann, Ute

    2011-09-01

    Three early 20th-century attempts at unifying separate areas of biology, in particular development, genetics, physiology, and evolution, are compared in regard to their success and fruitfulness for further research: Jacques Loeb's reductionist project of unifying approaches by physico-chemical explanations; Richard Goldschmidt's anti-reductionist attempts to unify by integration; and Sewall Wright's combination of reductionist research and vision of hierarchical genetic systems. Loeb's program, demanding that all aspects of biology, including evolution, be studied by the methods of the experimental sciences, proved highly successful and indispensible for higher level investigations, even though evolutionary change and properties of biological systems up to now cannot be fully explained on the molecular level alone. Goldschmidt has been appraised as pioneer of physiological and developmental genetics and of a new evolutionary synthesis which transcended neo-Darwinism. However, this study concludes that his anti-reductionist attempts to integrate genetics, development and evolution have to be regarded as failures or dead ends. His grand speculations were based on the one hand on concepts and experimental systems that were too vague in order to stimulate further research, and on the other on experiments which in their core parts turned out not to be reproducible. In contrast, Sewall Wright, apart from being one of the architects of the neo-Darwinian synthesis of the 1930s, opened up new paths of testable quantitative developmental genetic investigations. He placed his research within a framework of logical reasoning, which resulted in the farsighted speculation that examinations of biological systems should be related to the regulation of hierarchical genetic subsystems, possibly providing a mechanism for development and evolution. I argue that his suggestion of basing the study of systems on clearly defined properties of the components has proved superior to

  3. Studying parents and grandparents to assess genetic contributions to early-onset disease.

    PubMed

    Weinberg, Clarice R

    2003-02-01

    Suppose DNA is available from affected individuals, their parents, and their grandparents. Particularly for early-onset diseases, maternally mediated genetic effects can play a role, because the mother determines the prenatal environment. The proposed maximum-likelihood approach for the detection of apparent transmission distortion treats the triad consisting of the affected individual and his or her two parents as the outcome, conditioning on grandparental mating types. Under a null model in which the allele under study does not confer susceptibility, either through linkage or directly, and when there are no maternally mediated genetic effects, conditional probabilities for specific triads are easily derived. A log-linear model permits a likelihood-ratio test (LRT) and allows the estimation of relative penetrances. The proposed approach is robust against genetic population stratification. Missing-data methods permit the inclusion of incomplete families, even if the missing person is the affected grandchild, as is the case when an induced abortion has followed the detection of a malformation. When screening multiple markers, one can begin by genotyping only the grandparents and the affected grandchildren. LRTs based on conditioning on grandparental mating types (i.e., ignoring the parents) have asymptotic relative efficiencies that are typically >150% (per family), compared with tests based on parents. A test for asymmetry in the number of copies carried by maternal versus paternal grandparents yields an LRT specific to maternal effects. One can then genotype the parents for only the genes that passed the initial screen. Conditioning on both the grandparents' and the affected grandchild's genotypes, a third log-linear model captures the remaining information, in an independent LRT for maternal effects.

  4. Teacher quality moderates the genetic effects on early reading.

    PubMed

    Taylor, J; Roehrig, A D; Soden Hensler, B; Connor, C M; Schatschneider, C

    2010-04-23

    Children's reading achievement is influenced by genetics as well as by family and school environments. The importance of teacher quality as a specific school environmental influence on reading achievement is unknown. We studied first- and second-grade students in Florida from schools representing diverse environments. Comparison of monozygotic and dizygotic twins, differentiating genetic similarities of 100% and 50%, provided an estimate of genetic variance in reading achievement. Teacher quality was measured by how much reading gain the non-twin classmates achieved. The magnitude of genetic variance associated with twins' oral reading fluency increased as the quality of their teacher increased. In circumstances where the teachers are all excellent, the variability in student reading achievement may appear to be largely due to genetics. However, poor teaching impedes the ability of children to reach their potential.

  5. Crystal Genetics, Inc.

    PubMed

    Kermani, Bahram G

    2016-07-01

    Crystal Genetics, Inc. is an early-stage genetic test company, focused on achieving the highest possible clinical-grade accuracy and comprehensiveness for detecting germline (e.g., in hereditary cancer) and somatic (e.g., in early cancer detection) mutations. Crystal's mission is to significantly improve the health status of the population, by providing high accuracy, comprehensive, flexible and affordable genetic tests, primarily in cancer. Crystal's philosophy is that when it comes to detecting mutations that are strongly correlated with life-threatening diseases, the detection accuracy of every single mutation counts: a single false-positive error could cause severe anxiety for the patient. And, more importantly, a single false-negative error could potentially cost the patient's life. Crystal's objective is to eliminate both of these error types.

  6. Peptidic tools applied to redirect alternative splicing events.

    PubMed

    Nancy, Martínez-Montiel; Nora, Rosas-Murrieta; Rebeca, Martínez-Contreras

    2015-05-01

    Peptides are versatile and attractive biomolecules that can be applied to modulate genetic mechanisms like alternative splicing. In this process, a single transcript yields different mature RNAs leading to the production of protein isoforms with diverse or even antagonistic functions. During splicing events, errors can be caused either by mutations present in the genome or by defects or imbalances in regulatory protein factors. In any case, defects in alternative splicing have been related to several genetic diseases including muscular dystrophy, Alzheimer's disease and cancer from almost every origin. One of the most effective approaches to redirect alternative splicing events has been to attach cell-penetrating peptides to oligonucleotides that can modulate a single splicing event and restore correct gene expression. Here, we summarize how natural existing and bioengineered peptides have been applied over the last few years to regulate alternative splicing and genetic expression. Under different genetic and cellular backgrounds, peptides have been shown to function as potent vehicles for splice correction, and their therapeutic benefits have reached clinical trials and patenting stages, emphasizing the use of regulatory peptides as an exciting therapeutic tool for the treatment of different genetic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Identification of genetic variants predictive of early onset pancreatic cancer through a population science analysis of functional genomic datasets

    PubMed Central

    Chen, Jinyun; Wu, Xifeng; Huang, Yujing; Chen, Wei; Brand, Randall E.; Killary, Ann M.; Sen, Subrata; Frazier, Marsha L.

    2016-01-01

    Biomarkers are critically needed for the early detection of pancreatic cancer (PC) are urgently needed. Our purpose was to identify a panel of genetic variants that, combined, can predict increased risk for early-onset PC and thereby identify individuals who should begin screening at an early age. Previously, we identified genes using a functional genomic approach that were aberrantly expressed in early pathways to PC tumorigenesis. We now report the discovery of single nucleotide polymorphisms (SNPs) in these genes associated with early age at diagnosis of PC using a two-phase study design. In silico and bioinformatics tools were used to examine functional relevance of the identified SNPs. Eight SNPs were consistently associated with age at diagnosis in the discovery phase, validation phase and pooled analysis. Further analysis of the joint effects of these 8 SNPs showed that, compared to participants carrying none of these unfavorable genotypes (median age at PC diagnosis 70 years), those carrying 1–2, 3–4, or 5 or more unfavorable genotypes had median ages at diagnosis of 64, 63, and 62 years, respectively (P = 3.0E–04). A gene-dosage effect was observed, with age at diagnosis inversely related to number of unfavorable genotypes (Ptrend = 1.0E–04). Using bioinformatics tools, we found that all of the 8 SNPs were predicted to play functional roles in the disruption of transcription factor and/or enhancer binding sites and most of them were expression quantitative trait loci (eQTL) of the target genes. The panel of genetic markers identified may serve as susceptibility markers for earlier PC diagnosis. PMID:27486767

  8. Modeling Temporal Processes in Early Spacecraft Design: Application of Discrete-Event Simulations for Darpa's F6 Program

    NASA Technical Reports Server (NTRS)

    Dubos, Gregory F.; Cornford, Steven

    2012-01-01

    While the ability to model the state of a space system over time is essential during spacecraft operations, the use of time-based simulations remains rare in preliminary design. The absence of the time dimension in most traditional early design tools can however become a hurdle when designing complex systems whose development and operations can be disrupted by various events, such as delays or failures. As the value delivered by a space system is highly affected by such events, exploring the trade space for designs that yield the maximum value calls for the explicit modeling of time.This paper discusses the use of discrete-event models to simulate spacecraft development schedule as well as operational scenarios and on-orbit resources in the presence of uncertainty. It illustrates how such simulations can be utilized to support trade studies, through the example of a tool developed for DARPA's F6 program to assist the design of "fractionated spacecraft".

  9. A Time Scale for Major Events in Early Mars Crustal Evolution

    NASA Technical Reports Server (NTRS)

    Frey, Herbert V.

    2004-01-01

    The population of visible and buried impact basins > 200 km diameter revealed by high resolution gridded MOLA data and the cumulative frequency curves derived for these pvide a basis for a chronology of major events in early martian history. The relative chronology can be given in terms of N(200) crater retention ages; 'absolute ages' can be assigued using the Hartmann-Neukum (H&N) model chronology. In terms of billions of H&N years, the crustal dichotomy formed by large impact basins at 4.12 +/- 0.08 BYA (N(200) = 3.0-3.2) and the global magnetic field died at about or slightly before the same time (4.15 +/- 0.08 BYA (N(200) = 3.5). In this chronology, the buried lowlands are approx. 120 my younger than the buried highlands, approx. 160 my younger than the highlands overall and approx. 340 my younger than the oldest crater retention surface we see, defined by the largest impact basins.

  10. Early Molecular Events in Murine Gastric Epithelial Cells Mediated by Helicobacter pylori CagA.

    PubMed

    Banerjee, Aditi; Basu, Malini; Blanchard, Thomas G; Chintalacharuvu, Subba R; Guang, Wei; Lillehoj, Erik P; Czinn, Steven J

    2016-10-01

    Murine models of Helicobacter pylori infection are used to study host-pathogen interactions, but lack of severe gastritis in this model has limited its usefulness in studying pathogenesis. We compared the murine gastric epithelial cell line GSM06 to the human gastric epithelial AGS cell line to determine whether similar events occur when cultured with H. pylori. The lysates of cells infected with H. pylori isolates or an isogenic cagA-deficient mutant were assessed for translocation and phosphorylation of CagA and for activation of stress pathway kinases by immunoblot. Phosphorylated CagA was detected in both cell lines within 60 minutes. Phospho-ERK 1/2 was present within several minutes and distinctly present in GSM06 cells at 60 minutes. Similar results were obtained for phospho-JNK, although the 54 kDa phosphoprotein signal was dominant in AGS, whereas the lower molecular weight band was dominant in GSM06 cells. These results demonstrate that early events in H. pylori pathogenesis occur within mouse epithelial cells similar to human cells and therefore support the use of the mouse model for the study of acute CagA-associated host cell responses. These results also indicate that reduced disease in H. pylori-infected mice may be due to lack of the Cag PAI, or by differences in the mouse response downstream of the initial activation events. © 2016 John Wiley & Sons Ltd.

  11. Highly specific detection of genetic modification events using an enzyme-linked probe hybridization chip.

    PubMed

    Zhang, M Z; Zhang, X F; Chen, X M; Chen, X; Wu, S; Xu, L L

    2015-08-10

    The enzyme-linked probe hybridization chip utilizes a method based on ligase-hybridizing probe chip technology, with the principle of using thio-primers for protection against enzyme digestion, and using lambda DNA exonuclease to cut multiple PCR products obtained from the sample being tested into single-strand chains for hybridization. The 5'-end amino-labeled probe was fixed onto the aldehyde chip, and hybridized with the single-stranded PCR product, followed by addition of a fluorescent-modified probe that was then enzymatically linked with the adjacent, substrate-bound probe in order to achieve highly specific, parallel, and high-throughput detection. Specificity and sensitivity testing demonstrated that enzyme-linked probe hybridization technology could be applied to the specific detection of eight genetic modification events at the same time, with a sensitivity reaching 0.1% and the achievement of accurate, efficient, and stable results.

  12. Early event-related brain potentials that reflect interest for content information in the media.

    PubMed

    Adachi, Shinobu; Morikawa, Koji; Nittono, Hiroshi

    2012-03-28

    This study investigated the relationship between event-related brain potentials (ERPs) to abridged content information in the media and the subsequent decisions to view the full content. Student volunteers participated in a task that simulated information selection on the basis of the content information. Screenshots of television clips and headlines of news articles on the Web were used as content information for the image condition and the headline condition, respectively. Following presentation of a stimulus containing content information, participants decided whether or not they would view the full content by pressing a select or a reject button. When the select button was pressed, participants were presented with a television clip or a news article. When the reject button was pressed, participants continued on to the next trial, without viewing further. In comparison with rejected stimuli, selected stimuli elicited a larger negative component, with a peak latency of ∼250 ms. The increase in the negative component was independent of the type of visual stimulus. These results suggest that interest toward content information is reflected in early-stage event-related brain potential responses.

  13. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

    PubMed Central

    An, Seong Soo; Park, Sun Ah; Bagyinszky, Eva; Bae, Sun Oh; Kim, Yoon-Jeong; Im, Ji Young; Park, Kyung Won; Park, Kee Hyung; Kim, Eun-Joo; Jeong, Jee Hyang; Kim, Jong Hun; Han, Hyun Jeong; Choi, Seong Hye; Kim, SangYun

    2016-01-01

    Early-onset Alzheimer’s disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16–17), PSEN1 (exons 3–12), and PSEN2 (exons 3–12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be

  14. Dilated Cardiomyopathy: Genetic Determinants and Mechanisms.

    PubMed

    McNally, Elizabeth M; Mestroni, Luisa

    2017-09-15

    Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subtypes. Moreover, cascade genetic testing in family members can identify those who are at risk or with early stage disease, offering the opportunity for early intervention. This review will address diagnosis and management of DCM, including the role of genetic evaluation. We will also overview distinct genetic pathways linked to DCM and their pathogenetic mechanisms. Historically, cardiac morphology has been used to classify cardiomyopathy subtypes. Determining genetic variants is emerging as an additional adjunct to help further refine subtypes of DCM, especially where arrhythmia risk is increased, and ultimately contribute to clinical management. © 2017 American Heart Association, Inc.

  15. Early events in geotropism of seedling shoots

    NASA Technical Reports Server (NTRS)

    Pickard, B. G.

    1985-01-01

    Developments during the first ten minutes of geotropic stimulation in plant seedling shoots are reviewed. Topics include induction and curvature; early processes; the relationship between auxin, electric field, calcium, and differential growth; gravity reception leading to Went-Cholodny transport; and comparison of root and shoot. Early processes reviewed are sedimentation of amyloplasts, release of ethylene, rise of electrical and auxin asymmetry, redistribution of calcium, asymmetric vascular transport, increase in tendency to deposit callose, and simulation of putative exocytotic voltage transients.

  16. Eczema in early life: Genetics, the skin barrier, and lessons learned from birth cohort studies

    PubMed Central

    Biagini Myers, Jocelyn M.; Khurana Hershey, Gurjit K.

    2010-01-01

    Eczema is a chronic inflammatory disorder of the skin that affects up to 30% of children. It often afflicts infants in the first few months of life and can be the first indicator of the atopic march. Recent results from birth cohort studies have uncovered novel information regarding genetic and environmental factors that promote the development of eczema. Birth cohort studies provide an optimal study design to elucidate these associations and prospectively track longitudinal data including exposure assessment and health outcomes from birth into early life and childhood. This is especially relevant for eczema given the age specific emergence of this disease. In this review, we will provide a general overview of pediatric eczema and discuss the important findings in the literature with respect to genetics and environmental exposures, highlighting those derived from birth cohort studies. Additionally, we will review how these relate to the atopic march, the hygiene hypothesis and the integrity of the skin barrier. PMID:20739029

  17. A binary genetic programing model for teleconnection identification between global sea surface temperature and local maximum monthly rainfall events

    NASA Astrophysics Data System (ADS)

    Danandeh Mehr, Ali; Nourani, Vahid; Hrnjica, Bahrudin; Molajou, Amir

    2017-12-01

    The effectiveness of genetic programming (GP) for solving regression problems in hydrology has been recognized in recent studies. However, its capability to solve classification problems has not been sufficiently explored so far. This study develops and applies a novel classification-forecasting model, namely Binary GP (BGP), for teleconnection studies between sea surface temperature (SST) variations and maximum monthly rainfall (MMR) events. The BGP integrates certain types of data pre-processing and post-processing methods with conventional GP engine to enhance its ability to solve both regression and classification problems simultaneously. The model was trained and tested using SST series of Black Sea, Mediterranean Sea, and Red Sea as potential predictors as well as classified MMR events at two locations in Iran as predictand. Skill of the model was measured in regard to different rainfall thresholds and SST lags and compared to that of the hybrid decision tree-association rule (DTAR) model available in the literature. The results indicated that the proposed model can identify potential teleconnection signals of surrounding seas beneficial to long-term forecasting of the occurrence of the classified MMR events.

  18. Stressful Life Events and Predictors of Post-traumatic Growth among High-Risk Early Emerging Adults.

    PubMed

    Arpawong, Thalida E; Rohrbach, Louise A; Milam, Joel E; Unger, Jennifer B; Land, Helen; Sun, Ping; Spruijt-Metz, Donna; Sussman, Steve

    2016-01-01

    Stressful life events (SLEs) may elicit positive psychosocial change among youth, referred to as Post-traumatic Growth (PTG). We assessed types of SLEs experienced, degree to which participants reported PTG, and variables predicting PTG across 24 months among a sample of high risk, ethnically diverse early emerging adults. Participants were recruited from alternative high schools ( n = 564; mean age=16.8; 65% Hispanic). Multi-level regression models were constructed to examine the impact of environmental (SLE quantity, severity) and personal factors (hedonic ability, perceived stress, developmental stage, future time orientation) on a composite score of PTG. The majority of participants reported positive changes resulted from their most life-altering SLE of the past two years. Predictors of PTG included fewer SLEs, less general stress, having a future time perspective, and greater identification with the developmental stage of Emerging Adulthood. Findings suggest intervention targets to foster positive adaptation among early emerging adults who experience frequent SLEs.

  19. Genetic and Environmental Influences on Prereading Skills and Early Reading and Spelling Development in the United States, Australia, and Scandinavia

    ERIC Educational Resources Information Center

    Samuelsson, Stefan; Olson, Richard; Wadsworth, Sally; Corley, Robin; DeFries, John C.; Willcutt, Erik; Hulslander, Jacqueline; Byrne, Brian

    2007-01-01

    Genetic and environmental influences on prereading skills in preschool and on early reading and spelling development at the end of kindergarten were compared among samples of identical and fraternal twins from the U.S. (Colorado), Australia, and Scandinavia. Mean comparisons revealed significantly lower preschool print knowledge in Scandinavia,…

  20. An Overview of Inflammatory Bowel Disease: General Consideration and Genetic Screening Approach in Diagnosis of Early Onset Subsets

    PubMed Central

    Nemati, Shahram; Teimourian, Shahram

    2017-01-01

    Inflammatory bowel disease (IBD) is the consequence of an aberrant hemostasis of the immune cells at the gut mucosal border. Based on clinical manifestation, laboratory tests, radiological studies, endoscopic and histological features, this disease is divided into three main types including Crohn’s disease (CD), Ulcerative colitis (UC), and IBDunclassified (IBD-U). IBD is frequently presented in adults, but about 20% of IBD cases are diagnosed during childhood called pediatric IBD (PIBD). Some patients in the latter group emerge the first symptoms during infancy or under 5 years of age named infantile and very early onset IBD (VEO-IBD), respectively. These subtypes make a small fraction of PIBD, but they have exclusive phenotypic and genetic characteristics such that they are accompanied by severe disease course and resistance to conventional therapy. In this context, understanding the underlying molecular pathology opens a promising field for individualized and effective treatment. Here, we describe current hypotheses on IBD pathophysiology then explain the new idea about genetic screening technology as a good potential approach to identify the causal variants early in the disease manifestation, which is especially important for the fast and accurate treatment of VEO-IBD. PMID:28638582

  1. Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

    PubMed Central

    Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.

    2013-01-01

    Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. PMID:23532479

  2. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

    PubMed

    Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E

    2013-07-01

    Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

  3. Event-by-Event Simulations of Early Gluon Fields in High Energy Nuclear Collisions

    NASA Astrophysics Data System (ADS)

    Nickel, Matthew; Rose, Steven; Fries, Rainer

    2017-09-01

    Collisions of heavy ions are carried out at ultra relativistic speeds at the Relativistic Heavy Ion Collider and the Large Hadron Collider to create Quark Gluon Plasma. The earliest stages of such collisions are dominated by the dynamics of classical gluon fields. The McLerran-Venugopalan (MV) model of color glass condensate provides a model for this process. Previous research has provided an analytic solution for event averaged observables in the MV model. Using the High Performance Research Computing Center (HPRC) at Texas A&M, we have developed a C++ code to explicitly calculate the initial gluon fields and energy momentum tensor event by event using the analytic recursive solution. The code has been tested against previously known analytic results up to fourth order. We have also have been able to test the convergence of the recursive solution at high orders in time and studied the time evolution of color glass condensate.

  4. High-resolution carbonate isotopic study of the Mural Formation (Cerro Pimas section), Sonora, México: Implications for early Albian oceanic anoxic events

    NASA Astrophysics Data System (ADS)

    Madhavaraju, J.; Lee, Yong Il; Scott, R. W.; González-León, C. M.; Jenkyns, H. C.; Saucedo-Samaniego, J. C.; Ramasamy, S.

    2018-03-01

    The 420-m thick stratigraphic section of the Mural Formation that is exposed in the Cerro Pimas area of northern Sonora, Mexico, is composed of limestone lithofacies ranging from bioclastic wackestone to boundstone, whose biota is characterized by low diversity. Prominent age-diagnostic fossils are benthic foraminifera and long-ranging calcareous algae that indicate the Aptian/Albian boundary is close to the base of the Los Coyotes Member. The carbonates of this formation have negative to positive δ13C values (-4.63 to +2.6‰) and highly depleted δ18O values that range from -12.74 to -8.34‰. The absence of correlation between δ13C and δ18O values supports a primary marine origin for the δ13C values of these limestones. The carbon-isotopic curve of the Cerro Pimas stratigraphic section has well-defined δ13C segments (C8 - C15) that compare with published curves of similar age. In the lower part of the early Albian Los Coyotes Member, the presence of OAE 1b is indicated by an increase followed by a decrease in δ13C values, suggesting correlation with the Kilian Event. The middle part of the Los Coyotes Member has a significant negative carbon-isotope excursion correlated with the globally recognizable early Albian Paquier event. Moreover, another significant negative carbon-isotope shift is observed in the upper part of the Los Coyotes Member, which can be correlated with the Leenhardt Event. The occurrence of the Kilian, Paquier and Leenhardt Events (OAE 1b cluster) in the Cerro Pimas stratigraphy confirms the global nature of these early Albian disturbances of the carbon cycle.

  5. Turtle soup, Prohibition, and the population genetic structure of Diamondback Terrapins (Malaclemys terrapin).

    PubMed

    Converse, Paul E; Kuchta, Shawn R; Hauswaldt, J Susanne; Roosenburg, Willem M

    2017-01-01

    Diamondback terrapins (Malaclemys terrapin) were a popular food item in early twentieth century America, and were consumed in soup with sherry. Intense market demand for terrapin meat resulted in population declines, notably along the Atlantic seaboard. Efforts to supply terrapins to markets resulted in translocation events, as individuals were moved about to stock terrapin farms. However, in 1920 the market for turtle soup buckled with the enactment of the eighteenth amendment to the United States' Constitution-which initiated the prohibition of alcoholic drinks-and many terrapin fisheries dumped their stocks into local waters. We used microsatellite data to show that patterns of genetic diversity along the terrapin's coastal range are consistent with historical accounts of translocation and cultivation activities. We identified possible instances of human-mediated dispersal by estimating gene flow over historical and contemporary timescales, Bayesian model testing, and bottleneck tests. We recovered six genotypic clusters along the Gulf and Atlantic coasts with varying degrees of admixture, including increased contemporary gene flow from Texas to South Carolina, from North Carolina to Maryland, and from North Carolina to New York. In addition, Bayesian models incorporating translocation events outperformed stepping-stone models. Finally, we were unable to detect population bottlenecks, possibly due to translocation reintroducing genetic diversity into bottlenecked populations. Our data suggest that current patterns of genetic diversity in the terrapin were altered by the demand for turtle soup followed by the enactment of alcohol prohibition. In addition, our study shows that population genetic tools can elucidate metapopulation dynamics in taxa with complex genetic histories impacted by anthropogenic activities.

  6. Pathology, genetics and cytogenetics of Wilms' tumour.

    PubMed

    Md Zin, Reena; Murch, Ashleigh; Charles, Adrian

    2011-06-01

    Wilms' tumour (WT) is an embryonal cancer of childhood and is thought to be derived from embryonic kidney precursor cells. The Knudson two hit model was initially thought to occur in WT, but findings emerging from genetic and cytogenetic studies in the past two decades have implicated several genetic events. Recent techniques in genetic analysis have improved our ability to characterise changes in genes involved in WT which include WT1, CTNNB1, IGF2 and WTX. These genetic events have not only provided insight into the pathobiology of this malignancy, but the recognition of these candidate genes may offer potential targets for novel therapies. In this review, we will provide an overview of the pathological, genetic and cytogenetic characteristics of WT.

  7. Enhanced tocopherol levels during early germination events in Chamaerops humilis var. humilis seeds.

    PubMed

    Siles, Laura; Alegre, Leonor; Tijero, Verónica; Munné-Bosch, Sergi

    2015-10-01

    Most angiosperms accumulate vitamin E in the form of tocopherols in seeds, exerting a protective antioxidant role. However, several palm trees principally accumulate tocotrienols, rather than tocopherols, in seeds, as it occurs in other monocots. To unravel the protective role of either tocopherols or tocotrienols against lipid peroxidation during seed germination in Chamaerops humilis var. humilis; seed viability, natural and induced germination capacity, seed water content, malondialdehyde levels (as an indicator of the extent of lipid peroxidation) and vitamin E levels (including both tocopherols and tocotrienols) were examined at various germination phases in a simulated, natural seed bank. At the very early stages of germination (operculum removal), malondialdehyde levels increased 2.8-fold, to decrease later up to 74%, thus indicating a transient lipid peroxidation at early stages of germination. Tocopherol levels were absent in quiescent seeds and did not increase during operculum removal, but increased later presumably dampening malondialdehyde accumulation. Thereafter, tocopherols continued increasing, while lipid peroxidation levels decreased. By contrast, tocotrienols levels remained constant or even decreased as germination progressed, showing no correlation with lipid peroxidation levels. We hypothesize that despite their high tocotrienol content, seeds synthesize tocopherols during germination to protect lipids from peroxidation events. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Early life events and motor development in childhood and adolescence: a longitudinal study.

    PubMed

    Grace, Tegan; Bulsara, Max; Robinson, Monique; Hands, Beth

    2016-05-01

    Few studies have reported on early life risk factors for motor development outcomes past childhood. Antenatal, perinatal and neonatal factors affecting motor development from late childhood to adolescence were explored. As sex differences in motor development have been previously reported, males and females were examined separately. Participants (n = 2868) were from the Western Australian Pregnancy Cohort Study. Obstetric and neonatal data were examined to determine factors related to motor development at 10 (n = 1622), 14 (n = 1584) and 17 (n = 1221) years. The Neuromuscular Development Index (NDI) of the McCarron Assessment of Motor Development determined offspring motor proficiency. Linear mixed models were developed to allow for changes in motor development over time. Maternal pre-eclampsia, Caesarean section and low income were negatively related to male and female motor outcomes. Lower percentage of optimal birthweight was related to a lower male NDI. Younger maternal age, smoking during early pregnancy and stress during later pregnancy were related to lower female NDIs. Events experienced during pregnancy were related to motor development into late adolescence. Males and females were influenced differently by antenatal and perinatal risk factors; this may be due to sex-specific developmental pathways. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  9. Genetic mapping and identification of QTL for earliness in the globe artichoke/cultivated cardoon complex.

    PubMed

    Portis, Ezio; Scaglione, Davide; Acquadro, Alberto; Mauromicale, Giovanni; Mauro, Rosario; Knapp, Steven J; Lanteri, Sergio

    2012-05-23

    The Asteraceae species Cynara cardunculus (2n = 2x = 34) includes the two fully cross-compatible domesticated taxa globe artichoke (var. scolymus L.) and cultivated cardoon (var. altilis DC). As both are out-pollinators and suffer from marked inbreeding depression, linkage analysis has focussed on the use of a two way pseudo-test cross approach. A set of 172 microsatellite (SSR) loci derived from expressed sequence tag DNA sequence were integrated into the reference C. cardunculus genetic maps, based on segregation among the F1 progeny of a cross between a globe artichoke and a cultivated cardoon. The resulting maps each detected 17 major linkage groups, corresponding to the species' haploid chromosome number. A consensus map based on 66 co-dominant shared loci (64 SSRs and two SNPs) assembled 694 loci, with a mean inter-marker spacing of 2.5 cM. When the maps were used to elucidate the pattern of inheritance of head production earliness, a key commercial trait, seven regions were shown to harbour relevant quantitative trait loci (QTL). Together, these QTL accounted for up to 74% of the overall phenotypic variance. The newly developed consensus as well as the parental genetic maps can accelerate the process of tagging and eventually isolating the genes underlying earliness in both the domesticated C. cardunculus forms. The largest single effect mapped to the same linkage group in each parental maps, and explained about one half of the phenotypic variance, thus representing a good candidate for marker assisted selection.

  10. Genetic mapping and identification of QTL for earliness in the globe artichoke/cultivated cardoon complex

    PubMed Central

    2012-01-01

    Background The Asteraceae species Cynara cardunculus (2n = 2x = 34) includes the two fully cross-compatible domesticated taxa globe artichoke (var. scolymus L.) and cultivated cardoon (var. altilis DC). As both are out-pollinators and suffer from marked inbreeding depression, linkage analysis has focussed on the use of a two way pseudo-test cross approach. Results A set of 172 microsatellite (SSR) loci derived from expressed sequence tag DNA sequence were integrated into the reference C. cardunculus genetic maps, based on segregation among the F1 progeny of a cross between a globe artichoke and a cultivated cardoon. The resulting maps each detected 17 major linkage groups, corresponding to the species’ haploid chromosome number. A consensus map based on 66 co-dominant shared loci (64 SSRs and two SNPs) assembled 694 loci, with a mean inter-marker spacing of 2.5 cM. When the maps were used to elucidate the pattern of inheritance of head production earliness, a key commercial trait, seven regions were shown to harbour relevant quantitative trait loci (QTL). Together, these QTL accounted for up to 74% of the overall phenotypic variance. Conclusion The newly developed consensus as well as the parental genetic maps can accelerate the process of tagging and eventually isolating the genes underlying earliness in both the domesticated C. cardunculus forms. The largest single effect mapped to the same linkage group in each parental maps, and explained about one half of the phenotypic variance, thus representing a good candidate for marker assisted selection. PMID:22621324

  11. Indirect Effects of Attributional Style for Positive Events on Depressive Symptoms Through Self-Esteem During Early Adolescence.

    PubMed

    Rueger, Sandra Yu; George, Rachel

    2017-04-01

    Research on adolescent depression has overwhelmingly focused on risk factors, such as stressful negative events and cognitive vulnerabilities, but much important information can be gained by focusing on protective factors. Thus, the current study aimed to broaden understanding on adolescent depression by considering the role of two positive elements as protective factors, attributional style for positive events and self-esteem, in a model of depression. The sample included 491 middle school students (52 % female; n = 249) with an age range from 12 to 15 years (M = 13.2, SD = .70). The sample was ethnically/racially diverse, with 55 % White, 22 % Hispanic, 10 % Asian American, 3 % African American, and 10 % Biracial/Other. Correlational analyses indicated significant cross-sectional and longitudinal associations between an enhancing attributional style (internal, stable, global attributions for positive events), self-esteem and depressive symptoms. Further, prospective analyses using bootstrapping methodology demonstrated significant indirect effects of an enhancing attributional style on decreases in depressive symptoms through its effects on self-esteem. These findings highlight the importance of considering attributional style for positive events as a protective factor in the developmental course of depressive symptoms during early adolescence.

  12. Cytogenetic and molecular genetic characterization of immortalized human ovarian surface epithelial cell lines: consistent loss of chromosome 13 and amplification of chromosome 20.

    PubMed

    Jin, Yuesheng; Zhang, Hao; Tsao, Sai Wah; Jin, Charlotte; Lv, Mei; Strömbeck, Bodil; Wiegant, Joop; Wan, Thomas Shek Kong; Yuen, Po Wing; Kwong, Yok-Lam

    2004-01-01

    This study aimed at identifying the genetic events involved in immortalization of ovarian epithelial cells, which might be important steps in ovarian carcinogenesis. The genetic profiles of five human ovarian surface epithelial (HOSE) cell lines immortalized by retroviral transfection of the human papillomavirus (HPV) E6/E7 genes were thoroughly characterized by chromosome banding and fluorescence in situ hybridization (FISH), at various passages pre- and post-crisis. In pre-crisis, most cells had simple, non-clonal karyotypic changes. Telomere association was the commonest aberration, suggesting that tolermase dysfunction might be an important genetic event leading to cellular crisis. After immortalization post-crisis, however, the karyotypic patterns were non-random. Loss of genetic materials was a characteristic feature. The commonest numerical aberrations were -13, -14, -16, -17, -18, and +5. Among them, loss of chromosome 13 was common change observed in all lines. The only recurrent structural aberration was homogeneously staining regions (hsr) observed in three lines. FISH and combined binary ratio labeling (COBRA)-FISH showed in two cases that the hsrs were derived from chromosome 20. Clonal evolution was observed in four of the lines. In one line, hsr was the only change shared by all subclones, suggesting that it might be a primary event in cell immortalization. The results of the present study suggested that loss of chromosome 13 and the amplification of chromosome 20 might be early genetic events involved in ovarian cell immortalization, and might be useful targets for the study of genomic aberrations in ovarian carcinogenesis.

  13. Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: evidence from a new genus and species, Grimmenodon aureum

    PubMed Central

    Stumpf, Sebastian; Ansorge, Jörg; Pfaff, Cathrin; Kriwet, Jürgen

    2017-01-01

    ABSTRACT A new genus and species of pycnodontiform fishes, Grimmenodon aureum, from marginal marine, marine-brackish lower Toarcian (Harpoceras exaratum ammonite subzone) clay deposits of Grimmen in northeastern Germany is described. The single specimen represents a diagnostic left prearticular dentition characterized by unique tooth arrangement and ornamentation patterns. Grimmenodon aureum, gen. et sp. nov., is the second unambiguously identified pycnodontiform species from the Early Jurassic, in addition to Eomesodon liassicus from the early Lower Jurassic of western Europe. We also report an indeterminate pycnodontiform tooth crown from the upper Pliensbachian (Pleuroceras apyrenum ammonite subzone) of the same site. The material expands the Early Jurassic range of pycnodontiforms significantly northwards and confirms their presence before and immediately following the onset of the Toarcian Oceanic Anoxic Event (T-OAE) in the marginal marine ecosystems south of the Fennoscandian Shield. Moreover, the new records indicate that the Early Jurassic diversity of pycnodontiform fishes was greater than previously assumed and probably equaled that of the Late Triassic. Therefore, it is hypothesized that the Triassic-Jurassic mass extinction event did not affect pycnodontiform fishes significantly. Micro-computed tomography was used to study the internal anatomy of the prearticular of Grimmenodon aureum, gen. et sp. nov. Our results show that no replacement teeth were formed within the tooth-bearing bone but rather were added posteriorly to functional teeth. http://zoobank.org/urn:lsid:zoobank.org:pub:A56BDE9C-40C4-4CFA-9C2E-F5FA35A66F2 Citation for this article: Stumpf, S., J. Ansorge, C. Pfaff, and J. Kriwet. 2017. Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: Evidence from a new genus and species, Grimmenodon aureum. Journal of Vertebrate Paleontology. DOI: 10

  14. Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: evidence from a new genus and species, Grimmenodon aureum.

    PubMed

    Stumpf, Sebastian; Ansorge, Jörg; Pfaff, Cathrin; Kriwet, Jürgen

    2017-07-04

    A new genus and species of pycnodontiform fishes, Grimmenodon aureum , from marginal marine, marine-brackish lower Toarcian ( Harpoceras exaratum ammonite subzone) clay deposits of Grimmen in northeastern Germany is described. The single specimen represents a diagnostic left prearticular dentition characterized by unique tooth arrangement and ornamentation patterns. Grimmenodon aureum , gen. et sp. nov., is the second unambiguously identified pycnodontiform species from the Early Jurassic, in addition to Eomesodon liassicus from the early Lower Jurassic of western Europe. We also report an indeterminate pycnodontiform tooth crown from the upper Pliensbachian ( Pleuroceras apyrenum ammonite subzone) of the same site. The material expands the Early Jurassic range of pycnodontiforms significantly northwards and confirms their presence before and immediately following the onset of the Toarcian Oceanic Anoxic Event (T-OAE) in the marginal marine ecosystems south of the Fennoscandian Shield. Moreover, the new records indicate that the Early Jurassic diversity of pycnodontiform fishes was greater than previously assumed and probably equaled that of the Late Triassic. Therefore, it is hypothesized that the Triassic-Jurassic mass extinction event did not affect pycnodontiform fishes significantly. Micro-computed tomography was used to study the internal anatomy of the prearticular of Grimmenodon aureum , gen. et sp. nov. Our results show that no replacement teeth were formed within the tooth-bearing bone but rather were added posteriorly to functional teeth. http://zoobank.org/urn:lsid:zoobank.org:pub:A56BDE9C-40C4-4CFA-9C2E-F5FA35A66F2 Citation for this article: Stumpf, S., J. Ansorge, C. Pfaff, and J. Kriwet. 2017. Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: Evidence from a new genus and species, Grimmenodon aureum . Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2017.1344679.

  15. Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance.

    PubMed

    Nakano, Takashi; Okumura, Akihisa; Tanabe, Takuya; Niwa, Shimpei; Fukushima, Masato; Yonemochi, Rie; Eda, Hisano; Tsutsumi, Hiroyuki

    2013-06-01

    Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir early, based on post-marketing experiences. Spontaneous safety reports collected in the early post-marketing phase vigilance were analyzed. Adverse events of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious events were intensively reviewed by the Safety Evaluation Committee. Abnormal behavior/delirium was a frequently reported event. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.

  16. Brachial-ankle pulse wave velocity predicts decline in renal function and cardiovascular events in early stages of chronic kidney disease.

    PubMed

    Yoon, Hye Eun; Shin, Dong Il; Kim, Sung Jun; Koh, Eun Sil; Hwang, Hyeon Seok; Chung, Sungjin; Shin, Seok Joon

    2013-01-01

    In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m(2), eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m(2) (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (β=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03) CONCLUSIONS: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.

  17. Early Spatial and Temporal Events of Human T-Lymphotropic Virus Type 1 Spread following Blood-Borne Transmission in a Rabbit Model of Infection ▿

    PubMed Central

    Haynes, Rashade A. H.; Zimmerman, Bevin; Millward, Laurie; Ware, Evan; Premanandan, Christopher; Yu, Lianbo; Phipps, Andrew J.; Lairmore, Michael D.

    2010-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia/lymphoma (ATL) and is associated with a variety of lymphocyte-mediated disorders. HTLV-1 transmission occurs by transmission of infected cells via breast-feeding by infected mothers, sexual intercourse, and contaminated blood products. The route of exposure and early virus replication events are believed to be key determinants of virus-associated spread, antiviral immune responses, and ultimately disease outcomes. The lack of knowledge of early events of HTLV-1 spread following blood-borne transmission of the virus in vivo hinders a more complete understanding of the immunopathogenesis of HTLV-1 infections. Herein, we have used an established animal model of HTLV-1 infection to study early spatial and temporal events of the viral infection. Twelve-week-old rabbits were injected intravenously with cell-associated HTLV-1 (ACH-transformed R49). Blood and tissues were collected at defined intervals throughout the study to test the early spread of the infection. Antibody and hematologic responses were monitored throughout the infection. HTLV-1 intracellular Tax and soluble p19 matrix were tested from ex vivo cultured lymphocytes. Proviral copy numbers were measured by real-time PCR from blood and tissue mononuclear leukocytes. Our data indicate that intravenous infection with cell-associated HTLV-1 targets lymphocytes located in both primary lymphoid and gut-associated lymphoid compartments. A transient lymphocytosis that correlated with peak virus detection parameters was observed by 1 week postinfection before returning to baseline levels. Our data support emerging evidence that HTLV-1 promotes lymphocyte proliferation preceding early viral spread in lymphoid compartments to establish and maintain persistent infection. PMID:20219918

  18. Bottlenecks drive temporal and spatial genetic changes in alpine caddisfly metapopulations.

    PubMed

    Shama, Lisa N S; Kubow, Karen B; Jokela, Jukka; Robinson, Christopher T

    2011-09-27

    Extinction and re-colonisation of local populations is common in ephemeral habitats such as temporary streams. In most cases, such population turnover leads to reduced genetic diversity within populations and increased genetic differentiation among populations due to stochastic founder events, genetic drift, and bottlenecks associated with re-colonisation. Here, we examined the spatio-temporal genetic structure of 8 alpine caddisfly populations inhabiting permanent and temporary streams from four valleys in two regions of the Swiss Alps in years before and after a major stream drying event, the European heat wave in summer 2003. We found that population turnover after 2003 led to a loss of allelic richness and gene diversity but not to significant changes in observed heterozygosity. Within all valleys, permanent and temporary streams in any given year were not differentiated, suggesting considerable gene flow and admixture between streams with differing hydroperiods. Large changes in allele frequencies after 2003 resulted in a substantial increase in genetic differentiation among valleys within one to two years (1-2 generations) driven primarily by drift and immigration. Signatures of genetic bottlenecks were detected in all 8 populations after 2003 using the M-ratio method, but in no populations when using a heterozygosity excess method, indicating differential sensitivity of bottleneck detection methods. We conclude that genetic differentiation among A. uncatus populations changed markedly both temporally and spatially in response to the extreme climate event in 2003. Our results highlight the magnitude of temporal population genetic changes in response to extreme events. More specifically, our results show that extreme events can cause rapid genetic divergence in metapopulations. Further studies are needed to determine if recovery from this perturbation through gradual mixing of diverged populations by migration and gene flow leads to the pre-climate event state

  19. Impaired Early Attentional Processes in Parkinson’s Disease: A High-Resolution Event-Related Potentials Study

    PubMed Central

    Bocquillon, Perrine; Bourriez, Jean-Louis; Palmero-Soler, Ernesto; Defebvre, Luc; Derambure, Philippe; Dujardin, Kathy

    2015-01-01

    Introduction The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. A previous study using the P3 component of the event-related potentials suggested that a reduced ability to resist interference could be responsible for attention disorders at early stages of Parkinson’s disease (PD), with a possible role of the dorsolateral prefrontal cortex (DLPFC). Methods Our objective was to better determine the origin of this impairment, by studying an earlier ERP component, the N2, and its subcomponents, as they reflect early inhibition processes and as they are known to have sources in the anterior cingulate cortex (ACC), which is involved together with the DLPFC in inhibition processes. Fifteen early-stage PD patients and 15 healthy controls (HCs) performed a three-stimulus visual oddball paradigm, consisting in detecting target inputs amongst standard stimuli, while resisting interference from distracter ones. A 128-channel electroencephalogram was recorded during this task and the generators of the N2 subcomponents were identified using standardized weighted low-resolution electromagnetic tomography (swLORETA). Results PD patients displayed fewer N2 generators than HCs in both the DLPFC and the ACC, for all types of stimuli. In contrast to controls, PD patients did not show any differences between their generators for different N2 subcomponents. Conclusion Our data suggest that impaired inhibition in PD results from dysfunction of the DLPFC and the ACC during the early stages of attentional processes. PMID:26135906

  20. Genetics

    USDA-ARS?s Scientific Manuscript database

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  1. A novel quadruplex real-time PCR method for simultaneous detection of Cry2Ae and two genetically modified cotton events (GHB119 and T304-40).

    PubMed

    Li, Xiang; Wang, Xiuxiu; Yang, Jielin; Liu, Yueming; He, Yuping; Pan, Liangwen

    2014-05-16

    To date, over 150 genetically modified (GM) crops are widely cultivated. To comply with regulations developed for genetically modified organisms (GMOs), including labeling policies, many detection methods for GMO identification and quantification have been developed. To detect the entrance and exit of unauthorized GM crop events in China, we developed a novel quadruplex real-time PCR method for simultaneous detection and quantification of GM cotton events GHB119 and T304-40 in cotton-derived products (based on the 5'-flanking sequence) and the insect-resistance gene Cry2Ae. The limit of detection was 10 copies for GHB119 and Cry2Ae and 25 copies for T304-40. The limit of quantification was 25 copies for GHB119 and Cry2Ae and 50 copies for T304-40. Moreover, low bias and acceptable standard deviation and relative standard deviation values were obtained in quantification analysis of six blind samples containing different GHB119 and T304-40 ingredients. The developed quadruplex quantitative method could be used for quantitative detection of two GM cotton events (GHB119 and T304-40) and Cry2Ae gene ingredient in cotton derived products.

  2. The instrumental seismicity of the Barents and Kara sea region: relocated event catalog from early twentieth century to 1989

    NASA Astrophysics Data System (ADS)

    Morozov, Alexey Nikolaevich; Vaganova, Natalya V.; Asming, Vladimir E.; Konechnaya, Yana V.; Evtyugina, Zinaida A.

    2018-05-01

    We have relocated seismic events registered within the Barents and Kara sea region from early twentieth century to 1989 with a view to creating a relocated catalog. For the relocation, we collected all available seismic bulletins from the global network using data from the ISC Bulletin (International Seismological Centre), ISC-GEM project (International Seismological Centre-Global Earthquake Model), EuroSeismos project, and by Soviet seismic stations from Geophysical Survey of the Russian Academy of Sciences. The location was performed by applying a modified method of generalized beamforming. We have considered several travel time models and selected one with the best location accuracy for ground truth events. Verification of the modified method and selection of the travel time model were performed using data on four nuclear explosions that occurred in the area of the Novaya Zemlya Archipelago and in the north of the European part of Russia. The modified method and the Barents travel time model provide sufficient accuracy for event location in the region. The relocation procedure was applied to 31 of 36 seismic events registered within the Barents and Kara sea region.

  3. An EAS event observed in the early stage of development

    NASA Astrophysics Data System (ADS)

    Barroso, S. L. C.; Beggio, P. C.; de Carvalho, A. O.; Chinellato, J. A.; Mariano, A.; de Oliveira, R.; Shibuya, E. H.; Brazil-Japan Collaboration of Chacaltaya Emulsion Chamber Experiment

    2008-01-01

    Since 1969 the experiments of Brazil-Japan Collaboration showed the occurrence of a series of events, showing a region with a high concentration of electromagnetic particles, surrounded by isolated and/or groups of showers. These events were named "halo events" or "super-families". Currently, we have more than a dozen of such events. The first of them, due to its aspect, was named "Andromeda". We present here the main characteristics of a similar halo event, named C21S087I075. It has a halo region with many high energy showers in its border. Other small energy showers spread over the central and surrounding blocks (S088, S100, S101, I074). These isolated showers, classified as of hadronic or electromagnetic origin, present a fractional energy distribution compatible with that of a Centauro candidate event (C16S087I037), reported at this symposium [S.L.C. Barroso, P.C. Beggio, J.A. Chinellato, A.O. Carvalho, A. Mariano, R. Oliveira, E.H. Shibuya, in this issue of XIV ISVHECRI]. Moreover, the lateral distribution in the halo region is similar to that observed in other 3 halo events.

  4. Trial latencies estimation of event-related potentials in EEG by means of genetic algorithms

    NASA Astrophysics Data System (ADS)

    Da Pelo, P.; De Tommaso, M.; Monaco, A.; Stramaglia, S.; Bellotti, R.; Tangaro, S.

    2018-04-01

    Objective. Event-related potentials (ERPs) are usually obtained by averaging thus neglecting the trial-to-trial latency variability in cognitive electroencephalography (EEG) responses. As a consequence the shape and the peak amplitude of the averaged ERP are smeared and reduced, respectively, when the single-trial latencies show a relevant variability. To date, the majority of the methodologies for single-trial latencies inference are iterative schemes providing suboptimal solutions, the most commonly used being the Woody’s algorithm. Approach. In this study, a global approach is developed by introducing a fitness function whose global maximum corresponds to the set of latencies which renders the trial signals most aligned as possible. A suitable genetic algorithm has been implemented to solve the optimization problem, characterized by new genetic operators tailored to the present problem. Main results. The results, on simulated trials, showed that the proposed algorithm performs better than Woody’s algorithm in all conditions, at the cost of an increased computational complexity (justified by the improved quality of the solution). Application of the proposed approach on real data trials, resulted in an increased correlation between latencies and reaction times w.r.t. the output from RIDE method. Significance. The above mentioned results on simulated and real data indicate that the proposed method, providing a better estimate of single-trial latencies, will open the way to more accurate study of neural responses as well as to the issue of relating the variability of latencies to the proper cognitive and behavioural correlates.

  5. Finding the signal in the noise: Could social media be utilized for early hospital notification of multiple casualty events?

    PubMed Central

    Moore, Sara; Wakam, Glenn; Hubbard, Alan E.; Cohen, Mitchell J.

    2017-01-01

    Introduction Delayed notification and lack of early information hinder timely hospital based activations in large scale multiple casualty events. We hypothesized that Twitter real-time data would produce a unique and reproducible signal within minutes of multiple casualty events and we investigated the timing of the signal compared with other hospital disaster notification mechanisms. Methods Using disaster specific search terms, all relevant tweets from the event to 7 days post-event were analyzed for 5 recent US based multiple casualty events (Boston Bombing [BB], SF Plane Crash [SF], Napa Earthquake [NE], Sandy Hook [SH], and Marysville Shooting [MV]). Quantitative and qualitative analysis of tweet utilization were compared across events. Results Over 3.8 million tweets were analyzed (SH 1.8 m, BB 1.1m, SF 430k, MV 250k, NE 205k). Peak tweets per min ranged from 209–3326. The mean followers per tweeter ranged from 3382–9992 across events. Retweets were tweeted a mean of 82–564 times per event. Tweets occurred very rapidly for all events (<2 mins) and represented 1% of the total event specific tweets in a median of 13 minutes of the first 911 calls. A 200 tweets/min threshold was reached fastest with NE (2 min), BB (7 min), and SF (18 mins). If this threshold was utilized as a signaling mechanism to place local hospitals on standby for possible large scale events, in all case studies, this signal would have preceded patient arrival. Importantly, this threshold for signaling would also have preceded traditional disaster notification mechanisms in SF, NE, and simultaneous with BB and MV. Conclusions Social media data has demonstrated that this mechanism is a powerful, predictable, and potentially important resource for optimizing disaster response. Further investigated is warranted to assess the utility of prospective signally thresholds for hospital based activation. PMID:28982201

  6. Survival Outcomes and Effect of Early vs. Deferred cART Among HIV-Infected Patients Diagnosed at the Time of an AIDS-Defining Event: A Cohort Analysis

    PubMed Central

    Mussini, Cristina; Johnson, Margaret; d'Arminio Monforte, Antonella; Antinori, Andrea; Gill, M. John; Sighinolfi, Laura; Uberti-Foppa, Caterina; Borghi, Vanni; Sabin, Caroline

    2011-01-01

    Objectives We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997–2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30–270 days after AIDS event) cART. Results The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/µL and 5.2 (4.5, 5.7) log10 copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20). Conclusions Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting. PMID:22043301

  7. Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria

    PubMed Central

    Fiori, Elena; Oddi, Diego; Ventura, Rossella; Colamartino, Marco; Valzania, Alessandro; D’Amato, Francesca Romana; Bruinenberg, Vibeke; van der Zee, Eddy; Puglisi-Allegra, Stefano

    2017-01-01

    Phenylketonuria (PKU) is one of the most common human inborn errors of metabolism, caused by phenylalanine hydroxylase deficiency, leading to high phenylalanine and low tyrosine levels in blood and brain causing profound cognitive disability, if untreated. Since 1960, population is screened for hyperphenylalaninemia shortly after birth and submitted to early treatment in order to prevent the major manifestations of the disease. However, the dietetic regimen (phenylalanine free diet) is difficult to maintain, and despite the recommendation to a strict and lifelong compliance, up to 60% of adolescents partially or totally abandons the treatment. The development and the study of new treatments continue to be sought, taking advantage of preclinical models, the most used of which is the PAHenu2 (BTBR ENU2), the genetic murine model of PKU. To date, adult behavioral and neurochemical alterations have been mainly investigated in ENU2 mice, whereas there are no clear indications about the onset of these deficiencies. Here we investigated and report, for the first time, a comprehensive behavioral and neurochemical assay of the developing ENU2 mice. Overall, our findings demonstrate that ENU2 mice are significantly smaller than WT until pnd 24, present a significant delay in the acquisition of tested developmental reflexes, impaired communicative, motor and social skills, and have early reduced biogenic amine levels in several brain areas. Our results extend the understanding of behavioral and cerebral abnormalities in PKU mice, providing instruments to an early preclinical evaluation of the effects of new treatments. PMID:28850618

  8. Genetic Aspects of Alzheimer Disease

    PubMed Central

    Williamson, Jennifer; Goldman, Jill; Marder, Karen S.

    2011-01-01

    Background Alzheimer disease (AD) is a genetically complex disorder. Mutations in 3 genes, presenilin 1, amyloid precursor protein, and presenilin 2, lead to early-onset familial AD in rare families with onset of disease occurring prior to age 65. Specific polymorphisms in apolipoprotein E are associated with the more common, late-onset AD occurring after age 65. In this review, we discuss current advances in AD genetics, the implications of the known AD genes, presenilin 1, presenilin 2, amyloid precursor protein, and apolipoprotein E, and other possible genes on the clinical diagnosis, treatment, and genetic counseling of patients and families with early- and late-onset AD. Review Summary In addition to the mutations in 4 known genes associated with AD, mutations in other genes may be implicated in the pathogenesis of the disease. Most recently, 2 different research groups have reported genetic association between 2 genes, sortilin-related receptor and GAB2, and AD. These associations have not changed the diagnostic and medical management of AD. Conclusions New research in the genetics of AD have implicated novel genes as having a role in the disease, but these findings have not been replicated nor have specific disease causing mutations been identified. To date, clinical genetic testing is limited to familial early-onset disease for symptomatic individuals and asymptomatic relatives and, although not recommended, amyloid precursor protein apolipoprotein E testing as an adjunct to diagnosis of symptomatic individuals. PMID:19276785

  9. Paleomagnetic and Geochronologic Data from Central Asia: Inferences for Early Paleozoic Tectonic Evolution and Timing of Worldwide Glacial Events

    NASA Astrophysics Data System (ADS)

    Gregory, L. C.; Meert, J. G.; Levashova, N.; Grice, W. C.; Gibsher, A.; Rybanin, A.

    2007-12-01

    The Neoproterozoic to early Paleozoic Ural-Mongol belt that runs through Central Asia is crucial for determining the enigmatic amalgamation of microcontinents that make up the Eurasian subcontinent. Two unique models have been proposed for the evolution of Ural-Mongol belt. One involves a complex assemblage of cratonic blocks that have collided and rifted apart during diachronous opening and closing of Neoproterozoic to Devonian aged ocean basins. The opposing model of Sengor and Natal"in proposes a long-standing volcanic arc system that connected Central Asian blocks with the Baltica continent. The Aktau-Mointy and Dzabkhan microcontinents in Kazakhstan and Central Mongolia make up the central section of the Ural-Mongol belt, and both contain glacial sequences characteristic of the hypothesized snowball earth event. These worldwide glaciations are currently under considerable debate, and paleomagnetic data from these microcontients are a useful contribution to the snowball controversy. We have sampled volcanic and sedimentary sequences in Central Mongolia, Kazakhstan and Kyrgyzstan for paleomagnetic and geochronologic study. U-Pb data, 13C curves and abundant fossil records place age constraints on sequences that contain glacial deposits of the hypothesized snowball earth events. Carbonates in the Zavkhan Basin in Mongolia are likely remagnetized, but fossil evidence within the sequence suggests a readjusted age control on two glacial events that were previously labeled as Sturtian and Marinoan. U-Pb ages from both Kazakhstan and Mongolian volcanic sequences imply a similar evolution history of the areas as part of the Ural-Mongol fold belt, and these ages paired with paleomagnetic and 13C records have important tectonic implications. We will present these data in order to place better constraints on the Precambrian to early Paleozoic tectonic evolution of Central Asia and the timing of glacial events recorded in the area.

  10. Excessive Heat Events and National Security: Building Resilience based on Early Warning Systems

    NASA Astrophysics Data System (ADS)

    Vintzileos, A.

    2017-12-01

    Excessive heat events (EHE) affect security of Nations in multiple direct and indirect ways. EHE are the top cause for morbidity/mortality associated to any atmospheric extremes. Higher energy consumption used for cooling can lead to black-outs and social disorder. EHE affect the food supply chain reducing crop yield and increasing the probability of food contamination during delivery and storage. Distribution of goods during EHE can be severely disrupted due to mechanical failure of transportation equipment. EHE during athletic events e.g., marathons, may result to a high number of casualties. Finally, EHE may also affect military planning by e.g. reducing hours of exercise and by altering combat gear. Early warning systems for EHE allow for building resilience. In this paper we first define EHE as at least two consecutive heat days; a heat day is defined as a day with a maximum heat index with probability of occurrence that exceeds a certain threshold. We then use retrospective forecasts performed with a multitude of operational models and show that it is feasible to forecast EHE at forecast lead of week-2 and week-3 over the contiguous United States. We finally introduce an improved definition of EHE based on an intensity index and investigate forecast skill of the predictive system in the tropics and subtropics.

  11. Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra)

    PubMed Central

    Velo-Antón, G; Zamudio, K R; Cordero-Rivera, A

    2012-01-01

    Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (FST range: 0.06–0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts. PMID:22086081

  12. Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra).

    PubMed

    Velo-Antón, G; Zamudio, K R; Cordero-Rivera, A

    2012-04-01

    Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (F(ST) range: 0.06-0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts.

  13. Modeling long recovery early events (LOREs) produced by lightning-induced ionization of the nighttime upper mesosphere

    NASA Astrophysics Data System (ADS)

    Kotovsky, D. A.; Moore, R. C.

    2017-07-01

    We present results of a cylindrically symmetric, coupled electrodynamic, and photochemical model which simulates diffuse ionization of the middle atmosphere induced by strong lightning discharges (peak currents >150 kA). Scattering of subionospherically propagating, very low frequency radio waves is then evaluated using the Long-Wave Propagation Capability code. Some modeled sprite halos exhibit continued electron density growth up to timescales of seconds due to O- detachment, though it is not yet clear how this might relate to the slower onset durations (>20 ms) of some early VLF events. Modeled electron density enhancements in sprite halos, capable of strong VLF scattering, can persist for long periods of time (greater than hundreds of seconds) even at lower altitudes where their recovery is initially controlled by fast attachment processes. Consequently, our modeling results indicate that both typical recovery (20 to 240 s) and long recovery (LOREs, >300 s) VLF scattering events can be explained by scattering from conductivity changes associated with sprite halos. In contrast, modeled scattered fields resulting from elve-associated conductivity changes, though exhibiting long recovery times, are too weak to sufficiently explain typical LORE observations. Theoretical scattering from structured ionization events (e.g., sprites columns and gigantic jets) is not considered in this work.

  14. Genetic progression of malignant melanoma.

    PubMed

    Tímár, J; Vizkeleti, L; Doma, V; Barbai, T; Rásó, E

    2016-03-01

    Malignant melanoma of the skin is the most aggressive human cancer given that a primary tumor a few millimeters in diameter frequently has full metastatic competence. In view of that, revealing the genetic background of this potential may also help to better understand tumor dissemination in general. Genomic analyses have established the molecular classification of melanoma based on the most frequent driver oncogenic mutations (BRAF, NRAS, KIT) and have also revealed a long list of rare events, including mutations and amplifications as well as genetic microheterogeneity. At the moment, it is unclear whether any of these rare events have role in the metastasis initiation process since the major drivers do not have such a role. During lymphatic and hematogenous dissemination, the clonal selection process is evidently reflected by differences in oncogenic drivers in the metastases versus the primary tumor. Clonal selection is also evident during lymphatic progression, though the genetic background of this immunoselection is less clear. Genomic analyses of metastases identified further genetic alterations, some of which may correspond to metastasis maintenance genes. The natural genetic progression of melanoma can be modified by targeted (BRAF or MEK inhibitor) or immunotherapies. Some of the rare events in primary tumors may result in primary resistance, while further new genetic lesions develop during the acquired resistance to both targeted and immunotherapies. Only a few genetic lesions of the primary tumor are constant during natural or therapy-modulated progression. EGFR4 and NMDAR2 mutations, MITF and MET amplifications and PTEN loss can be considered as metastasis drivers. Furthermore, BRAF and MITF amplifications as well as PTEN loss are also responsible for resistance to targeted therapies, whereas NRAS mutation is the only founder genetic lesion showing any association with sensitivity to immunotherapies. Unfortunately, there are hardly any data on the

  15. The contribution of genetics and early rearing experiences to hierarchical personality dimensions in chimpanzees (Pan troglodytes).

    PubMed

    Latzman, Robert D; Freeman, Hani D; Schapiro, Steven J; Hopkins, William D

    2015-11-01

    A reliable literature finds that traits are related to each other in an organized hierarchy encompassing various conceptualizations of personality (e.g., Big Three, five-factor model). Recent work suggests the potential of a similar organization among our closest nonhuman relative, chimpanzees (Pan troglodytes), with significant links to neurobiology suggesting an evolutionarily and neurobiologically based hierarchical structure of personality. The current study investigated this hierarchical structure, the heritability of the various personality dimensions across levels of the hierarchy, and associations with early social rearing experience in a large sample (N = 238) of socially housed, captive chimpanzees residing in 2 independent colonies of apes. Results provide support for a hierarchical structure of personality in chimpanzees with significant associations with early rearing experiences. Further, heritabilities of the various dimensions varied by early rearing, with affective dimensions found to be significantly heritable among mother-reared apes, whereas personality dimensions were largely independent of relatedness among the nursery-reared apes. Taken together, these findings provide evidence for the influence of both genetic and environmental factors on personality profiles across levels of the hierarchy, supporting the importance of considering environmental variation in models of quantitative trait evolution. (c) 2015 APA, all rights reserved).

  16. The contribution of genetics and early rearing experiences to hierarchical personality dimensions in chimpanzees (Pan troglodytes)

    PubMed Central

    Latzman, Robert D.; Freeman, Hani D.; Schapiro, Steven J.; Hopkins, William D.

    2015-01-01

    A reliable literature finds that traits are related to each other in an organized hierarchy encompassing various conceptualizations of personality (e.g., Big Three, Five Factor Model). Recent work suggests the potential of a similar organization among our closest nonhuman relative, chimpanzees (Pan troglodytes), with significant links to neurobiology suggesting an evolutionarily- and neurobiologically-based hierarchical structure of personality. The current study investigated this hierarchical structure, the heritability of the various personality dimensions across levels of the hierarchy, and associations with early social rearing experience in a large sample (N = 238) of socially-housed, captive chimpanzees residing in two independent colonies of apes. Results provide support for a hierarchical structure of personality in chimpanzees with significant associations with early rearing experiences. Further, heritabilities of the various dimensions varied by early rearing, with affective dimensions found to be significantly heritable among mother-reared apes, while personality dimensions were largely independent of relatedness among the nursery-reared apes. Taken together, these findings provide evidence for the influence of both genetic and environmental factors on personality profiles across levels of the hierarchy, supporting the importance of considering environmental variation in models of quantitative trait evolution. PMID:25915132

  17. Sex differences in genetic and environmental contributions to alcohol consumption from early adolescence to young adulthood.

    PubMed

    Seglem, Karoline B; Waaktaar, Trine; Ask, Helga; Torgersen, Svenn

    2016-07-01

    To estimate genetic and environmental contributions to alcohol consumption from early adolescence to young adulthood, and test whether gender moderates these effects. Longitudinal twin cohort design. Population-based sample from Norway. A total of 2862 male and female twins, aged 14-22 years, were assessed at one (n = 881), two (n = 898) or three (n = 1083) occasions. The percentage of females was between 56 and 63 in the different age groups (in the different waves). Alcohol consumption was measured by two questionnaire items about frequency of alcohol use and frequency of being drunk. Additive genetic effects showed low to moderate contributions [proportion estimate, 95% confidence interval (CI) = range from 0.03 (0.00-0.14) to 0.49 (0.37-0.59) in males and from 0.09 (0.00-0.57) to 0.41 (0.24-0.58) in females] from adolescence to young adulthood, while environmental influences shared by twin pairs and contributing to twin similarity were moderate to highly influential during this developmental period [proportion estimate, 95% CI = range from 0.04 (0.00-0.13) to 0.45 (0.26-0.60) in males for shared environment in common with females, from 0.25 (0.09-0.42) to 0.54 (0.06-0.78) for shared environment specific to males and from 0.36 (0.20-0.52) to 0.51 (0.37-0.71) in females]. There was evidence of qualitative sex differences with shared environmental influences being largely sex-specific from middle adolescence onwards. Alcohol consumption from early adolescence to young adulthood appears to be influenced to a small to moderate degree by genetic factors and to a moderate to high degree by shared environmental factors (e.g. rearing influences, shared friends). The shared environmental factors influencing alcohol consumption appear to be largely gender-specific. © 2016 Society for the Study of Addiction.

  18. Early Verb Learning: How Do Children Learn How to Compare Events?

    PubMed Central

    Childers, Jane B.; Parrish, Rebecca; Olson, Christina V.; Burch, Clare; Fung, Gavin; McIntyre, Kevin

    2015-01-01

    An important problem verb learners must solve is how to extend verbs. Children could use cross-situational information to guide their extensions, however comparing events is difficult. Two studies test whether children benefit from initially seeing a pair of similar events (‘progressive alignment’) while learning new verbs, and whether this influence changes with age. In Study 1, 2 ½- and 3 ½-year-old children participated in an interactive task. Children who saw a pair of similar events and then varied events were able to extend verbs at test, differing from a control group; children who saw two pairs of varied events did not differ from the control group. In Study 2, events were presented on a monitor. Following the initial pair of events that varied by condition, a Tobii x120 eye tracker recorded 2 ½-, 3 ½- and 4 ½-year-olds’ fixations to specific elements of events (AOIs) during the second pair of events, which were the same across conditions. After seeing the pair of events that were highly similar, 2 ½-year-olds showed significantly longer fixation durations to agents and to affected objects as compared to the all varied condition. At test, 3 ½-year-olds were able to extend the verb, but only in the progressive alignment condition. These results are important because they show children’s visual attention to relevant elements in dynamic events is influenced by their prior comparison experience, and they show that young children benefit from seeing similar events as they learn to compare events to each other. PMID:27092030

  19. Genetics Home Reference: early-onset primary dystonia

    MedlinePlus

    ... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

  20. Reflections on some early events related to behavior analysis of child development

    PubMed Central

    Bijou, Sidney W.

    1996-01-01

    A series of events related to the early application of behavioral principles to child behavior and development is described. The events began in the 1930s at Columbia University with a solicited letter from John B. Watson suggesting a master's degree thesis problem, and continued through the 1950s and 1960s at the University of Washington. Specifically, these happenings resulted in (a) research demonstrating that Skinner's laboratory method for studying nonhuman organisms could be profitably applied to the laboratory study of young normal children; (b) a demonstration that by successive approximations, a normal child can be operantly conditioned to respond to an arbitrary situation; (c) research showing that the effects of simple schedules of reinforcement obtained with nonhuman organisms could be duplicated in young normal and retarded children; (d) the demonstration that Skinner's operant laboratory method could be adapted to study young children in field situations; (e) research showing that operant principles can be successfully applied to the treatment of a young autistic boy with a serious visual handicap; (f) laboratory studies showing that mothers can be trained to treat their own young children who have behavior problems; (g) an in-home study demonstrating that a mother can treat her own child who has behavior problems; (h) a demonstration that operant principles can be applied effectively to teaching reading, writing, and arithmetic to children with retardation; and (i) publication of a book, Child Development: A Systematic and Empirical Theory, in collaboration with Donald M. Baer, by Prentice Hall in their Century Psychological Series. PMID:22478239

  1. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

  2. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    PubMed Central

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  3. Influences of non-genetic factors on early growth of Adilo lambs under smallholder management systems, southern Ethiopia.

    PubMed

    Gemiyo, Deribe; Abebe, Girma; Tegegne, Azage

    2014-02-01

    Stagnant early growth and mortality are the major impediments for sheep production in southern Ethiopia. We evaluated the effects of non-genetic factors on early growth performance of lambs in Halaba district with 467 lambs owned by 60 households. Body weights (kilograms) of lambs at birth, 30, 60, 90, 120, and 150 days were 2.30 ± 0.03, 4.45 ± 0.11, 6.94 ± 0.13, 10.4 ± 0.19, 13.3 ± 0.19, and 15.7 ± 0.20, respectively. The average daily gain (ADG; gram) from birth to 30, 60, 90, 120, and 150 days were 71.18 ± 8.18, 77.18 ± 2.19, 89.20 ± 1.98, 91.18 ± 1.51, and 90.68 ± 1.27, respectively. Season effect was significant (p < 0.05) for weight at birth, 30, and 120 days. Similarly, season of birth influenced (p < 0.05) ADG (gram) at all ages except from birth to 60 days. Single-born lambs were heavier over multiple births (p < 0.01), 90 (p < 0.001) and 120 days (p < 0.05) and higher (p < 0.001) ADG from birth to 90 days. There were significant interaction effects of parity by sex at birth (p < 0.01) and parity by type of birth (p < 0.001) and 90 days (p < 0.01). From the non-genetic factors estimated in this study, season and type of birth, and their interaction had a more profound effect at early growth of lambs, and they need to be considered in the improvement plan of sheep under Halaba arid to semi-arid environments. Efforts geared towards planned breeding, improved nutrition, and health would assist farmers to exploit these indigenous and adaptable sheep resources efficiently.

  4. Transcriptomic dose-and-time-course indicators of early key events in a cytotoxicity-mediated mode of action for rodent urinary bladder tumorigenesis

    EPA Science Inventory

    TRANSCRIPTOMIC DOSE- AND TIME-COURSE INDICATORS OF EARLY KEY EVENTS IN A CYTOTOXICITY-MEDIATED MODE OF ACTION FOR RODENT URINARY BLADDER TUMORIGENESISDiuron is a substituted urea compound used globally as an herbicide. Urinary bladder tumors were induced in rats after chronic die...

  5. A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

    PubMed

    Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

    2011-10-01

    In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

  6. Excess of mutational jackpot events in expanding populations revealed by spatial Luria–Delbrück experiments

    PubMed Central

    Fusco, Diana; Gralka, Matti; Kayser, Jona; Anderson, Alex; Hallatschek, Oskar

    2016-01-01

    The genetic diversity of growing cellular populations, such as biofilms, solid tumours or developing embryos, is thought to be dominated by rare, exceptionally large mutant clones. Yet, the emergence of these mutational jackpot events is only understood in well-mixed populations, where they stem from mutations that arise during the first few cell divisions. To study jackpot events in spatially structured populations, we track mutant clones in microbial populations using fluorescence microscopy and population sequencing. High-frequency mutations are found to be massively enriched in microbial colonies compared with well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. Thus, jackpot events can be generated not only when mutations arise early but also when they occur at favourable locations, which exacerbates their role in adaptation and disease. In particular, because spatial competition with the wild type keeps most mutant clones in a quiescent state, strong selection pressures that kill the wild type promote drug resistance. PMID:27694797

  7. Excess of mutational jackpot events in expanding populations revealed by spatial Luria-Delbrück experiments.

    PubMed

    Fusco, Diana; Gralka, Matti; Kayser, Jona; Anderson, Alex; Hallatschek, Oskar

    2016-10-03

    The genetic diversity of growing cellular populations, such as biofilms, solid tumours or developing embryos, is thought to be dominated by rare, exceptionally large mutant clones. Yet, the emergence of these mutational jackpot events is only understood in well-mixed populations, where they stem from mutations that arise during the first few cell divisions. To study jackpot events in spatially structured populations, we track mutant clones in microbial populations using fluorescence microscopy and population sequencing. High-frequency mutations are found to be massively enriched in microbial colonies compared with well-shaken liquid cultures, as a result of late-occurring mutations surfing at the edge of range expansions. Thus, jackpot events can be generated not only when mutations arise early but also when they occur at favourable locations, which exacerbates their role in adaptation and disease. In particular, because spatial competition with the wild type keeps most mutant clones in a quiescent state, strong selection pressures that kill the wild type promote drug resistance.

  8. Framework for Interpretation of Trypsin–antitrypsin Imbalance and Genetic Heterogeneity in Pancreatitis

    PubMed Central

    Lin, Kun; Gao, Feng; Chen, Qingquan; Liu, Qicai; Chen, Shu

    2015-01-01

    Early intracellular premature trypsinogen activation was interpreted as the key initiator of pancreatitis. When the balance in the homeostasis of trypsin and antitrypsin system is disequilibrated, elevated aggressive enzymes directly attack the pancreatic tissue, which leads to pancreatic destruction and inflammation. However, trypsin alone is not enough to cause complications in pancreatitis, which may play a crucial role in modulating signaling events in the initial phase of the disease. NFκB activation is the major inflammatory pathway involved in the occurrence and development of pancreatitis and it can be induced by intrapancreatic activation of trypsinogen. Synthesis of trypsinogen occurs in endoplasmic reticulum (ER), and ER stress is an important early acinar cell event. Components of ER stress response are known to be able to trigger cell death as well as NFκB signaling cascade. The strongest evidence supporting the trypsin-centered theory is that gene mutations, which lead to the generation of more trypsin, or reduce the activity of trypsin inhibitors or trypsin degradation, are associated with pancreatitis. Thus, trypsin–antitrypsin imbalance may be the first step leading to pancreatic autodigestion and inducing other pathways. Continued experimental studies are necessary to determine the specific relationships between trypsin–antitrypsin imbalance and genetic heterogeneity in pancreatitis. In this article, we review the latest advances that contributed to the understanding of the basic mechanisms behind the occurrence and development of pancreatitis with a focus on the interpretation of trypsin–antitrypsin imbalance and their relationships with other inflammation pathways. We additionally highlight genetic predispositions to pancreatitis and possible mechanisms associated with them. PMID:26228362

  9. Multiple-Threshold Event Detection and Other Enhancements to the Virtual Seismologist (VS) Earthquake Early Warning Algorithm

    NASA Astrophysics Data System (ADS)

    Fischer, M.; Caprio, M.; Cua, G. B.; Heaton, T. H.; Clinton, J. F.; Wiemer, S.

    2009-12-01

    The Virtual Seismologist (VS) algorithm is a Bayesian approach to earthquake early warning (EEW) being implemented by the Swiss Seismological Service at ETH Zurich. The application of Bayes’ theorem in earthquake early warning states that the most probable source estimate at any given time is a combination of contributions from a likelihood function that evolves in response to incoming data from the on-going earthquake, and selected prior information, which can include factors such as network topology, the Gutenberg-Richter relationship or previously observed seismicity. The VS algorithm was one of three EEW algorithms involved in the California Integrated Seismic Network (CISN) real-time EEW testing and performance evaluation effort. Its compelling real-time performance in California over the last three years has led to its inclusion in the new USGS-funded effort to develop key components of CISN ShakeAlert, a prototype EEW system that could potentially be implemented in California. A significant portion of VS code development was supported by the SAFER EEW project in Europe. We discuss recent enhancements to the VS EEW algorithm. We developed and continue to test a multiple-threshold event detection scheme, which uses different association / location approaches depending on the peak amplitudes associated with an incoming P pick. With this scheme, an event with sufficiently high initial amplitudes can be declared on the basis of a single station, maximizing warning times for damaging events for which EEW is most relevant. Smaller, non-damaging events, which will have lower initial amplitudes, will require more picks to be declared an event to reduce false alarms. This transforms the VS codes from a regional EEW approach reliant on traditional location estimation (and it requirement of at least 4 picks as implemented by the Binder Earthworm phase associator) to a hybrid on-site/regional approach capable of providing a continuously evolving stream of EEW

  10. Genetic Dosage Compensation in a Family with Velo-cardio-facial/DiGeorge/22q11.2 Deletion Syndrome

    PubMed Central

    Alkalay, Avishai A.; Guo, Tingwei; Montagna, Cristina; Digilio, M. Cristina; Marino, Bruno; Dallapiccola, Bruno; Morrow, Bernice

    2014-01-01

    Cytogenetic studies of a male child carrying the 22q11.2 deletion common in patients with velo-cardio-facial/DiGeorge syndrome revealed an unexpected rearrangement of the 22q11.2 region in his normal appearing mother. The mother carries a 3 Mb deletion on one copy and a reciprocal, similar sized duplication on the other copy of chromosome 22q11.2 as revealed by fluorescence in situ hybridization and array comparative genome hybridization analysis. The most parsimonious mechanism for the rearrangement is a mitotic non-allelic homologous recombination event in a cell in the early embryo soon after fertilization. The normal phenotype of the mother can be explained by the theory of genetic dosage compensation. This is the second documented case of such an event for this or any genomic disorder. This finding helps to reinforce this phenomenon in a human model, and has significant implications for genetic counseling of future children. PMID:21337693

  11. Genetic diversity and population structure of native maize populations in Latin America and the Caribbean.

    PubMed

    Bedoya, Claudia A; Dreisigacker, Susanne; Hearne, Sarah; Franco, Jorge; Mir, Celine; Prasanna, Boddupalli M; Taba, Suketoshi; Charcosset, Alain; Warburton, Marilyn L

    2017-01-01

    This study describes the genetic diversity and population structure of 194 native maize populations from 23 countries of Latin America and the Caribbean. The germplasm, representing 131 distinct landraces, was genetically characterized as population bulks using 28 SSR markers. Three main groups of maize germplasm were identified. The first, the Mexico and Southern Andes group, highlights the Pre-Columbian and modern exchange of germplasm between North and South America. The second group, Mesoamerica lowland, supports the hypothesis that two separate human migration events could have contributed to Caribbean maize germplasm. The third, the Andean group, displayed early introduction of maize into the Andes, with little mixing since then, other than a regional interchange zone active in the past. Events and activities in the pre- and post-Columbian Americas including the development and expansion of pre-Columbian cultures and the arrival of Europeans to the Americas are discussed in relation to the history of maize migration from its point of domestication in Mesoamerica to South America and the Caribbean through sea and land routes.

  12. Genetic diversity and population structure of native maize populations in Latin America and the Caribbean

    PubMed Central

    Bedoya, Claudia A.; Dreisigacker, Susanne; Hearne, Sarah; Franco, Jorge; Mir, Celine; Prasanna, Boddupalli M.; Taba, Suketoshi; Charcosset, Alain; Warburton, Marilyn L.

    2017-01-01

    This study describes the genetic diversity and population structure of 194 native maize populations from 23 countries of Latin America and the Caribbean. The germplasm, representing 131 distinct landraces, was genetically characterized as population bulks using 28 SSR markers. Three main groups of maize germplasm were identified. The first, the Mexico and Southern Andes group, highlights the Pre-Columbian and modern exchange of germplasm between North and South America. The second group, Mesoamerica lowland, supports the hypothesis that two separate human migration events could have contributed to Caribbean maize germplasm. The third, the Andean group, displayed early introduction of maize into the Andes, with little mixing since then, other than a regional interchange zone active in the past. Events and activities in the pre- and post-Columbian Americas including the development and expansion of pre-Columbian cultures and the arrival of Europeans to the Americas are discussed in relation to the history of maize migration from its point of domestication in Mesoamerica to South America and the Caribbean through sea and land routes. PMID:28403177

  13. Is retinoic acid genetic machinery a chordate innovation?

    PubMed

    Cañestro, Cristian; Postlethwait, John H; Gonzàlez-Duarte, Roser; Albalat, Ricard

    2006-01-01

    Development of many chordate features depends on retinoic acid (RA). Because the action of RA during development seems to be restricted to chordates, it had been previously proposed that the "invention" of RA genetic machinery, including RA-binding nuclear hormone receptors (Rars), and the RA-synthesizing and RA-degrading enzymes Aldh1a (Raldh) and Cyp26, respectively, was an important step for the origin of developmental mechanisms leading to the chordate body plan. We tested this hypothesis by conducting an exhaustive survey of the RA machinery in genomic databases for twelve deuterostomes. We reconstructed the evolution of these genes in deuterostomes and showed for the first time that RA genetic machinery--that is Aldh1a, Cyp26, and Rar orthologs--is present in nonchordate deuterostomes. This finding implies that RA genetic machinery was already present during early deuterostome evolution, and therefore, is not a chordate innovation. This new evolutionary viewpoint argues against the hypothesis that the acquisition of gene families underlying RA metabolism and signaling was a key event for the origin of chordates. We propose a new hypothesis in which lineage-specific duplication and loss of RA machinery genes could be related to the morphological radiation of deuterostomes.

  14. Genetic Markers of Cardiovascular Disease in Rheumatoid Arthritis

    PubMed Central

    Rodríguez-Rodríguez, Luis; López-Mejías, Raquel; García-Bermúdez, Mercedes; González-Juanatey, Carlos; González-Gay, Miguel A.; Martín, Javier

    2012-01-01

    Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1∗04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA. PMID:22927710

  15. Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression.

    PubMed

    Vrshek-Schallhorn, Suzanne; Stroud, Catherine B; Mineka, Susan; Zinbarg, Richard E; Adam, Emma K; Redei, Eva E; Hammen, Constance; Craske, Michelle G

    2015-11-01

    Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (G×E). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a G×E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2). Analyses focused on 2 forms of interpersonal stress as environmental risk factors. Using 5 years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (hazard ratio [HR] = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The G×E effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the G×E effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research. (c) 2015 APA, all rights reserved).

  16. Additive Genetic Risk from Five Serotonin System Polymorphisms Interacts with Interpersonal Stress to Predict Depression

    PubMed Central

    Vrshek-Schallhorn, Suzanne; Stroud, Catherine B.; Mineka, Susan; Zinbarg, Richard E.; Adam, Emma K.; Redei, Eva E.; Hammen, Constance; Craske, Michelle G.

    2016-01-01

    Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (GxE). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a GxE predicting depression, we created an additive multilocus profile score from five serotonin system polymorphisms (one each in the genes HTR1A, HTR2A, HTR2C, and two in TPH2). Analyses focused on two forms of interpersonal stress as environmental risk factors. Using five years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (HR = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The GxE effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the GxE effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research. PMID:26595467

  17. Commerce and genetic diagnostics.

    PubMed

    Silverman, Paul H

    1995-01-01

    The revolution in molecular biology and molecular genetics has begun to reveal the sequence of events that links genes and disease. As a result of activities such as the Human Genome Project, a parallel revolution in technology is bringing nearer to hand the possibility of readily available genetic diagnostics. Genetic testing services have begun to move out of the academic medical centers and into the private enterprise arena. Under these circumstances it is important to understand the factors affecting the availability and application of this powerful predictive tool in a for-profit mode. How does the marketplace encourage or discourage genetic testing? Will the same market influences that generate pharmaceutical sales be operating to "sell" genetic tests?

  18. Genetic diversity of the NE Atlantic sea urchin Strongylocentrotus droebachiensis unveils chaotic genetic patchiness possibly linked to local selective pressure.

    PubMed

    Norderhaug, K M; Anglès d'Auriac, M B; Fagerli, C W; Gundersen, H; Christie, H; Dahl, K; Hobæk, A

    We compared the genetic differentiation in the green sea urchin Strongylocentrotus droebachiensis from discrete populations on the NE Atlantic coast. By using eight recently developed microsatellite markers, genetic structure was compared between populations from the Danish Strait in the south to the Barents Sea in the north (56-79°N). Urchins are spread by pelagic larvae and may be transported long distances by northwards-going ocean currents. Two main superimposed patterns were identified. The first showed a subtle but significant genetic differentiation from the southernmost to the northernmost of the studied populations and could be explained by an isolation by distance model. The second pattern included two coastal populations in mid-Norway (65°N), NH and NS, as well as the northernmost population of continental Norway (71°N) FV. They showed a high degree of differentiation from all other populations. The explanation to the second pattern is most likely chaotic genetic patchiness caused by introgression from another species, S. pallidus, into S. droebachiensis resulting from selective pressure. Ongoing sea urchin collapse and kelp forests recovery are observed in the area of NH, NS and FV populations. High gene flow between populations spanning more than 22° in latitude suggests a high risk of new grazing events to occur rapidly in the future if conditions for sea urchins are favourable. On the other hand, the possibility of hybridization in association with collapsing populations may be used as an early warning indicator for monitoring purposes.

  19. Early Diagnosis of Fibrodysplasia Ossificans Progressiva

    PubMed Central

    Kaplan, Frederick S.; Xu, Meiqi; Glaser, David L.; Collins, Felicity; Connor, Michael; Kitterman, Joseph; Sillence, David; Zackai, Elaine; Ravitsky, Vardit; Zasloff, Michael; Ganguly, Arupa; Shore, Eileen M.

    2012-01-01

    BACKGROUND Fibrodysplasia ossificans progressiva is a rare and disabling genetic condition characterized by congenital malformation of the great toes and by progressive heterotopic ossification in specific anatomic patterns. Most patients with fibrodys-plasia ossificans progressiva are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures that can cause lifelong disability. Recently, the genetic cause of fibrodysplasia ossificans progressiva was identified, and definitive genetic testing for fibrodysplasia ossificans progressiva is now available before the appearance of heterotopic ossification. METHODS We recently evaluated 7 children for diagnosis of fibrodysplasia ossificans progressiva before the onset of heterotopic ossification. A medical history, physical examination, and skeletal survey were obtained on all of the patients, as well as clinical genetic testing for the canonical fibrodysplasia ossificans progressiva mutation. RESULTS All 7 of the children (4 girls and 3 boys; ages 3 months to 6 years) had congenital malformations of the great toes, but none had radiographic evidence of heterotopic ossification at the time of evaluation. Five of the 7 children had soft tissue lesions of the neck and back, suggestive of early fibrodysplasia ossificans progressiva flare-ups, 3 of whom had undergone invasive diagnostic procedures that exacerbated their condition. Two children had no history or signs of soft tissue swelling or flare-ups. DNA sequence analysis found that all 7 of the children had the recurrent fibrodysplasia ossificans progressiva missense mutation, a single nucleotide substitution (c.617G>A) at codon 206 in the glycine-serine activation domain of activin receptor IA, a bone morphogenetic protein type 1 receptor. CONCLUSION Clinical suspicion of fibrodysplasia ossificans progressiva early in life on the basis of malformed great toes can lead to early clinical diagnosis, confirmatory

  20. Acute myeloid leukaemia at an early age: Reviewing the interaction between pesticide exposure and KMT2A-rearrangement

    PubMed Central

    Pombo-de-Oliveira, Maria S; Andrade, Francianne Gomes; Brisson, Gisele Dallapicola; dos Santos Bueno, Filipe Vicente; Cezar, Ingrid Sardou; Noronha, Elda Pereira

    2017-01-01

    Acute myeloid leukaemia (AML) in early childhood is characterised by a high frequency of recurrent genomic aberrations associated with distinct myeloid subtypes, clinical outcomes and pathogenesis. Genomic instability is the first step of pathogenic mechanism in early childhood AML. A sum of adverse events is necessary to the development of infant AML (i-AML), which includes latency of biochemical-molecular and cellular effects. Inherited genetic susceptibility associated with exposures to biotransformation substances can modulate the risk of DNA damage and it is a very important piece in the pathogenic puzzle. In this review, we have aimed to explore the chain of events in the time-points of the natural history of i-AML, which includes maternal exposures during pregnancy, the speculations about the formation of somatic mutations during foetal life and the secondary genomic aberrations associated with i-AML. The modulation of risk conferred by xenobiotic metabolism´s genes variants is the bottom line of the pathogenic process. Since we have conducted observational and molecular investigations in early childhood leukaemia, the data focused here is based on Brazilian findings with summarised results of our experience with epidemiological and molecular studies in early-age leukaemia. PMID:29225689

  1. Transgenerational latent early-life associated regulation unites environment and genetics across generations

    PubMed Central

    Lahiri, Debomoy K; Maloney, Bryan; Bayon, Baindu L; Chopra, Nipun; White, Fletcher A; Greig, Nigel H; Nurnberger, John I

    2016-01-01

    The origin of idiopathic diseases is still poorly understood. The latent early-life associated regulation (LEARn) model unites environmental exposures and gene expression while providing a mechanistic underpinning for later-occurring disorders. We propose that this process can occur across generations via transgenerational LEARn (tLEARn). In tLEARn, each person is a ‘unit’ accumulating preclinical or subclinical ‘hits’ as in the original LEARn model. These changes can then be epigenomically passed along to offspring. Transgenerational accumulation of ‘hits’ determines a sporadic disease state. Few significant transgenerational hits would accompany conception or gestation of most people, but these may suffice to ‘prime’ someone to respond to later-life hits. Hits need not produce symptoms or microphenotypes to have a transgenerational effect. Testing tLEARn requires longitudinal approaches. A recently proposed longitudinal epigenome/envirome-wide association study would unite genetic sequence, epigenomic markers, environmental exposures, patient personal history taken at multiple time points and family history. PMID:26950428

  2. A novel quadruplex real-time PCR method for simultaneous detection of Cry2Ae and two genetically modified cotton events (GHB119 and T304-40)

    PubMed Central

    2014-01-01

    Background To date, over 150 genetically modified (GM) crops are widely cultivated. To comply with regulations developed for genetically modified organisms (GMOs), including labeling policies, many detection methods for GMO identification and quantification have been developed. Results To detect the entrance and exit of unauthorized GM crop events in China, we developed a novel quadruplex real-time PCR method for simultaneous detection and quantification of GM cotton events GHB119 and T304-40 in cotton-derived products (based on the 5′-flanking sequence) and the insect-resistance gene Cry2Ae. The limit of detection was 10 copies for GHB119 and Cry2Ae and 25 copies for T304-40. The limit of quantification was 25 copies for GHB119 and Cry2Ae and 50 copies for T304-40. Moreover, low bias and acceptable standard deviation and relative standard deviation values were obtained in quantification analysis of six blind samples containing different GHB119 and T304-40 ingredients. Conclusions The developed quadruplex quantitative method could be used for quantitative detection of two GM cotton events (GHB119 and T304-40) and Cry2Ae gene ingredient in cotton derived products. PMID:24884946

  3. Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

    PubMed

    Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

    2011-01-01

    Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

  4. Cytokine Signatures Associated With Early Onset, Active Lesions and Late Cicatricial Events of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.

    PubMed

    Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Béla, Samantha Ribeiro; Costa, Julia Gatti Ladeia; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Coelho-Dos-Reis, Jordana Grazziela; Ferro, Eloisa Amália Vieira; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Martins-Filho, Olindo Assis

    2016-06-15

    Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. Genetics of Severe Early Onset Epilepsies

    ClinicalTrials.gov

    2017-08-24

    Epilepsy; Epileptic Encephalopathy; Ohtahara Syndrome; Infantile Spasms; Dravet Syndrome; Malignant Migrating Partial Epilepsy of Infancy; Early Myoclonic Epileptic Encephalopathy; PCDH19-related Epilepsy and Related Conditions

  6. [The origins of dogs: archaeozoology, genetics, and ancient DNA].

    PubMed

    Verginelli, Fabio; Capelli, Cristian; Coia, Valentina; Musiani, Marco; Falchetti, Mario; Ottini, Laura; Palmirotta, Raffaele; Tagliacozzo, Antonio; Mazzorin, Iacopo de Grossi; Mariani-Costantini, Renato

    2006-01-01

    The domestication of the dog from the wolf was a key step in the pathway that led to the Neolithic revolution. The earliest fossil dogs, dated to the end of the last glacial period (17,000 to 12,000 years ago), have been found in Russia, Germany and the Middle East. No dogs are represented in the naturalistic art of the European Upper Palaeolithic, suggesting that dogs were introduced at a later date. Genetic studies of extant dog and wolf mitochondrial DNA sequences were interpreted in favour of multiple dog founding events as early as 135-76,000 years ago, or of a single origin in East Asia, 40,000 or 15,000 years ago. Our study included mitochondrial DNA sequences from Italian fossil bones attributed to three Late Pleistocene-Early Holocene wolves (dated from a15,000 to a10,000 14C years ago) and two dogs, dated to a4000 and a3000 14C years ago respectively. Taking paleogeography into account, our phylogenetic data point to a contribution of European wolves to the three major dog clades, in agreement with archaeozoological data. Our phylogeographic studies also suggest genetic differentiation of dogs and wolves related to isolation by geographic distance, supporting multicentric origins of dogs from wolves throughout their vast range of sympatry.

  7. The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA

    PubMed Central

    Yarwood, Annie; Huizinga, Tom W. J.

    2016-01-01

    There is now a general consensus that RA has a spectrum of disease stages that can begin many years before the onset of clinical symptoms. It is widely thought that understanding the complex interplay between genetics and environment, and their role in pathogenesis, is essential in gaining further insight into the mechanisms that drive disease development and progression. More than 100 genetic susceptibility loci have now been identified for RA through studies that have focused on patients with established RA compared with healthy controls. Studying the early preclinical phases of disease will provide valuable insights into the biological events that precede disease and could potentially identify biomarkers to predict disease onset and future therapeutic targets. In this review we will cover recent advances in the knowledge of genetic and environmental risk factors and speculate on how these factors may influence the transition from one stage of disease to another. PMID:25239882

  8. Escherichia Coli--Key to Modern Genetics.

    ERIC Educational Resources Information Center

    Bregegere, Francois

    1982-01-01

    Mid-nineteenth century work by Mendel on plant hybrids and by Pasteur on fermentation gave birth by way of bacterial genetics to modern-day molecular biology. The bacterium Escherichia Coli has occupied a key position in genetic studies leading from early gene identification with DNA to current genetic engineering using recombinant DNA technology.…

  9. Technical Performance Scores are strongly associated with early mortality, postoperative adverse events, and intensive care unit length of stay-analysis of consecutive discharges for 2 years.

    PubMed

    Nathan, Meena; Karamichalis, John; Liu, Hua; Gauvreau, Kimberley; Colan, Steven; Saia, Matthew; Pigula, Frank; Fynn-Thompson, Francis; Emani, Sitaram; Baird, Christopher; Mayer, John E; del Nido, Pedro J

    2014-01-01

    Previous work in our institution has indicated that the Technical Performance Score (TPS) is highly associated with early outcomes in select subsets of procedures and age groups. We hypothesized that the TPS could predict early outcomes in a wide range of diagnoses and age groups. Consecutive patients discharged from January 2011 to March 2013 were prospectively evaluated. The TPS was assigned according to the discharge echocardiographic findings and the need for reinterventions in the anatomic area of interest. Case complexity was determined using Risk Adjustment for Congenital Heart Surgery (RACHS-1) categories. Early mortality and postoperative adverse events were recorded. Relationships between the TPS and outcomes were assessed after adjusting for the baseline patient characteristics. The median age of the 1926 patients was 1.8 years (range, 0 days to 68 years). Bypass was used in 1740 (90%); 322 (17%) were neonates, 520 (27%) infants, 873 (45%) children, 211 (11%) adults. TPS was class 1 (optimal) in 956 (50%), class 2 (adequate) in 584 (30%), and class 3 (inadequate) in 226 (12%); 160 patients (8%) could not be scored. A total of 51 early deaths (2.6%) and 111 adverse events (5.7%) occurred. On univariate analysis, age, RACHS-1 category, and TPS were significantly associated with mortality and the occurrence of adverse events. On multivariate modeling, class 3 (inadequate) TPS was strongly associated with mortality (odds ratio, 16.9; 95% confidence interval, 6.7-42.9; P < .001), adverse events (odds ratio, 6.9; 95% confidence interval, 4.1-11.6; P < .001), and postoperative intensive care unit length of stay (coefficient, 2.3; 95% confidence interval, 2.0-2.6; P < .001) after adjusting for other covariates. The TPS is strongly associated with early outcomes across a wide range of ages and disease complexity and can serve as important tool for self-assessment and quality improvement. Copyright © 2014 The American Association for Thoracic Surgery

  10. Pediatric genetic macular and choroidal diseases

    PubMed Central

    Bergman, Mica Y.; Nallasamy, Sudha

    2014-01-01

    Genetic diseases of the macula and choroid have various inheritance patterns and varying degrees of impact on vision. Herein, we review the literature including most recent advances in the understanding of the genetics of these diseases. Although many of these disorders have limited treatment options, knowledge of inheritance patterns can aid in early detection and with close monitoring can help the ophthalmologist preserve as much vision as possible (for example with early treatment of choroidal neovascularization). PMID:27625881

  11. Genetic Testing: How Genetics and Genomics Can Affect Healthcare Disparities
.

    PubMed

    Allen, Deborah

    2018-02-01

    Advances in oncology care have transformed treatment approaches as genetics and genomics analyses promote implementation of personalized medicine. Genetics and genomics research in TP53 have demonstrated that some mutations are prevalent in minority populations. This has implications on personalized treatment approaches, particularly in early disease stages. The purpose of this article is to describe oncology nurses' role in applying these findings in practice to reduce disparities observed in cancer and survivorship care.
.

  12. High resolution chronology of late Cretaceous-early Tertiary events determined from 21,000 yr orbital-climatic cycles in marine sediments

    NASA Technical Reports Server (NTRS)

    Herbert, Timothy D.; Dhondt, Steven

    1988-01-01

    A number of South Atlantic sites cored by the Deep Sea Drilling Project (DSDP) recovered late Cretaceous and early Tertiary sediments with alternating light-dark, high-low carbonate content. The sedimentary oscillations were turned into time series by digitizing color photographs of core segments at a resolution of about 5 points/cm. Spectral analysis of these records indicates prominent periodicity at 25 to 35 cm in the Cretaceous intervals, and about 15 cm in the early Tertiary sediments. The absolute period of the cycles that is determined from paleomagnetic calibration at two sites is 20,000 to 25,000 yr, and almost certainly corresponds to the period of the earth's precessional cycle. These sequences therefore contain an internal chronometer to measure events across the K/T extinction boundary at this scale of resolution. The orbital metronome was used to address several related questions: the position of the K/T boundary within magnetic chron 29R, the fluxes of biogenic and detrital material to the deep sea immediately before and after the K/T event, the duration of the Sr anomaly, and the level of background climatic variability in the latest Cretaceous time. The carbonate/color cycles that were analyzed contain primary records of ocean carbonate productivity and chemistry, as evidenced by bioturbational mixing of adjacent beds and the weak lithification of the rhythmic sequences. It was concluded that sedimentary sequences that contain orbital cyclicity are capable of providing resolution of dramatic events in earth history with much greater precision than obtainable through radiometric methods. The data show no evidence for a gradual climatic deterioration prior to the K/T extinction event, and argue for a geologically rapid revolution at this horizon.

  13. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

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

    Xia, Jing; Rocke, David M.; Perry, George

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  14. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

    DOE PAGES

    Xia, Jing; Rocke, David M.; Perry, George; ...

    2014-01-01

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  15. Comparative phylogeny and historical perspectives on population genetics of the Pacific hawksbill (Eretmochelys imbricata) and green turtles (Chelonia mydas), inferred from feeding populations in the Yaeyama Islands, Japan.

    PubMed

    Nishizawa, Hideaki; Okuyama, Junichi; Kobayashi, Masato; Abe, Osamu; Arai, Nobuaki

    2010-01-01

    Mitochondrial DNA sequence polymorphisms and patterns of genetic diversity represent the genealogy and relative impacts of historical, geographic, and demographic events on populations. In this study, historical patterns of population dynamics and differentiation in hawksbill (Eretmochelys imbricata) and green turtles (Chelonia mydas) in the Pacific were estimated from feeding populations in the Yaeyama Islands, Japan. Phylogenetic relationships of the haplotypes indicated that hawksbill and green turtles in the Pacific probably underwent very similar patterns and processes of population dynamics over the last million years, with population subdivision during the early Pleistocene and population expansion after the last glacial maximum. These significant contemporary historical events were suggested to have been caused by climatic and sea-level fluctuations. On the other hand, comparing our results to long-term population dynamics in the Atlantic, population subdivisions during the early Pleistocene were specific to Pacific hawksbill and green turtles. Therefore, regional differences in historical population dynamics are suggested. Despite limited sampling locations, these results are the first step in estimating the historical trends in Pacific sea turtles by using phylogenetics and population genetics.

  16. Sprites and Early ionospheric VLF perturbations

    NASA Astrophysics Data System (ADS)

    Haldoupis, Christos; Amvrosiadi, Nino; Cotts, Ben; van der Velde, Oscar; Chanrion, Olivier; Neubert, Torsten

    2010-05-01

    Past studies have shown a correlation between sprites and early VLF perturbations, but the reported correlation varies widely from ~ 50% to 100%. The present study resolves these large discrepancies by analyzing several case studies of sprite and narrowband VLF observations, in which multiple transmitter-receiver VLF links with great circle paths (GCPs) passing near a sprite-producing thunderstorm were available. In this setup, the multiple links act in a complementary way that makes the detection of early VLF perturbations much more probable compared to a single VLF link that can miss several of them, a fact that was overlooked in past studies. The evidence shows that sprites are accompanied by early VLF perturbations in a one-to-one correspondence. This implies that the sprite generation mechanism may cause also sub-ionospheric conductivity disturbances that produce early VLF events. However, the one-to-one "sprite to early" event relationship, if viewed conversely as "early to sprite", appears not to be always reciprocal. This is because the number of early events detected in some cases was considerably larger than the number of sprites. Since the great majority of the early events not accompanied by sprites was caused by positive cloud to ground (+CG) lightning discharges, it is possible that sprites or sprite halos were concurrently present in these events as well but were missed by the sprite-watch detection system. In order for this option to be resolved we need more studies using highly sensitive optical systems capable of detecting weaker sprites, sprite halos and elves.

  17. Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice

    PubMed Central

    Hogan, Chad H.; Oldenburg, Darby G.; Kara, Mehmet

    2018-01-01

    Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host. PMID:29390024

  18. Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice.

    PubMed

    Van Skike, Nick D; Minkah, Nana K; Hogan, Chad H; Wu, Gary; Benziger, Peter T; Oldenburg, Darby G; Kara, Mehmet; Kim-Holzapfel, Deborah M; White, Douglas W; Tibbetts, Scott A; French, Jarrod B; Krug, Laurie T

    2018-02-01

    Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host.

  19. A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

    PubMed

    Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Myers, Julia E; Keiffer, Timothy R; DiGiuseppe, Stephen; Polk, Paula; Bodily, Jason M; Scott, Rona S; Sapp, Martin

    2018-03-01

    Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16). This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

  20. Genetic and Epigenetic Events Generate Multiple Pathways in Colorectal Cancer Progression

    PubMed Central

    Pancione, Massimo; Remo, Andrea; Colantuoni, Vittorio

    2012-01-01

    Colorectal cancer (CRC) is one of the most common causes of death, despite decades of research. Initially considered as a disease due to genetic mutations, it is now viewed as a complex malignancy because of the involvement of epigenetic abnormalities. A functional equivalence between genetic and epigenetic mechanisms has been suggested in CRC initiation and progression. A hallmark of CRC is its pathogenetic heterogeneity attained through at least three distinct pathways: a traditional (adenoma-carcinoma sequence), an alternative, and more recently the so-called serrated pathway. While the alternative pathway is more heterogeneous and less characterized, the traditional and serrated pathways appear to be more homogeneous and clearly distinct. One unsolved question in colon cancer biology concerns the cells of origin and from which crypt compartment the different pathways originate. Based on molecular and pathological evidences, we propose that the traditional and serrated pathways originate from different crypt compartments explaining their genetic/epigenetic and clinicopathological differences. In this paper, we will discuss the current knowledge of CRC pathogenesis and, specifically, summarize the role of genetic/epigenetic changes in the origin and progression of the multiple CRC pathways. Elucidation of the link between the molecular and clinico-pathological aspects of CRC would improve our understanding of its etiology and impact both prevention and treatment. PMID:22888469

  1. Event-by-event gluon multiplicity, energy density, and eccentricities in ultrarelativistic heavy-ion collisions

    NASA Astrophysics Data System (ADS)

    Schenke, Björn; Tribedy, Prithwish; Venugopalan, Raju

    2012-09-01

    The event-by-event multiplicity distribution, the energy densities and energy density weighted eccentricity moments ɛn (up to n=6) at early times in heavy-ion collisions at both the BNL Relativistic Heavy Ion Collider (RHIC) (s=200GeV) and the CERN Large Hardron Collider (LHC) (s=2.76TeV) are computed in the IP-Glasma model. This framework combines the impact parameter dependent saturation model (IP-Sat) for nucleon parton distributions (constrained by HERA deeply inelastic scattering data) with an event-by-event classical Yang-Mills description of early-time gluon fields in heavy-ion collisions. The model produces multiplicity distributions that are convolutions of negative binomial distributions without further assumptions or parameters. In the limit of large dense systems, the n-particle gluon distribution predicted by the Glasma-flux tube model is demonstrated to be nonperturbatively robust. In the general case, the effect of additional geometrical fluctuations is quantified. The eccentricity moments are compared to the MC-KLN model; a noteworthy feature is that fluctuation dominated odd moments are consistently larger than in the MC-KLN model.

  2. Establishment of apoptotic regulatory network for genetic markers of colorectal cancer.

    PubMed

    Hao, Yibin; Shan, Guoyong; Nan, Kejun

    2017-03-01

    Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

  3. Seismology-based early identification of dam-formation landquake events.

    PubMed

    Chao, Wei-An; Zhao, Li; Chen, Su-Chin; Wu, Yih-Min; Chen, Chi-Hsuan; Huang, Hsin-Hua

    2016-01-12

    Flooding resulting from the bursting of dams formed by landquake events such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake events which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥20 s) waveforms for the landquake force histories (LFHs) of ten events, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1-3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake events (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents.

  4. Microgravity Effects on the Early Events of Biological Nitrogen Fixation in Medicago Truncatula: Results from the SyNRGE Experiment

    NASA Technical Reports Server (NTRS)

    Stutte, Gary W.; Roberts, Michael

    2012-01-01

    SyNRGE (Symbiotic Nodulation in a Reduced Gravity Environment) was a sortie mission on STS-135 in the Biological Research in Canisters (BRIC) hardware to study the effect of microgravity on a plant-microbe symbiosis resulting in biological nitrogen fixation. Medicago truncatula, a model species for th legume family, was inoculated with its bacterial symbiont, Sinorhizobium meliloti, to observe early biomolecular events associated with infection and nodulation in Petri Dish Fixation Units (PDFU's).

  5. Genetics Home Reference: early infantile epileptic encephalopathy 1

    MedlinePlus

    ... infantile epileptic encephalopathy 1 Early infantile epileptic encephalopathy 1 Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Early infantile epileptic encephalopathy 1 (EIEE1) is ...

  6. Constitutional Epi/Genetic Conditions: Genetic, Epigenetic, and Environmental Factors

    PubMed Central

    Schenkel, Laila C.; Rodenhiser, David; Siu, Victoria; McCready, Elizabeth; Ainsworth, Peter; Sadikovic, Bekim

    2016-01-01

    There are more than 4,000 phenotypes for which the molecular basis is at least partly known. Though defects in primary DNA structure constitute a major cause of these disorders, epigenetic disruption is emerging as an important alternative mechanism in the etiology of a broad range of congenital and developmental conditions. These include epigenetic defects caused by either localized (in cis) genetic alterations or more distant (in trans) genetic events but can also include environmental effects. Emerging evidence suggests interplay between genetic and environmental factors in the epigenetic etiology of several constitutional “epi/genetic” conditions. This review summarizes our broadening understanding of how epigenetics contributes to pediatric disease by exploring different classes of epigenomic disorders. It further challenges the simplistic dogma of “DNA encodes RNA encodes protein” to best understand the spectrum of factors that can influence genetic traits in a pediatric population. PMID:28180025

  7. Genetics Home Reference: early-onset glaucoma

    MedlinePlus

    ... called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma. Other individuals experience early onset of primary open-angle glaucoma, the most ...

  8. The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

    PubMed

    Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

    2017-08-01

    To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

  9. Genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins.

    PubMed

    Koeck, A; Miglior, F; Jamrozik, J; Kelton, D F; Schenkel, F S

    2013-07-01

    The aim of this study was to investigate the genetic associations of ketosis and displaced abomasum with milk production traits in early first lactation of Canadian Holsteins. Health data recorded by producers were available from the national dairy cattle health system in Canada. Test-day records of milk, fat, and protein yields were obtained from the routine milk recoding scheme. Ketosis and displaced abomasum were defined as binary traits (0 = healthy; 1 = sick) based on whether or not the cow had at least 1 case of the respective disease in the period from calving to 100 d after calving. Mean frequencies of ketosis and displaced abomasum were 4.1 and 2.7%, respectively. The following milk production traits were considered: milk yield, fat percentage (Fat%), protein percentage (Prot%), fat-to-protein (F:P) ratio, and F:P ratio >1.5. The trait F:P ratio >1.5 was scored as 1 or 0, based on whether or not the cow had an F:P ratio >1.5. For milk production traits, the first (5-30 d in milk) and the second (31-60 d in milk) test days were considered. Data were analyzed using bivariate linear animal models. Average heritabilities of 0.02 and 0.04 were obtained for ketosis and displaced abomasum, respectively. For milk production traits, the lowest heritabilities were obtained for F:P >1.5 (0.04 to 0.08), whereas the highest estimates were found for Prot% (0.27 to 0.38). Ketosis and displaced abomasum were genetically uncorrelated with milk yield in early lactation. Moderate favorable correlations were found between metabolic diseases and milk composition traits. Ketosis was significantly correlated with Fat% (0.33), F:P ratio (0.30), and F:P ratio >1.5 (0.35) at the first test day, whereas all genetic correlations with milk composition traits at the second test day were not significant and close to zero. Significant favorable genetic correlations were also found between displaced abomasum and F:P ratio (0.26), F:P ratio >1.5 (0.25) and Prot% (-0.19) at the first test

  10. Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

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

    Hong, Julian C.; Kruser, Tim J.; Gondi, Vinai

    Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the causemore » of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.« less

  11. The Incidence and Predictors of Early- and Mid-Term Clinically Relevant Neurological Events After Transcatheter Aortic Valve Replacement in Real-World Patients.

    PubMed

    Bosmans, Johan; Bleiziffer, Sabine; Gerckens, Ulrich; Wenaweser, Peter; Brecker, Stephen; Tamburino, Corrado; Linke, Axel

    2015-07-21

    Transcatheter aortic valve replacement (TAVR) enables treatment of high-risk patients with symptomatic aortic stenosis without open-heart surgery; however, the benefits are mitigated by the potential for neurological events. This study sought to determine the timing and causes of clinically relevant neurological events after self-expandable TAVR. We enrolled 1,015 patients, of whom 996 underwent TAVR with a self-expandable system at 44 TAVR-experienced centers in Europe, Colombia, and Israel. Neurological events were evaluated for 3 distinct time periods: periprocedural (0 to 1 days post TAVR); early (2 to 30 days); and late (31 to 730 days). In this real-world study, neurological events were first referred to the site neurologist and then reviewed by an independent neurologist. The overall stroke rate was 1.4% through the first day post-procedure, 3.0% at 30 days, and 5.6% at 2 years. There were no significant predictors of periprocedural stroke or stroke/transient ischemic attack (TIA) combined. Significant predictors of early stroke were acute kidney injury (p = 0.03), major vascular complication (p = 0.04), and female sex (p = 0.04). For stroke/TIA combined, prior atrial fibrillation (p = 0.03) and major vascular complication (p = 0.009) were predictive. Coronary artery bypass graft surgery was the only significant predictor of late stroke (p = 0.007) or late stroke/TIA (p = 0.06). Treatment of high-risk patients with aortic stenosis using a self-expandable system was associated with a low stroke rate at short- and long-term follow-up. Multivariable predictors of clinically relevant neurological events differed on the basis of the timing after TAVR. (CoreValve Advance International Post Market Study; NCT01074658). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. Persistent genetic signatures of historic climatic events in an Antarctic octopus.

    PubMed

    Strugnell, J M; Watts, P C; Smith, P J; Allcock, A L

    2012-06-01

    Repeated cycles of glaciation have had major impacts on the distribution of genetic diversity of the Antarctic marine fauna. During glacial periods, ice cover limited the amount of benthic habitat on the continental shelf. Conversely, more habitat and possibly altered seaways were available during interglacials when the ice receded and the sea level was higher. We used microsatellites and partial sequences of the mitochondrial cytochrome oxidase 1 gene to examine genetic structure in the direct-developing, endemic Southern Ocean octopod Pareledone turqueti sampled from a broad range of areas that circumvent Antarctica. We find that, unusually for a species with poor dispersal potential, P. turqueti has a circumpolar distribution and is also found off the islands of South Georgia and Shag Rocks. The overriding pattern of spatial genetic structure can be explained by hydrographic (with ocean currents both facilitating and hindering gene flow) and bathymetric features. The Antarctic Peninsula region displays a complex population structure, consistent with its varied topographic and oceanographic influences. Genetic similarities between the Ross and Weddell Seas, however, are interpreted as a persistent historic genetic signature of connectivity during the hypothesized Pleistocene West Antarctic Ice Sheet collapses. A calibrated molecular clock indicates two major lineages within P. turqueti, a continental lineage and a sub-Antarctic lineage, that diverged in the mid-Pliocene with no subsequent gene flow. Both lineages survived subsequent major glacial cycles. Our data are indicative of potential refugia at Shag Rocks and South Georgia and also around the Antarctic continent within the Ross Sea, Weddell Sea and off Adélie Land. The mean age of mtDNA diversity within these main continental lineages coincides with Pleistocene glacial cycles. © 2012 Blackwell Publishing Ltd.

  13. The effects of child maltreatment on early signs of antisocial behavior: Genetic moderation by Tryptophan Hydroxylase, Serotonin Transporter, and Monoamine Oxidase-A-Genes

    PubMed Central

    Cicchetti, Dante; Rogosch, Fred A.; Thibodeau, Eric

    2013-01-01

    Gene-environment interaction effects in predicting antisocial behavior in late childhood were investigated among maltreated and nonmaltreated low-income children (N = 627, M age = 11.27). Variants in three genes, TPH1, 5-HTTLPR, and MAOA uVNTR, were examined. In addition to child maltreatment status, we also considered the impact of maltreatment subtypes, developmental timing of maltreatment, and chronicity. Indicators of antisocial behavior were obtained from self-, peer-, and adult counselor-reports. In a series of ANCOVAs, child maltreatment and its parameters demonstrated strong main effects on early antisocial behavior as assessed by all forms of report. Genetic effects operated primarily in the context of gene-environment interactions, moderating the impact of child maltreatment on outcomes. Across the three genes, among nonmaltreated children no differences in antisocial behavior were found based on genetic variation. In contrast, among maltreated children specific polymorphisms of TPH1, 5-HTTLPR, and MAOA were each related to heightened self-report of antisocial behavior; the interaction of 5-HTTLPR and developmental timing of maltreatment also indicated more severe antisocial outcomes for children with early onset and recurrent maltreatment based on genotype. TPH1 and 5-HTTLPR interacted with maltreatment subtype to predict peer-report of antisocial behavior; genetic variation contributed to larger differences in antisocial behavior among abused children. TPH1 and 5-HTTLPR polymorphisms also moderated the effects of maltreatment subtype on adult report of antisocial behavior; again genetic effects were strongest for children who were abused. Additionally, TPH1 moderated the effect of developmental timing of maltreatment and chronicity on adult report of antisocial behavior. The findings elucidate how genetic variation contributes to identifying which maltreated children are most vulnerable to antisocial development. PMID:22781862

  14. Depletion of Key Meiotic Genes and Transcriptome-Wide Abiotic Stress Reprogramming Mark Early Preparatory Events Ahead of Apomeiotic Transition

    PubMed Central

    Shah, Jubin N.; Kirioukhova, Olga; Pawar, Pallavi; Tayyab, Muhammad; Mateo, Juan L.; Johnston, Amal J.

    2016-01-01

    Molecular dissection of apomixis – an asexual reproductive mode – is anticipated to solve the enigma of loss of meiotic sex, and to help fixing elite agronomic traits. The Brassicaceae genus Boechera comprises of both sexual and apomictic species, permitting comparative analyses of meiotic circumvention (apomeiosis) and parthenogenesis. Whereas previous studies reported local transcriptome changes during these events, it remained unclear whether global changes associated with hybridization, polyploidy and environmental adaptation that arose during evolution of Boechera might serve as (epi)genetic regulators of early development prior apomictic initiation. To identify these signatures during vegetative stages, we compared seedling RNA-seq transcriptomes of an obligate triploid apomict and a diploid sexual, both isolated from a drought-prone habitat. Uncovered were several genes differentially expressed between sexual and apomictic seedlings, including homologs of meiotic genes ASYNAPTIC 1 (ASY1) and MULTIPOLAR SPINDLE 1 (MPS1) that were down-regulated in apomicts. An intriguing class of apomict-specific deregulated genes included several NAC transcription factors, homologs of which are known to be transcriptionally reprogrammed during abiotic stress in other plants. Deregulation of both meiotic and stress-response genes during seedling stages might possibly be important in preparation for meiotic circumvention, as similar transcriptional alteration was discernible in apomeiotic floral buds too. Furthermore, we noted that the apomict showed better tolerance to osmotic stress in vitro than the sexual, in conjunction with significant upregulation of a subset of NAC genes. In support of the current model that DNA methylation epigenetically regulates stress, ploidy, hybridization and apomixis, we noted that ASY1, MPS1 and NAC019 homologs were deregulated in Boechera seedlings upon DNA demethylation, and ASY1 in particular seems to be repressed by global DNA

  15. [Autism: An early neurodevelopmental disorder].

    PubMed

    Bonnet-Brilhault, F

    2017-04-01

    With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. The fine scale genetic structure of the British population

    PubMed Central

    Davison, Dan; Boumertit, Abdelhamid; Day, Tammy; Hutnik, Katarzyna; Royrvik, Ellen C; Cunliffe, Barry; Lawson, Daniel J; Falush, Daniel; Freeman, Colin; Pirinen, Matti; Myers, Simon; Robinson, Mark; Donnelly, Peter; Bodmer, Walter

    2015-01-01

    Summary Fine-scale genetic variation between human populations is interesting as a signature of historical demographic events and because of its potential for confounding disease studies. We use haplotype-based statistical methods to analyse genome-wide SNP data from a carefully chosen geographically diverse sample of 2,039 individuals from the United Kingdom (UK). This reveals a rich and detailed pattern of genetic differentiation with remarkable concordance between genetic clusters and geography. The regional genetic differentiation and differing patterns of shared ancestry with 6,209 individuals from across Europe carry clear signals of historical demographic events. We estimate the genetic contribution to SE England from Anglo-Saxon migrations to be under half, identify the regions not carrying genetic material from these migrations, suggest significant pre-Roman but post-Mesolithic movement into SE England from the Continent, and show that in non-Saxon parts of the UK there exist genetically differentiated subgroups rather than a general “Celtic” population. PMID:25788095

  17. The spectral absorption coefficient at 254 nm as a real-time early warning proxy for detecting faecal pollution events at alpine karst water resources.

    PubMed

    Stadler, H; Klock, E; Skritek, P; Mach, R L; Zerobin, W; Farnleitner, A H

    2010-01-01

    Because spring water quality from alpine karst aquifers can change very rapidly during event situations, water abstraction management has to be performed in near real-time. Four summer events (2005-2008) at alpine karst springs were investigated in detail in order to evaluate the spectral absorption coefficient at 254 nm (SAC254) as a real-time early warning proxy for faecal pollution. For the investigation Low-Earth-Orbit (LEO) Satellite-based data communication between portable hydrometeorological measuring stations and an automated microbiological sampling device was used. The method for event triggered microbial sampling and analyzing was already established and described in a previous paper. Data analysis including on-line event characterisation (i.e. precipitation, discharge, turbidity, SAC254) and comprehensive E. coli determination (n>800) indicated that SAC254 is a useful early warning proxy. Irrespective of the studied event situations SAC254 always increased 3 to 6 hours earlier than the onset of faecal pollution, featuring different correlation phases. Furthermore, it seems also possible to use SAC254 as a real-time proxy parameter for estimating the extent of faecal pollution after establishing specific spring and event-type calibrations that take into consideration the variability of the occurrence and the transferability of faecal material It should be highlighted that diffuse faecal pollution from wildlife and live stock sources was responsible for spring water contamination at the investigated catchments. In this respect, the SAC254 can also provide useful information to support microbial source tracking efforts where different situations of infiltration have to be investigated.

  18. Knockin' on pollen's door: live cell imaging of early polarization events in germinating Arabidopsis pollen

    PubMed Central

    Vogler, Frank; Konrad, Sebastian S. A.; Sprunck, Stefanie

    2015-01-01

    Pollen tubes are an excellent system for studying the cellular dynamics and complex signaling pathways that coordinate polarized tip growth. Although several signaling mechanisms acting in the tip-growing pollen tube have been described, our knowledge on the subcellular and molecular events during pollen germination and growth site selection at the pollen plasma membrane is rather scarce. To simultaneously track germinating pollen from up to 12 genetically different plants we developed an inexpensive and easy mounting technique, suitable for every standard microscope setup. We performed high magnification live-cell imaging during Arabidopsis pollen activation, germination, and the establishment of pollen tube tip growth by using fluorescent marker lines labeling either the pollen cytoplasm, vesicles, the actin cytoskeleton or the sperm cell nuclei and membranes. Our studies revealed distinctive vesicle and F-actin polarization during pollen activation and characteristic growth kinetics during pollen germination and pollen tube formation. Initially, the germinating Arabidopsis pollen tube grows slowly and forms a uniform roundish bulge, followed by a transition phase with vesicles heavily accumulating at the growth site before switching to rapid tip growth. Furthermore, we found the two sperm cells to be transported into the pollen tube after the phase of rapid tip growth has been initiated. The method presented here is suitable to quantitatively study subcellular events during Arabidopsis pollen germination and growth, and for the detailed analysis of pollen mutants with respect to pollen polarization, bulging, or growth site selection at the pollen plasma membrane. PMID:25954283

  19. Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males.

    PubMed

    Páez, David James; Bernatchez, Louis; Dodson, Julian J

    2011-07-22

    Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance.

  20. Alternative life histories in the Atlantic salmon: genetic covariances within the sneaker sexual tactic in males

    PubMed Central

    Páez, David James; Bernatchez, Louis; Dodson, Julian J.

    2011-01-01

    Alternative reproductive tactics are ubiquitous in many species. Tactic expression often depends on whether an individual's condition surpasses thresholds that are responsible for activating particular developmental pathways. Two central goals in understanding the evolution of reproductive tactics are quantifying the extent to which thresholds are explained by additive genetic effects, and describing their covariation with condition-related traits. We monitored the development of early sexual maturation that leads to the sneaker reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for additive genetic variance in the timing of sexual maturity (which is a measure of the surpassing of threshold values) and body-size traits. This suggests that selection can affect the patterns of sexual development by changing the timing of this event and/or body size. Significant levels of covariation between these traits also occurred, implying a potential for correlated responses to selection. Closer examination of genetic covariances suggests that the detected genetic variation is distributed along at least five directions of phenotypic variation. Our results show that the potential for evolution of the life-history traits constituting this reproductive phenotype is greatly influenced by their patterns of genetic covariance. PMID:21177685

  1. Relationship between early and late stages of information processing: an event-related potential study

    PubMed Central

    Portella, Claudio; Machado, Sergio; Arias-Carrión, Oscar; Sack, Alexander T.; Silva, Julio Guilherme; Orsini, Marco; Leite, Marco Antonio Araujo; Silva, Adriana Cardoso; Nardi, Antonio E.; Cagy, Mauricio; Piedade, Roberto; Ribeiro, Pedro

    2012-01-01

    The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP) components, including P200, N200, premotor potential (PMP) and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2), N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) and the reaction time (RT). In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) was found. Therefore, we propose that if the secondary processing of visual input (P200 latency) occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency), motor response processing (PMP latency), reorganization of attention and working memory update (P300 latency), and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude). PMID:23355929

  2. Development and application of a multi-targeting reference plasmid as calibrator for analysis of five genetically modified soybean events.

    PubMed

    Pi, Liqun; Li, Xiang; Cao, Yiwei; Wang, Canhua; Pan, Liangwen; Yang, Litao

    2015-04-01

    Reference materials are important in accurate analysis of genetically modified organism (GMO) contents in food/feeds, and development of novel reference plasmid is a new trend in the research of GMO reference materials. Herein, we constructed a novel multi-targeting plasmid, pSOY, which contained seven event-specific sequences of five GM soybeans (MON89788-5', A2704-12-3', A5547-127-3', DP356043-5', DP305423-3', A2704-12-5', and A5547-127-5') and sequence of soybean endogenous reference gene Lectin. We evaluated the specificity, limit of detection and quantification, and applicability of pSOY in both qualitative and quantitative PCR analyses. The limit of detection (LOD) was as low as 20 copies in qualitative PCR, and the limit of quantification (LOQ) in quantitative PCR was 10 copies. In quantitative real-time PCR analysis, the PCR efficiencies of all event-specific and Lectin assays were higher than 90%, and the squared regression coefficients (R(2)) were more than 0.999. The quantification bias varied from 0.21% to 19.29%, and the relative standard deviations were from 1.08% to 9.84% in simulated samples analysis. All the results demonstrated that the developed multi-targeting plasmid, pSOY, was a credible substitute of matrix reference materials, and could be used as a reliable reference calibrator in the identification and quantification of multiple GM soybean events.

  3. Does silent reading speed in normal adult readers depend on early visual processes? evidence from event-related brain potentials.

    PubMed

    Korinth, Sebastian Peter; Sommer, Werner; Breznitz, Zvia

    2012-01-01

    Little is known about the relationship of reading speed and early visual processes in normal readers. Here we examined the association of the early P1, N170 and late N1 component in visual event-related potentials (ERPs) with silent reading speed and a number of additional cognitive skills in a sample of 52 adult German readers utilizing a Lexical Decision Task (LDT) and a Face Decision Task (FDT). Amplitudes of the N170 component in the LDT but, interestingly, also in the FDT correlated with behavioral tests measuring silent reading speed. We suggest that reading speed performance can be at least partially accounted for by the extraction of essential structural information from visual stimuli, consisting of a domain-general and a domain-specific expertise-based portion. © 2011 Elsevier Inc. All rights reserved.

  4. Realizing Aspects by Transforming for Events

    NASA Technical Reports Server (NTRS)

    Filman, Robert E.; Havelund, Klaus; Clancy, Daniel (Technical Monitor)

    2002-01-01

    We explore the extent to which concerns can be separated in programs by program transformation with respect to the events required by these concerns. We describe our early work on developing a system to perform event-driven transformation and discuss possible applications of this approach.

  5. 76 FR 8707 - Syngenta Seeds, Inc.; Determination of Nonregulated Status for Corn Genetically Engineered To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... for Corn Genetically Engineered To Produce an Enzyme That Facilitates Ethanol Production AGENCY... event 3272, which has been genetically engineered to produce a microbial enzyme that facilitates ethanol... transformation event 3272, which has been genetically engineered to produce a microbial enzyme that facilitates...

  6. The influence of deficient retro-aortic rim on technical success and early adverse events following device closure of secundum atrial septal defects: An Analysis of the IMPACT Registry®.

    PubMed

    O'Byrne, Michael L; Gillespie, Matthew J; Kennedy, Kevin F; Dori, Yoav; Rome, Jonathan J; Glatz, Andrew C

    2017-01-01

    Concern regarding aortic erosion has focused attention on the retro-aortic rim in patients undergoing device closure of atrial septal defects (ASD), but its effect on early outcomes is not well studied. A multicenter retrospective cohort study of patients undergoing device occlusion of ASD between 1/2011-10/2014 was performed, using data from the IMproving Pediatric and Adult Congenital Treatment Registry. Subjects were divided between those with retro-aortic rim <5 and ≥5 mm. Primary outcomes were technical failure and major early adverse events. Case times were measured as surrogates of technical complexity. The effect of deficient retro-aortic rim on primary outcomes was assessed using hierarchical logistic regression, adjusting for other suspected covariates and assessing whether they represent independent risk factors RESULTS: 1,564 subjects (from 77 centers) were included, with deficient retro-aortic rim present in 40%. Technical failure occurred in 91 subjects (5.8%) and a major early adverse event in 64 subjects (4.1%). Adjusting for known covariates, the presence of a deficient retro-aortic rim was not significantly associated with technical failure (OR: 1.3, 95% CI: 0.9-2.1) or major early adverse event (OR: 0.7, 95% CI: 0.4-1. 2). Total case (P = 0.01) and fluoroscopy time (P = 0.02) were greater in subjects with deficient rim, but sheath time was not significantly different (P = 0.07). Additional covariates independently associated with these outcomes were identified. Deficient retro-aortic rim was highly prevalent but not associated with increased risk of technical failure or early adverse events. Studies with longer follow-up are necessary to assess other outcomes, including device erosion. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Treatment decisions and the impact of adverse events before and during extended endocrine therapy in postmenopausal early breast cancer.

    PubMed

    Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

    2018-05-01

    Extended endocrine therapy beyond 5 years for postmenopausal breast cancer has been studied within multiple phase III trials. Treatment compliance in these trials is generally poor. In this analysis, we aimed to determine factors that were associated with participation in the phase III Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial and with early treatment discontinuation, and how this influenced survival outcome. In the IDEAL trial, postmenopausal patients were randomised between 2.5 or 5 years of extended letrozole, after completing 5 years of endocrine therapy for hormone receptor-positive early breast cancer. A subgroup of this population participated earlier in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in which we explored which factors were determinative for enrolment in the IDEAL study. In the IDEAL cohort, we evaluated which factors predicted for early treatment discontinuation and the effect of early treatment discontinuation on disease-free survival (DFS). Nodal status, younger age and adjuvant chemotherapy were significantly associated with higher enrolment in the IDEAL trial. In the IDEAL cohort, adverse events (AEs), the type of primary endocrine therapy and the interval between primary and extended therapy were associated with early treatment discontinuation. Among the reported AEs, depressive feelings (56%) were most frequently associated with early treatment discontinuation. Early treatment discontinuation was not associated with worse DFS (hazard ratio [HR] = 1.02, 95% confidence interval = 0.76-1.37). In this analysis, we found that risk factors were most strongly associated enrolment in the IDEAL trial. In contrast, patient experiences were the most significant factors leading to early treatment discontinuation, with no effect on DFS. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Molecular Evolution of Aminoacyl tRNA Synthetase Proteins in the Early History of Life

    NASA Astrophysics Data System (ADS)

    Fournier, Gregory P.; Andam, Cheryl P.; Alm, Eric J.; Gogarten, J. Peter

    2011-12-01

    Aminoacyl-tRNA synthetases (aaRS) consist of several families of functionally conserved proteins essential for translation and protein synthesis. Like nearly all components of the translation machinery, most aaRS families are universally distributed across cellular life, being inherited from the time of the Last Universal Common Ancestor (LUCA). However, unlike the rest of the translation machinery, aaRS have undergone numerous ancient horizontal gene transfers, with several independent events detected between domains, and some possibly involving lineages diverging before the time of LUCA. These transfers reveal the complexity of molecular evolution at this early time, and the chimeric nature of genomes within cells that gave rise to the major domains. Additionally, given the role of these protein families in defining the amino acids used for protein synthesis, sequence reconstruction of their pre-LUCA ancestors can reveal the evolutionary processes at work in the origin of the genetic code. In particular, sequence reconstructions of the paralog ancestors of isoleucyl- and valyl- RS provide strong empirical evidence that at least for this divergence, the genetic code did not co-evolve with the aaRSs; rather, both amino acids were already part of the genetic code before their cognate aaRSs diverged from their common ancestor. The implications of this observation for the early evolution of RNA-directed protein biosynthesis are discussed.

  9. Immunohistochemical characterization of endometrial carcinomas: endometrioid, serous and clear cell adenocarcinomas in association with genetic analysis.

    PubMed

    Yasuda, Masanori

    2014-12-01

    Developments in immunohistochemistry, which are closely linked with the advances in the analyses of genetic abnormalities and their associated molecular disorders as early and late histogenetic events, have contributed greatly to the improvement of pathological diagnostic confirmation and validation. Immunohistochemistry has also generated great benefit to the innovation of therapeutic strategies for various kinds of cancers. In this article, the three representative histological types of corpus cancer, namely, endometrioid adenocarcinoma, serous adenocarcinoma and clear cell adenocarcinoma, will be histologically approached in association with their immunohistochemical profiles as well as genetic disorders. First, the focus will be on 'Conventional/prototypic features,' followed by 'Controversy over conventional histological subclassification,' and subsequently 'Tumorigenesis and re-subclassification'. © 2014 The Author. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  10. Slow slip events in the early part of the earthquake cycle

    NASA Astrophysics Data System (ADS)

    Voss, Nicholas K.; Malservisi, Rocco; Dixon, Timothy H.; Protti, Marino

    2017-08-01

    In February 2014 a Mw = 7.0 slow slip event (SSE) took place beneath the Nicoya Peninsula, Costa Rica. This event occurred 17 months after the 5 September 2012, Mw = 7.6, earthquake and along the same subduction zone segment, during a period when significant postseismic deformation was ongoing. A second SSE occurred in the middle of 2015, 21 months after the 2014 SSE and 38 months after the earthquake. The recurrence interval for Nicoya SSEs was unchanged by the earthquake. However, the spatial distribution of slip for the 2014 event differed significantly from previous events, having only deep ( 40 km) slip, compared to previous events, which had both deep and shallow slip. The 2015 SSE marked a return to the combination of deep plus shallow slip of preearthquake SSEs. However, slip magnitude in 2015 was nearly twice as large (Mw = 7.2) as preearthquake SSEs. We employ Coulomb Failure Stress change modeling in order to explain these changes. Stress changes associated with the earthquake and afterslip were highest near the shallow portion of the megathrust, where preearthquake SSEs had significant slip. Lower stress change occurred on the deeper parts of the plate interface, perhaps explaining why the deep ( 40 km) region for SSEs remained unchanged. The large amount of shallow slip in the 2015 SSE may reflect lack of shallow slip in the prior SSE. These observations highlight the variability of aseismic strain release rates throughout the earthquake cycle.Plain Language SummaryWe analyzed small signals in continuous GPS time series. By averaging many GPS measurements over a day, we are able to get very precise measurements of the motion of the ground. We found two <span class="hlt">events</span> in the Nicoya Peninsula of Costa Rica where the GPS changed direction and began moving toward the oceanic trench in the opposite direction of subduction plate motion. These <span class="hlt">events</span> are called slow</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2006AGUFMAE51A0262C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2006AGUFMAE51A0262C"><span>VLF Observation of Long Ionospheric Recovery <span class="hlt">Events</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Cotts, B. R.; Inan, U. S.</p> <p>2006-12-01</p> <p>On the evening of 20 November 1992, three <span class="hlt">early</span>/fast <span class="hlt">events</span> were observed on the great circle path (GCP) from the NAU transmitter in Puerto Rico to Gander (GA), Newfoundland. These <span class="hlt">events</span> were found to have significantly longer recovery times (up to 20 minutes) than any previously documented <span class="hlt">events</span>. Typical <span class="hlt">early</span>/fast <span class="hlt">events</span> and Lightning-induced Electron Precipitation (LEP) <span class="hlt">events</span> affect the D-region ionosphere near the night-time VLF-reflection height of ~85 km and exhibit recovery to pre-<span class="hlt">event</span> levels of < 180 seconds [e.g., Sampath et al., 2000]. These lightning-associated long recovery VLF <span class="hlt">events</span> resemble the observed long ionospheric recovery of the VLF signature of the 27 December 2004 galactic gamma-ray flare <span class="hlt">event</span> [Inan et al., 2006], which was interpreted to be due to the unusually high electron detachment rates at low (below 40 km) altitudes, The region of the ionosphere affected in these long recovery VLF <span class="hlt">events</span> may thus also include the altitude range < 40 km, and may possibly be related to gigantic jets. In this context, preliminary results indicate that the lightning-associated VLF long recovery <span class="hlt">events</span> appear to be more common in oceanic thunderstorms. In this paper, we present occurrence statistics and other measured properties of VLF long recovery <span class="hlt">events</span>, observed on all-sea based and land based VLF great circle paths.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26812525','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26812525"><span>Specific Reaction Patterns to Distinct Positive Emotional Cues Related to Incentive Motivation in Dependence of the Taq1A-Polymorphism: Molecular <span class="hlt">Genetic</span> Associations of <span class="hlt">Early</span> and Late <span class="hlt">Event</span>-Related Potentials.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Munk, Aisha J L; Wielpuetz, Catrin; Osinsky, Roman; Müller, Erik M; Grant, Phillip; Hennig, Jürgen</p> <p>2016-01-01</p> <p><span class="hlt">Early</span> and late <span class="hlt">event</span>-related potential (ERP) responses, representing <span class="hlt">early</span> subconscious and late motivational processes, were recorded for positive emotional words related to 'wanting' and 'liking', in dependence of the dopamine-related Taq1A genotype (ANKK1/DRD2). Research suggests that 'wanting' as opposed to 'liking' is related to dopaminergic processes. Therefore, it was hypothesized that risk allele carriers of the Taq1A polymorphism exhibit late ERP changes in reaction to words representing incentive motivation, i.e. 'wanting' (word categories 'lust' and 'anticipation'), but not to words representing 'liking' ('closeness'). Seventy-two male participants performed an emotional-word Stroop task during EEG recording and were genotyped according to the Taq1A polymorphism of ANKK1/DRD2. Positive emotional words related to anticipation and lust revealed blunted responses in the late positive potential (LPP) in carriers of the A1 allele, an effect absent in response to 'liking'-related words. These differences were not evident in the earlier posterior negativity (EPN). As no differences in dependence of the Taq1A genotype were observed in reaction to 'wanting'- and 'liking'-related words in the EPN, but merely in the LPP, it can be assumed that incentive-motivational stimuli only modify motivation-related ERP responses in carriers of the A1 allele of the Taq1A polymorphism, indicating the role of dopamine in late ERP components. © 2016 S. Karger AG, Basel.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4629465','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4629465"><span>Inflammatory Bowel Disease: <span class="hlt">Genetics</span>, Epigenetics, and Pathogenesis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Loddo, Italia; Romano, Claudio</p> <p>2015-01-01</p> <p>Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Although etiology remains largely unknown, recent research has suggested that <span class="hlt">genetic</span> factors, environment, microbiota, and immune response are involved in the pathogenesis. Epidemiological evidence for a <span class="hlt">genetic</span> contribution is defined: 15% of patients with Crohn’s Disease (CD) have an affected family member with IBD, and twin studies for CD have shown 50% concordance in monozygotic twins compared to <10% in dizygotics. The most recent and largest <span class="hlt">genetic</span> association studies, which employed genome-wide association data for over 75,000 patients and controls, identified 163 susceptibility loci for IBD. More recently, a trans-ethnic analysis, including over 20,000 individuals, identified an additional 38 new IBD loci. Although most cases are correlated with polygenic contribution toward <span class="hlt">genetic</span> susceptibility, there is a spectrum of rare <span class="hlt">genetic</span> disorders that can contribute to <span class="hlt">early</span>-onset IBD (before 5 years) or very <span class="hlt">early</span> onset IBD (before 2 years). <span class="hlt">Genetic</span> variants that cause these disorders have a wide effect on gene function. These variants are so rare in allele frequency that the <span class="hlt">genetic</span> signals are not detected in genome-wide association studies of patients with IBD. With recent advances in sequencing techniques, ~50 <span class="hlt">genetic</span> disorders have been identified and associated with IBD-like immunopathology. Monogenic defects have been found to alter intestinal immune homeostasis through many mechanisms. Candidate gene resequencing should be carried out in <span class="hlt">early</span>-onset patients in clinical practice. The evidence that <span class="hlt">genetic</span> factors contribute in small part to disease pathogenesis confirms the important role of microbial and environmental factors. Epigenetic factors can mediate interactions between environment and genome. Epigenetic mechanisms could affect development and progression of IBD. Epigenomics is an emerging field, and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28133934','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28133934"><span>A novel immune function biomarker identifies patients at risk of clinical <span class="hlt">events</span> <span class="hlt">early</span> following liver transplantation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sood, Siddharth; Haifer, Craig; Yu, Lijia; Pavlovic, Julie; Churilov, Leonid; Gow, Paul J; Jones, Robert M; Angus, Peter W; Visvanathan, Kumar; Testro, Adam G</p> <p>2017-04-01</p> <p>Balancing immunosuppression after liver transplant is difficult, with clinical <span class="hlt">events</span> common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon γ (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict <span class="hlt">events</span> following transplantation. A total of 75 adult transplant recipients were prospectively monitored in a blinded, observational study; 55/75 (73.3%) patients experienced a total of 89 clinical <span class="hlt">events</span>. Most <span class="hlt">events</span> occurred within the first month. Low week 1 results were significantly associated with risk of <span class="hlt">early</span> infection (area under the receiver operating characteristic curve [AUROC], 0.74; P = 0.008). IFNγ ≤ 1.30 IU/mL (likelihood ratio positive, 1.93; sensitivity, 71.4%; specificity, 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ ≤ 1.30 IU/mL. Moreover, an elevated week 1 result was significantly associated with the risk of rejection within the first month after transplant (AUROC, 0.77; P = 0.002), but no episodes of infection. On multivariate logistic regression, IFNγ ≥ 4.49 IU/mL (odds ratio, 4.75) may be an independent predictor of rejection (P = 0.05). In conclusion, low IFNγ suggesting oversuppression is associated with infections, whereas high IFNγ indicating undersuppression is associated with rejection. This assay offers the potential to allow individualization and optimization of immunosuppression that could fundamentally alter the way patients are managed following transplantation. Liver Transplantation 23 487-497 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23845235','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23845235"><span>A porin-like protein from oral secretions of Spodoptera littoralis larvae induces defense-related <span class="hlt">early</span> <span class="hlt">events</span> in plant leaves.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Guo, Huijuan; Wielsch, Natalie; Hafke, Jens B; Svatoš, Aleš; Mithöfer, Axel; Boland, Wilhelm</p> <p>2013-09-01</p> <p>Insect herbivory on plants is a complex incident consisting of at least two different aspects, namely mechanical damage and chemical challenge, as feeding insects introduce oral secretions (OS) into the wounded tissue of the attacked plant. Mechanical wounding alone is sufficient to induce a set of defense-related reactions in host plants, but some <span class="hlt">early</span> <span class="hlt">events</span> such as membrane potential (Vm) changes and cytosolic Ca²⁺-elevations can be triggered only by herbivores suggesting that OS-derived molecules are involved in those processes. Following an assay-guided purification based on planar lipid bilayer membrane technique in combination with proteomic analysis, a porin-like protein (PLP) of most likely bacterial origin was determined from collected OS of Spodoptera littoralis larvae. PLP exhibited channel-forming activity. Further, <span class="hlt">early</span> defense-related <span class="hlt">events</span> in plant-insect interaction were evaluated by using a purified fraction and α-hemolysin (α-HL) as a commercial pore-forming compound. Both up-regulated the calmodulin-like CML42 in Arabidopsis thaliana, which only responds to oral secretion and not to wounding. An elevation of in vivo [Ca²⁺](cyt) was not observed. Because membrane channel formation is a widespread phenomenon in plant-insect interactions, this PLP might represent an example for microbial compounds from the insect gut which are initially involved in plant-insect interactions. Copyright © 2013 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4421862','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4421862"><span>Developmentally dynamic genome: Evidence of <span class="hlt">genetic</span> influences on increases and decreases in conduct problems from <span class="hlt">early</span> childhood to adolescence</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi</p> <p>2015-01-01</p> <p>The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems’ developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins <span class="hlt">Early</span> Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive <span class="hlt">genetic</span> influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that <span class="hlt">genetic</span> influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of <span class="hlt">genetic</span> and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact. PMID:25944445</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25944445','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25944445"><span>Developmentally dynamic genome: Evidence of <span class="hlt">genetic</span> influences on increases and decreases in conduct problems from <span class="hlt">early</span> childhood to adolescence.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi</p> <p>2015-05-06</p> <p>The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems' developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins <span class="hlt">Early</span> Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive <span class="hlt">genetic</span> influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that <span class="hlt">genetic</span> influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of <span class="hlt">genetic</span> and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/7199551-genetic-change-rates-cladogenesis','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/7199551-genetic-change-rates-cladogenesis"><span><span class="hlt">Genetic</span> change and rates of cladogenesis</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Avise, J.C.; Ayala, F.J.</p> <p>1975-12-01</p> <p>Models are introduced which predict ratios of mean levels of <span class="hlt">genetic</span> divergence in species-rich versus species-poor phylads under two competing assumptions: (1) <span class="hlt">genetic</span> differentiation is a function of time, unrelated to the number of cladogenetic <span class="hlt">events</span> and (2) <span class="hlt">genetic</span> differentiation is proportional to the number of speciation <span class="hlt">events</span> in the group. The models are simple, general, and biologically real, but not precise. They lead to qualitatively distinct predictions about levels of <span class="hlt">genetic</span> divergence depending upon the relationship between rates of speciation and amount of <span class="hlt">genetic</span> change. When <span class="hlt">genetic</span> distance between species is a function of time, mean <span class="hlt">genetic</span> distances inmore » speciose and depauperate phylads of equal evolutionary age are very similar. On the contrary, when <span class="hlt">genetic</span> distance is a function of the number of speciations in the history of a phylad, the ratio of mean <span class="hlt">genetic</span> distances separating species in speciose versus depauperate phylads is greater than one, and increases rapidly as the frequency of speciations in one group relative to the other increases. The models may be tested with data from natural populations to assess (1) possible correlations between rates of anagenesis and cladogenesis and (2) the amount of <span class="hlt">genetic</span> differentiation accompanying the speciation process. The data collected in electrophoretic surveys and other kinds of studies can be used to test the predictions of the models. For this purpose <span class="hlt">genetic</span> distances need to be measured in speciose and depauperate phylads of equal evolutionary age. The limited information presently available agrees better with the model predicting that <span class="hlt">genetic</span> change is primarily a function of time, and is not correlated with rates of speciation. Further testing of the models is, however, required before firm conclusions can be drawn. (auth)« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29166454','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29166454"><span>The clinical <span class="hlt">genetics</span> of phaeochromocytoma and paraganglioma.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kavinga Gunawardane, P T; Grossman, Ashley</p> <p>2017-10-01</p> <p>Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with germline mutations seen in approximately 30% of patients. They can be a part of <span class="hlt">genetic</span> syndromes such as MEN 2 or Neurofibromatosis type 1, or can be found as apparently sporadic tumours. Germline mutations are almost always found in syndromic patients. Nonetheless, apparently sporadic phaeochromocytoma too show high germline mutation rates. <span class="hlt">Early</span> detection of a <span class="hlt">genetic</span> mutation can lead to <span class="hlt">early</span> diagnosis of further tumours via surveillance, <span class="hlt">early</span> treatment and better prognosis. Apart from this, the <span class="hlt">genetic</span> profile has important relevance for tumour location and biochemical profile, and can be a useful predictor of future tumour behaviour. It also enables family screening and surveillance. Moreover, recent studies have demonstrated significant driver somatic mutations in up to 75% of all tumours. Arch Endocrinol Metab. 2017;61(5):490-500.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26162197','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26162197"><span><span class="hlt">Early</span> Adversity and Developmental Outcomes: Interaction Between <span class="hlt">Genetics</span>, Epigenetics, and Social Experiences Across the Life Span.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Champagne, Frances A</p> <p>2010-09-01</p> <p>Longitudinal studies in humans demonstrate the association between prenatal and postnatal experiences of adversity and long-term changes in neurodevelopment. These studies raise the question of how experiences become incorporated at a biological level to induce persistent changes in functioning. Laboratory studies using animal models and recent analyses in human cohorts implicate epigenetic mechanisms as a possible route through which these environmental effects are achieved. In particular, there is evidence that changes in DNA methylation are associated with <span class="hlt">early</span> life experiences with consequences for gene expression and behavior. Despite the potential stability of DNA methylation, it is apparent that this epigenetic mark can be dynamically modified through pharmacological targeting and behavioral experiences. Developmental plasticity may also be achieved through modification of the juvenile environment. Although these juvenile experiences may lead to common endpoints, there is evidence suggesting that the effects of <span class="hlt">early</span> and later life experiences may be achieved by different molecular pathways. This review discusses evidence for the role of epigenetic mechanisms in shaping developmental trajectories in response to <span class="hlt">early</span> life experience as well as the potential plasticity that can occur beyond the perinatal period. These studies have implications for approaches to intervention and suggest the importance of considering individual differences in <span class="hlt">genetic</span> and epigenetic vulnerability in developing treatment strategies. © The Author(s) 2010.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_21 --> <div id="page_22" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="421"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27657986','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27657986"><span><span class="hlt">Genetics</span> of gigantism and acromegaly.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hannah-Shmouni, Fady; Trivellin, Giampaolo; Stratakis, Constantine A</p> <p></p> <p>Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and <span class="hlt">genetic</span> etiologies of pituitary gigantism and acromegaly yielded several <span class="hlt">genetic</span> causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The <span class="hlt">early</span> diagnosis of these conditions helps guide <span class="hlt">early</span> intervention, screening, and <span class="hlt">genetic</span> counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the <span class="hlt">genetics</span> of gigantism and acromegaly. Published by Elsevier Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5154831','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5154831"><span><span class="hlt">Genetics</span> of Gigantism and Acromegaly</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Hannah-Shmouni, Fady; Trivellin, Giampaolo; Stratakis, Constantine A.</p> <p>2016-01-01</p> <p>Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and <span class="hlt">genetic</span> etiologies of pituitary gigantism and acromegaly yielded several <span class="hlt">genetic</span> causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The <span class="hlt">early</span> diagnosis of these conditions helps guide <span class="hlt">early</span> intervention, screening, and <span class="hlt">genetic</span> counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the <span class="hlt">genetics</span> of gigantism and acromegaly. PMID:27657986</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3885143','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3885143"><span>Interpersonal and <span class="hlt">Genetic</span> Origins of Adult Attachment Styles: A Longitudinal Study from Infancy to <span class="hlt">Early</span> Adulthood</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Fraley, R. Chris; Roisman, Glenn I.; Booth-LaForce, Cathryn; Owen, Margaret Tresch; Holland, Ashley S.</p> <p>2013-01-01</p> <p>One of the assumptions of attachment theory is that individual differences in adult attachment styles emerge from individuals’ developmental histories. To examine this assumption empirically the authors report data from an age 18 follow-up (Booth-LaForce & Roisman, 2012) of the NICHD Study of <span class="hlt">Early</span> Child Care and Youth Development, a longitudinal investigation that tracked a cohort of children and their parents from birth to age 15. Analyses indicate that individual differences in adult attachment can be traced to variations in the quality of individuals’ caregiving environments, their emerging social competence, and the quality of their best friendship. Analyses also indicate that assessments of temperament and most of the specific <span class="hlt">genetic</span> polymorphisms thus far examined in the literature on <span class="hlt">genetic</span> correlates of attachment styles were essentially uncorrelated with adult attachment, with the exception of a polymorphism in the serotonin receptor gene (HTR2A rs6313), which modestly predicted higher attachment anxiety and that revealed a G × E interaction such that changes in maternal sensitivity across time predicted attachment-related avoidance. The implications of these data for contemporary perspectives and debates concerning adult attachment theory are discussed. PMID:23397970</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23383577','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23383577"><span>[<span class="hlt">Genetic</span> information and future medicine].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sakurai, Akihiro</p> <p>2012-11-01</p> <p>Rapid technological advances in <span class="hlt">genetic</span> analysis have revealed the <span class="hlt">genetic</span> background of various diseases. Elucidation of the genes responsible for a disease enables better clinical management of the disease and helps to develop targeted drugs. Also, <span class="hlt">early</span> diagnosis and management of at-risk family members can be made by identification of a <span class="hlt">genetic</span> disease in the proband. On the other hand, <span class="hlt">genetic</span> issues often cause psychological distress to the family. To perform <span class="hlt">genetic</span> testing appropriately and to protect patients and family members from any harm, guidelines for <span class="hlt">genetic</span> testing were released from the alliance of Japanese <span class="hlt">genetics</span>-related academic societies in 2003. As <span class="hlt">genetic</span> testing is becoming incorporated into clinical practice more broadly, the guideline was revised and released by the Japanese Society of Medical Sciences in 2011. All medical professionals in Japan are expected to follow this guideline.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23011587','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23011587"><span>Resistance evolution to the first generation of <span class="hlt">genetically</span> modified Diabrotica-active Bt-maize <span class="hlt">events</span> by western corn rootworm: management and monitoring considerations.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Devos, Yann; Meihls, Lisa N; Kiss, József; Hibbard, Bruce E</p> <p>2013-04-01</p> <p>Western corn rootworm (Diabrotica virgifera virgifera; WCR) is a major coleopteran maize pest in North America and the EU, and has traditionally been managed through crop rotation and broad-spectrum soil insecticides. <span class="hlt">Genetically</span> modified Bt-maize offers an additional management tool for WCR and has been valuable in reducing insecticide use and increasing farm income. A concern is that the widespread, repeated, and exclusive deployment of the same Bt-maize transformation <span class="hlt">event</span> will result in the rapid evolution of resistance in WCR. This publication explores the potential of WCR to evolve resistance to plant-produced Bt-toxins from the first generation of Diabrotica-active Bt-maize <span class="hlt">events</span> (MON 863 and MON 88017, DAS-59122-7 and MIR604), and whether currently implemented risk management strategies to delay and monitor resistance evolution are appropriate. In twelve of the twelve artificial selection experiments reported, resistant WCR populations were yielded rapidly. Field-selected resistance of WCR to Cry3Bb1 is documented in some US maize growing areas, where an increasing number of cases of unexpected damage of WCR larvae to Bt-maize MON 88017 has been reported. Currently implemented insect resistance management measures for Bt-crops usually rely on the high dose/refuge (HDR) strategy. Evidence (including laboratory, greenhouse and field data) indicates that several conditions contributing to the success of the HDR strategy may not be met for the first generation of Bt-maize <span class="hlt">events</span> and WCR: (1) the Bt-toxins are expressed heterogeneously at a low-to-moderate dose in roots; (2) resistance alleles may be present at a higher frequency than initially assumed; (3) WCR may mate in a non-random manner; (4) resistance traits could have non-recessive inheritance; and (5) fitness costs may not necessarily be associated with resistance evolution. However, caution must be exercised when extrapolating laboratory and greenhouse results to field conditions. Model predictions</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17036059','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17036059"><span>The ripples of "The Big (agricultural) Bang": the spread of <span class="hlt">early</span> wheat cultivation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Abbo, Shahal; Gopher, Avi; Peleg, Zvi; Saranga, Yehoshua; Fahima, Tzion; Salamini, Francesco; Lev-Yadun, Simcha</p> <p>2006-08-01</p> <p>Demographic expansion and (or) migrations leave their mark in the pattern of DNA polymorphisms of the respective populations. Likewise, the spread of cultural phenomena can be traced by dating archaeological finds and reconstructing their direction and pace. A similar course of <span class="hlt">events</span> is likely to have taken place following the "Big Bang" of the agricultural spread in the Neolithic Near East from its core area in southeastern Turkey. Thus far, no attempts have been made to track the movement of the founder <span class="hlt">genetic</span> stocks of the first crop plants from their core area based on the <span class="hlt">genetic</span> structure of living plants. In this minireview, we re-interpret recent wheat DNA polymorphism data to detect the <span class="hlt">genetic</span> ripples left by the <span class="hlt">early</span> wave of advance of Neolithic wheat farming from its core area. This methodology may help to suggest a model charting the spread of the first farming phase prior to the emergence of truly domesticated wheat types (and other such crops), thereby increasing our resolution power in studying this revolutionary period of human cultural, demographic, and social evolution.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1367063','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1367063"><span><span class="hlt">Early</span> <span class="hlt">Events</span> in Insulin Fibrillization Studied by Time-Lapse Atomic Force Microscopy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Podestà, Alessandro; Tiana, Guido; Milani, Paolo; Manno, Mauro</p> <p>2006-01-01</p> <p>The importance of understanding the mechanism of protein aggregation into insoluble amyloid fibrils lies not only in its medical consequences, but also in its more basic properties of self-organization. The discovery that a large number of uncorrelated proteins can form, under proper conditions, structurally similar fibrils has suggested that the underlying mechanism is a general feature of polypeptide chains. In this work, we address the <span class="hlt">early</span> <span class="hlt">events</span> preceding amyloid fibril formation in solutions of zinc-free human insulin incubated at low pH and high temperature. Here, we show by time-lapse atomic force microscopy that a steady-state distribution of protein oligomers with a quasiexponential tail is reached within a few minutes after heating. This metastable phase lasts for a few hours, until fibrillar aggregates are observable. Although for such complex systems different aggregation mechanisms can occur simultaneously, our results indicate that the prefibrillar phase is mainly controlled by a simple coagulation-evaporation kinetic mechanism, in which concentration acts as a critical parameter. These experimental facts, along with the kinetic model used, suggest a critical role for thermal concentration fluctuations in the process of fibril nucleation. PMID:16239333</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24025423','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24025423"><span>Redox signaling is an <span class="hlt">early</span> <span class="hlt">event</span> in the pathogenesis of renovascular hypertension.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hartono, Stella P; Knudsen, Bruce E; Zubair, Adeel S; Nath, Karl A; Textor, Stephen J; Lerman, Lilach O; Grande, Joseph P</p> <p>2013-09-10</p> <p>Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress <span class="hlt">early</span> in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3⁺ T cells and F4/80⁺ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of <span class="hlt">events</span> leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22009557','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22009557"><span>Biological aspects of <span class="hlt">early</span> osteoarthritis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Madry, Henning; Luyten, Frank P; Facchini, Andrea</p> <p>2012-03-01</p> <p><span class="hlt">Early</span> OA primarily affects articular cartilage and involves the entire joint, including the subchondral bone, synovial membrane, menisci and periarticular structures. The aim of this review is to highlight the molecular basis and histopathological features of <span class="hlt">early</span> OA. Selective review of literature. Risk factors for developing <span class="hlt">early</span> OA include, but are not limited to, a <span class="hlt">genetic</span> predisposition, mechanical factors such as axial malalignment, and aging. In <span class="hlt">early</span> OA, the articular cartilage surface is progressively becoming discontinuous, showing fibrillation and vertical fissures that extend not deeper than into the mid-zone of the articular cartilage, reflective of OARSI grades 1.0-3.0. <span class="hlt">Early</span> changes in the subchondral bone comprise a progressive increase in subchondral plate and subarticular spongiosa thickness. <span class="hlt">Early</span> OA affects not only the articular cartilage and the subchondral bone but also other structures of the joint, such as the menisci, the synovial membrane, the joint capsule, ligaments, muscles and the infrapatellar fat pad. <span class="hlt">Genetic</span> markers or marker combinations may become useful in the future to identify <span class="hlt">early</span> OA and patients at risk. The high socioeconomic impact of OA suggests that a better insight into the mechanisms of <span class="hlt">early</span> OA may be a key to develop more targeted reconstructive therapies at this first stage of the disease. Systematic review, Level II.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27847612','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27847612"><span>A Value-Based Medicine cost-utility analysis of <span class="hlt">genetic</span> testing for neovascular macular degeneration.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Brown, Gary C; Brown, Melissa M; Lieske, Heidi B; Lieske, Philip A; Brown, Kathryn S</p> <p>2015-01-01</p> <p>There is a dearth of patient, preference-based cost-effectiveness analyses evaluating <span class="hlt">genetic</span> testing for neovascular age-related macular degeneration (NVAMD). A Value-Based Medicine, 12-year, combined-eye model, cost-utility analysis evaluated <span class="hlt">genetic</span> testing of Category 3 AMD patients at age 65 for progression to NVAMD. The benefit of <span class="hlt">genetic</span> testing was predicated upon the fact that <span class="hlt">early</span>-treatment ranibizumab therapy (baseline vision 20/40-20/80) for NVAMD confers greater patient value than late-treatment (baseline vision ≤20/160). Published <span class="hlt">genetic</span> data and MARINA Study ranibizumab therapy data were utilized in the analysis. Patient value (quality-of-life gain) and financial value (2012 US real dollar) outcomes were discounted at 3 % annually. <span class="hlt">Genetic</span> testing-enabled, <span class="hlt">early</span>-treatment ranibizumab therapy per patient conferred mean 20/40 -1 vision, a 0.845 QALY gain and 14.1 % quality-of-life gain over sham therapy. Late-treatment ranibizumab therapy conferred mean 20/160 +2 vision, a 0.250 QALY gain and 4.2 % quality-of-life gain over sham therapy. The gain from <span class="hlt">early</span>-treatment over late-treatment was 0.595 QALY (10.0 % quality-of-life gain). The per-patient cost for <span class="hlt">genetic</span> testing/closer monitoring was $2205 per screened person, $2.082 billion for the 944,000 estimated new Category 3 AMD patients annually. <span class="hlt">Genetic</span> testing/monitoring costs per <span class="hlt">early</span>-treatment patient totaled $66,180. Costs per <span class="hlt">early</span>-treatment patient included: <span class="hlt">genetic</span> testing costs: $66,180 + direct non-ophthalmic medical costs: -$40,914 + caregiver costs: -$172,443 + employment costs: -$14,098 = a net societal cost saving of $160,582 per <span class="hlt">early</span> treatment patient. When <span class="hlt">genetic</span> screening facilitated an incremental 12,965 (8.0 %) of the 161,754, new annual NVAMD patients aged ≥65 in the US to undergo <span class="hlt">early</span>-treatment ranibizumab therapy, each additional patient treated accrued an overall, net financial gain for society of $160,582. <span class="hlt">Genetic</span> screening was cost-effective, using World</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23025643','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23025643"><span>Moderating effects of autism on parent views of <span class="hlt">genetic</span> screening for aggression.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>May, Michael E; Brandt, Rachel C; Bohannan, Joseph K</p> <p>2012-10-01</p> <p>Advances in gene-environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of <span class="hlt">genetic</span> screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving <span class="hlt">genetic</span> linkage studies to behavior, including proactive approaches for parents to avoid <span class="hlt">events</span> leading to aggression. The purpose of this study was to solicit the perspectives of parents who have children with autism about screening for genes associated with aggression, compared to responses from those who have children without disabilities and those planning to have children. Parents of children with autism were more likely to support screening and the use of the results to seek treatment if necessary. Results are discussed in the context of surveillance screening and systematic <span class="hlt">early</span> intervention for behavioral symptoms related to autism. The results may provide insight for clincians, researchers, policymakers, and advocacy groups related to diagnosing and treating aggression in people with autism.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2692014','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2692014"><span>Co-ordination of <span class="hlt">early</span> and late ripening <span class="hlt">events</span> in apples is regulated through differential sensitivities to ethylene</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Johnston, Jason W.; Gunaseelan, Kularajathaven; Pidakala, Paul; Wang, Mindy; Schaffer, Robert J.</p> <p>2009-01-01</p> <p>In this study, it is shown that anti-sense suppression of Malus domestica 1-AMINO-CYCLOPROPANE-CARBOXYLASE OXIDASE (MdACO1) resulted in fruit with an ethylene production sufficiently low to be able to assess ripening in the absence of ethylene. Exposure of these fruit to different concentrations of exogenous ethylene showed that flesh softening, volatile biosynthesis, and starch degradation, had differing ethylene sensitivity and dependency. <span class="hlt">Early</span> ripening <span class="hlt">events</span> such as the conversion of starch to sugars showed a low dependency for ethylene, but a high sensitivity to low concentrations of ethylene (0.01 μl l−1). By contrast, later ripening <span class="hlt">events</span> such as flesh softening and ester volatile production showed a high dependency for ethylene but were less sensitive to low concentrations (needing 0.1 μl l−1 for a response). A sustained exposure to ethylene was required to maintain ripening, indicating that the role of ethylene may go beyond that of ripening initiation. These results suggest a conceptual model for the control of individual ripening characters in apple, based on both ethylene dependency and sensitivity. PMID:19429839</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-201408200012HQ.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-201408200012HQ.html"><span>Ancient Earth, Alien Earths <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2014-08-20</p> <p>Panelists pose for a group photo at the “Ancient Earth, Alien Earths” <span class="hlt">Event</span> at NASA Headquarters in Washington, DC Wednesday, August 20, 2014. The <span class="hlt">event</span> was sponsored by NASA, the National Science Foundation (NSF), and the Smithsonian Institution and highlighted how research on <span class="hlt">early</span> Earth could help guide our search for habitable planets orbiting other stars. Photo Credit: (NASA/Aubrey Gemignani)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1261410-longitudinal-hydrodynamics-from-event-event-landau-initial-conditions','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1261410-longitudinal-hydrodynamics-from-event-event-landau-initial-conditions"><span>Longitudinal hydrodynamics from <span class="hlt">event-by-event</span> Landau initial conditions</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Sen, Abhisek; Gerhard, Jochen; Torrieri, Giorgio; ...</p> <p>2015-02-02</p> <p>Here we investigate three-dimensional ideal hydrodynamic evolution, with Landau initial conditions, incorporating <span class="hlt">event-by-event</span> variation with many <span class="hlt">events</span> and transverse density inhomogeneities. We show that the transition to boost-invariant flow occurs too late for realistic setups, with corrections of θ (20%-30%) expected at freeze-out for most scenarios. Moreover, the deviation from boost invariance is correlated with both transverse flow and elliptic flow, with the more highly transversely flowing regions also showing the most violation of boost invariance. Therefore, if longitudinal flow is not fully developed at the <span class="hlt">early</span> stages of heavy ion collisions, hydrodynamics where boost invariance holds at midrapidity ismore » inadequate to extract transport coefficients of the quark-gluon plasma. We conclude by arguing that developing experimental probes of boost invariance is necessary, and suggest some promising directions in this regard.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27228435','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27228435"><span><span class="hlt">Early</span> blood pressure lowering treatment in acute stroke. Ordinal analysis of vascular <span class="hlt">events</span> in the Scandinavian Candesartan Acute Stroke Trial (SCAST).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jusufovic, Mirza; Sandset, Else Charlotte; Bath, Philip M; Berge, Eivind</p> <p>2016-08-01</p> <p><span class="hlt">Early</span> blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular <span class="hlt">events</span> in the Scandinavian Candesartan Acute Stroke Trial to see if the effect was dependent on the timing of treatment. Scandinavian Candesartan Acute Stroke Trial was a randomized controlled and placebo-controlled trial of candesartan within 30 h of ischaemic or haemorrhagic stroke. Of 2029 patients, 231 (11.4%) had a vascular <span class="hlt">event</span> (vascular death, nonfatal stroke or nonfatal myocardial infarction) during the first 6 months. The modified Rankin Scale (mRS) score following a vascular <span class="hlt">event</span> was used to categorize vascular <span class="hlt">events</span> in order of severity: no <span class="hlt">event</span> (n = 1798), minor (mRS 0-2, n = 59), moderately severe (mRS 3-4, n = 57) and major <span class="hlt">event</span> (mRS 5-6, n = 115). We used ordinal logistic regression for analysis and adjusted for predefined prognostic variables. Candesartan had no overall effect on vascular <span class="hlt">events</span> (adjusted common odds ratio 1.11, 95% confidence interval 0.84-1.47, P = 0.48), and the effects were the same in ischaemic and haemorrhagic stroke. Among the patients treated within 6 h, the adjusted common odds ratio for vascular <span class="hlt">events</span> was 0.37, 95% confidence interval 0.16-0.84, P = 0.02, and there was no heterogeneity of effect between ischaemic and haemorrhagic strokes. Ordinal analysis of vascular <span class="hlt">events</span> showed no overall effect of candesartan in the subacute phase of stroke. The effect of treatment given within 6 h of stroke onset appears promising, and will be addressed in ongoing trials. Ordinal analysis of vascular <span class="hlt">events</span> is feasible and can be used in future trials.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20952460','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20952460"><span>Childhood trauma and children's emerging psychotic symptoms: A <span class="hlt">genetically</span> sensitive longitudinal cohort study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Arseneault, Louise; Cannon, Mary; Fisher, Helen L; Polanczyk, Guilherme; Moffitt, Terrie E; Caspi, Avshalom</p> <p>2011-01-01</p> <p>Using longitudinal and prospective measures of trauma during childhood, the authors assessed the risk of developing psychotic symptoms associated with maltreatment, bullying, and accidents in a nationally representative U.K. cohort of young twins. Data were from the Environmental Risk Longitudinal Twin Study, which follows 2,232 twin children and their families. Mothers were interviewed during home visits when children were ages 5, 7, 10, and 12 on whether the children had experienced maltreatment by an adult, bullying by peers, or involvement in an accident. At age 12, children were asked about bullying experiences and psychotic symptoms. Children's reports of psychotic symptoms were verified by clinicians. Children who experienced mal-treatment by an adult (relative risk=3.16, 95% CI=1.92-5.19) or bullying by peers (relative risk=2.47, 95% CI=1.74-3.52) were more likely to report psychotic symptoms at age 12 than were children who did not experience such traumatic <span class="hlt">events</span>. The higher risk for psychotic symptoms was observed whether these <span class="hlt">events</span> occurred <span class="hlt">early</span> in life or later in childhood. The risk associated with childhood trauma remained significant in analyses controlling for children's gender, socioeconomic deprivation, and IQ; for children's <span class="hlt">early</span> symptoms of internalizing or externalizing problems; and for children's <span class="hlt">genetic</span> liability to developing psychosis. In contrast, the risk associated with accidents was small (relative risk=1.47, 95% CI=1.02-2.13) and inconsistent across ages. Trauma characterized by intention to harm is associated with children's reports of psychotic symptoms. Clinicians working with children who report <span class="hlt">early</span> symptoms of psychosis should inquire about traumatic <span class="hlt">events</span> such as maltreatment and bullying.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20416541','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20416541"><span><span class="hlt">Genetic</span> counselling issues in cystic fibrosis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Culling, Bronwyn; Ogle, Robert</p> <p>2010-06-01</p> <p>Cystic fibrosis is a chronic condition for which <span class="hlt">genetic</span> testing offers much for the individuals affected in terms of an <span class="hlt">early</span> diagnosis and offers timely additional information for families with regard to family planning and prenatal testing. <span class="hlt">Genetic</span> counselling encompasses a range of clinical issues for families and forms a complementary resource for clinicians caring for people with cystic fibrosis. This review will discuss the range of <span class="hlt">genetic</span> information readily available to patients and families through <span class="hlt">genetic</span> counselling. Copyright 2010 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20952801','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20952801"><span>Common <span class="hlt">genetic</span> variants are significant risk factors for <span class="hlt">early</span> menopause: results from the Breakthrough Generations Study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Murray, Anna; Bennett, Claire E; Perry, John R B; Weedon, Michael N; Jacobs, Patricia A; Morris, Danielle H; Orr, Nicholas; Schoemaker, Minouk J; Jones, Michael; Ashworth, Alan; Swerdlow, Anthony J</p> <p>2011-01-01</p> <p>Women become infertile approximately 10 years before menopause, and as more women delay childbirth into their 30s, the number of women who experience infertility is likely to increase. Tests that predict the timing of menopause would allow women to make informed reproductive decisions. Current predictors are only effective just prior to menopause, and there are no long-range indicators. Age at menopause and <span class="hlt">early</span> menopause (EM) are highly heritable, suggesting a <span class="hlt">genetic</span> aetiology. Recent genome-wide scans have identified four loci associated with variation in the age of normal menopause (40-60 years). We aimed to determine whether theses loci are also risk factors for EM. We tested the four menopause-associated <span class="hlt">genetic</span> variants in a cohort of approximately 2000 women with menopause≤45 years from the Breakthrough Generations Study (BGS). All four variants significantly increased the odds of having EM. Comparing the 4.5% of individuals with the lowest number of risk alleles (two or three) with the 3.0% with the highest number (eight risk alleles), the odds ratio was 4.1 (95% CI 2.4-7.1, P=4.0×10(-7)). In combination, the four variants discriminated EM cases with a receiver operator characteristic area under the curve of 0.6. Four common <span class="hlt">genetic</span> variants identified by genome-wide association studies, had a significant impact on the odds of having EM in an independent cohort from the BGS. The discriminative power is still limited, but as more variants are discovered they may be useful for predicting reproductive lifespan.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4612769','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4612769"><span>Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular <span class="hlt">Events</span> Leading to Degeneration at the Neuromuscular Junction</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Lincoln, Barron L.; Alabsi, Sahar H.; Frendo, Nicholas; Freund, Robert; Keller, Lani C.</p> <p>2015-01-01</p> <p>Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of <span class="hlt">events</span> that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative <span class="hlt">events</span>, occurring at 24 hours post injury. Our data provide insights into the <span class="hlt">early</span> molecular <span class="hlt">events</span> that occur during axonal and neuromuscular degeneration in a <span class="hlt">genetically</span> tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular <span class="hlt">events</span> that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments. PMID:26512206</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25385898','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25385898"><span>Eye coding mechanisms in <span class="hlt">early</span> human face <span class="hlt">event</span>-related potentials.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rousselet, Guillaume A; Ince, Robin A A; van Rijsbergen, Nicola J; Schyns, Philippe G</p> <p>2014-11-10</p> <p>In humans, the N170 <span class="hlt">event</span>-related potential (ERP) is an integrated measure of cortical activity that varies in amplitude and latency across trials. Researchers often conjecture that N170 variations reflect cortical mechanisms of stimulus coding for recognition. Here, to settle the conjecture and understand cortical information processing mechanisms, we unraveled the coding function of N170 latency and amplitude variations in possibly the simplest socially important natural visual task: face detection. On each experimental trial, 16 observers saw face and noise pictures sparsely sampled with small Gaussian apertures. Reverse-correlation methods coupled with information theory revealed that the presence of the eye specifically covaries with behavioral and neural measurements: the left eye strongly modulates reaction times and lateral electrodes represent mainly the presence of the contralateral eye during the rising part of the N170, with maximum sensitivity before the N170 peak. Furthermore, single-trial N170 latencies code more about the presence of the contralateral eye than N170 amplitudes and <span class="hlt">early</span> latencies are associated with faster reaction times. The absence of these effects in control images that did not contain a face refutes alternative accounts based on retinal biases or allocation of attention to the eye location on the face. We conclude that the rising part of the N170, roughly 120-170 ms post-stimulus, is a critical time-window in human face processing mechanisms, reflecting predominantly, in a face detection task, the encoding of a single feature: the contralateral eye. © 2014 ARVO.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_22 --> <div id="page_23" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="441"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29642852','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29642852"><span>Parapatric <span class="hlt">genetic</span> divergence among deep evolutionary lineages in the Mediterranean green crab, Carcinus aestuarii (Brachyura, Portunoidea, Carcinidae), accounts for a sharp phylogeographic break in the Eastern Mediterranean.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Deli, Temim; Kalkan, Evrim; Karhan, Selahattin Ünsal; Uzunova, Sonya; Keikhosravi, Alireza; Bilgin, Raşit; Schubart, Christoph D</p> <p>2018-04-11</p> <p>Recently, population <span class="hlt">genetic</span> studies of Mediterranean marine species highlighted patterns of <span class="hlt">genetic</span> divergence and phylogeographic breaks, due to the interplay between impacts of Pleistocene climate shifts and contemporary hydrographical barriers. These factors markedly shaped the distribution of marine organisms and their <span class="hlt">genetic</span> makeup. The present study is part of an ongoing effort to understand the phylogeography and evolutionary history of the highly dispersive Mediterranean green crab, Carcinus aestuarii (Nardo, 1847), across the Mediterranean Sea. Recently, marked divergence between two highly separated haplogroups (<span class="hlt">genetic</span> types I and II) of C. aestuarii was discerned across the Siculo-Tunisian Strait, suggesting an <span class="hlt">Early</span> Pleistocene vicariant <span class="hlt">event</span>. In order to better identify phylogeographic patterns in this species, a total of 263 individuals from 22 Mediterranean locations were analysed by comparing a 587 basepair region of the mitochondrial gene Cox1 (cytochrome oxidase subunit 1). The examined dataset is composed of both newly generated sequences (76) and previously investigated ones (187). Our results unveiled the occurrence of a highly divergent haplogroup (<span class="hlt">genetic</span> type III) in the most north-eastern part of the Mediterranean Sea. Divergence between the most distinct type III and the common ancestor of both types I and II corresponds to the <span class="hlt">Early</span> Pleistocene and coincides with the historical episode of separation between types I and II. Our results also revealed strong <span class="hlt">genetic</span> divergence among adjacent regions (separating the Aegean and Marmara seas from the remaining distribution zone) and confirmed a sharp phylogeographic break across the Eastern Mediterranean. The recorded parapatric <span class="hlt">genetic</span> divergence, with the potential existence of a contact zone between both groups in the Ionian Sea and notable differences in the demographic history, suggest the likely impact of paleoclimatic <span class="hlt">events</span>, as well as past and contemporary oceanographic processes</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29573659','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29573659"><span>Evaluating the <span class="hlt">genetic</span> susceptibility to peer reported bullying behaviors.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Musci, Rashelle J; Bettencourt, Amie F; Sisto, Danielle; Maher, Brion; Uhl, George; Ialongo, Nicholas; Bradshaw, Catherine P</p> <p>2018-05-01</p> <p>Bullying is a significant public health concern with lasting impacts on youth. Although environmental risk factors for bullying have been well-characterized, <span class="hlt">genetic</span> influences on bullying are not well understood. This study explored the role of <span class="hlt">genetics</span> on <span class="hlt">early</span> childhood bullying behavior. Participants were 561 children who participated in a longitudinal randomized control trial of a preventive intervention beginning in first grade who were present for the first grade peer nominations used to measure <span class="hlt">early</span> childhood bullying and who provided <span class="hlt">genetic</span> data during the age 19-21 year follow-up in the form of blood or saliva. Measures included a polygenic risk score (PRS) derived from a conduct disorder genome wide association study. Latent profile analysis identified three profiles of bullying behaviors during <span class="hlt">early</span> childhood. Results suggest that the PRS was significantly associated with class membership, with individuals in the moderate bully-victim profile having the highest levels of the PRS and those in the high bully-victim profile having the lowest levels. This line of research has important implications for understanding <span class="hlt">genetic</span> vulnerability to bullying in <span class="hlt">early</span> childhood. Copyright © 2018 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22848412','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22848412"><span><span class="hlt">Genetic</span> markers enhance coronary risk prediction in men: the MORGAM prospective cohorts.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hughes, Maria F; Saarela, Olli; Stritzke, Jan; Kee, Frank; Silander, Kaisa; Klopp, Norman; Kontto, Jukka; Karvanen, Juha; Willenborg, Christina; Salomaa, Veikko; Virtamo, Jarmo; Amouyel, Phillippe; Arveiler, Dominique; Ferrières, Jean; Wiklund, Per-Gunner; Baumert, Jens; Thorand, Barbara; Diemert, Patrick; Trégouët, David-Alexandre; Hengstenberg, Christian; Peters, Annette; Evans, Alun; Koenig, Wolfgang; Erdmann, Jeanette; Samani, Nilesh J; Kuulasmaa, Kari; Schunkert, Heribert</p> <p>2012-01-01</p> <p>More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus <span class="hlt">genetic</span> risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design. Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on <span class="hlt">genetic</span> variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD <span class="hlt">events</span> occurred. <span class="hlt">Genetic</span> risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). <span class="hlt">Genetic</span> risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived. Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of <span class="hlt">early</span> onset CHD <span class="hlt">events</span>. <span class="hlt">Genetic</span> risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25101912','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25101912"><span>Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic <span class="hlt">events</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Baudhuin, Linnea M; Kotzer, Katrina E; Lagerstedt, Susan A</p> <p>2015-03-01</p> <p>Marfan syndrome is a systemic disorder that typically involves FBN1 mutations and cardiovascular manifestations. We investigated FBN1 genotype-phenotype correlations with aortic <span class="hlt">events</span> (aortic dissection and prophylactic aortic surgery) in patients with Marfan syndrome. Genotype and phenotype information from probands (n = 179) with an FBN1 pathogenic or likely pathogenic variant were assessed. A higher frequency of truncating or splicing FBN1 variants was observed in Ghent criteria-positive patients with an aortic <span class="hlt">event</span> (n = 34) as compared with all other probands (n = 145) without a reported aortic <span class="hlt">event</span> (79 vs. 39%; P < 0.0001), as well as Ghent criteria-positive probands (n = 54) without an aortic <span class="hlt">event</span> (79 vs. 48%; P = 0.0039). Most probands with an <span class="hlt">early</span> aortic <span class="hlt">event</span> had a truncating or splicing variant (100% (n = 12) and 95% (n = 21) of patients younger than 30 and 40 years old, respectively). Aortic <span class="hlt">events</span> occurred at a younger median age in patients with truncating/splicing variants (29 years) as compared with those with missense variants (51 years). A trend toward a higher frequency of truncating/splicing variants in patients with aortic dissection (n = 21) versus prophylactic surgery (n = 13) (85.7 vs. 69.3%; not significant) was observed. These aortic <span class="hlt">event</span>- and age-associated findings may have important implications for the management of Marfan syndrome patients with FBN1 truncating and splicing variants.<span class="hlt">Genet</span> Med 17 3, 177-187.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015AGUFMAE33B0487M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015AGUFMAE33B0487M"><span>Observation of Long Ionospheric Recoveries from Lightning-induced Electron Precipitation <span class="hlt">Events</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Mohammadpour Salut, M.; Cohen, M.</p> <p>2015-12-01</p> <p>Lightning strokes induces lower ionospheric nighttime disturbances which can be detected through Very Low Frequency (VLF) remote sensing via at least two means: (1) direct heating and ionization, known as an <span class="hlt">Early</span> <span class="hlt">event</span>, and (2) triggered precipitation of energetic electrons from the radiation belts, known as Lightning-induced Electron Precipitation (LEP). For each, the ionospheric recover time is typically a few minutes or less. A small class of <span class="hlt">Early</span> <span class="hlt">events</span> have been identified as having unusually long ionospheric recoveries (10s of minutes), with the underlying mechanism still in question. Our study shows for the first time that some LEP <span class="hlt">events</span> also demonstrate unusually long recovery. The VLF <span class="hlt">events</span> were detected by visual inspection of the recorded data in both the North-South and East-West magnetic fields. Data from the National Lightning Detection Network (NLDN) are used to determine the location and peak current of the lightning responsible for each lightning-associated VLF perturbation. LEP or <span class="hlt">Early</span> VLF <span class="hlt">events</span> are determined by measuring the time delay between the causative lightning discharges and the onset of all lightning-associated perturbations. LEP <span class="hlt">events</span> typically possess an onset delay greater than ~ 200 msec following the causative lightning discharges, while the onset of <span class="hlt">Early</span> VLF <span class="hlt">events</span> is time-aligned (<20 msec) with the lightning return stroke. Nonducted LEP <span class="hlt">events</span> are distinguished from ducted <span class="hlt">events</span> based on the location of the causative lightning relative to the precipitation region. From 15 March to 20 April and 15 October to 15 November 2011, a total of 385 LEP <span class="hlt">events</span> observed at Indiana, Montana, Colorado and Oklahoma VLF sites, on the NAA, NLK and NML transmitter signals. 46 of these <span class="hlt">events</span> exhibited a long recovery. It has been found that the occurrence rate of ducted long recovery LEP <span class="hlt">events</span> is higher than nonducted. Of the 46 long recovery LEP <span class="hlt">events</span>, 33 <span class="hlt">events</span> were induced by ducted whistlers, and 13 <span class="hlt">events</span> were associated with</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29189923','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29189923"><span>Congenital myasthenic syndrome with episodic apnoea: clinical, neurophysiological and <span class="hlt">genetic</span> features in the long-term follow-up of 19 patients.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>McMacken, Grace; Whittaker, Roger G; Evangelista, Teresinha; Abicht, Angela; Dusl, Marina; Lochmüller, Hanns</p> <p>2018-01-01</p> <p>Congenital myasthenic syndrome with episodic apnoea (CMS-EA) is a rare but potentially treatable cause of apparent life-threatening <span class="hlt">events</span> in infancy. The underlying mechanisms for sudden and recurrent episodes of respiratory arrest in these patients are unclear. Whilst CMS-EA is most commonly caused by mutations in CHAT, the list of associated genotypes is expanding. We reviewed clinical information from 19 patients with CMS-EA, including patients with mutations in CHAT, SLC5A7 and RAPSN, and patients lacking a <span class="hlt">genetic</span> diagnosis. Lack of <span class="hlt">genetic</span> diagnosis was more common in CMS-EA than in CMS without EA (56% n = 18, compared to 7% n = 97). Most patients manifested intermittent apnoea in the first 4 months of life (74%, n = 14). A degree of clinical improvement with medication was observed in most patients (74%, n = 14), but the majority of cases also showed a tendency towards complete remission of apnoeic <span class="hlt">events</span> with age (mean age of resolution 2 years 5 months). Signs of impaired neuromuscular transmission were detected on neurophysiology studies in 79% (n = 15) of cases, but in six cases, this was only apparent following specific neurophysiological testing protocols (prolonged high-frequency stimulation). A relatively large proportion of CMS-EA remains <span class="hlt">genetically</span> undiagnosed, which suggests the existence of novel causative CMS genes which remain uncharacterised. In light of the potential for recurrent life-threatening apnoeas in <span class="hlt">early</span> life and the positive response to therapy, <span class="hlt">early</span> diagnostic consideration of CMS-EA is critical, but without specific neurophysiology tests, it may go overlooked.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20040110937','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20040110937"><span>Optimization of Operations Resources via Discrete <span class="hlt">Event</span> Simulation Modeling</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Joshi, B.; Morris, D.; White, N.; Unal, R.</p> <p>1996-01-01</p> <p>The resource levels required for operation and support of reusable launch vehicles are typically defined through discrete <span class="hlt">event</span> simulation modeling. Minimizing these resources constitutes an optimization problem involving discrete variables and simulation. Conventional approaches to solve such optimization problems involving integer valued decision variables are the pattern search and statistical methods. However, in a simulation environment that is characterized by search spaces of unknown topology and stochastic measures, these optimization approaches often prove inadequate. In this paper, we have explored the applicability of <span class="hlt">genetic</span> algorithms to the simulation domain. <span class="hlt">Genetic</span> algorithms provide a robust search strategy that does not require continuity and differentiability of the problem domain. The <span class="hlt">genetic</span> algorithm successfully minimized the operation and support activities for a space vehicle, through a discrete <span class="hlt">event</span> simulation model. The practical issues associated with simulation optimization, such as stochastic variables and constraints, were also taken into consideration.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24240285','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24240285"><span><span class="hlt">Genetics</span> of nonsyndromic obesity.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lee, Yung Seng</p> <p>2013-12-01</p> <p>Common obesity is widely regarded as a complex, multifactorial trait influenced by the 'obesogenic' environment, sedentary behavior, and <span class="hlt">genetic</span> susceptibility contributed by common and rare <span class="hlt">genetic</span> variants. This review describes the recent advances in understanding the role of <span class="hlt">genetics</span> in obesity. New susceptibility loci and <span class="hlt">genetic</span> variants are being uncovered, but the collective effect is relatively small and could not explain most of the BMI heritability. Yet-to-be identified common and rare variants, epistasis, and heritable epigenetic changes may account for part of the 'missing heritability'. Evidence is emerging about the role of epigenetics in determining obesity susceptibility, mediating developmental plasticity, which confers obesity risk from <span class="hlt">early</span> life experiences. <span class="hlt">Genetic</span> prediction scores derived from selected <span class="hlt">genetic</span> variants, and also differential DNA methylation levels and methylation scores, have been shown to correlate with measures of obesity and response to weight loss intervention. <span class="hlt">Genetic</span> variants, which confer susceptibility to obesity-related morbidities like nonalcoholic fatty liver disease, were also discovered recently. We can expect discovery of more rare <span class="hlt">genetic</span> variants with the advent of whole exome and genome sequencing, and also greater understanding of epigenetic mechanisms by which environment influences <span class="hlt">genetic</span> expression and which mediate the gene-environment interaction.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014AGUFM.S53C4520F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014AGUFM.S53C4520F"><span>Imaging of <span class="hlt">early</span> acceleration phase of the 2013-2014 Boso slow slip <span class="hlt">event</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Fukuda, J.; Kato, A.; Obara, K.; Miura, S.; Kato, T.</p> <p>2014-12-01</p> <p>Based on GPS and seismic data, we examine the spatiotemporal evolution of a slow slip <span class="hlt">event</span> (SSE) and associated seismic activity that occurred off the Boso peninsula, central Japan, from December 2013 to January 2014. We use GPS data from 71 stations of the GEONET and 6 stations operated by Earthquake Research Institute of the University of Tokyo and Tohoku University around the Boso peninsula. We apply a modified version of the Network Inversion Filter to the GPS time series at the 77 stations to estimate the spatiotemporal evolution of daily cumulative slip and slip rate on the subducting Philippine Sea plate. In addition, we create an improved earthquake catalog by applying a matched filter technique to continuous seismograms and examine the spatiotemporal relations between slow slip and seismicity. We find that the SSE started in <span class="hlt">early</span> December 2013. The spatiotemporal evolution of slow slip and seismicity is divided into two distinct phases, an earlier slow phase from <span class="hlt">early</span> to 30 December 2013 (Phase I) and a subsequent faster phase from 30 December 2013 to 9 January 2014 (Phase II). During Phase I, slip accelerated slowly up to a maximum rate of 1.6 m/yr with potentially accelerating along-strike propagation at speeds on the order of 1 km/day or less and no accompanying seismicity. On the other hand, during Phase II, slip accelerated rapidly up to a maximum rate of 4.5 m/yr and then rapidly decelerated. The slip front propagated along strike at a constant speed of ~10 km/day. During the Phase II, slow slip was accompanied by seismic swarm activity that was highly correlated in space and time with slip rate, suggesting that the swarm activity was triggered by stress loading due to slow slip. <span class="hlt">Early</span> slow acceleration of slip has not been identified in the past Boso SSEs in 1996, 2002, 2007, and 2011. It is not clear at this point whether the past Boso SSEs started with slow acceleration similarly to the 2013-2014 SSE. The transition from the slow to the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25207640','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25207640"><span><span class="hlt">Early</span> spring, severe frost <span class="hlt">events</span>, and drought induce rapid carbon loss in high elevation meadows.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Arnold, Chelsea; Ghezzehei, Teamrat A; Berhe, Asmeret Asefaw</p> <p>2014-01-01</p> <p>By the end of the 20th century, the onset of spring in the Sierra Nevada mountain range of California has been occurring on average three weeks earlier than historic records. Superimposed on this trend is an increase in the presence of highly anomalous "extreme" years, where spring arrives either significantly late or <span class="hlt">early</span>. The timing of the onset of continuous snowpack coupled to the date at which the snowmelt season is initiated play an important role in the development and sustainability of mountain ecosystems. In this study, we assess the impact of extreme winter precipitation variation on aboveground net primary productivity and soil respiration over three years (2011 to 2013). We found that the duration of snow cover, particularly the timing of the onset of a continuous snowpack and presence of <span class="hlt">early</span> spring frost <span class="hlt">events</span> contributed to a dramatic change in ecosystem processes. We found an average 100% increase in soil respiration in 2012 and 2103, compared to 2011, and an average 39% decline in aboveground net primary productivity observed over the same time period. The overall growing season length increased by 57 days in 2012 and 61 days in 2013. These results demonstrate the dependency of these keystone ecosystems on a stable climate and indicate that even small changes in climate can potentially alter their resiliency.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21994016','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21994016"><span><span class="hlt">Genetic</span> ancestry and indigenous heritage in a Native American descendant community in Bermuda.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gaieski, Jill B; Owings, Amanda C; Vilar, Miguel G; Dulik, Matthew C; Gaieski, David F; Gittelman, Rachel M; Lindo, John; Gau, Lydia; Schurr, Theodore G</p> <p>2011-11-01</p> <p>Discovered in the <span class="hlt">early</span> 16th century by European colonists, Bermuda is an isolated set of islands located in the mid-Atlantic. Shortly after its discovery, Bermuda became the first English colony to forcibly import its labor by trafficking in enslaved Africans, white ethnic minorities, and indigenous Americans. Oral traditions circulating today among contemporary tribes from the northeastern United States recount these same <span class="hlt">events</span>, while, in Bermuda, St. David's Islanders consider their histories to be linked to a complex Native American, European, and African past. To investigate the influence of historical <span class="hlt">events</span> on biological ancestry and native cultural identity, we analyzed <span class="hlt">genetic</span> variation in 111 members of Bermuda's self-proclaimed St. David's Island Native Community. Our results reveal that the majority of mitochondrial DNA (mtDNA) and Y-chromosome haplotypes are of African and West Eurasian origin. However, unlike other English-speaking New World colonies, most African mtDNA haplotypes appear to derive from central and southeast Africa, reflecting the extent of maritime activities in the region. In light of genealogical and oral historical data from the St. David's community, the low frequency of Native American mtDNA and NRY lineages may reflect the influence of <span class="hlt">genetic</span> drift, the demographic impact of European colonization, and historical admixture with persons of non-native backgrounds, which began with the settlement of the islands. By comparing the <span class="hlt">genetic</span> data with genealogical and historical information, we are able to reconstruct the complex history of this Bermudian community, which is unique among New World populations. Copyright © 2011 Wiley-Liss, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22675906','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22675906"><span>Social-emotional development through a behavior <span class="hlt">genetics</span> lens: infancy through preschool.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>DiLalla, Lisabeth Fisher; Mullineaux, Paula Y; Biebl, Sara J W</p> <p>2012-01-01</p> <p>The field of developmental behavior <span class="hlt">genetics</span> has added significantly to the collective understanding of what factors influence human behavior and human development. Research in this area has helped to explain not only how genes and environment contribute to individual differences but also how the interplay between genes and environment influences behavior and human development. The current chapter provides a background of the theory and methodology behind behavior <span class="hlt">genetic</span> research and the field of developmental behavior <span class="hlt">genetics</span>. It also examines three specific developmental periods as they relate to behavior <span class="hlt">genetic</span> research: infancy, toddlerhood, and <span class="hlt">early</span> preschool. The behavior <span class="hlt">genetic</span> literature is reviewed for key socioemotional developmental behaviors that fit under each of these time periods. Temperament, attachment, frustration, empathy, and aggression are behaviors that develop in <span class="hlt">early</span> life that were examined here. Thus, the general purpose of this chapter is to provide an overview of how genes and environment, as well as the interplay between them, relate to <span class="hlt">early</span> socioemotional behaviors.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24341070','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24341070"><span>[A case report of <span class="hlt">early</span>-onset Alzheimer's disease with multiple psychotic symptoms, finally diagnosed as APPV717I mutation by <span class="hlt">genetic</span> testing].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ishimaru, Takashi; Ochi, Shinichiro; Matsumoto, Teruhisa; Yoshida, Taku; Abe, Masao; Toyota, Yasutaka; Fukuhara, Ryuji; Tanimukai, Satoshi; Ueno, Shu-ichi</p> <p>2013-01-01</p> <p>It is difficult to confirm a diagnosis of <span class="hlt">early</span>-onset Alzheimer's disease (EOAD) because patients sometimes have non-specific cortical features, such as psychiatric symptoms, executive functional impairment, and pyramidal symptoms, along with typical symptoms, such as recent memory impairment and disorientation. We encountered a patient with multiple psychotic symptoms, finally diagnosed with EOAD on <span class="hlt">genetic</span> testing. A right-handed sixty-year-old man, whose mother was suspected of having dementia, developed memory impairment at the age of fifty, disorientation at the age of fifty-six, and both visual hallucination and dressing apraxia at the age of fifty-nine. After admission to a psychiatric hospital for treatment, his symptoms disappeared with antipsychotic medication. However, his ADL were declining and so he was referred to our university hospital. He had frontal lobe symptoms, pyramidal signs, and extrapyramidal signs with severe dementia. Neuropsychological examinations were not possible because of sedation. On brain MRI, he showed diffuse atrophy of the cerebral cortex and hippocampus. HMPO-SPECT showed hypoperfusion of cerebral cortices diffusely. We decided to perform <span class="hlt">genetic</span> testing because he had both family and alcohol abuse histories. He showed EOAD with V717I mutation of the amyloid precursor protein gene. After the discontinuation of antipsychotics, excessive sedation and extrapyramidal signs disappeared. A dose of 10 mg of donepezil was effective to improve motivation and activity, and his mini mental examination score was calculable after recovery. The case supports usefulness of applying <span class="hlt">genetic</span> testing for Alzheimer's disease to patients with <span class="hlt">early</span> onset dementia, even when they do not have a family history.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27402751','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27402751"><span>The integration of quantitative <span class="hlt">genetics</span>, paleontology, and neontology reveals <span class="hlt">genetic</span> underpinnings of primate dental evolution.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hlusko, Leslea J; Schmitt, Christopher A; Monson, Tesla A; Brasil, Marianne F; Mahaney, Michael C</p> <p>2016-08-16</p> <p>Developmental <span class="hlt">genetics</span> research on mice provides a relatively sound understanding of the genes necessary and sufficient to make mammalian teeth. However, mouse dentitions are highly derived compared with human dentitions, complicating the application of these insights to human biology. We used quantitative <span class="hlt">genetic</span> analyses of data from living nonhuman primates and extensive osteological and paleontological collections to refine our assessment of dental phenotypes so that they better represent how the underlying <span class="hlt">genetic</span> mechanisms actually influence anatomical variation. We identify ratios that better characterize the output of two dental <span class="hlt">genetic</span> patterning mechanisms for primate dentitions. These two newly defined phenotypes are heritable with no measurable pleiotropic effects. When we consider how these two phenotypes vary across neontological and paleontological datasets, we find that the major Middle Miocene taxonomic shift in primate diversity is characterized by a shift in these two <span class="hlt">genetic</span> outputs. Our results build on the mouse model by combining quantitative <span class="hlt">genetics</span> and paleontology, and thereby elucidate how <span class="hlt">genetic</span> mechanisms likely underlie major <span class="hlt">events</span> in primate evolution.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24462783','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24462783"><span>Accuracy of episodic autobiographical memory in children with <span class="hlt">early</span> thyroid hormone deficiency using a staged <span class="hlt">event</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Willoughby, Karen A; McAndrews, Mary Pat; Rovet, Joanne F</p> <p>2014-07-01</p> <p>Autobiographical memory (AM) is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical <span class="hlt">event</span>, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO) exposed during gestation to insufficient maternal thyroid hormone (TH), a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH), who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged <span class="hlt">event</span> than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with <span class="hlt">early</span> TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28073956','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28073956"><span>The effect of rheumatoid arthritis-associated autoantibodies on the incidence of cardiovascular <span class="hlt">events</span> in a large inception cohort of <span class="hlt">early</span> inflammatory arthritis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Barra, Lillian J; Pope, Janet E; Hitchon, Carol; Boire, Gilles; Schieir, Orit; Lin, Daming; Thorne, Carter J; Tin, Diane; Keystone, Edward C; Haraoui, Boulos; Jamal, Shahin; Bykerk, Vivian P</p> <p>2017-05-01</p> <p>. RA is associated with an increased risk of cardiovascular <span class="hlt">events</span> (CVEs). The objective was to estimate independent effects of RA autoantibodies on the incident CVEs in patients with <span class="hlt">early</span> RA. Patients were enrolled in the Canadian <span class="hlt">Early</span> Inflammatory Arthritis Cohort, a prospective multicentre inception cohort. Incident CVEs, including acute coronary syndromes and cerebrovascular <span class="hlt">events</span>, were self-reported by the patient and partially validated by medical chart review. Seropositive status was defined as either RF or ACPA positive. Multivariable Cox proportional hazards survival analysis was used to estimate the effects of seropositive status on incident CVEs, controlling for RA clinical variables and traditional cardiovascular risk factors. . A total of 2626 patients were included: the mean symptom duration at diagnosis was 6.3 months ( s . d . 4.6), the mean age was 53 years ( s . d . 15), 72% were female and 86% met classification criteria for RA. Forty-six incident CVEs occurred over 6483 person-years [incidence rate 7.1/1000 person-years (95% confidence interval 5.3, 9.4)]. The CVE rate did not differ in seropositive vs seronegative subjects and seropositivity was not associated with incident CVEs in multivariable Cox regression models. Baseline covariates independently associated with incident CVEs were older age, a history of hypertension and a longer duration of RA symptoms prior to diagnosis. The rate of CVEs <span class="hlt">early</span> in the course of inflammatory arthritis was low; however, delays in the diagnosis of arthritis increased the rate of CVEs. Hypertension was the strongest independent risk factor for CVEs. Results support <span class="hlt">early</span> aggressive management of RA disease activity and co-morbidities to prevent severe complications. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5314367','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5314367"><span>Ecology and <span class="hlt">genetics</span> affect relative invasion success of two Echium species in southern Australia</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zhu, Xiaocheng; Weston, Paul A.; Skoneczny, Dominik; Gopurenko, David; Meyer, Lucie; Lepschi, Brendan J.; Callaway, Ragan M.; Gurr, Geoff M.; Weston, Leslie A.</p> <p>2017-01-01</p> <p>Echium plantagineum and E. vulgare are congeneric exotics first introduced to Australia in the <span class="hlt">early</span> 1800 s. There, E. plantagineum is now highly invasive, whereas E. vulgare has a limited distribution. Studies were conducted to evaluate distribution, ecology, <span class="hlt">genetics</span> and secondary chemistry to shed light on factors associated with their respective invasive success. When sampled across geographically diverse locales, E. plantagineum was widespread and exhibited a small genome size (1 C = 0.34 pg), an annual life cycle, and greater <span class="hlt">genetic</span> diversity as assessed by DNA sequence analysis. It was found frequently in areas with temperature extremes and low rainfall. In contrast, E. vulgare exhibited a larger genome size (1 C = 0.43 pg), a perennial lifecycle, less chloroplast <span class="hlt">genetic</span> diversity, and occurred in areas with lower temperatures and higher rainfall. Twelve chloroplast haplotypes of E. plantagineum were evident and incidence aligned well with reported historical introduction <span class="hlt">events</span>. In contrast, E. vulgare exhibited two haplotypes and was found only sporadically at higher elevations. Echium plantagineum possessed significantly higher levels of numerous pyrrolizidine alkaloids involved in plant defence. We conclude that elevated <span class="hlt">genetic</span> diversity, tolerance to environmental stress and capacity for producing defensive secondary metabolites have contributed to the successful invasion of E. plantagineum in Australia. PMID:28211478</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-201408200003HQ.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-201408200003HQ.html"><span>Ancient Earth, Alien Earths <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2014-08-20</p> <p>Panelists discuss how research on <span class="hlt">early</span> Earth could help guide our search for habitable planets orbiting other stars at the “Ancient Earth, Alien Earths” <span class="hlt">Event</span> at NASA Headquarters in Washington, DC Wednesday, August 20, 2014. The <span class="hlt">event</span> was sponsored by NASA, the National Science Foundation (NSF), and the Smithsonian Institution and was moderated by Dr. David H. Grinspoon, Senior Scientist at the Planetary Science Institute. Photo Credit: (NASA/Aubrey Gemignani)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-201408200011HQ.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-201408200011HQ.html"><span>Ancient Earth, Alien Earths <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2014-08-20</p> <p>Dr. David H. Grinspoon, Senior Scientist, Planetary Science Institute, moderates a panel at the “Ancient Earth, Alien Earths” <span class="hlt">Event</span> at NASA Headquarters in Washington, DC Wednesday, August 20, 2014. The <span class="hlt">event</span> was sponsored by NASA, the National Science Foundation (NSF), and the Smithsonian Institution and highlighted how research on <span class="hlt">early</span> Earth could help guide our search for habitable planets orbiting other stars. Photo Credit: (NASA/Aubrey Gemignani)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10392796','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10392796"><span><span class="hlt">Genetic</span> analysis of motor milestones attainment in <span class="hlt">early</span> childhood.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Peter, I; Vainder, M; Livshits, G</p> <p>1999-03-01</p> <p>The age of attainment for four motor developmental traits, such as turning over, sitting up without support, pulling up to a standing position and walking without support, was examined in 822 children, including 626 siblings from families with 2 to 6 children, 68 pairs of dizygotic twins and 30 pairs of monozygotic twins. Correlation analysis, carried out separately for each type of sibship, showed the highest pairwise correlations in monozygotic twins and the lowest correlation in non-twin siblings for all motor milestones. Variance component analysis was used to decompose the different independent components forming the variation of the studied trait, such as <span class="hlt">genetic</span> effect, common twin environment, common sib environment and residual factors. The results revealed that the major proportion of the total variance after adjustment for gestation age for the attainment of each motor skill, except pulling up to standing position, is explained by the common twin environment (50.5 to 66.6%), whilst a moderate proportion is explained by additive <span class="hlt">genetic</span> factors (22.2 to 33.5%). Gestational age was found to be an important predictor of appearance of all motor milestones, affecting delay of 4.5 to 8.6 days for the attainment of the motor abilities for each week of earlier gestation. The age of attainment of the standing position was affected only by shared sibs environment (33.3% of the total variance) and showed no influence of either <span class="hlt">genetic</span> or common twin environment. Phenotypic between trait correlations were high and significant for all studied traits (range between 0.40 and 0.67, P < 0.01 in all instances). <span class="hlt">Genetic</span> cross correlations, however, were not easily interpreted and did not show clear variance trends among the different groups of children.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_23 --> <div id="page_24" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="461"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5351980','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5351980"><span>Repetitive mammalian dwarfing during ancient greenhouse warming <span class="hlt">events</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>D’Ambrosia, Abigail R.; Clyde, William C.; Fricke, Henry C.; Gingerich, Philip D.; Abels, Hemmo A.</p> <p>2017-01-01</p> <p>Abrupt perturbations of the global carbon cycle during the <span class="hlt">early</span> Eocene are associated with rapid global warming <span class="hlt">events</span>, which are analogous in many ways to present greenhouse warming. Mammal dwarfing has been observed, along with other changes in community structure, during the largest of these ancient global warming <span class="hlt">events</span>, known as the Paleocene-Eocene Thermal Maximum [PETM; ~56 million years ago (Ma)]. We show that mammalian dwarfing accompanied the subsequent, smaller-magnitude warming <span class="hlt">event</span> known as Eocene Thermal Maximum 2 [ETM2 (~53 Ma)]. Statistically significant decrease in body size during ETM2 is observed in two of four taxonomic groups analyzed in this study and is most clearly observed in <span class="hlt">early</span> equids (horses). During ETM2, the best-sampled lineage of equids decreased in size by ~14%, as opposed to ~30% during the PETM. Thus, dwarfing appears to be a common evolutionary response of some mammals during past global warming <span class="hlt">events</span>, and the extent of dwarfing seems related to the magnitude of the <span class="hlt">event</span>. PMID:28345031</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20594379','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20594379"><span>Life <span class="hlt">events</span> and borderline personality features: the influence of gene-environment interaction and gene-environment correlation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Distel, M A; Middeldorp, C M; Trull, T J; Derom, C A; Willemsen, G; Boomsma, D I</p> <p>2011-04-01</p> <p>Traumatic life <span class="hlt">events</span> are generally more common in patients with borderline personality disorder (BPD) than in non-patients or patients with other personality disorders. This study investigates whether exposure to life <span class="hlt">events</span> moderates the <span class="hlt">genetic</span> architecture of BPD features. As the presence of genotype-environment correlation (rGE) can lead to spurious findings of genotype-environment interaction (G × E), we also test whether BPD features increase the likelihood of exposure to life <span class="hlt">events</span>. The extent to which an individual is at risk to develop BPD was assessed with the Personality Assessment Inventory - Borderline features scale (PAI-BOR). Life <span class="hlt">events</span> under study were a divorce/break-up, traffic accident, violent assault, sexual assault, robbery and job loss. Data were available for 5083 twins and 1285 non-twin siblings. Gene-environment interaction and correlation were assessed by using structural equation modelling (SEM) and the co-twin control design. There was evidence for both gene-environment interaction and correlation. Additive <span class="hlt">genetic</span> influences on BPD features interacted with the exposure to sexual assault, with <span class="hlt">genetic</span> variance being lower in exposed individuals. In individuals who had experienced a divorce/break-up, violent assault, sexual assault or job loss, environmental variance for BPD features was higher, leading to a lower heritability of BPD features in exposed individuals. Gene-environment correlation was present for some life <span class="hlt">events</span>. The genes that influence BPD features thus also increased the likelihood of being exposed to certain life <span class="hlt">events</span>. To our knowledge, this study is the first to test the joint effect of <span class="hlt">genetic</span> and environmental influences and the exposure to life <span class="hlt">events</span> on BPD features in the general population. Our results indicate the importance of both <span class="hlt">genetic</span> vulnerability and life <span class="hlt">events</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009iip..book..220C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009iip..book..220C"><span>A Risk Assessment System with Automatic Extraction of <span class="hlt">Event</span> Types</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Capet, Philippe; Delavallade, Thomas; Nakamura, Takuya; Sandor, Agnes; Tarsitano, Cedric; Voyatzi, Stavroula</p> <p></p> <p>In this article we describe the joint effort of experts in linguistics, information extraction and risk assessment to integrate <span class="hlt">Event</span>Spotter, an automatic <span class="hlt">event</span> extraction engine, into ADAC, an automated <span class="hlt">early</span> warning system. By detecting as <span class="hlt">early</span> as possible weak signals of emerging risks ADAC provides a dynamic synthetic picture of situations involving risk. The ADAC system calculates risk on the basis of fuzzy logic rules operated on a template graph whose leaves are <span class="hlt">event</span> types. <span class="hlt">Event</span>Spotter is based on a general purpose natural language dependency parser, XIP, enhanced with domain-specific lexical resources (Lexicon-Grammar). Its role is to automatically feed the leaves with input data.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ghr.nlm.nih.gov/condition/hereditary-myopathy-with-early-respiratory-failure','NIH-MEDLINEPLUS'); return false;" href="https://ghr.nlm.nih.gov/condition/hereditary-myopathy-with-early-respiratory-failure"><span><span class="hlt">Genetics</span> Home Reference: hereditary myopathy with <span class="hlt">early</span> respiratory failure</span></a></p> <p><a target="_blank" href="http://medlineplus.gov/">MedlinePlus</a></p> <p></p> <p></p> <p>... Home Health Conditions HMERF Hereditary myopathy with <span class="hlt">early</span> respiratory failure Printable PDF Open All Close All Enable ... expand/collapse boxes. Description Hereditary myopathy with <span class="hlt">early</span> respiratory failure ( HMERF ) is an inherited muscle disease that ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12551774','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12551774"><span>Nutrient-gene interactions in <span class="hlt">early</span> pregnancy: a vascular hypothesis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Steegers-Theunissen, R P M; Steegers, E A P</p> <p>2003-02-10</p> <p>It is hypothesized that the following periconceptional and <span class="hlt">early</span> pregnancy nutrient-gene interactions link vascular-related reproductive complications and cardiovascular diseases in adulthood: (1) Maternal and paternal <span class="hlt">genetically</span> controlled nutrient status affects the quality of gametes and fertilization capacity; (2) The embryonic <span class="hlt">genetic</span> constitution, derived from both parents, and the maternal <span class="hlt">genetically</span> controlled nutrient environment determine embryogenesis and fetal growth; (3) Trophoblast invasion of decidua and spiral arteries is driven by genes derived from both parents as well as by maternal nutritional factors; (4) Angiogenesis, vasculogenesis and vascular function are dependent on the <span class="hlt">genetic</span> constitution of the embryo, derived from both parents, and the maternal <span class="hlt">genetically</span> controlled nutritional environment.<span class="hlt">Early</span> intra-uterine programming of vessels may concern the same (in)dependent determinants of vascular-related complications during pregnancy and cardiovascular diseases in later life.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://epi.grants.cancer.gov/early_life_exposures/','NCI'); return false;" href="https://epi.grants.cancer.gov/early_life_exposures/"><span><span class="hlt">Early</span> Life Exposures and Cancer</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p><span class="hlt">Early</span>-life <span class="hlt">events</span> and exposures have important consequences for cancer development later in life, however, epidemiological studies of <span class="hlt">early</span>-life factors and cancer development later in life have had significant methodological challenges.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29045471','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29045471"><span>Parental and offspring contribution of <span class="hlt">genetic</span> markers of adult blood pressure in <span class="hlt">early</span> life: The FAMILY study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Robiou-du-Pont, Sébastien; Anand, Sonia S; Morrison, Katherine M; McDonald, Sarah D; Atkinson, Stephanie A; Teo, Koon K; Meyre, David</p> <p>2017-01-01</p> <p>Previous genome wide association studies (GWAS) identified associations of multiple common variants with diastolic and systolic blood pressure traits in adults. However, the contribution of these loci to variations of blood pressure in <span class="hlt">early</span> life is unclear. We assessed the child and parental contributions of 33 GWAS single-nucleotide polymorphisms (SNPs) for blood pressure in 1,525 participants (515 children, 406 mothers and 237 fathers) of the Family Atherosclerosis Monitoring In <span class="hlt">early</span> life (FAMILY) study followed-up for 5 years. Two genotype scores for systolic (29 SNPs) and diastolic (24 SNPs) blood pressure were built. Linear mixed-effect regressions showed significant association between rs1378942 in CSK and systolic blood pressure (β = 0.98±0.46, P = 3.4×10-2). The child genotype scores for diastolic and systolic blood pressure were not associated in children. Nominally significant parental <span class="hlt">genetic</span> effects were found between the SNPs rs11191548 (CYP17A1) (paternal, β = 2.78±1.49, P = 6.1×10-2 for SBP and β = 3.60±1.24, P = 3.7×10-3 for DBP), rs17367504 (MTHFR) (paternal, β = 2.42±0.93, P = 9.3×10-3 for SBP and β = 1.89±0.80, P = 1.8×10-2 for DBP and maternal, β = -1.32±0.60, P = 2.9×10-2 and β = -1.97±0.77, P = 1.0×10-2, for SBP and DBP respectively) and child blood pressure. Our study supports the view that adult GWAS loci have a limited impact on blood pressure during the five first years of life. The parental <span class="hlt">genetic</span> effects observed on blood pressure in children may suggest epigenetic mechanisms in the transmission of the risk of hypertension. Further replication is needed to confirm our results.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2012AGUFMPP11C2035H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2012AGUFMPP11C2035H"><span>Timing of the Toarcian Ocean Anoxic <span class="hlt">Event</span> (<span class="hlt">Early</span> Jurassic) from correlation of astronomically forced global stratigraphic sections</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Huang, C.; Hinnov, L. A.; Hesselbo, S. P.</p> <p>2012-12-01</p> <p>The <span class="hlt">Early</span> Toarcian Oceanic Anoxic <span class="hlt">Event</span> (OAE) in the <span class="hlt">Early</span> Jurassic Period is associated with a major negative carbon isotope excursion (CIE), mass extinction, marine transgression and global warming. The Toarcian OAE is thought to have been caused by flood basalt magmatism, and may have been a trigger for mass extinction. However, these proposed causes of the Toarcian OAE and associated biotic crisis are not adequately resolved by a precise chronology. The duration of the Toarcian OAE has been estimated to be anywhere from ~0.12 to ~0.9 Myr, most recently 0.74 to 3.26 Myr from U-Pb dating. The CIE associated with the Toarcian OAE has a similar pattern at numerous localities, and there is evidence for astronomical forcing of marine carbon isotopes. Here we estimate a duration of ~625 kyr for the main negative CIE, ~860 kyr for the polymorphum zone and >1.58 Myr for the levisoni zone based on 405-kyr astronomical eccentricity tuning of the marine section at Peniche (Portugal). This 405-kyr tuned series provides a ~2.5 Myr continuous high-resolution chronology through the <span class="hlt">Early</span> Toarcian. There are 6, or possibly 7 short eccentricity cycles in the main CIE interval at Peniche. To confirm this astronomically based estimate, we analyzed five other sections at Yorkshire (UK), Dotternhausen (Germany), Valdorbia (Italy), Mechowo (Poland) and Serrucho, Neuquén (Argentina), from marine and terrestrial carbon isotopic series. These six stratigraphic sections from <span class="hlt">Early</span> Jurassic western Tethys and eastern Panthalassa record the Toarcian OAE with ~6 prominent carbon isotope cycles in the CIE that provide us a 600 ± 100 kyr duration. The Peniche 405 kyr-tuned series indicates that the pre- and post-CIE intervals experienced strong precession-eccentricity-forced climate change, whereas the CIE interval is marked by dominant obliquity forcing. These dramatic and abrupt changes in astronomical response in the carbon isotopes point to fundamental shifting in the <span class="hlt">Early</span> Toarcian</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4915781','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4915781"><span><span class="hlt">Genetics</span> of Inflammatory Bowel Diseases</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>McGovern, Dermot; Kugathasan, Subra; Cho, Judy H.</p> <p>2015-01-01</p> <p>In this Review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and non-coding <span class="hlt">genetic</span> variation. In the small minority of loci where major association signals correspond to non-synonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve non-coding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that expression of the large majority of human genes is regulated by non-coding <span class="hlt">genetic</span> variation. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD <span class="hlt">genetics</span> studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare <span class="hlt">genetic</span> variation of higher effects (i.e. odds ratios markedly deviating from one) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in very-<span class="hlt">early</span> onset, more severe cases. A major challenge in IBD <span class="hlt">genetics</span> will be harnessing the vast array of <span class="hlt">genetic</span> discovery for clinical utility, through emerging precision medicine initiatives. We discuss the rapidly evolving area of direct to consumer <span class="hlt">genetic</span> testing, as well as the current utility of clinical exome sequencing, especially in very <span class="hlt">early</span> onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect of partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19634033','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19634033"><span>Learning abilities and disabilities: generalist genes in <span class="hlt">early</span> adolescence.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Davis, Oliver S P; Haworth, Claire M A; Plomin, Robert</p> <p>2009-01-01</p> <p>The new view of cognitive neuropsychology that considers not just case studies of rare severe disorders but also common disorders, as well as normal variation and quantitative traits, is more amenable to recent advances in molecular <span class="hlt">genetics</span>, such as genome-wide association studies, and advances in quantitative <span class="hlt">genetics</span>, such as multivariate <span class="hlt">genetic</span> analysis. A surprising finding emerging from multivariate quantitative <span class="hlt">genetic</span> studies across diverse learning abilities is that most <span class="hlt">genetic</span> influences are shared: they are "generalist", rather than "specialist". We exploited widespread access to inexpensive and fast Internet connections in the United Kingdom to assess over 5000 pairs of 12-year-old twins from the Twins <span class="hlt">Early</span> Development Study (TEDS) on four distinct batteries: reading, mathematics, general cognitive ability (g) and, for the first time, language. <span class="hlt">Genetic</span> correlations remain high among all of the measured abilities, with language as highly correlated <span class="hlt">genetically</span> with g as reading and mathematics. Despite developmental upheaval, generalist genes remain important into <span class="hlt">early</span> adolescence, suggesting optimal strategies for molecular <span class="hlt">genetic</span> studies seeking to identify the genes of small effect that influence learning abilities and disabilities.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2006QuRes..66..401W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2006QuRes..66..401W"><span>Climate forcing due to the 8200 cal yr BP <span class="hlt">event</span> observed at <span class="hlt">Early</span> Neolithic sites in the eastern Mediterranean</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Weninger, Bernhard; Alram-Stern, Eva; Bauer, Eva; Clare, Lee; Danzeglocke, Uwe; Jöris, Olaf; Kubatzki, Claudia; Rollefson, Gary; Todorova, Henrieta; van Andel, Tjeerd</p> <p>2006-11-01</p> <p>We explore the hypothesis that the abrupt drainage of Laurentide lakes and associated rapid switch of the North Atlantic thermohaline circulation 8200 yr ago had a catastrophic influence on Neolithic civilisation in large parts of southeastern Europe, Anatolia, Cyprus, and the Near East. The <span class="hlt">event</span> at 8200 cal yr BP is observed in a large number of high-resolution climate proxies in the Northern Hemisphere, and in many cases corresponds to markedly cold and arid conditions. We identify the relevant archaeological levels of major Neolithic settlements in Central Anatolia, Cyprus, Greece and Bulgaria, and examine published stratigraphic, architectural, cultural and geoarchaeological studies for these sites. The specific archaeological <span class="hlt">events</span> and processes we observe at a number of these sites during the study interval 8400-8000 cal yr BP lead us to refine some previously established Neolithisation models. The introduction of farming to South-East Europe occurs in all study regions (Thrace, Macedonia, Thessaly, Bulgaria) near 8200 cal yr BP. We observe major disruptions of Neolithic cultures in the Levant, North Syria, South-East Anatolia, Central Anatolia and Cyprus, at the same time. We conclude that the 8200 cal yr BP aridity <span class="hlt">event</span> triggered the spread of <span class="hlt">early</span> farmers, by different routes, out of West Asia and the Near East into Greece and Bulgaria.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010EGUGA..12.4185L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010EGUGA..12.4185L"><span>Impacts of a water stress followed by an <span class="hlt">early</span> frost <span class="hlt">event</span> on beech (Fagus sylvatica L.) susceptibility to Scolytine ambrosia beetles - Research strategy and first results</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>La Spina, Sylvie; de Cannière, Charles; Molenberg, Jean-Marc; Vincke, Caroline; Deman, Déborah; Grégoire, Jean-Claude</p> <p>2010-05-01</p> <p>Climate change tends to induce more frequent abiotic and biotic extreme <span class="hlt">events</span>, having large impacts on tree vitality. Weakened trees are then more susceptible to secondary insect outbreaks, as it happened in Belgium in the <span class="hlt">early</span> 2000s: after an <span class="hlt">early</span> frost <span class="hlt">event</span>, secondary Scolytine ambrosia beetles attacks were observed on beech trees. In this study, we test if a combination of stress, i.e. a soil water deficit preceding an <span class="hlt">early</span> frost, could render trees more attractive to beetles. An experimental study was set in autumn 2008. Two parcels of a beech forest were covered with plastic tents to induce a water stress by rain interception. The parcels were surrounded by 2-meters depth trenches to avoid water supply by streaming. Soil water content and different indicators of tree water use (sap flow, predawn leaf water potential, tree radial growth) were followed. In autumn 2010, artificial frost injuries will be inflicted to trees using dry ice. Trees attractivity for Scolytine insects, and the success of insect colonization will then be studied. The poster will focus on experiment setting and first results (impacts of soil water deficit on trees).</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010EGUGA..12.8463L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010EGUGA..12.8463L"><span>The record of Tethyan planktonic foraminifera at the <span class="hlt">early</span> Paleogene hyperthermal <span class="hlt">events</span> and Middle Eocene Climatic Optimum in northeastern Italy: are they comparable?</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Luciani, Valeria; Giusberti, Luca; Agnini, Claudia; Fornaciari, Eliana; Rio, Domenico</p> <p>2010-05-01</p> <p>The <span class="hlt">early</span> Paleogene is one of the more climatically and evolutionary dynamic periods in the Earth history that records a pronounced warming trend peaking in the <span class="hlt">Early</span> Eocene, and a successive composite transition towards the modern icehouse world. Ever increasingly scientific attention is dedicated to definitely comprehend timing, nature and characters of the complex, non-linear evolution of the Paleogene climate. Several complete and expanded Paleogene successions (Forada, Possagno, Alano, Farra), with a sound magneto-biochronostratigraphic and stable isotope record crop out in the Venetian Southern Alps (Northeast Italy). Recent studies (Giusberti et. al., 2007; Luciani et al., 2007; Agnini et al., 2008) and unpublished data document the presence in these section of the main short-lived warming <span class="hlt">events</span> (hyperthermals) of the Eocene (Paleocene-Eocene Thermal Maximum, PETM, ca 55 Ma, Eocene Layer of Mysterious Origin (ELMO, ca 53,6 Ma), X-<span class="hlt">event</span> (ca 52.5 Ma), of the <span class="hlt">Early</span> Eocene Climatic Optimum (EECO, ca 50-52 Ma) and of the Middle Eocene Climatic Optimum (MECO, ca 40 Ma; Zachos et al., 2001. 2008). All these <span class="hlt">events</span> are typified by marked negative shifts in δ13C curves that correspond to carbonate decrease related to rise of the carbonate compensation depth in turn induced by large introduction in the ocean-atmosphere system of CO2. Common features to the warming <span class="hlt">events</span> are pronounced and complex changes in planktonic foraminiferal assemblages, indicating strong environmental perturbations that perfectly parallel the variations of the stable isotope curves in all the examined <span class="hlt">events</span>. These strict correspondences indicate close cause-effect relationships between changes in environmental conditions and modifications of the assemblages. Our analysis shows that the most striking variations are recorded by the PETM and MECO assemblages that reflect highly perturbed environments. The ELMO, X-<span class="hlt">event</span> and EECO exhibit planktic foraminiferal responses that are similar to</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4116082','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4116082"><span>Rumination as a Mechanism Linking Stressful Life <span class="hlt">Events</span> to Symptoms of Depression and Anxiety: Longitudinal Evidence in <span class="hlt">Early</span> Adolescents and Adults</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Michl, Louisa C.; McLaughlin, Katie A.; Shepherd, Kathrine; Nolen-Hoeksema, Susan</p> <p>2014-01-01</p> <p>Rumination is a well-established risk factor for the onset of major depression and anxiety symptomatology in both adolescents and adults. Despite the robust associations between rumination and internalizing psychopathology, there is a dearth of research examining factors that might lead to a ruminative response style. In the current study, we examined whether social environmental experiences were associated with rumination. Specifically, we evaluated whether self-reported exposure to stressful life <span class="hlt">events</span> predicted subsequent increases in rumination. We also investigated whether rumination served as a mechanism underlying the longitudinal association between self-reported stressful life <span class="hlt">events</span> and internalizing symptoms. Self-reported stressful life <span class="hlt">events</span>, rumination, and symptoms of depression and anxiety were assessed in 2 separate longitudinal samples. A sample of <span class="hlt">early</span> adolescents (N = 1,065) was assessed at 3 time points spanning 7 months. A sample of adults (N = 1,132) was assessed at 2 time points spanning 12 months. In both samples, self-reported exposure to stressful life <span class="hlt">events</span> was associated longitudinally with increased engagement in rumination. In addition, rumination mediated the longitudinal relationship between self-reported stressors and symptoms of anxiety in both samples and the relationship between self-reported life <span class="hlt">events</span> and symptoms of depression in the adult sample. Identifying the psychological and neurobiological mechanisms that explain a greater propensity for rumination following stressors remains an important goal for future research. This study provides novel evidence for the role of stressful life <span class="hlt">events</span> in shaping characteristic responses to distress, specifically engagement in rumination, highlighting potentially useful targets for interventions aimed at preventing the onset of depression and anxiety. PMID:23713497</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27164422','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27164422"><span>Wedelolactone mitigates UVB induced oxidative stress, inflammation and <span class="hlt">early</span> tumor promotion <span class="hlt">events</span> in murine skin: plausible role of NFkB pathway.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ali, Farrah; Khan, Bilal Azhar; Sultana, Sarwat</p> <p>2016-09-05</p> <p>UVB (Ultra-violet B) radiation is one of the major etiological factors in various dermal pathology viz. dermatitis, actinic folliculitis, solar urticaria, psoriasis and cancer among many others. UVB causes toxic manifestation in tissues by inciting inflammatory and tumor promoting <span class="hlt">events</span>. We have designed this study to assess the anti-inflammatory and anti-tumor promotion effect of Wedelolactone (WDL) a specific IKK inhibitor. Results indicate significant restoration of anti-oxidative enzymes due to WDL treatments. We also found that WDL was effective in mitigating inflammatory markers consisting of MPO (myeloperoxidase), Mast cells trafficking, Langerhans cells suppression and COX 2 expression up regulation due to UVB exposure. We also deduce that WDL presented a promising intervention in attenuating <span class="hlt">early</span> tumor promotion <span class="hlt">events</span> caused by UVB exposure as indicated by the results of ODC (Ornithine Decarboxylase), Thymidine assay, Vimentin and VEGF (Vascular-endothelial growth factor) expression. This study was able to provide substantial cues for the therapeutic ability of Wedelolactone against inflammatory and tumor promoting <span class="hlt">events</span> in murine skin depicting plausible role of NFkB pathway. Copyright © 2016 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=Genetics&pg=4&id=EJ1119047','ERIC'); return false;" href="https://eric.ed.gov/?q=Genetics&pg=4&id=EJ1119047"><span>Longitudinal Effects on <span class="hlt">Early</span> Adolescent Language: A Twin Study</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Harlarr, Nicole; De Thorne, Laura Segebart; Smith, Jamie Mahurin; Betancourt, Mariana Aparicio; Petrill, Stephen A.</p> <p>2016-01-01</p> <p>Purpose: We evaluated <span class="hlt">genetic</span> and environmental contributions to individual differences in language skills during <span class="hlt">early</span> adolescence, measured by both language sampling and standardized tests, and examined the extent to which these <span class="hlt">genetic</span> and environmental effects are stable across time. Purpose: We evaluated <span class="hlt">genetic</span> and environmental…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3732434','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3732434"><span>Utilization of <span class="hlt">Genetic</span> Testing Prior to Subspecialist Referral for Cerebellar Ataxia</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Fogel, Brent L.; Vickrey, Barbara G.; Walton-Wetzel, Jenny; Lieber, Eli</p> <p>2013-01-01</p> <p>Objective: To evaluate the utilization of laboratory testing in the diagnosis of cerebellar ataxia, including the completeness of initial standard testing for acquired causes, the <span class="hlt">early</span> use of <span class="hlt">genetic</span> testing, and associated clinical and nonclinical factors, among a cohort referred for subspecialty consultation. Methods: Data were abstracted from records of 95 consecutive ataxia patients referred to one neurogenetics subspecialist from 2006–2010 and linked to publicly available data on characteristics of referral clinicians. Multivariable logistic and linear regression models were used to analyze unique associations of clinical and nonclinical factors with laboratory investigation of acquired causes and with <span class="hlt">early</span> <span class="hlt">genetic</span> testing prior to referral. Results: At referral, 27 of 95 patients lacked evidence of any of 14 laboratory studies suggested for initial work-up of an acquired cause for ataxia (average number of tests=4.5). In contrast, 92% of patients had undergone brain magnetic resonance imaging prior to referral. Overall, 41.1% (n=39) had <span class="hlt">genetic</span> testing prior to referral; there was no association between family history of ataxia and obtaining <span class="hlt">genetic</span> testing prior to referral (p=0.39). The level of <span class="hlt">early</span> <span class="hlt">genetic</span> testing was 31.6%, primarily due to <span class="hlt">genetic</span> testing despite an incomplete laboratory evaluation for acquired causes and no family history. A positive family history was consistently associated with less extensive laboratory testing (p=0.004), and referral by a neurologist was associated with higher levels of <span class="hlt">early</span> <span class="hlt">genetic</span> testing. Conclusions: Among consecutive referrals to a single center, a substantial proportion of sporadic cases had <span class="hlt">genetic</span> testing without evidence of a work-up for acquired causes. Better strategies to guide decision making and subspecialty referrals in rare neurologic disorders are needed, given the cost and consequences of <span class="hlt">genetic</span> testing. PMID:23725007</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-201203080002HQ.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-201203080002HQ.html"><span>Women, Innovation and Aerospace <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2012-03-08</p> <p>NASA Deputy Administrator, Lori Garver, gives the keynote address at the Women, Innovation and Aerospace <span class="hlt">event</span> celebrating Women's History Month at the George Washington University Jack Morton Auditorium, Thursday, March 8, 2012 in Washington. The WIA day-long <span class="hlt">event</span> will help to foster a discussion for students and <span class="hlt">early</span> career professionals about how to continue to encourage women to enter and succeed in the field of aerospace. Photo Credit: (NASA/Carla Cioffi)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-201203080003HQ.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-201203080003HQ.html"><span>Women, Innovation and Aerospace <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2012-03-08</p> <p>NASA Deputy Administrator, Lori Garver, far right, gives the keynote address at the Women, Innovation and Aerospace <span class="hlt">event</span> celebrating Women's History Month at the George Washington University Jack Morton Auditorium, Thursday, March 8, 2012 in Washington. The WIA day-long <span class="hlt">event</span> will help to foster a discussion for students and <span class="hlt">early</span> career professionals about how to continue to encourage women to enter and succeed in the field of aerospace. Photo Credit: (NASA/Carla Cioffi)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-201203080011HQ.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-201203080011HQ.html"><span>Women, Innovation and Aerospace <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2012-03-08</p> <p>Marcia Smith, President, spacepolicyonline.com, participates in a panel discussion at the Women, Innovation and Aerospace <span class="hlt">event</span> celebrating Women's History Month at the George Washington University Jack Morton Auditorium, Thursday, March 8, 2012 in Washington. The WIA day-long <span class="hlt">event</span> will help to foster a discussion for students and <span class="hlt">early</span> career professionals about how to continue to encourage women to enter and succeed in the field of aerospace. Photo Credit: (NASA/Carla Cioffi)</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_24 --> <div id="page_25" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="481"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=event&pg=2&id=EJ1090686','ERIC'); return false;" href="https://eric.ed.gov/?q=event&pg=2&id=EJ1090686"><span><span class="hlt">Early</span> Verb Learning: How Do Children Learn How to Compare <span class="hlt">Events</span>?</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Childers, Jane B.; Parrish, Rebecca; Olson, Christina V.; Burch, Clare; Fung, Gavin; McIntyre, Kevin P.</p> <p>2016-01-01</p> <p>An important problem verb learners must solve is how to extend verbs. Children could use cross-situational information to guide their extensions; however, comparing <span class="hlt">events</span> is difficult. In 2 studies, researchers tested whether children benefit from initially seeing a pair of similar <span class="hlt">events</span> ("progressive alignment") while learning new…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015RScEd..45..485S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015RScEd..45..485S"><span>A Tri-part Model for <span class="hlt">Genetics</span> Literacy: Exploring Undergraduate Student Reasoning About Authentic <span class="hlt">Genetics</span> Dilemmas</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Shea, Nicole A.; Duncan, Ravit Golan; Stephenson, Celeste</p> <p>2015-08-01</p> <p><span class="hlt">Genetics</span> literacy is becoming increasingly important as advancements in our application of <span class="hlt">genetic</span> technologies such as stem cell research, cloning, and <span class="hlt">genetic</span> screening become more prevalent. Very few studies examine how <span class="hlt">genetics</span> literacy is applied when reasoning about authentic <span class="hlt">genetic</span> dilemmas. However, there is evidence that situational features of a reasoning task may influence how students apply content knowledge as they generate and support arguments. Understanding how students apply content knowledge to reason about authentic and complex issues is important for considering instructional practices that best support student thinking and reasoning. In this conceptual report, we present a tri-part model for <span class="hlt">genetics</span> literacy that embodies the relationships between content knowledge use, argumentation quality, and the role of situational features in reasoning to support <span class="hlt">genetics</span> literacy. Using illustrative examples from an interview study with <span class="hlt">early</span> career undergraduate students majoring in the biological sciences and late career undergraduate students majoring in <span class="hlt">genetics</span>, we provide insights into undergraduate student reasoning about complex <span class="hlt">genetics</span> issues and discuss implications for teaching and learning. We further discuss the need for research about how the tri-part model of <span class="hlt">genetics</span> literacy can be used to explore students' thinking and reasoning abilities in <span class="hlt">genetics</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25188543','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25188543"><span><span class="hlt">Early</span> intervention following trauma may mitigate <span class="hlt">genetic</span> risk for PTSD in civilians: a pilot prospective emergency department study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rothbaum, Barbara O; Kearns, Megan C; Reiser, Emily; Davis, Jennifer S; Kerley, Kimberly A; Rothbaum, Alex O; Mercer, Kristina B; Price, Matthew; Houry, Debra; Ressler, Kerry J</p> <p>2014-12-01</p> <p>Civilian posttraumatic stress disorder (PTSD) and combat PTSD are major public health concerns. Although a number of psychosocial risk factors have been identified related to PTSD risk, there are no accepted, robust biological predictors that identify who will develop PTSD or who will respond to <span class="hlt">early</span> intervention following trauma. We wished to examine whether <span class="hlt">genetic</span> risk for PTSD can be mitigated with an <span class="hlt">early</span> intervention. 65 emergency department patients recruited in 2009-2010 at Grady Memorial Hospital in Atlanta, Georgia, who met criterion A of DSM-IV PTSD received either 3 sessions of an exposure intervention, beginning in the emergency department shortly after trauma exposure or assessment only. PTSD symptoms were assessed 4 and 12 weeks after trauma exposure. A composite additive risk score was derived from polymorphisms in 10 previously identified genes associated with stress-response (ADCYAP1R1, COMT, CRHR1, DBH, DRD2, FAAH, FKBP5, NPY, NTRK2, and PCLO), and gene x treatment effects were examined. The intervention included 3 sessions of imaginal exposure to the trauma memory and additional exposure homework. The primary outcome measure was the PTSD Symptom Scale-Interview Version or DSM-IV-based PTSD diagnosis in patients related to genotype and treatment group. A gene x intervention x time effect was detected for individual polymorphisms, in particular the PACAP receptor, ADCYAP1R1, as well as with a combined genotype risk score created from independent SNP markers. Subjects who did not receive treatment had higher symptoms than those who received intervention. Furthermore, subjects with the "risk" genotypes who did not receive intervention had higher PTSD symptoms compared to those with the "low-risk" or "resilience" genotypes or those who received intervention. Additionally, PTSD symptoms correlated with level of <span class="hlt">genetic</span> risk at week 12 (P < .005) in the assessment-only group, but with no relationship in the intervention group, even after controlling</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016EGUGA..1814279F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016EGUGA..1814279F"><span>The <span class="hlt">Early</span> Toarcian Oceanic Anoxic <span class="hlt">Event</span>: A Southern Hemisphere record from Chile</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Fantasia, Alicia; Föllmi, Karl B.; Adatte, Thierry; Spangenberg, Jorge E.; Bernárdez, Enrique; Mattioli, Emanuela</p> <p>2016-04-01</p> <p>The <span class="hlt">Early</span> Toarcian was marked by important environmental changes, marine oxygen deficiency and extensive organic-rich sediment deposition (T-OAE; ˜182 Ma, <span class="hlt">Early</span> Jurassic). The T-OAE coincides with a marked negative carbon isotope excursion (CIE) recorded in marine carbonate, and marine and terrestrial organic carbon. This is commonly attributed to the massive release of isotopically light carbon to the atmospheric and oceanic reservoirs derived from the destabilization of methane hydrates from marine sediments and/or the emissions of thermogenic methane from the eruption of the Karoo-Ferrar LIP (e.g., Hesselbo et al., 2000; Kemp et al., 2005; Svensen et al., 2007; Mazzini et al., 2010). Moreover, in most documented marine sections, this episode is marked by a generalized crisis in carbonate production and marine invertebrate extinctions (e.g. Jenkyns, 1988; Röhl et al., 2005; Suan et al., 2001). Several studies of the T-OAE have been conducted on sediments in central and northwest Europe, but only few data are available from the Southern Hemisphere, leading to large uncertainty concerning the exact expression of this <span class="hlt">event</span> in this part of the world. The aims of this study are to characterize the sediments deposited during the Andean equivalents of the tenuicostatum and falciferum European Zones and establish in which way the T-OAE affected this region. In the <span class="hlt">Early</span> Jurassic, the Andean basin was in a back-arc setting with marine corridors connected to Panthalassa. In this study, we have generated new high-resolution sedimentological, geochemical and mineralogical data from the sections of El Peñon and Quebrada Asiento, located in Chile in the northeastern area of the city of Copiapó, Atacama region. The biostratigraphy of these sections has been studied by von Hillebrandt and Schidt-Effing (1981) and complemented here by a biostratigraphy based on calcareous nannofossils. The sections consist of a succession of marl, limestone and siltstone of Pliensbachian and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://pubs.er.usgs.gov/publication/70116322','USGSPUBS'); return false;" href="https://pubs.er.usgs.gov/publication/70116322"><span><span class="hlt">Genetic</span> diversity of a newly established population of golden eagles on the Channel Islands, California</span></a></p> <p><a target="_blank" href="http://pubs.er.usgs.gov/pubs/index.jsp?view=adv">USGS Publications Warehouse</a></p> <p>Sonsthagen, Sarah A.; Coonan, Timothy J.; Latta, Brian C.; Sage, George K.; Talbot, Sandra L.</p> <p>2012-01-01</p> <p>Gene flow can have profound effects on the <span class="hlt">genetic</span> diversity of a founding population depending on the number and relationship among colonizers and the duration of the colonization <span class="hlt">event</span>. Here we used data from nuclear microsatellite and mitochondrial DNA control region loci to assess <span class="hlt">genetic</span> diversity in golden eagles of the recently colonized Channel Islands, California. <span class="hlt">Genetic</span> diversity in the Channel Island population was low, similar to signatures observed for other recent colonizing island populations. Differences in levels of <span class="hlt">genetic</span> diversity and structure observed between mainland California and the islands suggests that few individuals were involved in the initial founding <span class="hlt">event</span>, and may have comprised a family group. The spatial <span class="hlt">genetic</span> structure observed between Channel Island and mainland California golden eagle populations across marker types, and <span class="hlt">genetic</span> signature of population decline observed for the Channel Island population, suggest a single or relatively quick colonization <span class="hlt">event</span>. Polarity in gene flow estimates based on mtDNA confirm an initial colonization of the Channel Islands by mainland golden eagles, but estimates from microsatellite data suggest that golden eagles on the islands were dispersing more recently to the mainland, possibly after reaching the carrying capacity of the island system. These results illustrate the strength of founding <span class="hlt">events</span> on the <span class="hlt">genetic</span> diversity of a population, and confirm that changes to <span class="hlt">genetic</span> diversity can occur within just a few generations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ars.usda.gov/research/publications/publication/?seqNo115=313476','TEKTRAN'); return false;" href="http://www.ars.usda.gov/research/publications/publication/?seqNo115=313476"><span>Improved <span class="hlt">genetic</span> disease resistance solutions for potato</span></a></p> <p><a target="_blank" href="https://www.ars.usda.gov/research/publications/find-a-publication/">USDA-ARS?s Scientific Manuscript database</a></p> <p></p> <p></p> <p>The Halterman Lab research program is focused on understanding the <span class="hlt">genetic</span> basis of disease resistance in potato. Several diseases, such as late blight, <span class="hlt">early</span> blight, potato virus Y, and verticillium wilt, are particularly problematic in Wisconsin. With the exception of <span class="hlt">early</span> blight, major genes hav...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014EGUGA..1613072C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014EGUGA..1613072C"><span>The PRESSCA operational <span class="hlt">early</span> warning system for landslide forecasting: the 11-12 November 2013 rainfall <span class="hlt">event</span> in Central Italy.</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Ciabatta, Luca; Brocca, Luca; Ponziani, Francesco; Berni, Nicola; Stelluti, Marco; Moramarco, Tommaso</p> <p>2014-05-01</p> <p>The Umbria Region, located in Central Italy, is one of the most landslide risk prone area in Italy, almost yearly affected by landslides <span class="hlt">events</span> at different spatial scales. For <span class="hlt">early</span> warning procedures aimed at the assessment of the hydrogeological risk, the rainfall thresholds represent the main tool for the Italian Civil Protection System. As shown in previous studies, soil moisture plays a key-role in landslides triggering. In fact, acting on the pore water pressure, soil moisture influences the rainfall amount needed for activating a landslide. In this work, an operational physically-based <span class="hlt">early</span> warning system, named PRESSCA, that takes into account soil moisture for the definition of rainfall thresholds is presented. Specifically, the soil moisture conditions are evaluated in PRESSCA by using a distributed soil water balance model that is recently coupled with near real-time satellite soil moisture product obtained from ASCAT (Advanced SCATterometer) and from in-situ monitoring data. The integration of three different sources of soil moisture information allows to estimate the most accurate possible soil moisture condition. Then, both observed and forecasted rainfall data are compared with the soil moisture-based thresholds in order to obtain risk indicators over a grid of ~ 5 km. These indicators are then used for the daily hydrogeological risk evaluation and management by the Civil Protection regional service, through the sharing/delivering of near real-time landslide risk scenarios (also through an open source web platform: www.cfumbria.it). On the 11th-12th November, 2013, Umbria Region was hit by an exceptional rainfall <span class="hlt">event</span> with up to 430mm/72hours that resulted in significant economic damages, but fortunately no casualties among the population. In this study, the results during the rainfall <span class="hlt">event</span> of PRESSCA system are described, by underlining the model capability to reproduce, two days in advance, landslide risk scenarios in good spatial and temporal</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/AD1034458','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/AD1034458"><span>Model Based Verification of Cyber Range <span class="hlt">Event</span> Environments</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>2015-12-10</p> <p>Model Based Verification of Cyber Range <span class="hlt">Event</span> Environments Suresh K. Damodaran MIT Lincoln Laboratory 244 Wood St., Lexington, MA, USA...apply model based verification to cyber range <span class="hlt">event</span> environment configurations, allowing for the <span class="hlt">early</span> detection of errors in <span class="hlt">event</span> environment...Environment Representation (CCER) ontology. We also provide an overview of a methodology to specify verification rules and the corresponding error</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3992691','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3992691"><span>Chronology in lesion tolerance gives priority to <span class="hlt">genetic</span> variability</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Naiman, Karel; Philippin, Gaëlle; Fuchs, Robert P.; Pagès, Vincent</p> <p>2014-01-01</p> <p>The encounter of a replication fork with a blocking DNA lesion is a common <span class="hlt">event</span> that cells need to address properly to preserve genome integrity. Cells possess two main strategies to tolerate unrepaired lesions: potentially mutagenic translesion synthesis (TLS) and nonmutagenic damage avoidance (DA). Little is known about the partitioning between these two strategies. Because genes involved in DA mechanisms (i.e., recA) are expressed <span class="hlt">early</span> and genes involved in TLS (i.e., Pol V) are expressed late during the bacterial SOS response, it has long been thought that TLS was the last recourse to bypass DNA lesions when repair and nonmutagenic DA mechanisms have failed. By using a recently described methodology, we followed the fate of a single replication-blocking lesion introduced in the Escherichia coli genome during acute genotoxic stress. We show that lesion tolerance <span class="hlt">events</span> (i) only occur when the SOS response is fully induced and (ii) are executed in chronological order, with TLS coming first, followed by DA. Therefore, in response to genotoxic stress, bacterial cells give priority to TLS, a minor pathway able to generate <span class="hlt">genetic</span> diversity before implementing the major nonmutagenic pathway that ensures survival. PMID:24706928</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25218753','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25218753"><span><span class="hlt">Genetic</span> analysis of milk β-hydroxybutyrate and its association with fat-to-protein ratio, body condition score, clinical ketosis, and displaced abomasum in <span class="hlt">early</span> first lactation of Canadian Holsteins.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Koeck, A; Jamrozik, J; Schenkel, F S; Moore, R K; Lefebvre, D M; Kelton, D F; Miglior, F</p> <p>2014-11-01</p> <p>The aim of this study was to estimate <span class="hlt">genetic</span> parameters for milk β-hydroxybutyrate (BHBA) in <span class="hlt">early</span> first lactation of Canadian Holstein cows and to examine its <span class="hlt">genetic</span> association with indicators of energy balance (fat-to-protein ratio and body condition score) and metabolic diseases (clinical ketosis and displaced abomasum). Data for milk BHBA recorded between 5 and 100 d in milk was obtained from Valacta (Sainte-Anne-de-Bellevue, Québec, Canada), the Canadian Dairy Herd Improvement organization responsible for Québec and Atlantic provinces. Test-day milk samples were analyzed by mid-infrared spectrometry using previously developed calibration equations for milk BHBA. Test-day records of fat-to-protein ratio were obtained from the routine milk recording scheme. Body condition score records were available from the routine type classification system. Data on clinical ketosis and displaced abomasum recorded by producers were available from the national dairy cattle health system in Canada. Data were analyzed using linear animal models. Heritability estimates for milk BHBA at different stages of <span class="hlt">early</span> lactation were between 0.14 and 0.29. <span class="hlt">Genetic</span> correlations between milk BHBA were higher between adjacent lactation intervals and decreased as intervals were further apart. Correlations between breeding values for milk BHBA and routinely evaluated traits revealed that selection for lower milk BHBA in <span class="hlt">early</span> lactation would lead to an improvement of several health and fertility traits, including SCS, calving to first service, number of services, first service to conception, and days open. Also, lower milk BHBA was associated with a longer herd life, better conformation, and better feet and legs. A higher <span class="hlt">genetic</span> merit for milk yield was associated with higher milk BHBA, and, therefore, a greater susceptibility to hyperketonemia. Milk BHBA at the first test-day was moderately <span class="hlt">genetically</span> correlated with fat-to-protein ratio (0.49), body condition score (-0.35), and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5397498','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5397498"><span>Quantitative <span class="hlt">Genetic</span> Analysis Reveals Potential to <span class="hlt">Genetically</span> Improve Fruit Yield and Drought Resistance Simultaneously in Coriander</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Khodadadi, Mostafa; Dehghani, Hamid; Jalali Javaran, Mokhtar</p> <p>2017-01-01</p> <p>Enhancing water use efficiency of coriander (Coriandrum sativum L.) is a major focus for coriander breeding to cope with drought stress. The purpose of this study was; (a) to identify the predominant mechanism(s) of drought resistance in coriander and (b) to evaluate the <span class="hlt">genetic</span> control mechanism(s) of traits associated with drought resistance and higher fruit yield. To reach this purpose, 15 half-diallel hybrids of coriander and their six parents were evaluated under well-watered and water deficit stressed (WDS) in both glasshouse lysimetric and field conditions. The parents were selected for their different response to water deficit stress following preliminary experiments. Results revealed that the <span class="hlt">genetic</span> control mechanism of fruit yield is complex, variable and highly affected by environment. The mode of inheritance and nature of gene action for percent assimilate partitioned to fruits were similar to those for flowering time in both well-watered and WDS conditions. A significant negative <span class="hlt">genetic</span> linkage was found between fruit yield and percent assimilate partitioned to root, percent assimilate partitioned to shoot, root number, root diameter, root dry mass, root volume, and <span class="hlt">early</span> flowering. Thus, to improve fruit yield under water deficit stress, selection of low values of these traits could be used. In contrast, a significant positive <span class="hlt">genetic</span> linkage between fruit yield and percent assimilate partitioned to fruits, leaf relative water content and chlorophyll content indicate selection for high values of these traits. These secondary or surrogate traits could be selected during <span class="hlt">early</span> segregating generations. The <span class="hlt">early</span> ripening parent (P1; TN-59-230) contained effective genes involved in preferred percent assimilate partitioning to fruit and drought stress resistance. In conclusion, <span class="hlt">genetic</span> improvement of fruit yield and drought resistance could be simultaneously gained in coriander when breeding for drought resistance. PMID:28473836</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3891765','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3891765"><span>Comprehensive <span class="hlt">Genetic</span> Analysis of <span class="hlt">Early</span> Host Body Reactions to the Bioactive and Bio-Inert Porous Scaffolds</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ehashi, Tomo; Takemura, Taro; Hanagata, Nobutaka; Minowa, Takashi; Kobayashi, Hisatoshi; Ishihara, Kazuhiko; Yamaoka, Tetsuji</p> <p>2014-01-01</p> <p>To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in <span class="hlt">genetic</span> analysis technologies, <span class="hlt">genetically</span> comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of <span class="hlt">early</span> host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1β and IL-10 are important cytokines in tissue responses to biomaterials because IL-1β promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1β was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1- and M2-macrophage-related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these <span class="hlt">genetic</span> regulations. PMID:24454803</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5061919','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5061919"><span>Effects of complex life cycles on <span class="hlt">genetic</span> diversity: cyclical parthenogenesis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Rouger, R; Reichel, K; Malrieu, F; Masson, J P; Stoeckel, S</p> <p>2016-01-01</p> <p>Neutral patterns of population <span class="hlt">genetic</span> diversity in species with complex life cycles are difficult to anticipate. Cyclical parthenogenesis (CP), in which organisms undergo several rounds of clonal reproduction followed by a sexual <span class="hlt">event</span>, is one such life cycle. Many species, including crop pests (aphids), human parasites (trematodes) or models used in evolutionary science (Daphnia), are cyclical parthenogens. It is therefore crucial to understand the impact of such a life cycle on neutral <span class="hlt">genetic</span> diversity. In this paper, we describe distributions of <span class="hlt">genetic</span> diversity under conditions of CP with various clonal phase lengths. Using a Markov chain model of CP for a single locus and individual-based simulations for two loci, our analysis first demonstrates that strong departures from full sexuality are observed after only a few generations of clonality. The convergence towards predictions made under conditions of full clonality during the clonal phase depends on the balance between mutations and <span class="hlt">genetic</span> drift. Second, the sexual <span class="hlt">event</span> of CP usually resets the <span class="hlt">genetic</span> diversity at a single locus towards predictions made under full sexuality. However, this single recombination <span class="hlt">event</span> is insufficient to reshuffle gametic phases towards full-sexuality predictions. Finally, for similar levels of clonality, CP and acyclic partial clonality (wherein a fixed proportion of individuals are clonally produced within each generation) differentially affect the distribution of <span class="hlt">genetic</span> diversity. Overall, this work provides solid predictions of neutral <span class="hlt">genetic</span> diversity that may serve as a null model in detecting the action of common evolutionary or demographic processes in cyclical parthenogens (for example, selection or bottlenecks). PMID:27436524</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27436524','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27436524"><span>Effects of complex life cycles on <span class="hlt">genetic</span> diversity: cyclical parthenogenesis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rouger, R; Reichel, K; Malrieu, F; Masson, J P; Stoeckel, S</p> <p>2016-11-01</p> <p>Neutral patterns of population <span class="hlt">genetic</span> diversity in species with complex life cycles are difficult to anticipate. Cyclical parthenogenesis (CP), in which organisms undergo several rounds of clonal reproduction followed by a sexual <span class="hlt">event</span>, is one such life cycle. Many species, including crop pests (aphids), human parasites (trematodes) or models used in evolutionary science (Daphnia), are cyclical parthenogens. It is therefore crucial to understand the impact of such a life cycle on neutral <span class="hlt">genetic</span> diversity. In this paper, we describe distributions of <span class="hlt">genetic</span> diversity under conditions of CP with various clonal phase lengths. Using a Markov chain model of CP for a single locus and individual-based simulations for two loci, our analysis first demonstrates that strong departures from full sexuality are observed after only a few generations of clonality. The convergence towards predictions made under conditions of full clonality during the clonal phase depends on the balance between mutations and <span class="hlt">genetic</span> drift. Second, the sexual <span class="hlt">event</span> of CP usually resets the <span class="hlt">genetic</span> diversity at a single locus towards predictions made under full sexuality. However, this single recombination <span class="hlt">event</span> is insufficient to reshuffle gametic phases towards full-sexuality predictions. Finally, for similar levels of clonality, CP and acyclic partial clonality (wherein a fixed proportion of individuals are clonally produced within each generation) differentially affect the distribution of <span class="hlt">genetic</span> diversity. Overall, this work provides solid predictions of neutral <span class="hlt">genetic</span> diversity that may serve as a null model in detecting the action of common evolutionary or demographic processes in cyclical parthenogens (for example, selection or bottlenecks).</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-201203080009HQ.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-201203080009HQ.html"><span>Women, Innovation and Aerospace <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2012-03-08</p> <p>Catherine Didion, Senior Fellow, National Academy of Engineering, participates in a panel discussion at the Women, Innovation and Aerospace <span class="hlt">event</span> celebrating Women's History Month at the George Washington University Jack Morton Auditorium, Thursday, March 8, 2012 in Washington. The WIA day-long <span class="hlt">event</span> will help to foster a discussion for students and <span class="hlt">early</span> career professionals about how to continue to encourage women to enter and succeed in the field of aerospace. Photo Credit: (NASA/Carla Cioffi)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-201203080001HQ.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-201203080001HQ.html"><span>Women, Innovation and Aerospace <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2012-03-08</p> <p>Rebecca Spyke-Keiser, NASA's Associate Deputy Administrator for policy integration, gives opening remarks at the Women, Innovation and Aerospace <span class="hlt">event</span> celebrating Women's History Month at the George Washington University Jack Morton Auditorium, Thursday, March 8, 2012 in Washington. The WIA day-long <span class="hlt">event</span> will help to foster a discussion for students and <span class="hlt">early</span> career professionals about how to continue to encourage women to enter and succeed in the field of aerospace. Photo Credit: (NASA/Carla Cioffi)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=emotional+AND+reasoning&pg=6&id=EJ914728','ERIC'); return false;" href="https://eric.ed.gov/?q=emotional+AND+reasoning&pg=6&id=EJ914728"><span>Non-Verbal Reasoning Ability and Academic Achievement as Moderators of the Relation between Adverse Life <span class="hlt">Events</span> and Emotional and Behavioural Problems in <span class="hlt">Early</span> Adolescence: The Importance of Moderator and Outcome Specificity</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Flouri, Eirini; Tzavidis, Nikos</p> <p>2011-01-01</p> <p>This study was carried out to model the functional form of the effect of contextual risk (number of adverse life <span class="hlt">events</span>) on emotional and behavioural problems in <span class="hlt">early</span> adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life <span class="hlt">events</span> on emotional and behavioural…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20947701','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20947701"><span>A novel protein kinase D inhibitor attenuates <span class="hlt">early</span> <span class="hlt">events</span> of experimental pancreatitis in isolated rat acini.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Thrower, Edwin C; Yuan, Jingzhen; Usmani, Ashar; Liu, Yannan; Jones, Courtney; Minervini, Samantha N; Alexandre, Martine; Pandol, Stephen J; Guha, Sushovan</p> <p>2011-01-01</p> <p>Novel protein kinase C isoforms (PKC δ and ε) mediate <span class="hlt">early</span> <span class="hlt">events</span> in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial <span class="hlt">events</span> leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Gö6976 (10 μM). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 μM), carbachol (CCh, 1 mM), or bombesin (10 μM) to induce initial <span class="hlt">events</span> of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-κB activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) ∼3.75-5 μM but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Gö6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-κB activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-κB activation induced by a range of secretagogues in pancreatic acinar cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24430894','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24430894"><span>Age-related variation in <span class="hlt">genetic</span> control of height growth in Douglas-fir.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Namkoong, G; Usanis, R A; Silen, R R</p> <p>1972-01-01</p> <p>The development of <span class="hlt">genetic</span> variances in height growth of Douglas-fir over a 53-year period is analyzed and found to fall into three periods. In the juvenile period, variances in environmental error increase logarithmically, <span class="hlt">genetic</span> variance within populations exists at moderate levels, and variance among populations is low but increasing. In the <span class="hlt">early</span> reproductive period, the response to environmental sources of error variance is restricted, <span class="hlt">genetic</span> variance within populations disappears, and populational differences strongly emerge but do not increase as expected. In the later period, environmental error again increases rapidly, but <span class="hlt">genetic</span> variance within populations does not reappear and population differences are maintained at about the same level as established in the <span class="hlt">early</span> reproductive period. The change between the juvenile and <span class="hlt">early</span> reproductive periods is perhaps associated with the onset of ecological dominance and significant allocations of energy to reproduction.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/1230831','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/1230831"><span>[<span class="hlt">Genetics</span> and criminology: a new concept].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jeffery, C R; Jeffery, I A</p> <p>1975-01-01</p> <p>The <span class="hlt">early</span> history of criminology was one of interaction with <span class="hlt">genetics</span> and biology, but since the sociological school emerged in the 1920's there has occurred a major split between sociological criminology and biology. Behavioral <span class="hlt">genetics</span> as it has developed since 1950 has great relevance to criminology in terms of neurological and brain functioning, learning processes, violence and the XYY syndrome, and the sociopathy. A new interdisciplinary research effort must be undertaken in order to look at the interaction of <span class="hlt">genetics</span>, human behavior, criminal law and criminology. If criminology is interested in learning, motivation, aggression and behavior, it must incorporate the new <span class="hlt">genetics</span> into its theoretical structure.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_25 --> <div class="footer-extlink text-muted" style="margin-bottom:1rem; text-align:center;">Some links on this page may take you to non-federal websites. 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